bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Multipurpose Solution Combined With Autophagy Inhibitors on Adhesion of Acanthamoeba trophozoites to Silicone Hydrogel Contact Lenses
Authors: Lee Seung-Mok , Lee Da-In , Park Sung-Hee , Yu Hak-Sun , Lee Ji-Eun , Lee Jong-Soo
Published: August 2017

Purpose:

The aim of the study was to evaluate the effect of multipurpose contact lens (CL) solution (MPS) combined with autophagy inhibitors on the adhesion properties of Acanthamoeba castellanii (AC) trophozoites to silicone hydrogel CLs.

Methods:

AC trophozoites were inoculated onto discs trimmed from a silicone hydrogel CL with plasma surface treatment. After 18 hours, the number of adherent AC trophozoites on the CL treated with MPS was counted under phase-contrast microscopy. We analyzed the efficacy of MPS combined with autophagy inhibitors, 3-methyladenine (0.1, 1, and 5 mM) and chloroquine (10, 100 μM, and 1 mM), on Acanthamoeba adhesion by electron microscopy.

Results:

Adhesion of AC trophozoites to the CL treated with MPS (average number of trophozoites adhered to the CL: 61.2 ± 8.1) was significantly lower compared with that of the CL treated without MPS (83.8 ± 10.2) (P = 0.027). In MPS application, the number of adhered AC trophozoites treated with 3-methyladenine [8.2 ± 2.5 for 5 mM (P = 0.008)] or chloroquine [19.4 ± 7.6 for 100 μM (P = 0.038) and 5.3 ± 1.9 for 1 mM (P = 0.001)] was significantly reduced compared with the sample without autophagy inhibitors. However, the number of adherent AC trophozoites was not significantly reduced in less than 5 mM in 3-methyladenine [50.4 ± 5.1 for 0.1 mM (P = 0.084) and 43.1 ± 5.0 for 1 mM (P = 0.079)] and 100 μM in chloroquine [40.6 ± 13.5 for 10 μM (P = 0.075)]. 3-methyladenine induced blebby structures or disrupted the membranes of AC trophozoites. AC trophozoites treated with chloroquine showed undigested organelles in the cytoplasm of Acanthamoeba cells.

Conclusions:

MPS combined with 3-methyladenine or chloroquine reduced the adhesion rate of AC trophozoites rather than MPS containing only polyhexamethylene biguanide. Appropriate concentrations of autophagy inhibitors, 3-methyladenine and chloroquine, added to commercial MPS should be considered to decrease the clinical rate of Acanthamoeba keratitis.
Intraocular Pressure Fluctuations and 24-Hour Continuous Monitoring for Glaucoma Risk in Wind Instrument Players
Authors: de Crom Ronald M.P.C. , Webers Carroll A.B. , van Kooten-Noordzij Marina A.W. , Michiels Agnes C. , Schouten Jan S.A.G. , Berendschot Tos T.J.M. , Beckers Henny J.M.
Published: August 2017

Purpose:

The purpose of this study is to investigate the influence of playing a wind instrument on intraocular pressure (IOP) and to monitor 24-hour (IOP) fluctuations in wind musicians of symphony and wind orchestras to compare IOP levels during normal daily activities with IOP levels during playing.

Methods:

Professional and amateur musicians of symphony and wind orchestras were invited to participate. A total of 42 participants, 9 with glaucoma, underwent a routine ophthalmologic examination. IOP measurements were taken before and immediately after 20 minutes of playing wind instruments. In addition, 6 participants underwent 24-hour IOP monitoring with the Triggerfish (Sensimed AG, Switzerland) sensing contact lens, during which they kept an activity logbook.

Results:

Eleven professionals and 31 amateur musicians participated in the study. A total of 7 eyes of 6 patients underwent additional 24-hour IOP monitoring. Mean IOP before playing was 13.6±2.6 mm Hg, IOP change after playing was +1.5±2.2 mm Hg with a significant difference between professionals (2.5±1.5 mm Hg) and amateurs (1.1±2.3 mm Hg). There were no significant differences in IOP change between subjects with or without glaucoma. During 24-hour IOP monitoring there were slight increases in IOP while playing an instrument, but also during other activities and overnight. These latter IOP levels were similar or even higher than the IOP rise caused by playing a wind instrument.

Conclusions:

IOP often rises after playing wind instruments, but similar or even higher IOP levels seem to occur during common other daily activities or at night. These peaks may be relevant for glaucomatous field progression and treatment of glaucoma patients.
Valsalva Maneuver-induced Changes in Anterior Lamina Cribrosa Surface DEPTH: A Comparison Between Normal and Glaucomatous Eyes
Authors: Kim Young Kook , Ha Ahnul , Song Yong Ju , Na Kyeong Ik , Lee Won June , Jeoung Jin Wook , Park Ki Ho
Published: August 2017

Purpose:

The purpose of this study is to investigate the influence of the Valsalva maneuver (VM) on anterior lamina cribrosa surface depth (ALCSD), and to compare normal with treated glaucomatous eyes in terms of this effect.

