bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of systemic sclerosis-associated interstitial lung disease
Authors: Roofeh David , Jaafar Sara , Vummidi Dharshan , Khanna Dinesh
Published: March 2019

Purpose of review

To review the recently published data and provide a practical overview for management of systemic sclerosis-interstitial lung disease (SSc-ILD).

Recent findings

Published evidence shows considerable practitioner variability in screening patients for ILD. Recent published data support use of cyclophosphamide or mycophenolate mofetil as first-line treatment of SSc-ILD. For patients not responding to first-line therapies, consideration is given to rituximab as rescue therapy. Recent trials of hematopoietic autologous stem cell transplantation have demonstrated benefit in patients with progressive SSc-ILD. Antifibrotic agents are approved in idiopathic pulmonary fibrosis; studies with antifibrotics are underway for SSc-ILD.

The specter of rapidly progressive lung disease requires clinicians to risk stratify patients according to known predictors for progression and rigorously monitor for symptoms and advancing disease. The abovementioned therapies promise improved efficacy and favorable side-effect profiles compared to cyclophosphamide.
Arthritis risk with immune checkpoint inhibitor therapy for cancer
Authors: Pundole Xerxes , Abdel-Wahab Noha , Suarez-Almazor Maria E.
Published: March 2019

Purpose of review

This review summarizes the current evidence on inflammatory arthritis following cancer treatment with immune checkpoint inhibitors (ICI), and the effects of these therapies in patients with preexisting autoimmune arthritis.

Recent findings

As the use of ICI for cancer therapy continues to expand, a myriad of immune-related adverse events (irAE) caused by these therapies are being recognized. Arthritis has been increasingly reported as a de novo irAE, presenting sometimes as a well defined disorder, such as rheumatoid arthritis or psoriatic arthritis, and in other occasions as undifferentiated monoarthritis, oligoarthritis, or polyarthritis. Remitting seronegative symmetric synovitis with pitting edema (RS3PE) and tenosynovitis have also been reported. Most published cases are reported as mild to moderate in severity. The most common treatment for arthritis has been systemic corticosteroids, although several patients have been treated with traditional disease-modifying antirheumatic drugs (DMARD), and a few, with biologic DMARD.

Arthritis following ICI therapy is pleomorphic. Prompt identification and treatment are imperative to achieve optimal outcomes. Management should be multidisciplinary, including rheumatologists and oncologists, to ensure prompt symptomatic and functional management and continuation of cancer therapy as appropriate.
Opioid use in rheumatoid arthritis: trends, efficacy, safety, and best practices
Authors: Day Alvin Lee , Curtis Jeffrey R.
Published: March 2019

Purpose of review

The opioid epidemic remains prominent in both the medical literature and popular media. Rheumatologists are among the physicians at the forefront of the epidemic because of the prominent role of pain in rheumatoid arthritis (RA) and the limited options for treatment of pain. The purpose of this review is to provide an update on the trends of opioid use among patients with RA, to discuss the various mechanisms of RA pain, review the available evidence for opioid efficacy in RA, and to promote a guideline for best practices in opioid prescribing.

Recent findings

Recent cohort studies have estimated that up to 40% of patients with RA are regular users of opioids, and the effects of disease-modifying antirheumatic drugs are minimal in reducing opioid use. Although the literature supports the efficacy of short-term opioids for the improvement in pain, long-term use is associated with reduced efficacy and increased safety concerns.

Although the data supporting the use of long-term opioid use in patients with RA is poor, rheumatologists can adhere to best practices for determining when and if initiation of opioids is appropriate. Identification of the nature of the pain can help determine the appropriate course of treatment.
Clinical and Radiographic Evaluation of Multilevel Lateral Lumbar Interbody Fusion in Adult Degenerative Scoliosis
Authors: Katz Austen D. , Singh Hardeep , Greenwood Matthew , Cote Mark , Moss Isaac L.
Published: March 2019

Study Design:

Retrospective review of prospective data.

Objective:

The objective of this study was to describe the clinical, radiographic, and complication-related outcomes through ≥1-year of 27 patients who underwent lateral lumbar interbody fusion (LLIF) with posterior instrumentation to treat ≥3 contiguous levels of degenerative lumbar scoliosis.

