bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of Outcome Domain for Patients With Musculoskeletal Pain: Characterizing Subgroups and Their Response to Treatment
Authors: Zeppieri Jr Giorgio , Bialosky Joel , George Steven Z
Published: January 2020

Background

Patient-centered care models allow for the ability to tailor treatment to outcomes of importance to patients.

Objective

The purposes of this study were to (1) define patient subgroups based on outcomes of importance; (2) determine whether patient subgroups based on outcomes of importance differed in demographic, clinical, and psychological measures; and (3) determine whether outcome domain subgroups differed in treatment responses.

Design

This was a prospective, longitudinal observational study.

Methods

This was a secondary analysis of the Optimal Screening for Prediction of Referral and Outcome study. Patients in the development phase completed the Patient Centered Outcome Questionnaire (PCOQ) and questionnaires related to negative mood, fear avoidance, and positive coping, as well as region-specific questionnaires. Patients in the validation cohort completed the PCOQ, measures of treatment satisfaction and region-specific questionnaires at 4 weeks, 6 months, and 1 year. A hierarchical agglomerative cluster analysis identified profiles based on importance outcomes as determined by the PCOQ. Analysis of variance and chi-squared assessed baseline subgroup differences in demographics, psychological factors, and clinical outcomes. Repeated-measure analysis of variance considered subgroup differences in outcomes longitudinally.

Results

Cluster analysis identified 3 subgroups: (1) “Multiple Outcome Domains Important” subgroup characterized by high importance attached to improvement in all domains, (2) “Pain and Function Outcomes Important” subgroup characterized by high importance attached to improvement in pain and interference, and (3) “Pain Important” subgroup characterized by greatest importance attached to improvement in pain.

Limitations

Our sample included patients from outpatient physical therapy and may not be representative of patients in other settings.

Conclusion

Patients can be characterized by the importance attached to improvement in outcome domains. The identified subgroups differed in baseline measures as well as response to treatment.
Reproductive rights on the path of liberation: from deconstructing the concept of control in our society to emphasizing pro-attachment attitudes
Authors: Giroux Caroline , Hategan Ana , Bourne Christina
Published: January 2020

The debate about abortion is recurrently pervading not only politics and public health but also society at large, even within the utilization of mass media. The authors reinforce that access to reproductive health is a human rights issue and discuss facts and misconceptions associated with the procedure. They reframe the discussion and scripts sometimes found in pop culture, illuminating how attitudes towards reproductive rights may affect people. To address the polarization impasse, they propose using the lens of attachment relationships and offer corresponding solutions on three core levels: educational, social and narrative.
The Tyrant’s Vein: Misrule and Popularity in the Elizabethan Playhouse
Authors: Womack Peter
Published: January 2020

The fashion for tyrants on the Elizabethan stage reflected a sort of affinity between tyranny and theatre. How did the two things fit together? A tyrant is not a true king, but only seems to be one, and so is like an actor playing a king. Because he has no right to the throne, he must assert his rule by personal and rhetorical force—the actor’s resources. Moreover, a tyrant is understood to be a figure in whom appetite conquers reason, self-control gives way to desire—as happens (according to hostile accounts) in the theatre. This logic applies particularly to popular theatre, where the tyrant is sustained by his dynamic relationship with the audience. In comparison with the tyrants of academic or humanist drama, who are uneasy and isolated, the tyrant on the common stage is energetic and happy amid the crowd. He is the imagined monarch of the theatre’s populace—their representative, their creature, affiliated to them not by political forms but by the symbolic repertoire of festivity: misrule, inversion, masquerade. In this way, people without rights recognize themselves in the unrighteous ruler: arguably, that is how tyranny works in reality.
Is This My Home? A Palliative Care Journey Through Life and Death in the NICU
Authors: Walters Aurora , Grosse Jordan
Published: January 2020

Background:

With advancements in neonatology, patients in the neonatal intensive care unit (NICU) are living in the hospital with complex life-limiting illnesses until their first birthday or beyond. As palliative care (PC) becomes a standard of care in neonatology, a level IV NICU developed an interdisciplinary PC team with the mission to ease the physical, mental, and moral distress of the patients, families, and staff. This case report highlights the teamwork and long-term palliative care and ultimately end-of-life care that an infant received by this dedicated NICU palliative care team.

Clinical Findings:

This case discusses a premature ex-27-week gestation male infant who initially presented to the emergency department at 5 months of age with significant tachypnea, increased work of breathing, and poor appetite.

Primary Diagnosis:

The primary diagnosis was severe pulmonary vein stenosis resulting in severe pulmonary hypertension.