Methods:

Thirty-two patients (32 eyes) with early-to-moderate glaucoma under treatment and 30 normal healthy participants (30 eyes) were prospectively enrolled. Study subjects performed the VM by blowing through a mouthpiece attached to a handheld manometer; expiratory pressure during the maneuver ranged from 35 to 40 mm Hg. Swept-source optical coherence tomography B-scans were performed during phase 2 of the VM (from 10 to 15 s).

Results:

The ALCSD was significantly different in the normal eyes only, decreasing by 31.90±14.81 μm (−8.79%; 394.85±53.63 μm at baseline vs. 362.95±44.23 μm during the VM; P<0.001). In the glaucomatous eyes, the ALCSD decreased by only 3.57±4.91 μm (−0.75%; 473.85±64.35 μm at baseline vs. 470.28±68.18 μm during the VM; P=0.092). In multivariate regression analysis, the mean ALCSD change was greater when the central corneal thickness was thinner in glaucomatous eyes (standardized β value=0.21; P=0.02), whereas that was greater in normal eye when baseline IOP was lower (standardized β value=0.37; P<0.001).

Conclusions:

During the VM, the ALCSD was decreased in normal eyes, but was not significantly changed in eyes with treated glaucoma. These results suggest that the physiology of LC displacement in response to IOP and cerebrospinal fluid pressure dynamics might differ between normal and glaucomatous eyes.
Adverse Events Following Vaccination With Bivalent rLP2086 (Trumenba®): An Observational, Longitudinal Study During a College Outbreak and a Systematic Review
Authors: Fiorito Theresa M. , Baird Grayson L. , Alexander-Scott Nicole , Bornschein Suzanne , Kelleher Catherine , Du Nan , Dennehy Penelope H.
Published: August 2017

Background:

In February 2015, two unlinked culture-confirmed cases of Neisseria meningitidis serogroup B (MenB) disease occurred at a local college in Rhode Island (“college X”) within 3 days. This represented a 489-fold increase in the incidence of MenB disease, and an outbreak was declared. For the first time, bivalent rLP2086 (Trumenba®) was selected as a mandatory intervention response. A mass vaccination clinic was coordinated, which provided a unique opportunity to collect safety data in a real-world population of college-age participants. Though the Advisory Committee on Immunization Practices recommends MenB vaccination for college-age individuals (16–23 year olds), there is limited quantifiable safety data available for this population.

Methods:

The Dillman total design survey method was used. Adverse events of bivalent rLP2086 were solicited and quantified retrospectively 2–4 months following each dose of vaccine. Safety data from six clinical trials were used as comparison tools.

Results:

The most commonly reported adverse event following vaccination was injection site pain. Reported rates of injection site pain, fatigue, myalgia, fever, and chills were similar than those reported in clinical trials. Reported rates of headache were lower than in clinical trials.

Conclusions:

This study is the first to examine adverse events of bivalent rLP2086 in a real-world setting where more than 90% of a college-age population was vaccinated.
Higher Transplacental Pathogen-Specific Antibody Transfer Among Pregnant Women Randomized to Triple Antiretroviral Treatment Versus Short Course Zidovudine
Authors: Bosire Rose , Farquhar Carey , Nduati Ruth , Broliden Kristina , Luchters Stanley , Van de Perre Philippe , De Vincenzi Isabelle , Merkel Michele , Wachuka Veronicah , Mbori-Ngacha Dorothy , John-Stewart Grace , Lohman-Payne Barbara , Reilly Marie
Published: August 2017

Background:

HIV-1 infection may impair transplacental antibody transfer to infants. The impact of highly active antiretroviral treatment (ART) given during pregnancy on transplacental antibody transport is unknown.

Methods:

HIV-1 infected pregnant women with CD4 counts between 200 – 500 were randomized to short-course zidovudine (ZDV) or triple ART at 32 weeks gestation for prevention of mother-to-child HIV-1 transmission. Levels of maternal antibody against measles, pneumococcus and rotavirus at delivery, and antibody transfer to the baby through cord blood, were compared between trial arms.

Results:

Overall, 141 and 148 women were randomized to triple ART and ZDV, respectively; cord blood was available for a subset (n = 20 in triple ART and n = 22 in ZDV). Maternal antibody levels to all pathogens during pregnancy and at delivery were not significantly different between arms. Within each arm, antibody levels at delivery were lower than at enrolment. For all antibodies, a woman’s levels before delivery were an important predictor of amount transferred to her infant. Women on triple ART transferred higher levels of pathogen-specific antibodies when compared with women on short course ZDV.