Summary of Background Data:

Multilevel disease has traditionally been treated with open posterior fusion. Literature on multilevel LLIF is limited. We present our experience with utilizing LLIF to treat multilevel degenerative scoliosis.

Methods:

Clinical outcomes were evaluated using VAS, SF-12, and ODI. Radiographic outcomes included pelvic tilt, pelvic incidence, lumbar lordosis, pelvic incidence-lumbar lordosis mismatch, Cobb angle, and cage subsidence. Perioperative and long-term complications through the ≥1-year final-postoperative visit were reviewed; transient neurological disturbances were assessed independently. Demographic, comorbidity, operative, and recovery variables, including opioid use, were explored for association with primary outcomes.

Results:

Mean time to final-postoperative visit was 22.5 months; levels treated with LLIF per patient, 3.7; age, 66 years; and lateral operative time, 203 minutes. EBL was ≤100 mL in 74% of cases. Clinical outcomes remained significantly improved at ≥1-year. Cobb angle was corrected from 21.1 to 7.9 degrees (P<0.001), lordosis from 47.3 to 52.6 degrees (P<0.001), and mismatch from 11.4 to 6.4 degrees (P=0.003). High-grade subsidence occurred in 3 patients. Subsidence did not significantly impact primary outcomes. In total, 11.1% returned to the operating room for complication-related intervention over nearly 2-years; 37% experienced complications. Experiencing a complication was associated with having an open-posterior portion (P=0.048), but not with number of LLIF levels treated, or with clinical or radiographic outcomes. No patients experienced protracted neurological deficits; psoas weakness was associated with increased lateral operative time (P=0.049) and decreased surgeon experience (P=0.028).

Conclusions:

Patients who underwent multilevel LLIF with adjunctive posterior surgery had significant clinical and radiographic improvements. Complication rates were similar compared to literature on single-level LLIF. LLIF is a viable treatment for multilevel degenerative scoliosis.
Combination of Sclerotherapy and Dual-Wavelength Laser in the Management of Infantile Hemangiomas in Chinese Infants
Authors: Lin Li , Guo Peng , Cao Yongqian , Li Qiang , Zhang Jian , Huo Ran
Published: March 2019

OBJECTIVE

To evaluate the efficacy and safety of combination therapy with sclerotherapy and dual-wavelength pulsed dye laser (PDL) & Nd:YAG for infantile hemangiomas (IHs).

PATIENTS AND METHODS

Fifty-nine patients with IH received treatment with sclerotherapy and dual-wavelength PDL & Nd:YAG treatment at 4-week intervals. Observers assessed the size and color of IH using a size rating scale and color rating scale before and after treatments.

RESULTS

The study showed that IH improved significantly after several sessions of treatment. Sclerotherapy reduced the size of IH, whereas dual-wavelength laser lightened the color of IH. No serious adverse effects occurred.

CONCLUSION

Combined sclerotherapy and dual-wavelength laser treatment is an effective and safe option for IH.
Influence of Age, Sex, and Body Mass Index on the Depth of the Superficial Fascia in the Face and Neck
Authors: Casabona Gabriela , Frank Konstantin , Koban Konstantin C. , Schenck Thilo L. , Lopez Valeria P. , Webb Katherine L. , Hamade Hassan , Freytag David L. , Green Jeremy B. , Cotofana Sebastian
Published: March 2019

BACKGROUND

Nonsurgical skin-tightening procedures are increasing in popularity, as patients seek aesthetic interventions that are safe with minimal downtime.

OBJECTIVE

This study was designed to provide precise data on the depth of the superficial fascia—the structure of action—of the face and neck.

METHODS

One hundred fifty Caucasian individuals (75 men and 75 women) were investigated with a balanced distribution of age (n = 30 per decade: 20–29, 30–39, 40–49, 50–59, and 60–69 years) and body mass index (BMI) (n = 50 per group: BMI ≤ 24.9 kg/m2, BMI between 25.0 and 29.9 kg/m2, and BMI ≥ 30 kg/m2). The distance between skin surface and the superficial fascia was measured through ultrasound in the buccal region, premasseteric region, and lateral neck.

