bluuebunny/crossref_metadata_2025 huggingface dataset:
F-104 Decoding the regulatory networks of leukemic stem cells Through ubiquitylation
Authors: Rathinam Chozha
Published: April 2018

In the recent years, it has become increasingly evident that hematopoietic stem cells (HSCs) are directly involved in the recognition of both acute and chronic infections. HSCs sense immune insults by both cell intrinsic, through the pattern recognition receptors (PRRs), and extrinsic, mediated mainly by the pro-inflammatory cytokines, mechanisms. However, prolonged exposure of HSCs to inflammatory conditions results in defective differentiation of the immune cells. Even though earlier studies suggested that a tight control on inflammatory signals is essential for proper development of the immune system, precise molecular mechanisms that control inflammatory signals in HSCs and the effects of individual pro-inflammatory cytokines on HSC fate decisions have not been elucidated. In this study, we utilized several animal models including mice that either lack the ubiquitin editing enzyme-A20, that functions as a negative regulator of NF-κB, or express a constitutively active form of IKK2, which results in augmented NF-B signals, in the presence or absence of specific pro-inflammatory cytokines, to study the impact of inflammation in the determination of HSC fate. Our data indicate that deregulated NF-κB signals in HSCs lead to pathologic hematopoiesis, including a striking loss of lymphoid differentiation and skewing towards the myeloid lineage. Furthermore, NF-κB mediated lymphopenia was caused by both cell intrinsic (changes in genetic and molecular signatures) and extrinsic (elevated expression of pro-inflammatory cytokines) mechanisms. At this annual meeting, we would be discussing the precise molecular pathways through which inflammatory signals affect the development of Normal and Leukemic Stem Cells.
G-105 Role of microbiome in cancer
Authors: Trinchiero Giorgio
Published: April 2018

Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and non-immune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions and increased susceptibility to infection. The commensal microbiota not only may affect the development, progression and immune evasion of cancer but it has also important effects on the response to cancer immune- and chemo-therapy. Myeloid cells are a major component of the tumor microenvironment where they play a dual role inducing anti-tumor immune responses but mostly promoting immune evasion, tumor progression and metastases formation. Myeloid cells respond to environmental factors including signals derived from commensal microbes that modulate their function and reactivity thus impacting the response to cancer therapy.
G-107 HPV vaccines: where are we now, and where are we going?
Authors: Trimble Cornelia L.
Published: April 2018

On a global scale, at least 20% of human malignancies are caused by known infectious pathogens. Most are viruses; of these, human papillomavirus (HPV) causes more cancers than any other. In populations which do not have herd immunity because of insufficient uptake of the preventive vaccines, HPV infections are endemic, in part, because they are asymptomatic. In the cervix, disease is clinically indolent. In immune- competent persons, a transition from the intraepithelial cancer precursor lesion, cervical intraepithelial neoplasia 3 (CIN3) or high grade squamous intraepithelial lesion (HSIL), to invasive carcinoma is thought to take on the order of 10–15 years. Moreover, not all HSILs progress to cancer; in a relatively short observational window, we and others have reported spontaneous regression of biopsy-confirmed cervical HSIL in a subset of women. The current standard of care treatment is surgical resection. In women who are HIV seropositive, less is known. Persistent infections are common, and the incidence of cervical cancer is three-fold that of immune-competent women.

HPV lesions are relatively accessible, thereby providing a clinical setting in which to better understand the immunobiology of disease, and to test proof-of-principle of potential non-surgical interventions. The infectious etiology presents an opportunity to manipulate immune responses to viral antigens. Indeed, the preventative HPV vaccines, Gardasil and Cervarix, are nearly (100%) effective in vaccinated persons. Immune-based therapies for established HPV disease would address two significant clinical settings: (1) in eradicating established cancer precursor lesions (CIN3/HSIL), and (2) in recurrent or metastatic HPV cancers. Early studies have established proof-of-principle in both. Challenges presented in eradicating HPV disease will be discussed, as well as strategies moving forward.
G-108 Molecular etiology of cervical cancer, HPV and gene methylation
Authors: Wentzensen Nicholas
Published: April 2018

Most cervical cancers are caused by persistent infections with one of a dozen carcinogenic human papillomaviruses (HPV). The cancer risk differs by HPV genotype, with HPV16 and HPV18 accounting for over 70% of all cervical cancers. E6 and E7, are potent oncoproteins that inhibit apoptosis by disabling p53 and activate the cell cycle by disrupting the pRB pathway. In addition, the viral oncogenes cause major chromosomal instability already at precancerous stages and may induce integration of the viral genome into the host cells. Despite these strong oncogenic features of HPV, only a small subset of HPV infections ever progress to precancer or cancer. Recently, the important role of host and viral methylation in the molecular etiology of cervical cancer has been recognized. We recently conducted a discovery effort that yielded a set of host gene methylation markers that showed promising performance to detect cervical precancer. Similarly, we recently showed that regions of the HPV genome of 11 carcinogenic types are highly methylated in women with CIN3 compared to women with transient infections, suggesting that methylation is a general phenomenon in the transition from infection to precancer. Methylation patterns were found to be similar between closely related HPV genotypes. These findings may improve our understanding of the molecular basis for viral persistence and increase our ability to identify women who are more likely to progress to cervical cancer. Measuring host or HPV DNA methylation could serve as a specific marker for cervical precancer in cervical cancer screening.
I-104 Cardiovascular disease in HIV and chronic hepatitis C-infected patients
Authors: Bagchi Shashwatee
Published: April 2018