Conclusions:

Women on triple ART transferred higher levels of pathogen-specific antibodies compared with women on ZDV alone.
Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain
Authors: Bannister Kirsty , Qu Chaoling , Navratilova Edita , Oyarzo Janice , Xie Jennifer Yanhua , King Tamara , Dickenson Anthony H. , Porreca Frank
Published: August 2017

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective–motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.
Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model
Authors: Kim Hyunyoung , Thompson Jeremy , Ji Guangchen , Ganapathy Vadivel , Neugebauer Volker
Published: August 2017

Neuroplasticity in the amygdala, a brain center for emotions, leads to increased neuronal activity and output that can generate emotional-affective behaviors and modulate nocifensive responses. Mechanisms of increased activity in the amygdala output region (central nucleus, CeA) include increased reactive oxygen species, and so we explored beneficial effects of monomethyl fumarate (MMF), which can have neuroprotective effects through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant response pathway. Systemic (intraperitoneal) MMF dose-dependently inhibited vocalizations and mechanosensitivity (hindlimb withdrawal reflexes) of rats in an arthritis pain model (kaolin-carrageenan-induced monoarthritis in the knee). Stereotaxic administration of MMF into the CeA by microdialysis also inhibited vocalizations but had a limited effect on mechanosensitivity, suggesting a differential contribution to emotional-affective vs sensory pain aspects. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that stereotaxic administration of MMF into the CeA by microdialysis inhibited background activity and responses of CeA neurons to knee joint stimulation in the arthritis pain model. Monomethyl fumarate had no effect on behaviors and neuronal activity under normal conditions. The results suggest that MMF can inhibit emotional-affective responses in an arthritis pain model through an action that involves the amygdala (CeA).
Uses and Limitations of Claims-based Performance Feedback Reports: Lessons From the Comprehensive Primary Care Initiative
Authors: Gerteis Margaret , Peikes Deborah , Ghosh Arkadipta , Timmins Lori , O'Malley Ann S. , Barna Michael , Taylor Erin F. , Day Timothy J. , Swankoski Kaylyn , Payne Perry W. , Brown Randall
Published: August 2017

Background:

Performance feedback is central to data-driven models of quality improvement, but the use of claims-based data for feedback has received little attention.

Purpose:

To examine the challenges, uses, and limitations of quarterly Medicare claims-based performance feedback reports generated for practices participating in the Comprehensive Primary Care (CPC) initiative from 2012 to 2015.

Methods:

Mixed methods study of nearly 500 CPC practices in seven regions, combining pilot testing; systematic monitoring; surveys; in-depth interviews; user feedback; and input from data feedback team.

Results:

Designing reports required addressing issues about timing, data completeness and reliability, variations in patient risk across practices, and use of benchmarks and metrics understandable to users. Practices' ability to use reports constructively depended on their experience, analytic resources, expectations, and perceptions about the role of primary care in improving reported outcomes.

Conclusions:

Generating claims-based feedback reports that support practices' quality improvement efforts requires a significant investment of analytic expertise, time, resources, continuous improvement, and technical assistance.

Implications:

Claims-based performance feedback can provide insight into patterns of patients' care across provider settings and opportunities for improvement, but practices need data from other sources to manage patients in real time or assess the short-term effects of specific changes in care delivery.
A Content Analysis on the Media Portrayal of Characters with Limb Loss
Authors: Abernethy Lisa , Duncan John Chad , Childers Walter Lee
Published: August 2017

Background

Mass media, such as movies, may be a factor in how society views people with limb loss. If the portrayal is inaccurate or negative, then this could create additional challenges for people with limb loss to cope with their amputation and reintegrate with society. The purpose of this study was to define the portrayal of characters with amputation in movies. The hypothesis was that positive portrayal of characters with amputation, defined as heroism and realistic prostheses, would increase over time.

Methods

Quantitative content analysis was performed to systematically and objectively analyze the media's portrayal of characters with amputations. Movies released in US theaters from 1966 to 2015 were selected from the International Movie Database. Characters were identified as being portrayed as a hero or a villain and by the type of prosthetic technology they used.

Results

A total of 162 characters in 118 movies were identified, but only 92 characters could be identified as hero or villain for subsequent analysis. Time was found to have no effect on positive portrayal (p = 0.324). Heroism alone was found to increase significantly over time (p = 0.007), whereas realistic prostheses demonstrated a trend to decline over time (p = 0.238).