Interventions:

The severity of the infant's pulmonary vein stenosis was incurable. He required substantial life-extending surgical procedures and daily intensive care interventions. In addition to his life-extending therapies, the infant and his family received palliative care support by the NICU PC team and the hospital-wide PC team (REACH team) throughout his admission. This was specialized care that focused on easing pain and suffering while also addressing any social/emotional needs in the infant, his family, and in the hospital staff. The PC teams also focused on protecting the families' goals of care, memory making, and providing a positive end-of-life experience for the infant and his family. The infant's end-of-life care involved providing adequate pain and symptom management, education, and communication to his family about the dying process and allowing unlimited family time before and after his death.

Outcomes:

After 11 months in the NICU and despite aggressive therapies, he required more frequent trips to the cardiac catheterization laboratory for restenosis of his pulmonary veins. He was dependent on iNO to treat his pulmonary hypertension and he continued to require an ICU ventilator. His parents ultimately decided to pursue comfort care. He died peacefully in his mother's arms.

Practice Recommendations:

The American Academy of Pediatrics and the National Association of Neonatal Nurses both have statements recommending that palliative care be standard of care in NICUs. Establishing a NICU-dedicated interdisciplinary PC team can improve outcomes for infants and families living in the NICU with complex life-limiting illnesses.
Hysterectomy Route and Numbers Reported by Graduating Residents in Obstetrics and Gynecology Training Programs
Authors: Gressel Gregory M. , Potts John R. , Cha Sandolsam , Valea Fidel A. , Banks Erika
Published: January 2020

OBJECTIVE:

To characterize trends in self-reported numbers and routes of hysterectomy for obstetrics and gynecology residents using the Accreditation Council for Graduate Medical Education (ACGME) case log database.

METHODS:

Hysterectomy case log data for obstetrics and gynecology residents completing training between 2002–2003 and 2017–2018 were abstracted from the ACGME database. Total numbers of hysterectomies and modes of approach (abdominal, laparoscopic, and vaginal) were compared using bivariate statistics, and trends over time were analyzed using simple linear regression.

RESULTS:

Hysterectomy data were collected from 18,982 obstetrics and gynecology residents in a median of 243 (interquartile range 241–246) ACGME-accredited programs. The number of graduating residents increased significantly over time (12.1/year, P<.001), whereas the number of residency programs decreased significantly (0.52 fewer programs per year, P<.001) over the 16-year period. For cases logged as “surgeon,” the median number of abdominal hysterectomies decreased by 56.5% from 85 (interquartile range 69–102) to 37 (interquartile range 34–43) (P<.001). The median number of vaginal hysterectomies decreased by 35.5% from 31 (interquartile range 24–39) to 20 (interquartile range 17–25) (P=.002). The median total number of hysterectomies per resident decreased by 6.3% from 112 (interquartile range 97–132) to 105 (interquartile range 92–121) (P=.036). In contrast, the median number of laparoscopic hysterectomies increased by 115% from 20 (interquartile range 13–28) in 2008–2009 to 43 (interquartile range 32–56) in 2017–2018, despite the decrease in overall number of hysterectomies (P<.001). These trends were statistically significant.

CONCLUSIONS:

The total number of hysterectomies performed by obstetrics and gynecology residents in the United States is decreasing, and the routes are changing with decreases in abdominal and vaginal approaches, and an increase in use of laparoscopic hysterectomy.
Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users
Authors: Spotnitz Matthew E. , Natarajan Karthik , Ryan Patrick B. , Westhoff Carolyn L.
Published: January 2020

OBJECTIVE:

To evaluate the relative risk of cervical neoplasms among copper intrauterine device (Cu IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) users.

METHODS:

We performed a retrospective cohort analysis of 10,674 patients who received IUDs at Columbia University Medical Center. Our data were transformed to a common data model and are part of the Observational Health Data Sciences and Informatics network. The cohort patients and outcomes were identified by a combination of procedure codes, condition codes, and medication exposures in billing and claims data. We adjusted for confounding with propensity score stratification and propensity score 1:1 matching.

RESULTS:

Before propensity score adjustment, the Cu IUD cohort included 8,274 patients and the LNG-IUS cohort included 2,400 patients. The median age for both cohorts was 29 years at IUD placement. More than 95% of the LNG-IUS cohort used a device with 52 mg LNG. Before propensity score adjustment, we identified 114 cervical neoplasm outcomes. Seventy-seven (0.9%) cervical neoplasms were in the Cu IUD cohort and 37 (1.5%) were in the LNG-IUS cohort. The propensity score matching analysis identified 7,114 Cu IUD and 2,174 LNG-IUS users, with covariate balance achieved over 16,827 covariates. The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort (2.4 [95% CI 1.5–4.0] cases/1,000 person-years and 5.2 [95% CI 3.7–7.1] cases/1,000 person-years, respectively). The relative risk of high-grade cervical neoplasms among Cu IUD users was 0.38 (95% CI 0.16–0.78, P<.02) compared with LNG-IUS users. By inspection, the Kaplan-Meier curves for each cohort diverged over time.