Use of antiretroviral therapy has markedly reduced morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Nonetheless, all-cause mortality rates remain high in HIV-infected patients compared to the general population, with non-AIDS conditions comprising almost half of deaths. Rates of coronary artery disease (CHD) are over twice as high in HIV-infected compared to matched uninfected controls, with rates anticipated to increase as this population ages. Factors contributing to increased risk of CHD in HIV-infected patients remain to be clearly elucidated. While some studies have strongly suggested that hepatitis C (HCV) co-infection is associated with increased rates of CHD in HIV-infected patients, results in all studies have not been consistent. Since HIV, HCV, and atherosclerosis are all associated with chronic inflammation and immune activation, it can be challenging to understand relative disease pathogenesis when found concurrently in individual patients. Identifying predictors of CHD progression from overlapping pathways has the potential to suggest novel preventive and therapeutic intervention strategies to mitigate CHD progression. In addition, if HCV infection is confirmed to confer additional risk for CHD among HIV-infected patients, this would provide further justification to treat HCV early and aggressively in this population irrespective of liver fibrosis stage.

The presentation will review the data on the individual contribution of HIV and chronic hepatitis C infection on the development of cardiovascular disease and the proposed mechanisms for these observations. Finally, new research investigating the intersections of these three disease processes with potential for future preventive and therapeutic interventions will be discussed.
Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram
Authors: Scheinin Annalotta , Kallionpää Roosa E. , Li Duan , Kallioinen Minna , Kaisti Kaike , Långsjö Jaakko , Maksimow Anu , Vahlberg Tero , Valli Katja , Mashour George A. , Revonsuo Antti , Scheinin Harry
Published: April 2018

Background

Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesized that drug- and state-related changes can be separated.

Methods

Forty-seven healthy participants were randomized to receive dexmedetomidine (n = 23) or propofol (n = 24) as target-controlled infusions until loss of responsiveness. Then, an attempt was made to arouse the participant to regain responsiveness while keeping the drug infusion constant. Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness. We conducted statistical comparisons between the drugs and different states of consciousness for spectral bandwidths, and observed how drug-induced electroencephalogram patterns reversed upon awakening. Cross-frequency coupling was also analyzed between slow-wave phase and alpha power.

Results

Eighteen (78%) and 10 (42%) subjects were arousable during the constant drug infusion in the dexmedetomidine and propofol groups, respectively (P = 0.011 between the drugs). Corresponding with deepening anesthetic level, slow-wave power increased, and a state-dependent alpha anteriorization was detected with both drugs, especially with propofol. The slow-wave and frontal alpha activities were momentarily disrupted as the subjects regained responsiveness at awakening. Negative phase-amplitude coupling before and during loss of responsiveness frontally and positive coupling during the highest drug concentration posteriorly were observed in the propofol but not in the dexmedetomidine group.

Conclusions

Electroencephalogram effects of dexmedetomidine and propofol are strongly drug- and state-dependent. Changes in slow-wave and alpha activity seemed to best detect different states of consciousness.
Evidence-Based Inclusion Criteria for Cochlear Implantation in Patients With Postlingual Deafness
Authors: Snel-Bongers Jorien , Netten Anouk P. , Boermans Peter-Paul B. M. , Rotteveel Liselotte J. C. , Briaire Jeroen J. , Frijns Johan H. M.
Published: April 2018

Objectives:

This study determined the relationship between preoperative phoneme and word scores and the gain in speech perception after cochlear implantation in a large cohort of patients. The authors aimed to define evidence-based selection criteria for cochlear implantations in adults with postlingual deafness.

Design:

This retrospective study included 364 adults with postlingual deafness who received a cochlear implant between 2000 and 2013 at the Leiden University Medical Center. The gain in speech perception observed postimplantation was compared with preoperative-aided/binaural speech perception scores, measured at 65 dB SPL in quiet. Patients who showed preoperative phoneme scores on monosyllabic words above 50% were also tested for speech perception in the presence of speech-shaped background noise, at a +5 dB signal to noise ratio.

Results:

Speech perception in quiet improved after implantation in all except 7 patients. Average scores in quiet continued to improve, up to approximately 1 year after implantation. When participants were divided into five groups, based on preoperative speech perception scores, all groups showed gains in speech perception, except for the group with aided preoperative phoneme scores above 80%. However, all patients who were tested preoperatively with the addition of background noise showed improvements in speech perception in noise after the cochlear implantation.