Conclusion

Positive portrayal did not increase over time. However, heroism did increase over time, whereas inaccurate depictions of prosthetic limbs were more frequent overall, regardless of time. This means that when a character with amputation was a hero, he/she was more likely using prosthetic technology that does not exist in reality. These data demonstrate a need to better educate the public and encourage more accurate depictions in the media.
Marfanoid habitus is a nonspecific feature of Perrault syndrome
Authors: Zerkaoui Maria , Demain Leigh A.M. , Cherkaoui Jaouad Imane , Ratbi Ilham , Amjoud Karima , Urquhart Jill E. , O’Sullivan James , Newman William G. , Sefiani Abdelaziz
Published: August 2017

The objective of this study was to report the clinical and biological characteristics of two Perrault syndrome cases in a Moroccan family with homozygous variant c.1565C>A in the LARS2 gene and to establish genotype–phenotype correlation of patients with the same mutation by review of the literature. Whole-exome sequencing was performed. Data analysis was carried out and confirmed by Sanger sequencing and segregation. The affected siblings were diagnosed as having Perrault syndrome with sensorineural hearing loss at low frequencies; the female proband had primary amenorrhea and ovarian dysgenesis. Both affected individuals had a marfanoid habitus and no neurological features. Both patients carried the homozygous variant c.1565C>A; p.Thr522Asn in exon 13 of the LARS2 gene. This variant has already been reported as a homozygous variant in three other Perrault syndrome families. Both affected siblings of a Moroccan consanguineous family with LARS2 variants had low-frequency sensorineural hearing loss, marfanoid habitus, and primary ovarian insufficiency in the affected girl. According to the literature, this variant, c.1565C>A; p.Thr522Asn, can be correlated with low-frequency hearing loss. However, marfanoid habitus was been considered a nonspecific feature in Perrault syndrome, but we believe that it may be more specific than considered previously. This diagnosis allowed us to provide appropriate management to the patients and to provide more accurate genetic counseling to this family.
Autologous hematopoietic cell transplantation of mantle cell lymphoma: emerging trends
Authors: Falcone Umberto , Kuruvilla John
Published: August 2017

Purpose of review

The management of mantle cell lymphoma has changed significantly with the adoption of immunochemotherapy and dose intensive treatment strategies in specific patient populations. Randomized controlled trials have established the role of rituximab-based treatments and autologous stem cell transplantation as standards of care. Novel therapeutics are also being integrated into these treatment strategies.

Recent findings

Rituximab-based primary treatment has been shown to significantly improve complete remission rates. The addition of autologous stem cell transplantation has also improved progression-free survival (PFS) although data regarding potential overall survival (OS) benefits are not clear. Complete remission and minimal residual disease (MRD) negative disease states are predictive of outcome. Rituximab maintenance post SCT has also been shown to significantly improves PFS and OS.

Current therapeutic standards in mantle cell lymphoma have clearly improved patient outcomes with improvements in remission rates, PFS, and OS. Autologous stem cell transplant (ASCT) as a consolidation strategy of primary treatment has improved outcomes, and the incorporation of novel drugs into frontline therapy may further improve the efficacy of the treatment. MRD-driven strategies may ultimately define appropriate patient subsets towards ASCT or alternative approaches.
Trial designs for statin muscle intolerance
Authors: Rosenson Robert S.
Published: August 2017

Purpose of review

This article aims to review the spectrum of statin-associated muscle symptoms (SAMS), the consequences of downtitration of statin therapy on cardiovascular events, the published trials of nonstatin therapy in patients who report SAMS, and to provide a framework for future trials in SAMS patients.

Recent findings

SAMS is reported in 10–25% of patients prescribed statin therapy; however, the few patients enrolled in randomized, double-blind, controlled clinical trials (RCTs) discontinue statin therapy due to adverse events. Several possible reasons for this discrepancy in clinical practice versus RCTs may results from patient selection in clinical trials that excludes patients with characteristics that increase the risk of SAMS, widespread use of higher intensity statins in low-risk populations that evaluated in nearly all RCTs, and perceptions concerning harm of statin therapy. Clinical trials of nonstatin therapy have shown that most patients tolerate statin therapy upon repeat challenge, and thus better tools are needed to more accurately identify SAMS patients and enroll these patients in RCTs of nonstatin therapy.

Clinical trials in patients who report SAMS have shown better tolerability of certain classes of nonstatin therapy. Low rates of recurrent SAMS in double-blind rechallenge have led some to challenge the concept of statin muscle intolerance. However, patients with perceived SAMS downtitrate their statin therapy and suffer more cardiovascular events. A revised paradigm for evaluation of SAMS is proposed.
Robot ZORA in rehabilitation and special education for children with severe physical disabilities: a pilot study
Authors: van den Heuvel Renée J.F. , Lexis Monique A.S. , de Witte Luc P.
Published: August 2017