CONCLUSION:

Copper IUD users have a lower risk of high-grade cervical neoplasms compared with LNG-IUS users. The relative risk of cervical neoplasms of LNG-IUS users compared with the general population is unknown.
Can Differences in Early Hearing Development Be Distinguished by the LittlEARs Auditory Questionnaire?
Authors: Ganek Hillary , James Adrian , Papaioannou Vicky , Gordon Karen
Published: January 2020

Objective:

This study asks whether the LittlEARs Auditory Questionnaire (LEAQ), a caregiver measure, can differentiate between the early auditory development of children with bilateral cochlear implants (CIs), bilateral hearing aids (HAs), and children with Auditory Neuropathy Spectrum Disorder (ANSD) who wear CIs or HAs. The LEAQ is sensitive to impaired auditory development but has not previously been used to distinguish developmental changes between groups of children using different hearing technologies or with different types of hearing loss.

Design:

We collected retrospective longitudinal LEAQ results from 43 children with HAs, 43 with CIs, and 18 with ANSD. The children with ANSD wore hearing technology. They were a similar age to the children without ANSD (23 months; SD = 15), while the CI group (14 months; SD = 8) was younger than the HA group (24 months; SD = 18) [F(2,98.48) = 3.4; p = 0.04]. The CI group often participated in their first LEAQ pretreatment. Participants completed between one and seven LEAQs. Scores ranged between zero and 35 (mean = 18.36). We conducted a linear mixed-effects analysis, which included age or time since device fitting, hearing type (HA, CI, or ANSD), and presence of a comorbidity as fixed effects. A secondary analysis assessed effects of device audibility, measured by the Speech Intelligibility Index or Articulation Index, and consistency of device use obtained from device datalogs.

Results:

Children with CIs progressed faster than their peers with HAs or ANSD [χ2(8) = 24.51; p = 0.002]. However, within a subsample that included consistency of device use (β

7
= −0.20 ± 0.38, t = −0.52; β

8
= 0.93 ± 0.82, t = 1.13) and audibility (β

6
= −0.70 ± 1.45, t = −1.87; β

7
= 0.87 ± 0.89, t = 0.98), study group did not significantly influence rate of improvement on the LEAQ. In addition, children with developmental delays in all three study groups demonstrated significantly slower LEAQ score improvement [χ2(6) = 23.60; p < 0.001] and a trend toward decreased consistency of device use [F(1) = 3.31; p = 0.07]. As we expected, children in the CI and HA groups were more likely to achieve auditory skills indicated in early rather than later LEAQ questions. There was less variability in the responses of the ANSD group [CI: interquartile range (IQR) = 9; HA: IQR = 8; ANSD: IQR = 1]. There was no connection between LEAQ growth and speech perception outcomes in a subsample [r(6) = 0.42; p = 0.30].

Conclusions:

The LEAQ is a useful tool for monitoring initial auditory development in very young children and can inform early treatment decisions.
Use of an Extensile Posterior Approach to the Elbow Joint: Early Results of the Anconeus Approach
Authors: Landrum Matthew , Sager Brian , Youngman Tyler , Green Adam , Sathy Ashoke , Starr Adam , Sanders Drew
Published: January 2020

Commonly used surgical approaches to the elbow typically limit the surgeon to either medial or lateral exposure, can provide visualization limited by an intact radial head, and may not be extensile. We describe the use of a well recognized, but uncommonly used, extensile approach to the medial and lateral compartments of the elbow joint. This approach provides access to address pathology of the proximal radius, ulna, and the distal humerus and can be made extensile both proximally and distally. The anconeus approach is easy to perform and well tolerated by patients. A retrospective review of 42 patients is included.
Treatment of infertility and menopause in a patient with multiple sclerosis affecting the pituitary stalk: a case report
Authors: Aserlind Alexandra , DeCherney Alan
Published: January 2020

Introduction:

Multiple sclerosis (MS) is an immune-mediated inflammatory disease characterized by demyelination of the central nervous system that affects women in their child-bearing years. There has been no absolute data to suggest infertility in this population; however, women with MS may exhibit decreased fertility due to various etiologies. Furthermore, their transition into menopause presents unique aspects in patient care.

Methods:

We report a case of a 38-year-old woman with a diagnosis of MS with subsequent secondary amenorrhea and primary infertility. Multidisciplinary work-up with was consistent with hypothalamic hypogonadism secondary to MS affecting the pituitary stalk. She was treated for infertility in our clinic as well as management of her menopausal symptoms.

Results:

The patient conceived triplets after 2 cycles of ovarian stimulation with injectable gonadotropins and intrauterine insemination. She underwent fetal reduction to twins. After completion of child-bearing, she was treated for menopausal symptoms with various hormonal therapies and ultimately remained on oral conjugated estrogens with no symptoms.