Conclusions:

Although the decision to implant should consider individual ear differences and other factors that might apply to a particular case, based on our data, all patients with preoperative scores of either 80% (phonemes correct) or 60% (words correct) and lower in an optimal-aided situation are potential candidates for a cochlear implant, provided that their preoperative speech perception score decreases below 50% (phonemes correct) or 20% (words correct), when background noise is added at a +5 dB signal to noise ratio.
Targeted Distraction
Authors: Mardare Mihai , Kieser David Christopher , Ahmad Adil , Subramanian Thejasvi , Haleem Shahnawaz , Thakar Chrishan , Wilson-MacDonald James , Nnadi Colin
Published: April 2018

Study Design.

Prospective cohort study

Objective.

To understand the efficacy of a tail-gating technique (TGT) to mirror the normal spinal growth of children with early-onset scoliosis (EOS) treated with magnetically controlled growing rods (MCGR).

Summary of Background Data.

MCGR allow outpatient distraction and guided spinal growth without the need for repeat surgery. Two techniques (maximal and targeted) are currently employed to determine the distraction amount, however the efficacy of each is unknown. This study specifically assesses the ability of targeted distraction to achieve physiological growth.

Methods.

We performed a retrospective review of European children treated with MCGR using a TGT and analyzed the post-operative clinical and radiographic outcomes, including the sitting height, standing height, coronal Cobb angle, T1-T12 and T1-S1 height. Furthermore, we compared the post-operative sitting/standing height ratio every 6 months to those reported for normal age- and sex-matched European children.

Results.

Thirty-five children were included with a mean follow-up of 3.4 years (1.8–5.8 years). All clinical and radiographic parameters significantly (P < 0.05) improved immediately post-operatively and were maintained until final follow-up. The TGT mirrored the normative sitting/standing height ratios for expected spinal growth (Pearson correlation 0.95 for males and 0.90 for females). The mean difference between the reference values for the sitting/standing height ratio and our results was 0.0124 (P < 0.001) for males and 0.0068 (P = 0.010) for females.

Conclusion.

MCGR can reliably improve the coronal deformity in children with EOS while maintaining spinal growth. A TGT to determine the distraction amount at follow-up accurately mirrors the normal growth pattern of age-, sex-, and ethnicity-matched children. However, patients treated with this technique have a statistically significant, but clinically insignificant, shorter than physiologically normal spinal height.

Level of Evidence: 3
The Prognostic Significance of Pedicle Enhancement from Contrast-enhanced MRI for the Further Collapse in Osteoporotic Vertebral Compression Fractures
Authors: Hyun Sung Eun , Ko Jin Young , Lee Eugene , Ryu Ju Seok
Published: April 2018

Study Design.

A retrospective observational study.

Objective.

The aim of this study was to investigate the prognostic significance of contrast-enhanced magnetic resonance imaging (MRI) for detecting pedicle enhancement and predicting future collapse in patients with acute benign osteoporotic vertebral compression fracture (OVCF).

Summary of Background Data.

Traditional morphological classification regarding compression versus burst fractures cannot accurately anticipate the prognosis of further collapse. Identifying subgroups with a higher risk for further collapse may be beneficial in determining the treatment modality, which should be decided immediately after the injury.

Methods.

One hundred fourteen patients with benign OVCFs who, at the onset, underwent contrast-enhanced spine MRI between 2003 and 2016 were retrospectively analyzed. Patients were recruited on the basis of predefined inclusion and exclusion criteria. The primary outcome was the compression progression rate; other potential variables included demographic and clinical characteristics, initial compression rates, and kyphotic angles. In addition, other structural abnormalities on MRI were assessed. The compression progression rates were compared according to pedicle enhancement, and the prognostic significance of pedicle enhancement for further collapse were analyzed.

Results.

Further compression progression rates were significantly higher in the pedicle-enhanced (PE) group than in the nonenhanced (NE) group. Multivariate logistic analysis revealed that pedicle enhancement may be associated with further compression progression ≥10%. The vertebral augmentation (VAG) protective effect against collapse was only significant within the PE group, while bone densitometry and patients’ mobility were significant only within the NE group. The log-rank test revealed a statistically significant difference in the rates of further collapse ≥10% during the 1 year between the groups.

Conclusion.

Sign of pedicle enhancement is a potential risk factor for further compression progression. Contrast-enhanced MRI should be performed at the onset to better determine the future risk of collapse and to choose a better treatment modality for benign OVCF patients.

Level of Evidence: 3
Activity of Daily Living After Long Level Fusion in Adult Spinal Deformity
Authors: Kim Whoan Jeang , Lee Jae Won , Hwang Seok Young , Park Kun Young , Chang Shann Haw , Song Dae Geon , Choy Won Sik
Published: April 2018

Study Design.

Prospective single center study.

Objective.

The aim of this study was to evaluate 1) the activity of daily living (ADL) of three categorized patients group; over 60-year-old degenerative spine patients without adult spinal deformity (ASD), nonoperative ASD patients, and operative ASD patients, 2) what kinds of activities would be impaired, and 3) how the ADL changes over time after long level fusion.

Summary of Background Data.

There is still debate how surgeons could decide treatment methods for old-aged adult spinal deformity, operatively or not. There was lack of information how long level fusion impacts daily activities, especially sedentary Asian lifestyle. In Asia, impaired ADL is much more important issue because of different lifestyle.

Methods.