The aim of this study was to explore the potential of ZORA robot-based interventions in rehabilitation and special education for children with severe physical disabilities. A two-centre explorative pilot study was carried out over a 2.5-month period involving children with severe physical disabilities with a developmental age ranging from 2 to 8 years. Children participated in six sessions with the ZORA robot in individual or in group sessions. Qualitative and quantitative methods were used to collect data on aspects of feasibility, usability, barriers and facilitators for the child as well as for the therapist and to obtain an indication of the effects on playfulness and the achievement of goals. In total, 17 children and seven professionals participated in the study. The results of this study show a positive contribution of ZORA in achieving therapy and educational goals. Moreover, sessions with ZORA were indicated as playful. Three main domains were indicated to be the most promising for the application of ZORA: movement skills, communication skills and cognitive skills. Furthermore, ZORA can contribute towards eliciting motivation, concentration, taking initiative and improving attention span of the children. On the basis of the results of the study, it can be concluded that ZORA has potential in therapy and education for children with severe physical disabilities. More research is needed to gain insight into how ZORA can be applied best in rehabilitation and special education.
2017 National Quality and Safety Education for Nurses Faculty Survey Results
Authors: Altmiller Gerry , Armstrong Gail
Published: August 2017

The Quality and Safety Education for Nurses (QSEN) national initiative, started in 2005, has supported the adoption and integration of updated quality and safety competencies in nursing education. However, faculty needs regarding QSEN competency integration, and the degree to which QSEN competencies are reflected in current nursing curricula, have not been assessed nationally. This study (N = 2037) reports the findings of the 2017 National QSEN Faculty Survey and discusses implications for nurse educators and programs of nursing education.
Quality and Safety Education for Nurses Implementation
Authors: Cooper Elizabeth
Published: August 2017

Is the Quality and Safety Education for Nurses (QSEN) initiative still advancing in prelicensure nursing education? The purpose of this article is to report a 2-part evaluation regarding QSEN within the curricula. The evaluation included an online survey and conference for faculty in the San Francisco Bay Area (SFBA). This article discusses survey results and the ideas and suggestions of SFBA faculty that were made at the conference. The results were positive. Most schools continue to advance QSEN into their curricula. Ten ways to strengthen integration of QSEN in the curriculum and barriers are identified.
Implementation Science
Authors: Dolansky Mary A. , Schexnayder Julie , Patrician Patricia A. , Sales Anne
Published: August 2017

Although quality and safety competencies were developed and disseminated nearly a decade ago by the Quality and Safety Education for Nurses (QSEN) project, the uptake in schools of nursing has been slow. The use of implementation science methods may be useful to accelerate quality and safety competency integration in nursing education. The article includes a definition and description of implementation science methods and practical implementation strategies for nurse educators to consider when integrating the QSEN competencies into nursing curriculum.
Rapid Health Care Improvement Science Curriculum Integration Across Programs in a School of Nursing
Authors: Oliver Brant J. , Potter Mertie , Pomerleau Mimi , Phillips Andrew , O’Donnell Mimi , Cowley Connie , Sipe Margie
Published: August 2017

This article describes the systematic efforts undertaken by a school of nursing in the Northeastern United States to foster innovation in health professions education. We present an application of modified team coaching and plan-do-study-act improvement methods in an educational context to rapidly integrate a quality and safety curriculum across programs. We discuss applications in generalist, advanced practice, doctoral, residency, and advanced fellowship programs and provide examples of each.
Outcomes of Preexposure Prophylaxis Referrals From Public STI Clinics and Implications for the Preexposure Prophylaxis Continuum
Authors: Bhatia Ramona , Modali Laxmi , Lowther Matthew , Glick Nancy , Bell Margo , Rowan Sarah , Keglovitz Kristin , Schneider John
Published: August 2017

Background

Human immunodeficiency virus preexposure prophylaxis (PrEP) uptake remains low in high-risk populations. Sexually transmitted infection (STI) clinics reach PrEP-eligible persons and may be ideal settings to model PrEP implementation.

Methods

Consenting PrEP-eligible patients identified at Chicago Department of Public Health STI Clinics were actively referred to PrEP partner sites between June 1, 2015, and May 31, 2016. Outcomes included successful contact by a partner site, linkage to a partner site, and receipt of a PrEP prescription. Bivariable and time to event analyses were conducted to determine significant associations of outcomes.

Results

One hundred thirty-seven patients were referred; 126 (92%) were men who have sex with men, and mean age was 29 years. Ninety-eight (72%) were contacted by a PrEP partner, 43 (31%) were linked, and 40 (29%) received a prescription. Individuals aged 25 years and older were more likely to link (odds ratio, 3.10; 95% confidence interval, 1.30–7.41) and receive a PrEP prescription (odds ratio, 2.70; 95% confidence interval, 1.12–6.45) compared with individuals 24 years and younger. The average time between each step was greater for those 24 years and younger compared with those aged 25 years and older for all steps. Time to event analyses revealed that those aged 25 years and older were significantly more likely to receive a prescription compared to those aged 24 years and younger (hazard ratio, 3.62; 95% risk limits, 1.47–8.92).