RESULTS

The mean distance between skin surface and superficial fascia was for the buccal region 4.82 ± 0.9 mm, range (2.60–6.90); for the premasseteric region 4.25 ± 0.6 mm, range (2.60–5.80); and for the lateral neck 3.71 ± 0.5 mm, range (2.0–5.0). The depth of the superficial fascia increased with increasing BMI, whereas it decreased with advanced age.

CONCLUSION

Knowing the precise depth of the superficial fascia for nonsurgical skin-tightening procedures will guide practitioners toward safer and more effective outcomes.
Diminished ovarian reserve versus ovarian aging: overlaps and differences
Authors: Ata Baris , Seyhan Ayse , Seli Emre
Published: March 2019

Purpose of review

Diminished ovarian reserve, in general, implies a quantitative decline in the oocyte pool. However, whether this quantitative decline is necessarily accompanied by a qualitative decline, remains to be determined.

Recent findings

Studies of natural conception suggest that fecundity of women with a quantitative decline in ovarian reserve is similar to age-matched women with normal ovarian reserve. Data on rates of pregnancy loss and fetal chromosomal abnormality do not consistently suggest a decline in oocyte quality in women who has a lower ovarian reserve. In assisted reproductive technology (ART) cycles, oocytes from women with diminished ovarian reserve have similar potential for euploid blastocyst development. Likewise, available evidence does not strongly suggest an increased risk of pregnancy loss in women with diminished reserve undergoing ART treatment as compared with similarly aged woman with normal ovarian reserve.

Quantitative decline in ovarian reserve may not be necessarily accompanied by a qualitative decline. Although a decreased number of follicles and poor response to ovarian stimulation are hallmarks of ovarian aging, younger women with diminished ovarian reserve may not be experiencing the distinct effects of aging on oocyte quality.
POSTERIORLY INSERTED VITREOUS BASE
Authors: Sohn Elliott H. , Strohbehn Austin , Stryjewski Tomasz , Brodowska Katarzyna , Flamme-Wiese Miles J. , Mullins Robert F. , Eliott Dean
Published: March 2019

Purpose:

To determine the preoperative characteristics, intraoperative and postoperative complications, and outcomes of eyes with posteriorly inserted vitreous base.

Methods:

In this retrospective, observational, consecutive case series at 2 academic centers, 37 patients were studied who had posteriorly inserted vitreous base noted during vitrectomy. Posteriorly inserted vitreous base was defined as the insertion of the posterior hyaloid membrane being located posterior to the vortex veins. Fifteen eyes were analyzed in a histopathologic study of donor eyes to determine the average distance of the ora serrata from the vortex veins as this distance is uncertain.

Results:

Posteriorly inserted vitreous base was identified during vitrectomy in 31 eyes with rhegmatogenous retinal detachment (84%), 4 with macular hole (11%), 1 with vitreous hemorrhage, and 1 with epiretinal membrane. Adjunctive buckle was used in 24%; 54% had 360° laser. Average number of tears seen preoperatively in those with rhegmatogenous retinal detachment was 3.1. Thirty percent had new breaks identified intraoperatively. Forty-one percent had lattice degeneration; new breaks were found in 40% of eyes with lattice. Thirteen percent of rhegmatogenous retinal detachments developed proliferative vitreoretinopathy. Average distance from the ora serrata to the vortex veins was 7.6 mm.

Conclusion:

Any eye undergoing vitrectomy may have posteriorly inserted vitreous base, but those with a high number of retinal breaks and lattice near the equator may be at highest risk. Redetachment and proliferative vitreoretinopathy still occur despite knowledge of the disorder and adjuvant treatments.
Peripheral Endothelial Cell Density in Descemet Membrane Endothelial Keratoplasty Grafts
Authors: Lee Brian A. , Qureshi Saima , Lee Sung , Hou Gene J. , Bedard Peter , Hou Joshua H.
Published: March 2019

Purpose:

To compare the variation in corneal endothelial cell density (ECD) from the center to the periphery in unpeeled and peeled donor corneas and to determine the impact of eccentric trephining on total endothelial cells in Descemet membrane endothelial keratoplasty (DMEK) grafts.