Patients were categorized into three groups; Group 1 was over 60-year old aged degenerative spine disease without deformity, Group 2 was ASD patients who did not have surgery, and Group 3 was ASD patients who had surgery for deformity correction. Patients were evaluated using answer Oswestry Low Back Pain Disability Questionnaire, and Assessment activities of daily living for sedentary Asian culture (ADL-SA) questionnaire.

Results.

Group 1 showed nearly full functions in every activity (ADL-SA: 41.4). ADL-SA scores of Group 2 were similar to Group 1 (P = 0.452). However, get up from bottom (P < 0.001), and pick up object (P < 0.001) were impaired. After long level fusion, ADL was impaired but gradually improved by time. From postoperative 1 year, total ADL score recovered to acceptable range. However, among ADL, activities associated sedentary lifestyle (get up from bottom, wipe floor, pick up object, and sit cross-legged) were still impaired after 2 years postoperatively.

Conclusion.

ADL was impaired after long level fusion; however it would improve as time goes by. However, among ADL, activities associated sedentary lifestyle was still impaired. Hence give enough information to patients about limited activities before deciding operation.

Level of Evidence: 3
Providing Culturally Competent Acute Care Physical Therapy for a Complex Medical Patient of Amish Heritage
Authors: Horton Roy C. , Irwin Kent E.
Published: April 2018

Background and Purpose:

Health care providers, including physical therapists, should identify and incorporate sociocultural, educational, and environmental factors in their clinical decisions for patients of various cultural backgrounds—specifically Amish heritage as illustrated in this case report. The purpose of this case report is to describe how cultural beliefs affected acute care physical therapy (PT) and discharge planning for an older adult of Amish heritage.

Case Description:

The patient was a 65-year-old woman of Amish heritage 2 days post thoracic aortic aneurysm dissection surgery with an unexpected subsequent stroke. Due to their Amish beliefs, the patient and the family declined the physical therapist's initial postacute care discharge recommendation to an off-site skilled nursing facility. Significant discussion with multiple family members throughout the entire therapy process emphasized continued skilled services in accord with Amish cultural beliefs to promote safe reintegration into the Amish community. PT interventions primarily focused on culturally sensitive patient and family education and functional mobility to encourage safe patient resumption of activities of daily living and role in society.

Outcomes:

By the end of 2 weeks of PT (1 initial examination and 8 intervention sessions), the patient demonstrated improvements in all aspects of functional mobility and total Functional Independence Measure scores (21/126 to 86/126). On postoperative day 14, the patient transitioned to an on-site inpatient rehabilitation facility. After completing only 4 days in the inpatient rehabilitation facility, the family firmly advocated that the patient be discharged home with assistance from the family and Amish community.

Discussion:

Physical therapists may be unfamiliar with patients of Amish heritage due to the infrequency of PT services used by these individuals. This case report demonstrates a physical therapist's sensitivity to and acceptance of the Amish cultural beliefs, which ensured appropriate clinical decisions and positive patient- and family-centered outcomes. Engaging the patient's family in dialogue about realistic discharge options early in the acute care stay allowed the family time to understand the complexity of the patient's diagnoses and challenges of the health care environment as well as align decisions with their cultural beliefs.
Acute and 6-Month Outcomes in Recipients of Lung Transplantation Following Lower Extremity Strength Training: Pilot Study
Authors: Smith Barbara K. , Carter Nicole , Arteaga Angela , Dinh Amy C. , Martin A. Daniel
Published: April 2018

Purpose:

Individuals who receive lung transplantation (LTx) have prolonged lower extremity weakness that limits exercise capacity and function. The purposes of this pilot study were to measure whether acute, intense, gym-based rehabilitation significantly increased walking distance and lower extremity strength after LTx and to identify whether gains were retained at 6-month follow-up.

Methods:

Nine men (mean age =57 years) completed 4 weeks of daily (5×/wk), gym-based acute care rehabilitation after LTx. Rehabilitation included stretching, aerobic conditioning, education, and either low- or high-volume strength training. Outcomes were assessed at baseline, 4 weeks, and 6 months post-LTx and included 1-repetition maximum (1-RM) tests, isokinetic torque, isometric torque, and 6-minute walk distance.

Results:

Patients attended an average of 17 acute rehabilitation sessions. Following acute rehabilitation, walking distance was increased and patients achieved greater 1-RM for leg press and for knee extension. Regardless of the volume of strength training, knee extension isometric torque and isokinetic torque were significantly increased (P < .05). At 6 months, subjects achieved further gains in leg press 1-RM and grip strength (P < .05), while walking and other strength measures were maintained.

Conclusions:

Intense rehabilitation produced acute lower extremity strength improvements that were retained after 6-months. Further study is needed in a larger sample.
Preliminary Outcomes Report for CO2 Laser Assisted Electric-Acoustic Cochlear Implantation
Authors: Stevens Shawn M. , Redmann Andrew , Whitaker Kayla , Ruotanen Alyson , Houston Lisa , Hammer Theresa , Samy Ravi N.
Published: April 2018

Objective:

Report on the safety/efficacy of a novel, carbon dioxide (CO2) laser-assisted protocol for hearing-preservation cochlear implantation (HPCI) and electric-acoustic stimulation (EAS).