Conclusions

Preexposure prophylaxis active referrals from STI clinics to partner sites are feasible, though drop out was prominent in the initial steps of the continuum. Youth were less likely to link or receive prescriptions, indicating the need for tailored interventions for this vulnerable population.
Cerebral Syphilitic Gumma Can Arise Within Months of Reinfection: A Case of Histologically Proven Treponema pallidum Strain Type 14b/f Infection With Human Immunodeficiency Virus Positivity
Authors: Koizumi Yusuke , Watabe Takeya , Ota Yasunori , Nakayama Shu-ichi , Asai Nobuhiro , Hagihara Mao , Yamagishi Yuka , Suematsu Hiroyuki , Tsuzuki Toyonori , Takayasu Masakazu , Ohnishi Makoto , Mikamo Hiroshige
Published: August 2017

A 44-year-old man with human immunodeficiency virus positivity developed cerebral gumma 6 months after appropriate therapy for secondary syphilis. It was surgically resected and histologically, Treponema pallidum (14b/f, a relatively rare strain type) was proven. A complete set of modern techniques was performed to depict rare complication of this classic disease.
High-grade Müllerian Adenosarcoma
Authors: Hodgson Anjelica , Amemiya Yutaka , Seth Arun , Djordjevic Bojana , Parra-Herran Carlos
Published: August 2017

Müllerian adenosarcoma harbors low malignant potential, except in cases with myometrial invasion or sarcomatous overgrowth. The presence of a high-grade stromal component has been proposed as an important pathologic predictor of outcome. We hypothesized that high-grade adenosarcoma has distinct clinical and molecular features, distinct from low-grade adenosarcoma. We analyzed the clinicopathologic features and follow-up of 9 high-grade adenosarcomas and a control group of 9 low-grade adenosarcomas. Comprehensive genomic analysis of the high-grade group was performed targeting exons of 409 oncogenes and tumor suppressor genes. In 1 case, the high-grade and low-grade components were separately sequenced. High-grade and low-grade adenosarcomas were comparable in patient age, myometrial invasion, and stage at presentation. Sarcomatous overgrowth was observed in 2/9 (22%) low-grade and 8/9 (89%) high-grade adenosarcomas. Six of 9 (67%) patients with high-grade adenosarcoma developed rapid recurrence; 1 died of her disease. Conversely, no low-grade tumors recurred or metastasized. Sequencing of high-grade adenosarcomas revealed frequent TP53 pathway alterations, identified in 7/9 (78%) cases. p53 expression by immunohistochemistry highly correlated with mutation status. Copy number variations occurred at a mean of 28.8 per tumor; most frequently involved genes included CDK4, MDM2, GNAS, SGK1, and DICER1. High-grade adenosarcoma is an aggressive neoplasm with propensity for short-interval recurrence and metastasis. The proportion of copy number alterations is similar to that reported for adenosarcoma with sarcomatous overgrowth. However, the high frequency of TP53 abnormalities is a novel finding, indicating that high-grade adenosarcoma is a distinct subset with driver TP53 pathway alterations. p53 immunohistochemistry can be used to confirm the presence of a high-grade component. Given its aggressive potential, the presence of any high-grade component in an adenosarcoma should be reported, even in the absence of sarcomatous overgrowth.
BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics
Authors: Karamzadeh Dashti Nooshin , Bahrami Armita , Lee Seung J. , Jenkins Sarah M. , Rodriguez Fausto J. , Folpe Andrew L. , Boland Jennifer M.
Published: August 2017

Glomus tumors are rare mesenchymal neoplasms with a phenotype akin to the modified smooth muscle cells of the glomus body. Most are benign, but rare examples show malignant histologic characteristics and aggressive behavior. We recently encountered a malignant glomus tumor with BRAF V600E mutation. We sought to study a large cohort for this mutation, with particular attention to associated malignant histologic characteristics. Tumors were classified based on WHO criteria as benign, uncertain malignant potential (glomus tumors of uncertain malignant potential—GT-UMP), or malignant. Tumors were screened for BRAF V600E by immunohistochemistry, and positive staining was evaluated further by Sanger sequencing. A total of 102 glomus tumors were included and classified as benign (57, 56%), GT-UMP (15, 15%) and malignant (30, 29%). Tumors occurred in patients aged 8 to 89.9 years (median: 50.2), without sex predilection (55% men). Most occurred in the superficial soft tissue (84%) and upper extremities (55%). Six of 95 tested cases had BRAF V600E mutation (6%), including 0 of 57 benign tumors, 3 of 14 GT-UMP (21%), and 3 of 24 malignant tumors (12%). Follow-up was obtained for 59 cases (median: 75.7 mo, range: 7.8 to 268.5). Three of 11 malignant tumors (27%) had progressive disease: 1 with metastasis to brain and heart, 1 with enlarging residual disease, and 1 with recurrence. Two of 4 GT-UMP (50%) had progressive disease: 1 with metastasis to lung, and 1 with local recurrence (50%). Three of 44 benign tumors (7%) had local recurrence. Two of 5 patients with BRAF V600E had progression, including 1 GT-UMP with local recurrence and 1 malignant tumor with enlarging residual disease. In summary, BRAF V600E mutation was detected in 6% of glomus tumors, all of which were malignant or GT-UMP. This mutation may be associated with a malignant phenotype, although study of additional cases is needed. In patients with progressive disease, BRAF could be a promising therapeutic target.
Perceived Facilitators and Barriers to Local Health Department Workers' Participation in Infectious Disease Emergency Responses
Authors: Rutkow Lainie , Paul Amy , Taylor Holly A. , Barnett Daniel J.
Published: August 2017