Methods:

Mated donor cornea pairs were obtained. One cornea from each pair was peeled for DMEK, whereas the other was left unpeeled. Alizarin Red was used to stain the endothelial cells. High-resolution images at fixed magnification were obtained for the center, midperiphery (2.5 mm from the center), and the periphery (5 mm from the center). The cells were then counted, and ECD was calculated by a masked evaluator using ImageJ software. Regression analysis was then performed to evaluate the change in ECD as a function of radius (distance from the corneal center). The impact of eccentric trephining on total endothelial cells in a given DMEK graft was then calculated using numerical integration.

Results:

Ten pairs of corneas were evaluated. ECD increased by 1.4% (40.0 cells/mm2) (P = 0.03) for peeled corneas and 1.8% (51.5 cells/mm2) (P < 0.01) for unpeeled corneas for each millimeter from the center. There was no difference between peeled and unpeeled corneas in the mean central (P = 0.98) or peripheral (P = 0.35) ECD. Based on the increase in ECD as a function of radius, eccentric trephining of a 7.5-mm DMEK graft by 2.25 mm yields 0.95% more total endothelial cells per graft.

Conclusions:

Corneal ECD increases from the center to the periphery in both peeled and unpeeled corneas. Eccentric trephining increases the number of transplanted endothelial cells per graft.
Natural Course of Mild Graves Orbitopathy: Increase of Orbital Fat But Decrease of Muscle Volume With Increased Muscle Fatty Degeneration During a 4-Year Follow-Up
Authors: Potgieser Peter W. , de Win Maartje M. M. L. , Wiersinga Wilmar M. , Mourits Maarten P.
Published: March 2019

Purpose:

To describe the natural course of orbital fat volume and extraocular muscle volume in mild Graves orbitopathy during a 4-year follow-up. To describe fatty changes within the extraocular muscles.

Patients:

Twenty-five patients with mild Graves orbitopathy, who did not require any therapeutic intervention other than supportive therapy, were followed for 4 years.

Methods:

CT scans were performed in all patients at baseline and follow-up. A validated technique using Mimics (Materialise) was used to calculate fat and muscle volumes. Outcomes were compared with previously collected data. The amount of intramuscular fat was assessed on CT scans in a semi-quantitative way by two blinded observers according to a four-point scale.

Results:

After a median follow-up of 4.3 years, the median fat to orbital volume ratio increased with 0.08 from 0.57 to 0.65 (p = 0.000), whereas the median muscle volume to orbital volume ratio decreased with 0.03 from 0.17 to 0.14 (p = 0.000). In this control group in patients between 49 and 54 years old, the changes were 0.01 and −0.002, respectively. The Clinical Activity Score decreased to zero (p = 0.000), and the median eyelid aperture decreased from 12 to 10 mm (p = 0.007). A significant increase of intramuscular fat was found in patients with Graves orbitopathy.

Conclusions:

The natural course of mild Graves orbitopathy, as observed over 4 years, is characterized by an increase of orbital fat volume, a decrease in muscle volume, and an increased intramuscular fatty degeneration.
Altered Surfactant Protein Expression in Primary Acquired Nasolacrimal Duct Obstruction
Authors: Ali Mohammad Javed , Bráuer Lars , Schicht Martin , Paulsen Friedrich
Published: March 2019

In cases of primary-acquired nasolacrimal duct obstruction, the expression of multiple surfactant proteins was either deranged or lost in the lining epithelium of the lacrimal sac and nasolacrimal ducts.

Purpose:

To investigate the presence and distribution patterns of 6 surfactant proteins in lacrimal drainage tissues of patients with primary acquired nasolacrimal duct (NLD) obstruction.

Methods:

The presence and distribution of surfactant proteins (SP)-G and SP-H was first assessed in normal cadaveric lacrimal systems. The study was then performed in 10 samples of lacrimal sac and the respective NLDs obtained from patients suffering from primary acquired NLD obstruction who underwent either a dacryocystorhinostomy or a dacryocystectomy. The lacrimal sac samples were further divided into fundus and body, soon after their removal. Immunohistochemical labeling was performed for assessing the presence and distribution of SPs: SP-A, SP-B, SP-C, SP-D, SP-G/SFTA2, and SP-H/SFTA3. The results were then scored as positive or negative and the distribution pattern, if any, within the lacrimal sac and NLDs was assessed. Human lung tissues were used as controls.