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Adult patients meeting established criteria for HPCI and EAS.

Intervention:

Therapeutic/rehabilitative. A standardized protocol used CO2 laser to achieve meticulous hemostasis and perform cochleostomy was evaluated.

Main Outcome Measures:

Audiometric assessments included low-tone pure tone average (LtPTA), consonant-nucleus-consonant (CNC), and AzBio scores. Primary outcomes were low-tone hearing-preservation (LtHP) and EAS usage rates. Secondary outcomes included change in LtPTA, outcomes durability, and the rate/onset/presentation of delayed hearing loss (DHL). Subset analyses stratified data by presenting LtPTA and surgeon experience.

Results:

Forty-seven patients and 52 ears were included. Mean follow-up was 20.7 ± 12.6 months. When adjusted for preoperative LtPTA less than 60 dB, the LtHP rate was 77%. This was significantly better than for patients with LtPTA more than 60 dB (24%; p < 0.0001). Outcomes were highly durable. EAS usage was excellent in those with LtPTA less than 60 dB (100%). Nine patients developed DHL. Three additional patients (25%) were successfully salvaged via steroids. Both CNC and AzBio scores improved significantly (p < 0.0001) at definitive testing. Speech-hearing scores did not differ significantly between patients using/not using EAS. The complication rate was 3.8%; none were caused by the laser. Surgeon experience was associated with significantly better outcomes.

Conclusion:

Use of a CO2 laser-assisted HPCI protocol was safe and effective. Outcomes were consistent with contemporary literature reporting. Patient selection and surgeon experience both significantly impacted outcomes.
Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods
Authors: Lee Sang Hun , Yoo Myung Hoon , Park Jun Woo , Kang Byung Chul , Yang Chan Joo , Kang Woo Suk , Ahn Joong Ho , Chung Jong Woo , Park Hong Ju
Published: April 2018

Objectives:

To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis.

Study Design:

Prospective study.

Methods:

vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals.

Results:

The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study.

Conclusion:

vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.
Recurrence in Benign Paroxysmal Positional Vertigo: A Large, Single-Institution Study
Authors: Luryi Alexander L. , Lawrence Juliana , Bojrab Dennis I. , LaRouere Michael , Babu Seilesh , Zappia John , Sargent Eric W. , Chan Eleanor , Naumann Ilka , Hong Robert S. , Schutt Christopher A.
Published: April 2018

Objective:

To report rates of recurrence in benign paroxysmal positional vertigo (BPPV) and associated patient and disease factors.

Study Design:

Retrospective chart review.

Setting:

Single high-volume otology practice.

Patients:

Patients diagnosed with BPPV from 2007 to 2016 with documented resolution of symptoms.

Intervention:

Diagnostic and particle repositioning maneuvers for BPPV.

Main Outcome Measures:

BPPV recurrence, time to recurrence, and ear(s) affected at recurrence.

Results:

A total of 1,105 patients meeting criteria were identified. Of this population, 37% had recurrence of BPPV in either ear or both ears. Overall same-ear recurrence rate was 28%; 76% of recurrences involved the same ear(s) as initial presentation. Recurrences that occurred after longer disease-free intervals were more likely to involve the opposite ear than early recurrences (p = 0.02). Female sex (40.4% versus 32.7%, p = 0.01) and history of previous BPPV (57.5% versus 32.4%, p < 0.0005) were associated with increased risk of recurrence, while history of Menière's disease, diabetes mellitus, and traumatic etiology were not. Approximately, half (56%) of recurrences occurred within 1 year of resolution.

Conclusions:

A large single-institution study of recurrence in BPPV is presented along with Kaplan–Meier disease-free survival curves. Female sex and history of previous BPPV were associated with increased recurrence, while previously suspected risk factors for recurrence including history of Menière's disease, diabetes, and trauma were not. Remote recurrence is more likely to involve the contralateral ear than early recurrence. These data solidify the expected course of treated BPPV allowing for improved clinical care and patient counseling.
Birth Month as a Risk Factor for the Diagnosis of Celiac Disease Later in Life
Authors: Assa Amit , Waisbourd‐Zinman Orith , Daher Saleh , Shamir Raanan
Published: April 2018

Various perinatal factors have been implicated in association with the risk of developing celiac disease (CD) in genetically susceptible individuals. Our aim was to investigate the association of month and season of birth with the development of CD later in life in a large National cohort in Israel. Data were retrieved from a National database of more than 2 million Israeli Jewish adolescents born between 1971 and 1998. Overall, 10,566 CD cases out of 2,001,353 subjects (0.53%) were identified and analyzed. CD risk was significantly higher for subjects born in May (odds ratio [OR] 1.07, P = 0.04) and June (OR 1.09, P = 0.008). Birth during the winter season (December to February) showed a marginal significance toward reduced risk (OR 0.97, P = 0.05). In conclusion, children born in May and June are at increased risk for CD. This increased risk provides further evidence that perinatal environmental factors increase the risk of developing CD.
Transcutaneous Electrical Nerve Stimulation Reduces Resting Pain in Head and Neck Cancer Patients
Authors: Lee Jennifer E. , Anderson Carryn M. , Perkhounkova Yelena , Sleeuwenhoek Brittany M. , Louison Rebecca R.
Published: April 2018

Background

Individuals receiving radiation for head and neck cancer (HNC) often develop painful oral mucositis that impairs function, possibly leading to feeding tubes, hospitalization, and treatment delays. Although pharmacologic medications provide some relief, many report inadequate analgesia and adverse effects. Transcutaneous electrical nerve stimulation (TENS) is a safe, nonpharmacologic intervention; it decreases pain and analgesics and improves function, yet no studies examined TENS for HNC.