Conclusions:

To our knowledge, this is the first report of infertility caused by suspected MS involvement of the pituitary stalk. In this patient population, infertility treatment can be successful with gonadotropins and alleviation of menopausal symptoms can be achieved with hormone replacement.
Subconjunctival microinvasive glaucoma surgeries: an update on the Xen gel stent and the PreserFlo MicroShunt
Authors: Do Anna T. , Parikh Hardik , Panarelli Joseph F.
Published: January 2020

Purpose of review

This review will provide an update on surgical techniques, outcomes, and complications for two new translimbal bleb-forming surgical glaucoma devices.

Recent findings

The XEN Gel Microstent and PreserFlo MicroShunt comprise a category of subconjunctival microinvasive glaucoma surgery developed with the aim of improving the predictability and safety profile of bleb-forming procedures. Both devices are made of noninflammatory material which limits postsurgical inflammation and scarring and have a valve-less intrinsic flow-limiting design, which decreases the risk of hypotony. There are various techniques of implantation for the XEN Gel Microstent each with their own advantages and disadvantages.

These devices have demonstrated promising outcomes in early experimental literature with similar intraocular pressure-lowering effects to traditional incisional surgery such as trabeculectomy or tube shunt surgery, but with fewer risks. Future randomized, prospective studies should be done to compare these gel stents and microshunts both to each other and to other traditional glaucoma surgeries.
Prospective Evaluation of Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio for Intravenous Immunoglobulin Resistance in a Large Cohort of Kawasaki Disease Patients
Authors: Liu Xiaoliang , Zhou Kaiyu , Hua Yimin , Wu Mei , Liu Lei , Shao Shuran , Wang Chuan
Published: January 2020

The evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for intravenous immunoglobulin resistance prediction was prospectively performed in a large cohort of Kawasaki disease patients. It was found that the predictive values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, alone or combined, were not good enough although they were identified as independent risk factors for intravenous immunoglobulin resistance.
Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries
Authors: Fay Aaron , Nallasamy Nambi , Allen Richard C. , Bernardini Francesco P. , Bilyk Jurij R. , Cockerham Kimberly , Cruz Antonio Augusto , Devoto Martin , Dolman Peter J. , Dutton Jonathan J. , Jordan David R. , Kersten Robert , Kim Yoon-Duck , Lucarelli Mark J. , McNab Alan A. , Mombaerts Ilse , Mourits Maarten , Nerad Jeffrey , Perry Julian D. , Rose Geoffrey , Saeed Peerooz , Seah Lay Leng , Selva Dinesh , Sivak-Callcott Jennifer , Strianese Diego , Verity David H.
Published: January 2020

Purpose:

Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery.

Methods:

A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately.

Results:

Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5.

Conclusions:

In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.
Bilateral IgG4-related Ophthalmic Disease With Diffuse Large B-cell Lymphoma of the Right Eye: A Case Report
Authors: Peng Xiaolin , Jing Hou , He Weimin
Published: January 2020

Lymphoma is common in IgG4-related disease, but diffuse large B-cell lymphoma in IgG4-related ophthalmic disease is rare, especially involving the same organ affected by IgG4-related ophthalmic disease. The authors report a 44-year-old man presented with bilateral proptosis for 10 years and rapid loss of vision in the right eye for the last 1 month. The authors performed orbital exenteration for the right eye and resected the tumor in the left eye. Based on the clinicopathologic findings, tumors of the right and left eyes were diagnosed as diffuse large B-cell lymphoma and IgG4-related ophthalmic disease, respectively. This case highlights the risk of malignant transformation of IgG4-related ophthalmic disease.
Musculoskeletal pain in 6-year-old children: the Generation R Study
Authors: van den Heuvel Marleen M. , Jansen Pauline W. , Bindels Patrick J.E. , Bierma-Zeinstra Sita M.A. , van Middelkoop Marienke
Published: January 2020

Musculoskeletal (MSK) pain is frequently reported among adolescents and children and is a common reason for consultation in primary care. Our aim is to examine its prevalence in 6-year-old children in a general population and to assess associations with physical and psychosocial factors. Data from the Generation R Study, a population-based cohort, was used. Prevalence and characteristics of MSK pain were assessed with parent-reported questionnaires at 6 years of age (N = 6200). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain, and behavioral problems were extracted from questionnaires. The body mass index SD score was calculated from objectively measured weight and height. A 3-month prevalence of 10.0% was found for MSK pain in children, of which one-third was chronic, and 44.6% experienced together with pain at other sites. Univariate analyses showed that boys and children with lower socioeconomic status reported MSK pain more frequently compared to other pain and no pain. Although no associations were found between MSK pain and children's body mass index and physical activity level, children with MSK pain were more likely to watch television ≥2 hours/day. Multivariable analysis showed significant associations for MSK pain at 3 years of age (odds ratio 5.10, 95% confidence interval 3.25-7.98) and behavioral problems (odds ratio 2.10, 95% confidence interval 1.19-3.72) with the presence of MSK pain. So, MSK pain is already common in young children and is often chronic or recurrent. Previous reported MSK pain and behavioral problems are independently associated with MSK pain in the studied population.
Prescription of analgesics to long-term survivors of cancer in early adulthood, adolescence, and childhood in Norway: a national cohort study
Authors: Fredheim Olav Magnus , Skurtveit Svetlana , Loge Jon Håvard , Sjøgren Per , Handal Marte , Hjellvik Vidar
Published: January 2020