Results:

SP-H was demonstrated in the lining epithelia of the normal lacrimal drainage systems, whereas SP-G was uniformly negative. Immunohistochemical labeling revealed wide variations in the staining patterns of different SPs in different regions of the lacrimal sac and the NLD. SP-D and SP-G revealed uniformly negative immunoreactivity. Variable staining patterns were also noted between the superficial and basal layers of the lining epithelia. However, the goblet cells and intraepithelial mucous glands did not express any of the SPs.

Conclusions:

This study provides a proof of principle for the presence of SP-H and absence of SP-G in the normal lacrimal drainage systems. In cases of primary acquired nasolacrimal duct obstruction, there were alterations or loss of SP expression in the lining epithelia of the lacrimal sac and NLDs, reflecting their possible role in the etiopathogenesis of primary acquired nasolacrimal duct obstruction.
Improvement in Kidney Function After Ventricular Assist Device Implantation and Its Influence on Thromboembolism, Hemorrhage, and Mortality
Authors: Davis Brittney H. , Boehme Amelia K. , Pamboukian Salpy V. , Allon Michael , George James F. , Dillon Chrisly , Kirklin James K. , Tallaj Jose , Levitan Emily B. , Griffin Russell , McGwin Gerald , Beasley T. Mark , Limdi Nita A.
Published: March 2019

Although heart transplantation remains the gold standard for management of heart failure, ventricular assist devices (VAD) have emerged as viable alternatives. VAD implantation improves kidney function. However, whether the improvement is sustained or associated with improved outcomes is unclear. Herein we assess kidney function improvement, predictors of improvement, and associations with thromboembolism, hemorrhage, and mortality in VAD patients. Kidney function was defined using chronic kidney disease (CKD) stages: stage 1 (glomerular filtration rate [eGFR] ≥ 90 ml/min/1.73 m2), stage 2 (eGFR 60–90 ml/min/1.73 m2), stage 3a (eGFR 45–59 ml/min/1.73 m2), stage 3b (eGFR 30–44 ml/min/1.73 m2), stage 4 (eGFR 15–30 ml/min/1.73 m2), and stage 5 (eGFR < 15 ml/min/1.73 m2). Improvement in kidney function was defined as an improvement in eGFR that resulted in a CKD stage change to one of lesser severity. Kidney function improved post implant, and was maintained over 1 year for all patients, except those with baseline stage 5 CKD. Younger age at implantation (OR 0.93, 95% CI: 0.90–0.96, P < 0.0001) was associated with sustained improvement in kidney function. Poor kidney function was associated increased mortality but not with thromboembolism or hemorrhage. Compared to patients with baseline eGFR > 45 ml/min/1.73 m2; patients with eGFR < 45 ml/min/1.73 m2 had a higher mortality risk (HR 3.32, 95% CI: 1.10–9.98, p = 0.03 for stage 3b; HR 4.07, 95% CI: 1.27–13.1, p = 0.02 for stage 4; and HR 4.01, 95% CI: 1.17–13.7, p = 0.03 for stage 5 CKD). Kidney function was not associated with thromboembolism or hemorrhage, and sustained improvement was not associated with lower risk of death. However, poor kidney function at implantation was associated with an increased risk of mortality.
Clinical Scenarios for Which Spinal Mobilization and Manipulation Are Considered by an Expert Panel to be Inappropriate (and Appropriate) for Patients With Chronic Low Back Pain
Authors: Herman Patricia M. , Hurwitz Eric L. , Shekelle Paul G. , Whitley Margaret D. , Coulter Ian D.
Published: March 2019

Background:

Spinal mobilization and manipulation are 2 therapies found to be generally safe and effective for chronic low back pain (CLBP). However, the question remains whether they are appropriate for all CLBP patients.

Research Design:

An expert panel used a well-validated approach, including an evidence synthesis and clinical acumen, to develop and then rate the appropriateness of the use of spinal mobilization and manipulation across an exhaustive list of clinical scenarios which could present for CLBP. Decision tree analysis (DTA) was used to identify the key patient characteristics that affected the ratings.