Context:

Local health departments play a key role in emergency preparedness and respond to a wide range of threats including infectious diseases such as seasonal influenza, tuberculosis, H1N1, Ebola virus disease, and Zika virus disease. To successfully respond to an infectious disease outbreak, local health departments depend upon the participation of their workforce; yet, studies indicate that sizable numbers of workers would not participate in such a response. The reasons why local health department workers participate, or fail to participate, in infectious disease responses are not well understood.

Objective:

To understand why local health department workers are willing, or not willing, to report to work during an infectious disease response.

Design:

From April 2015 to January 2016, we conducted 28 semistructured interviews with local health department directors, preparedness staff, and nonpreparedness staff.

Setting:

Interviews were conducted with individuals throughout the United States.

Participants:

We interviewed 28 individuals across 3 groups: local health department directors (n = 8), preparedness staff (n = 10), and nonpreparedness staff (n = 10).

Main Outcome Measures:

Individuals' descriptions of why local health department workers are willing, or not willing, to report to work during an infectious disease response.

Results:

Factors that facilitate willingness to respond to an infectious disease emergency included availability of vaccines and personal protective equipment; flexible work schedule and childcare arrangements; information sharing via local health department trainings; and perceived commitments to one's job and community. Factors that hinder willingness to respond to an infectious disease emergency included potential disease exposure for oneself and one's family; logistical considerations for care of children, the elderly, and pets; and perceptions about one's role during an infectious disease response.

Conclusion:

Our findings highlight opportunities for local health departments to revisit their internal policies and engage in strategies likely to promote willingness to respond among their staff. As LHDs face the persistent threat of infectious diseases, they must account for response willingness when planning for and fielding emergency responses. Our findings highlight opportunities for local health departments to revisit their internal policies and engage in strategies likely to promote response willingness to infectious disease emergencies among their staff.
Evacuation Decision Making and Expanded Roles of Adult Daycare Services in the Great East Japan Earthquake: Qualitative Analysis Using Semistructured Interviews
Authors: Mori Hiroko , Sugawara Yasuhiro , Obuchi Shuichi P. , Shimmei Masaya , Takahashi Ryutaro
Published: August 2017

Context:

The roles of adult daycare services during disaster evacuations in the relationships with community resilience are unknown. The initial 72 hours after a disaster are crucial because people in the disaster area depend on their own efforts or the resources available at the moment until the arrival of external support.

Objective:

To clarify the evacuation-related decision making of the administrators of adult daycare services within 72 hours after the Great East Japan Earthquake and to describe the roles of adult daycare services during the month following the earthquake.

Design:

Qualitative study using semistructured interviews. The transcribed interviews were analyzed anonymously through an inductive qualitative content analysis using ATLAS.ti.

Setting:

Kesennuma City, Miyagi Prefecture.

Participants:

Eleven key informants (3 primary care providers and 8 administrators) from 8 institutions.

Results:

Immediately after the disaster, 6 institutions implemented shelter-in-place. The evacuation behaviors of the adult daycare institutions were diverse, but each institution was transformed repeatedly within 72 hours. With respect to evacuation decision making, the primary issues involved whether to go to mandatory evacuation sites. However, after 3 days, the institutions relocated from these sites to other places. During a period of approximately 1 month, 7 institutions managed the evacuation of service users and care providers. The expanded institutional roles were as follows: “confirming the safety of the users' families,” “substituting residential facilities,” and “imposing leadership during the evacuation.”

Conclusions:

If institutions choose to shelter-in-place, it should be sustained for as long as possible. Sufficiently planned stores of food and water to accommodate daytime users are needed. Institutions that employ shelter-in-place as an evacuation plan should maintain close contact with local governments. Furthermore, local governments should predetermine how to manage these institutions in the event of a disaster. To build community resilience for disasters, developing linkage with private organizations' resilience is beneficial.
Regular physical activity prevents development of chronic muscle pain through modulation of supraspinal opioid and serotonergic mechanisms
Authors: Brito Renan G. , Rasmussen Lynn A. , Sluka Kathleen A.
Published: August 2017

Introduction:

It is generally believed that exercise produces its effects by activating central opioid receptors; there are little data that support this claim. The periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) are key nuclei in opioid-induced analgesia, and opioids interact with serotonin to produce analgesia.