Increasing numbers survive cancers in childhood and adolescence. Long-term survivors of cancers in adulthood have increased prevalence of pain and consumption of analgesics. It is not established whether long-term survivors of cancers in childhood and adolescence also have an increased use of analgesics. However, based on increased use of antidepressants and anxiolytics in long-term survivors of cancers in childhood and adolescence, we hypothesized that this group also had increased use of analgesics. Based on data from the 2 nationwide registers, the Cancer Registry of Norway and the Norwegian Prescription Database, a cohort of 5585 (52% males) long-term survivors of cancers in childhood, adolescence, and early adult life was established. Age- and sex-adjusted comparisons were made to the general population. The age-adjusted one-year periodic prevalence of receiving prescriptions of opioids, benzodiazepines, and benzodiazepine-related hypnotics in the study population was increased by 20% to 50%, and the one-year periodic prevalence of receiving prescriptions of gabapentinoids was approximately increased 2-fold compared to the general population. For paracetamol and nonsteroidal anti-inflammatory drugs, no difference was found. For those survivors, who were persistent or high-dose users of opioids, comedication with high doses of benzodiazepines and/or benzodiazepine-related hypnotics was far more common than among persistent and high-dose opioid users in the general population. The high prevalence of gabapentinoids may indicate increased prevalence of neuropathic pain in this group. The high degree of comedication with benzodiazepines and/or benzodiazepine-related hypnotics in survivors on persistent and high-dose opioids might be an indication of problematic opioid use or addiction.
Developing a Patient Classification System for a Neonatal ICU
Authors: Daraiseh Nancy M. , Vidonish William P. , Kiessling Pam , Lin Li
Published: January 2020

OBJECTIVE:

The purpose of this study was to develop a valid and reliable patient classification system (PCS) for a neonatal ICU (NICU).

BACKGROUND:

PCSs have been widely used to determine required care hours, budgeting, and staffing. There is a lack of and a vital need for a valid and reliable pediatric PCS because of differences in needs and treatment from adults.

METHODS:

Data were collected in a NICU using work sampling, chart reviews, and expert opinion. The resulting PCS was assessed for validity and reliability, ease of use, effectiveness, and satisfaction.

RESULTS:

The PCS showed significantly high reliability and validity. Survey scores revealed nurses perceived the tool to be easy to use and effective.

CONCLUSIONS:

Using subjective and objective methods, a NICU PCS was shown to be a valid and reliable measure to determine the hours per patient day required to provide care.
Subcutaneous Fat Reduction with Injected Ice Slurry
Authors: Garibyan Lilit , Moradi Tuchayi Sara , Javorsky Emilia , Farinelli William A. , Wang Ying , Purschke Martin , Tam Josh , Ni Peiyun , Lian Christine G. , Anderson R. Rox
Published: January 2020

Background:

Cryolipolysis is a noninvasive method for removal of subcutaneous fat for body contouring. Conventional cryolipolysis with topical cooling requires extracting heat from subcutaneous fat by conduction across the skin, thus limiting the amount and the location of the fat removed. The authors hypothesized that local injection of a physiological ice slurry directly into target adipose tissue would lead to more efficient and effective cryolipolysis.

Methods:

Injectable slurries containing 20 percent and 40 percent ice content were made using common parenteral agents (normal saline and glycerol), then locally injected into the subcutaneous fat of swine. Ultrasound imaging, photography, histological, and gross tissue responses were monitored before and periodically up to 8 weeks after injection.

Results:

Fat loss occurred gradually over several weeks following a single ice slurry injection. There was an obvious and significant 55 ± 6 percent reduction in adipose tissue thickness compared with control sites injected with the same volume of melted slurry (p < 0.001, t test). The amount of fat loss correlated with the total volume of ice injected. There was no scarring or damage to surrounding tissue.

Conclusion:

Physiological ice slurry injection is a promising new strategy for selective and nonsurgical fat removal.
Improvement in Jowl Fat following ATX-101 Treatment: Results from a Single-Site Study
Authors: Shridharani Sachin M.
Published: January 2020

Background:

Jowl fat overhang can reduce jawline definition. The most common treatment to reduce jowl fat is liposuction. ATX-101 (deoxycholic acid injection), a minimally invasive treatment approved for submental fat reduction, may also be an effective treatment for jowl fat. The current study evaluated the efficacy and safety of ATX-101 treatment for reducing jowl fat.