Results:

Nine hundred clinical scenarios were defined and then rated by a 9-member expert panel as to the appropriateness of spinal mobilization and manipulation. Across clinical scenarios more were rated appropriate than inappropriate. However, the number patients presenting with each scenario is not yet known. Nevertheless, DTA indicates that all clinical scenarios that included major neurological findings, and some others involving imaging findings of central herniated nucleus pulposus, spinal stenosis, or free fragments, were rated as inappropriate for both spinal mobilization and manipulation. DTA also identified the absence of these imaging findings and no previous laminectomy as the most important patient characteristics in predicting ratings of appropriate.

Conclusions:

A well-validated expert panel-based approach was used to develop and then rate the appropriateness of the use of spinal mobilization and manipulation across the clinical scenarios which could present for CLBP. Information on the clinical scenarios for which these therapies are inappropriate should be added to clinical guidelines for CLBP.
Synadenium umbellatum and the Ehrlich's solid tumor treatment
Authors: da Silva Emerson B. , Chagas Camila S. , Fonseca Alexandre L. A. , Alves Beatriz da C. A. , Bagatin Izilda , Perazzo Fábio F. , Rosa Paulo , Feder David , Fonseca Fernando Luiz A.
Published: March 2019

Introduction:

Studies have been attributed to cancer treatment, including the potential of several plants with putative anticancer activity. Among these is “Cola-note” (Synadenium umbellatum).

Methods:

We evaluated the effects of macerated S umbellatum at a concentration of 10 mg/kg in Bagg albino strain c mice and its myelotoxic, hepatotoxic, and antitumor activity as well as the expression of inflammatory genes (TGF-β1 and TNF-α). Cells from Ehrlich tumor were implanted in the dorsolateral region of 8 mice of the Bagg albino strain c mice; these animals were divided into control (treated with NaCl 0.9%) and treatment group (treated with macerated Cola-Nota 10 mg/kg).

Results:

Treatment group animals showed no hepatotoxicity, but a potential myelotoxicity. The results suggest that treatment with Cola-Note macerate causes a decrease in expression of TNF-α and an increased expression of TGF-β1.

Discussion:

The S umbellatum (10 mg/kg) is shown to be effective in reducing the concentration of neoplastic cachexia, but there was no antitumor activity.
The Medical Resuscitation Committee
Authors: Mittiga Matthew R. , Frey Mary , Kerrey Benjamin T. , Rinderknecht Andrea S. , Eckerle Michelle D. , Sobolewski Brad , Johnson Laurie H. , Oehler Jennifer L. , Bennett Berkeley L. , Chan Steven , Frey Theresa M. , Krummen Kelly M. , Lindsay Claire , Wolfangel Kelsey , Richert Alison , Masur Tonya J. , Bria Corinne L. , Hoehn Erin F. , Geis Gary L.
Published: March 2019

Provision of optimal care to critically ill patients in a pediatric emergency department is challenging. Specific challenges include the following: (a) patient presentations are highly variable, representing the full breadth of human disease and injury, and are often unannounced; (b) care team members have highly variable experience and skills and often few meaningful opportunities to practice care delivery as a team; (c) valid data collection, for quality assurance/improvement and clinical research, is limited when relying on traditional approaches such as medical record review or self-report; (d) specific patient presentations are relatively uncommon for individual providers, providing few opportunities to establish and refine the requisite knowledge and skill; and (e) unscientific or random variation in care delivery. In the current report, we describe our efforts for the last decade to address these challenges and optimize care delivery to critically ill patients in a pediatric emergency department. We specifically describe the grassroots development of an interprofessional medical resuscitation program. Key components of the program are as follows: (a) a database of all medical patients undergoing evaluation in the resuscitation suite, (b) peer review and education through video-based case review, (c) a program of emergency department in situ simulation, and (d) the development of cognitive aids for high-acuity, low-frequency medical emergencies.
Colorectal Cancer Screening in People With and Without HIV in an Integrated Health Care Setting
Authors: Lam Jennifer O. , Hurley Leo B. , Udaltsova Natalia , Alexeeff Stacey E. , Klein Daniel B. , Corley Douglas A. , Silverberg Michael J.
Published: March 2019

Background:

As people with HIV (PWH) live longer, age-appropriate colorectal cancer (CRC) screening is increasingly important. Limited data exist on CRC screening and outcomes comparing PWH and persons without HIV.