Objective

The aim of this study was to examine the efficacy of TENS for pain and function in HNC patients.

Methods

This study used a randomized, double-blinded crossover design; participants received 3 TENS treatments during weeks 4 to 6 of radiation: active, placebo, and no TENS over the temporomandibular joint and upper cervical region. Pain (McGill Pain Questionnaire, visual analog scale [VAS] resting and function), function (mouth opening, tongue movement, speaking), fatigue (VAS), and treatment effectiveness (VAS) were assessed before and after TENS at 3 visits.

Results

Resting pain (McGill Pain Questionnaire and VAS) decreased significantly more after active TENS than placebo or no TENS; changes in function and pain with function did not differ between conditions. Active TENS decreased fatigue significantly more than no TENS and was rated as more effective than placebo TENS.

Conclusion

Transcutaneous electrical nerve stimulation improves pain in HNC patients receiving radiation but not function or pain with function relative to placebo or no TENS.

Implications for Practice

Transcutaneous electrical nerve stimulation may be a viable tool for radiation-induced HNC pain to complement pharmacologic approaches. This nonpharmacologic intervention could decrease the debilitating effects of radiation and analgesics, and improve quality of life. Clinical trials should examine the effects and safety of repeated, daily TENS in HNC patients receiving radiation.
Common and Dissociable Neural Activity After Mindfulness-Based Stress Reduction and Relaxation Response Programs
Authors: Sevinc Gunes , Hölzel Britta K. , Hashmi Javeria , Greenberg Jonathan , McCallister Adrienne , Treadway Michael , Schneider Marissa L. , Dusek Jeffery A. , Carmody James , Lazar Sara W.
Published: April 2018

Objective

We investigated common and dissociable neural and psychological correlates of two widely used meditation-based stress reduction programs.

Methods

Participants were randomized to the Relaxation Response (RR; n = 18; 56% female) or the Mindfulness-Based Stress Reduction (MBSR; n = 16; 56% female) programs. Both programs use a “bodyscan” meditation; however, the RR program explicitly emphasizes physical relaxation during this practice, whereas the MBSR program emphasizes mindful awareness with no explicit relaxation instructions. After the programs, neural activity during the respective meditation was investigated using functional magnetic resonance imaging.

Results

Both programs were associated with reduced stress (for RR, from 14.1 ± 6.6 to 11.3 ± 5.5 [Cohen's d = 0.50; for MBSR, from 17.7 ± 5.7 to 11.9 ± 5.0 [Cohen's d = 1.02]). Conjunction analyses revealed functional coupling between ventromedial prefrontal regions and supplementary motor areas (p < .001). The disjunction analysis indicated that the RR bodyscan was associated with stronger functional connectivity of the right inferior frontal gyrus—an important hub of intentional inhibition and control—with supplementary motor areas (p < .001, family-wise error [FWE] rate corrected). The MBSR program was uniquely associated with improvements in self-compassion and rumination, and the within-group analysis of MBSR bodyscan revealed significant functional connectivity of the right anterior insula—an important hub of sensory awareness and salience—with pregenual anterior cingulate during bodyscan meditation compared with rest (p = .03, FWE corrected).

Conclusions

The bodyscan exercises in each program were associated with both overlapping and differential functional coupling patterns, which were consistent with each program's theoretical foundation. These results may have implications for the differential effects of these programs for the treatment of diverse conditions.
EEG Patterns in Patients With Calcified Neurocysticercosis With or Without Hippocampal Atrophy
Authors: Issa Naoum P. , Sedler Mark J. , Del Brutto Victor J. , Darsan Elizabeth , Milla Lucía , Montes Jessica , Zambrano Mauricio , Del Brutto Oscar H.
Published: April 2018

Purpose:

To assess whether hippocampal atrophy develops in conjunction with clinical or subclinical epileptiform or encephalopathic activity in subjects with neurocysticercosis (NCC).

Methods:

Using a population-based and nested case–control study design, scalp EEGs and brain MRIs were performed in Atahualpa residents aged ≥40 years, who have imaging-confirmed NCC (case patients), as well as in age- and sex-matched NCC-free control subjects.

Results:

Sixty-two case patients and 62 control subjects were included. Encephalopathic EEG patterns were more common in five NCC subjects with epilepsy than in those without a history of seizures. Epileptiform EEG activity was noted in one patient with NCC but in none of the control subjects. This subject's focal epileptiform discharges correlated with the location of calcified cysticerci in the brain parenchyma, and the hippocampus ipsilateral to the epileptiform discharges was more atrophic than the contralateral hippocampus. The degree of hippocampal atrophy in patients with NCC without a history of seizures was significantly greater than in control subjects (P < 0.01) and tended to be even greater in patients with NCC with a history of seizures.