Methods:

In this prospective single-site study, 66 adults were treated for excess jowl fat with ATX-101 (area-adjusted dose: 2 mg/cm2). Eligible patients had pinchable fat on the jawline and relatively minimal skin laxity in the jowl. Depending on the size of the treatment area, ATX-101 injections of 0.2 ml spaced 1.0 cm apart or 0.1 ml spaced 0.50 to 0.75 cm apart were administered. Improvement in jowl appearance was assessed 6 months or more after the last treatment in person by the clinician. Improvement was also assessed by the patient and two independent plastic surgeons using blinded before/after treatment photographs. Safety was evaluated via adverse events.

Results:

The mean number of ATX-101 treatments received was 1.8, with a mean injection volume of 0.8 ml per treatment per jowl. The majority of patients (98 percent) experienced an improvement in jowl appearance. Common adverse events were injection-site edema, numbness, tenderness, and bruising. Injection-site marginal mandibular nerve paresis and alopecia were experienced by three patients each; all events resolved without sequelae.

Conclusions:

ATX-101 effectively reduced jowl fat and was well tolerated in this small cohort. Care should be taken when injecting ATX-101 into jowl fat to avoid underlying anatomic structures such as the marginal mandibular nerve.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Double Low-Dose Dual-Energy Liver CT in Patients at High-Risk of HCC
Authors: Yoon Jeong Hee , Chang Won , Lee Eun Sun , Lee Sang Min , Lee Jeong Min
Published: January 2020

Objectives

The aim of this study was to investigate the clinical feasibility of the simultaneous reduction of radiation and contrast doses using spectral computed tomography (CT) in patients at high-risk for hepatocellular carcinoma.

Materials and Methods

Between May 2017 and March 2018, this prospective study recruited participants at risk of hepatocellular carcinoma with body mass indexes less than 30 and randomly assigned them to either the standard-dose group or the double low-dose group, which targeted 30% reductions in both radiation and contrast media (NCT03045445). Lesion conspicuity as a primary endpoint and lesion detection rates were then compared between hybrid iterative reconstruction (iDose) images of standard-dose group and low monoenergetic (50 keV) images of double low-dose group. Qualitative and quantitative image noise and contrast were also compared between the 2 groups. Participants and reviewers were blinded for scan protocols and reconstruction algorithms. Lesion conspicuity was analyzed using generalized estimating equation analysis. Lesion detection was evaluated using weighted jackknife alternative free-response receiver operating characteristic analysis.

Results

Sixty-seven participants (male-to-female ratio, 59:8; mean age, 64 ± 9 years) were analyzed. Compared with the standard-dose group (n = 32), significantly lower CTDIvol (8.8 ± 1.7 mGy vs 6.1 ± 0.6 mGy) and contrast media (116.9 ± 15.7 mL vs 83.1 ± 9.9 mL) were utilized in the double low-dose group (n = 35; P < 0.001). Comparative analysis demonstrated that lesion conspicuity was significantly higher on 50 keV images of double low-dose group than on iDose images of standard dose on both arterial (2.62 [95% confidence interval (CI), 2.31–2.93] vs 2.02 [95% CI, 1.73–2.30], respectively, P = 0.004) and portal venous phases (2.39 [95% CI, 2.11–2.67] vs 1.88 [95% CI, 1.67–2.10], respectively, P = 0.005). No differences in lesion detection capability were observed between the 2 groups (figure of merit: 0.63 in standard-dose group; 0.65, double low-dose group; P = 0.52). Fifty kiloelectronvolt images of double low-dose group showed better subjective image noise and contrast than iDose image of standard-dose group on arterial and portal venous phases (P < 0.001 for all). Contrast-to-noise ratio of the aorta and portal vein was also higher in double low-dose group than in standard-dose group (P < 0.001 for all), whereas there was no significant difference of quantitative image noise between the 2 groups on arterial and portal phases (P = 0.4~0.5).