Objectives:

The purpose was to examine central inhibitory mechanisms involved in analgesia produced by wheel running.

Methods:

C57/Black6 mice were given access to running wheels in their home cages before induction of chronic muscle hyperalgesia and compared with those without running wheels. Systemic, intra-PAG, and intra-RVM naloxone tested the role of central opioid receptors in the antinociceptive effects of wheel running in animals with muscle insult. Immunohistochemistry for the serotonin transporter (SERT) in the spinal cord and RVM, and pharmacological blockade of SERT, tested whether the serotonin system was modulated by muscle insult and wheel running.

Results:

Wheel running prevented the development of muscle hyperalgesia. Systemic naloxone, intra-PAG naloxone, and intra-RVM naloxone reversed the antinociceptive effect of wheel running in animals that had received muscle insult. Induction of chronic muscle hyperalgesia increased SERT in the RVM, and blockade of SERT reversed the hyperalgesia in sedentary animals. Wheel running reduced SERT expression in animals with muscle insult. The serotonin transporter in the superficial dorsal horn of the spinal cord was unchanged after muscle insult, but increased after wheel running.

Conclusion:

These data support the hypothesis that wheel running produced analgesia through central inhibitory mechanisms involving opioidergic and serotonergic systems.
Effect of bupivacaine lozenges on oral mucositis pain: a randomized controlled multicenter phase II study
Authors: Mogensen Stine , Treldal Charlotte , Kristensen Claus A. , Bentzen Jens , Lawson-Smith Louise , Petersen Janne , Andersen Ove
Published: August 2017

Introduction:

A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management.

Objective:

The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher).

Method:

Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data.

Results:

Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups −16 mm, 95% confidence interval: −26 to −6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported.

Conclusion:

These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis.

ClinicalTrials.gov:

NCT02252926.
Stress and Addiction: When a Robust Stress Response Indicates Resiliency
Authors: al'Absi Mustafa
Published: August 2017

Objective

Stress reactivity research has traditionally focused on the idea that exaggerated responses to stress may have adverse effects on health. Accumulating evidence suggests that attenuated responses to stress and delayed recovery may also be problematic.

Methods

This review focuses on the role of the stress response of the hypothalamic-pituitary-adrenocortical axis, the endogenous opioid system, and the cardiovascular system in hypertension, pain perception, and addictive behaviors. Results from multiple methods of assessment and stress paradigms conducted in our laboratory over the past two decades are integrated with research from other investigators and with existing theories.

Results

Research indicates that exaggerated biological and physiological responses to stress and attenuated pain perception are associated with hypertension and risk for cardiovascular diseases. This research complements work linking reduced stress responses with enhanced pain sensitivity and discomfort. Multiple studies have also demonstrated that an attenuated stress response is linked to exacerbation of withdrawal symptoms and relapse in nicotine addiction. Evidence indicates important moderators (i.e., sex, personality traits, and early life adversity) and hypothalamic-pituitary-adrenocortical– and endogenous opioid system–related mechanisms in the altered response to stress. I integrate these findings in a conceptual model emphasizing that robust stress responses in the context of addiction and relapse should be considered as a marker of resiliency.

Conclusions

A blunted stress response may indicate long-term physiological dysregulation that could usher harmful consequences for cardiovascular disease, pain perception, and addictive disorders. The impact of dysregulation is influenced by multiple individual and situational factors that should be considered in evaluating the clinical significance of stress response dysregulation.
Estimated Coverage to Address Financial Barriers to HIV Preexposure Prophylaxis Among Persons With Indications for Its Use, United States, 2015
Authors: Smith Dawn K. , Van Handel Michelle , Huggins Rebecca
Published: August 2017

Background:

An estimated 1.2 million American adults engage in sexual and drug use behaviors that place them at significant risk of acquiring HIV infection. Engagement in health care for the provision of daily oral antiretroviral medication as preexposure prophylaxis (PrEP), when clinically indicated, could substantially reduce the number of new HIV infections in these persons. However, resources to cover the financial cost of PrEP care are anticipated barriers for many of the populations with high numbers of new HIV infections.

Methods:

Using nationally representative data, we estimated the current national met and unmet need for financial assistance with covering the cost of PrEP medication, clinical visits, and laboratory tests among adults with indications for its use, overall and by transmission risk population.

Results:

This study found that of the 1.2 million adults estimated to have indications for PrEP use, <1% (∼7300) are in need of financial assistance for both PrEP medication and clinical care, at an estimated annual cost of $89 million. An additional 7% (∼86,300) are in need of financial assistance only for PrEP clinical care at an estimated annual cost of $119 million.

Conclusions:

This information on PrEP care costs, insurance coverage, and unmet financial need among persons in key HIV transmission risk subpopulations can inform policy makers at all levels as they consider how to address remaining financial barriers to the use of PrEP and accommodate any changes in eligibility for various insurance and financial assistance programs that may occur in coming years.