Conclusions:

Hippocampal atrophy may not be exclusively related to seizure activity in patients with NCC. Other mechanisms, such as recurrent bouts of inflammation around calcified cysticerci, might explain the association between NCC and hippocampal atrophy.
Structural MRI Correlates of Cognitive Event-Related Potentials in Multiple Sclerosis
Authors: Artemiadis Artemios K. , Anagnostouli Maria C. , Zalonis Ioannis G. , Chairopoulos Konstantinos G. , Triantafyllou Nikos I.
Published: April 2018

Purpose:

Cognitive impairment in multiple sclerosis has been associated with cognitive event-related potentials and MRI abnormalities. This study aims to explore for the first time the association between P300 and MRI in multiple sclerosis.

Methods:

Fifty-eight relapsing–remitting patients (41.5 ± 10.5 years old, 41 women, disease duration 139.7 ± 84.9 months) and 51 healthy controls were used. Visual P300 responses and a set of 2- or 3-dimensional MRI indices were obtained. Neuropsychological testing and psychological evaluations were also performed.

Results:

Multiple sclerosis patients had significantly lower P300 amplitude and more prolonged P300 latencies and reaction times than healthy controls. In total, 67.2% of patients were identified with abnormal P300 response. These patients had greater disability and physical fatigue and had lower visuospatial memory scores than those with normal P300 response. Abnormally low P300 amplitude was associated with lower peripheral gray matter volume and was correlated only with normalized frontal horn width and normalized brain volume, after adjusting for age and education. The moderating role of brain reserve was also documented.

Conclusions:

P300 event-related potential was related to both linear and volumetric MRI markers. Future studies should expand these results in other disease types and longitudinally. Event-related potentials could serve as an ancillary tool for cognitive assessment in multiple sclerosis.
Lysosome-dependent cell death and deregulated autophagy induced by amine-modified polystyrene nanoparticles
Authors: Wang Fengjuan , Salvati Anna , Boya Patricia
Published: April 2018

Nanoparticles (NPs) typically accumulate in lysosomes. However, their impact on lysosomal function, as well as autophagy, a lysosomal degradative pathway, is still not well known. We have previously reported in the 1321N1 cell line that amine-modified polystyrene (NH
2
-PS) NPs induce apoptosis through damage initiated in the lysosomes leading ultimately to release of lysosomal content in the cytosol, followed by apoptosis. Here, by using a combination of biochemical and cell biological approaches, we have characterized in a mouse embryonic fibroblast cell line that the lysosomal alterations induced by NH
2
-PS NPs is progressive, initiating from mild lysosomal membrane permeabilization (LMP), to expansion of lysosomal volume and intensive LMP before the summit of cell death. Though the cells initially seem to induce autophagy as a surviving mechanism, the damage of NH
2
-PS NPs to lysosomes probably results in lysosomal dysfunctions, leading to blockage of autophagic flux at the level of lysosomes and the eventual cell death.
Reliability modelling and analysis of a multi-state element based on a dynamic Bayesian network
Authors: Li Zhiqiang , Xu Tingxue , Gu Junyuan , Dong Qi , Fu Linyu
Published: April 2018

This paper presents a quantitative reliability modelling and analysis method for multi-state elements based on a combination of the Markov process and a dynamic Bayesian network (DBN), taking perfect repair, imperfect repair and condition-based maintenance (CBM) into consideration. The Markov models of elements without repair and under CBM are established, and an absorbing set is introduced to determine the reliability of the repairable element. According to the state-transition relations between the states determined by the Markov process, a DBN model is built. In addition, its parameters for series and parallel systems, namely, conditional probability tables, can be calculated by referring to the conditional degradation probabilities. Finally, the power of a control unit in a failure model is used as an example. A dynamic fault tree (DFT) is translated into a Bayesian network model, and subsequently extended to a DBN. The results show the state probabilities of an element and the system without repair, with perfect and imperfect repair, and under CBM, with an absorbing set plotted by differential equations and verified. Through referring forward, the reliability value of the control unit is determined in different kinds of modes. Finally, weak nodes are noted in the control unit.
Noise-induced transitions and shifts in a climate–vegetation feedback model
Authors: Alexandrov Dmitri V. , Bashkirtseva Irina A. , Ryashko Lev B.
Published: April 2018