Conclusions

Low monoenergetic spectral CT images (50 keV) can provide better focal liver lesion conspicuity than hybrid iterative reconstruction image of standard-dose CT in nonobese patients while using lower radiation and contrast media doses.
Mirror movement-like muscle hypertonia stroke model based on ipsilateral weight load
Authors: Matsuura Akihiro , Karita Tetsuya , Nakaso Naoyuki , Kondo Yoshihiro , Mori Futoshi
Published: January 2020

In stroke patients, muscle tone on the unaffected side is often increased during voluntary tasks. This is known as a mirror movement and might be an impediment to function recovery, but its neural background is still unclear. In this study, we investigated the effect of unilateral muscle hypertonia on ipsilateral cortical activity and contralateral motor function. Fourteen right-handed healthy young subjects lifted a weight of 10% body weight with the right upper limb to increase muscle tone (weight task), while no weight lifting was set as the control ‘nonweight’ task. We recorded the motor-evoked potential (MEP), resting motor threshold and H-reflex from the left flexor carpi radialis muscle during both tasks. To estimate the functional effect of the weight task, subjects performed the ‘Purdue pegboard test’, consisting of examination for 30 seconds (peg-30) and assembly for 60 seconds (peg assembly). Left-hand grip strength was also measured. When subjects performed the weight task, the MEP amplitude increased significantly and the MT decreased significantly. There was no significant difference of H-reflex amplitude between the two tasks. No significant difference of the peg-30 score was observed between weight and nonweight tasks, but the peg assembly score was significantly lower during the weight task. Grip strength showed a significant increase during the weight task. These results indicate that the present weight load model may have the potential to advance our understanding of the mechanisms underlying mirror movements after stroke.
Inhibition mechanism of human sterol O-acyltransferase 1 by competitive inhibitor
Authors: Guan Chengcheng , Niu Yange , Chen Si-Cong , Kang Yunlu , Wu Jing-Xiang , Nishi Koji , Chang Catherine C. Y. , Chang Ta-Yuan , Luo Tuoping , Chen Lei
Published: January 2020

Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family1. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage2. SOAT1 is a target to treat several human diseases3. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that the small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design of SOAT1 and other mammalian MBOAT family members.
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics
Authors: Buchholz David E. , Carroll Thomas S. , Kocabas Arif , Zhu Xiaodong , Behesti Hourinaz , Faust Phyllis L. , Stalbow Lauren , Fang Yin , Hatten Mary E.
Published: January 2020

Comparative transcriptomics between differentiating human pluripotent stem cells (hPSC) and developing mouse neurons offers a powerful approach to compare genetic and epigenetic pathways in human and mouse neurons. To analyze human Purkinje cell (PC) differentiation, we optimized a protocol to generate hPSC-PCs that formed synapses when cultured with mouse cerebellar glia and granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. To directly compare global gene expression of hPSC-PCs with developing mouse PCs, we used translating ribosomal affinity purification (TRAP). As a first step, we usedTg(Pcp2-L10a-Egfp)TRAP mice to profile actively transcribed genes in developing postnatal mouse PCs, and used metagene projection to identify the most salient patterns of PC gene expression over time. We then created a transgenicPcp2-L10a-EgfpTRAP hESC line to profile gene expression in differentiating hPSC-PCs, finding that the key gene expression pathways of differentiated hPSC-PCs most closely matched those of late juvenile, mouse PCs (P21). Comparative bioinformatics identified classical PC gene signatures as well as novel mitochondrial and autophagy gene pathways during the differentiation of both mouse and human PCs. In addition, we identified genes expressed in hPSC-PCs but not mouse PCs and confirmed protein expression of a novel human PC gene, CD40LG, expressed in both hPSC-PCs and native human cerebellar tissue. This study therefore provides the first direct comparison of hPSC-PC and mouse PC gene expression and a robust method for generating differentiated hPSC-PCs with human-specific gene expression for modeling developmental and degenerative cerebellar disorders.

Significance Statement

To compare global gene expression features of differentiating human pluripotent stem cell-derived Purkinje cells (hPSC-PC) and developing mouse Purkinje cells (PC) we derived hPSC-PCs and compared gene expression datasets from human and mouse PCs. We optimized a differentiation protocol that generated hPSC-PCs most similar in gene expression to mouse P21 PCs. Metagene projection analysis of mouse PC gene expression over postnatal development identified both classical PC marker genes as well as novel mitochondrial and autophagy gene pathways. These key gene expression patterns were conserved in differentiating hPSC-PCs. We further identified differences in timing and expression of key gene sets between mouse and hPSC-PCs and confirmed expression of a novel human PC marker, CD40LG, in human cerebellar tissue.
Infestation dynamics between parasitic Antarctic fish leeches (Piscicolidae) and their crocodile icefish hosts (Channichthyidae)
Authors: Parker Elyse , Jones Christopher , Arana Patricio M. , Alegría Nicolás A. , Sarralde Roberto , Gallardo Francisco , Phillips A.J. , Williams B.W. , Dornburg A.
Published: January 2020

An understanding of host-parasite interactions represents an important, but often overlooked, axis for predicting how marine biodiversity may be impacted by continued environmental change over the next century. For host and parasite communities in the Southern Ocean, investigations of many major groups of parasites have largely been limited to taxonomic and phylogenetic studies, creating an urgent need for the collection of baseline ecological data if we are to detect changes in host-parasite interactions in the future. Here, we survey three species of Crocodile icefish (Notothenioidei: Channichthyidae) collected from two island archipelagos in Antarctica’s South Scotia Arc region for evidence of leech infestations. Specifically, we report on infestation prevalence and intensity of three leech species (Trulliobdella bacilliformis,Trulliobdella capitis, andNototheniobdella sawyeri) on the host fish speciesChaenocephalus aceratus,Champsocephalus gunnari, andChionodraco rastrospinosus.Additionally, we characterize spatial patterns of relative abundances of each leech species across the Elephant and South Orkney Islands, size distribution of parasitized fish, and patterns of host and attachment site specificity. Our results reveal high levels of attachment area fidelity for each leech species. These results suggest skin thickness and density of the vascular network constrain leech attachment sites and further suggest trophic transmission to be an important axis of parasitization. We also demonstrate that, while leech species appear to be clustered spatially, this clustering does not appear to be correlated with fish biomass. This study illuminates the complex interactions among fish hosts and leech parasites in the Southern Ocean and lays the groundwork for future studies of Antarctic marine leech ecology that can aid in forecasting how host-parasite interactions may shift in the face of ongoing climate change.
Multiple resource use strategies confer resilience to the socio-ecosystem in a protected area in the Yucatan Peninsula, Mexico
Authors: García Jácome Luis Guillermo , García-Frapolli Eduardo , Moheno Martha Bonilla , Rivera Coral Rangel , Benítez Mariana , Ramos-Fernández Gabriel
Published: January 2020

Natural Protected Areas (NPAs) are the main biodiversity conservation strategy in Mexico. Generally, NPAs are established on the territories of indigenous and rural groups driving important changes in their local resource management practices. In this paper we study the case ofOtoch Ma’ax Yetel Kooh, an NPA in the Yucatan Peninsula, Mexico, that has been studied in a multidisciplinary way for more than twenty years. This reserve and its buffer zone is homeland to Yucatec Mayan communities that until recently used to manage their resources following a multiple use strategy (MUS), which involves local agricultural practices and has been proposed as resilience-enhancing mechanism. However, due to the restrictions imposed by the decree of the reserve and the growth of tourism in the region, some of these communities have started to abandon the MUS and specialize on tourism-related activities. We build a dynamical computational model to explore the effects of some of these changes on the capacity of this NPA to conserve the biodiversity and on the resilience of households to some frequent disturbances in the region. The model, through the incorporation of agent-based and boolean network modelling, explores the interaction between the forest, the monkey population and some productive activities done by the households (milpa agriculture, ecotourism, agriculture, charcoal production). We calibrated the model, explored its sensibility, compared it with empirical data and simulated different management scenarios. Our results suggest that those management strategies that do not exclude traditional activities may be compatible with conservation objectives, supporting previous studies. Also, our results support the hypothesis that the MUS, throughout a balanced integration of traditional and alternative activities, is a mechanism to enhance household resilience in terms of income and food availability, as it reduces variability and increases the resistance to some disturbances. Our study, in addition to highlighting the importance of local management practices for resilience, also illustrates how computational modeling and systems perspective are effective means of integrating and synthesizing information from different sources.
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation
Authors: Passmore Josiah B. , Carmichael Ruth E. , Schrader Tina A. , Godinho Luis F. , Ferdinandusse Sacha , Lismont Celien , Wang Yunhong , Hacker Christian , Islinger Markus , Fransen Marc , Richards David M. , Freisinger Peter , Schrader Michael
Published: January 2020

Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed.
Partitioning gene-based variance of complex traits by gene score regression
Authors: Zhang Wenmin , Li Si Yi , Liu Tianyi , Li Yue
Published: January 2020

The majority of genome-wide association studies (GWAS) loci are not annotated to known genes in the human genome, which renders biological interpretations difficult. Transcriptome-wide association studies (TWAS) associate complex traits with genotype-based prediction of gene expression deriving from expression quantitative loci(eQTL) studies, thus improving the interpretability of GWAS findings. However, these results can sometimes suffer from a high false positive rate, because predicted expression of different genes may be highly correlated due to linkage disequilibrium between eQTL. We propose a novel statistical method, Gene Score Regression (GSR), to detect causal gene sets for complex traits while accounting for gene-to-gene correlations. We consider non-causal genes that are highly correlated with the causal genes will also exhibit a high marginal association with the complex trait. Consequently, by regressing on the marginal associations of complex traits with the sum of the gene-to-gene correlations in each gene set, we can assess the amount of variance of the complex traits explained by the predicted expression of the genes in each gene set and identify plausible causal gene sets. GSR can operate either on GWAS summary statistics or observed gene expression. Therefore, it may be widely applied to annotate GWAS results and identify the underlying biological pathways. We demonstrate the high accuracy and computational efficiency of GSR compared to state-of-the-art methods through simulations and real data applications. GSR is openly available athttps://github.com/li-lab-mcgill/GSR.