Motivated by the extremely important role of the Earth’s vegetation dynamics in climate changes, we study the stochastic variability of a simple climate–vegetation system. In the case of deterministic dynamics, the system has one stable equilibrium and limit cycle or two stable equilibria corresponding to two opposite (cold and warm) climate–vegetation states. These states are divided by a separatrix going across a point of unstable equilibrium. Some possible stochastic scenarios caused by different externally induced natural and anthropogenic processes inherit properties of deterministic behaviour and drastically change the system dynamics. We demonstrate that the system transitions across its separatrix occur with increasing noise intensity. The climate–vegetation system therewith fluctuates, transits and localizes in the vicinity of its attractor. We show that this phenomenon occurs within some critical range of noise intensities. A noise-induced shift into the range of smaller global average temperatures corresponding to substantial oscillations of the Earth’s vegetation cover is revealed. Our analysis demonstrates that the climate–vegetation interactions essentially contribute to climate dynamics and should be taken into account in more precise and complex models of climate variability.
Controlled fluorescence quenching by antibody-conjugated graphene oxide to measure tau protein
Authors: Huang Ao , Zhang Luning , Li Weiwei , Ma Zeyu , Shuo Shi , Yao Tianming
Published: April 2018

We report an ultrasensitive immunoassay for tau protein—a key marker of Alzheimer's disease. This sensing platform relies on graphene oxide (GO) surfaces conjugated with anti-human tau antibody to provide quantitative binding sites for the tau protein. The GO quenches standard fluorescein isothiocyanate labelled tau (tau-FITC) when tau protein and tau-FITC are both present and compete for the binding sites. This change in fluorescence signal can be used to quantitate tau protein. In contrast with traditional enzyme-linked immunosorbent assay (ELISA), our method does not require enzyme-linked secondary antibodies for protein recognition nor does it require an enzyme substrate for optical signal generation. This requires fewer reagents and has less systematic error than the antigen–antibody recognition steps in ELISA. Our method has a tau protein detection limit of 0.14 pmol ml
−1
in buffer. This approach could be developed into a promising biosensor for the detection of tau protein and may be useful in the clinical diagnosis of tau-induced neurodegeneration syndromes.
Graphene platelets enhanced pressureless- sintered B
4
C ceramics
Authors: Gao Dezhi , Jing Jie , Yu Jincheng , Guo Xue , Zhang Yubai , Gong Hongyu , Zhang Yujun
Published: April 2018

B
4
C ceramics with different contents of graphene platelets (GPL) were synthesized by a pressureless process in Ar atmosphere. The influences of GPL on mechanical properties, thermal conductivity and electrical resistivity of the B
4
C ceramics were investigated. Mechanical properties ran up to optimal condition with hardness of 29.1 GPa, bending strength of 383.9 GPa and fracture toughness of 5.72 MPa m
1/2
with 0.8 wt% GPL separately. Thermal conductivity and electrical resistivity reached extreme values of 26.35 W m
−1
 k
−1
and 0.1 Ω cm
−1
. Performances of the ceramics were mainly affected by the generation of non-functional-GPL and the result indicated that a large amount of non-functional-GPL could contribute to poorer overall performance. Meanwhile, two particular pullout mechanisms concerning toughness enhancing was discussed in detail.
Adsorption behaviour of hydrogarnet for humic acid
Authors: Maeda Hirotaka , Kurosaki Yuichi , Nakayama Masanobu , Ishida Emile Hideki , Kasuga Toshihiro
Published: April 2018

Discharge of humic acid (HA) in aqueous environments is a key health and aesthetic issue. The present work investigates the use of hydrogarnet as a novel adsorbent for HA. Hydrogarnet was hydrothermally synthesized with different solvents to control the chemical composition. Hydrogarnet with three types of chemical compositions had better adsorption properties for HA than hydrogarnet with a single chemical composition. Controlling the chemical composition of hydrogarnet increased the number of hydroxyl groups and the overall binding energy of the system, leading to changes in the zeta potential. The enhancement of these adsorption properties is related to the increased numbers of hydroxyl groups on the surface and their diverse binding energies.
Self-assembly behaviours of peptide–drug conjugates: influence of multiple factors on aggregate morphology and potential self-assembly mechanism
Authors: Fan Qin , Ji Yujie , Wang Jingjing , Wu Li , Li Weidong , Chen Rui , Chen Zhipeng
Published: April 2018

Peptide–drug conjugates (PDCs) as self-assembly prodrugs have the unique and specific features to build one-component nanomedicines. Supramolecular structure based on PDCs could form various morphologies ranging from nanotube, nanofibre, nanobelt to hydrogel. However, the assembly process of PDCs is too complex to predict or control. Herein, we investigated the effects of extrinsic factors on assembly morphology and the possible formation of nanostructures based on PDCs. To this end, we designed a PDC consisting of hydrophobic drug (
S
)-ketoprofen (Ket) and valine–glutamic acid dimeric repeats peptide (L-VEVE) to study their assembly behaviour. Our results showed that the critical assembly concentration of Ket-L-VEVE was 0.32 mM in water to form various nanostructures which experienced from micelle, nanorod, nanofibre to nanoribbon. The morphology was influenced by multiple factors including molecular design, assembly time, pH and hydrogen bond inhibitor. On the basis of experimental results, we speculated the possible assembly mechanism of Ket-L-VEVE. The π–π stacking interaction between Ket molecules could serve as an anchor, and hydrogen bonded-induced β-sheets and hydrophilic/hydrophobic balance between L-VEVE peptide play structure-directing role in forming filament-like or nanoribbon morphology. This work provides a new sight to rationally design and precisely control the nanostructure of PDCs based on aromatic fragment.