Setting:

Large integrated health care system.

Methods:

This study included PWH and demographically matched persons without HIV who were aged 50–75 years during 2005–2016 and had no previous CRC screening. We evaluated time to first CRC screening (fecal test, sigmoidoscopy, or colonoscopy). We also assessed detection of adenoma and CRC with sigmoidoscopy or colonoscopy by HIV status, accounting for CRC risk factors including sex, age, race/ethnicity, number of outpatient visits, smoking, body mass index, type-2 diabetes, and inflammatory bowel disease. Among PWH, we evaluated whether CD4 count (<200/200–499/≥500 cells/µL) was associated with adenoma and CRC.

Results:

Among 3177 PWH and 29,219 persons without HIV, PWH were more likely to be screened (85.6% vs. 79.1% within 5 years, P < 0.001). Among those with sigmoidoscopy or colonoscopy, adenoma was detected in 161 (19.6%) PWH and 1498 (22.6%) persons without HIV, and CRC was detected in 4 (0.5%) PWH and 69 (1.0%) persons without HIV. In adjusted analyses, we found no difference in prevalence of either adenoma or CRC by HIV status (adjusted prevalence ratio = 0.97, 95% confidence interval: 0.83 to 1.12). Lower CD4 count did not increase likelihood of adenoma or CRC.

Conclusions:

Within an integrated health care system with an organized CRC screening program, we found no disparities in CRC screening uptake or outcomes among people with and without HIV, and CD4 count did not influence CRC risk among PWH.
Issues in the future development of new analgesic drugs
Authors: David-Pereira Ana , Dickenson Anthony H.
Published: March 2019

Purpose of review

There is a clear unmet need for either the development of new drugs for the treatment of painful pathologies or the better use of the existing agents denoted by the lack of efficacy of many existing drugs in a number of patients, limitations of their use due to severity of side effects, and by the high number of drugs that fail to reach clinical efficacy from preclinical development. This account considers the efforts being made to better validate new analgesic components and to improve translational efficacy of existing drugs.

Recent findings

A better use of the available models and tools can improve the predictive validity of new analgesic drugs, as well as using intermediate steps when translating drugs to clinical context such as characterizing drugs using stem cell-sensory derived neurones. Profiling patient sensory phenotypes can decrease the number of failed clinical trials and improve patient outcome.

An integrative approach, comprising the use of complementary techniques to fully characterize drug profiles, is necessary to improve translational success of new analgesics.
Drug-Induced Parkinsonism Manifesting as Gait Freezing in a Patient With Traumatic Brain Injury: A Case Report
Authors: Yoo Ho Sang , Kim Yong Wook , Kim Na Young
Published: March 2019

Background

Among the neuropsychiatric complications commonly induced by traumatic brain injury (TBI), behavioral disorders, such as agitation and aggression, can hinder neurological recovery and deteriorate rehabilitation outcomes. Pharmacological treatment for behavioral disorders might be beneficial but could lead to drug-induced parkinsonism. We report a case of a patient with drug-induced parkinsonism manifested as freezing of gait after TBI, which improved with the cessation of the offending drugs and comprehensive rehabilitation.

Case Presentation

A 35-year-old male patient left with a TBI after a car accident was referred to our hospital. He had been on many neuropsychiatric medications, including atypical antipsychotics, for his agitated behaviors. He could walk independently but showed freezing of gait at the initiation of his gait, when turning to the side, when reaching his destination, and passing through narrow corridors. Under the impression of drug-induced parkinsonism, we gradually tapered the patient off his neuropsychiatric medications. He also underwent comprehensive rehabilitation, including gait training under visual and auditory cues and balance training. Five weeks after admission to the hospital, the patient's freezing of gait improved, with disappearance of his hesitation at gait initiation and a decreased freezing duration while turning around.

Conclusions

This is a rare report of drug-induced parkinsonism manifested as freezing of gait, which showed improvement after discontinuation of the causative drugs and subsequent rehabilitation.
Sertraline-Related Amenorrhea in an Adolescent
Authors: Ekinci Nuran , Güneş Serkan , Kalinli Merve , Ekinci Özalp
Published: March 2019

Amenorrhea is one of the clinical consequences of hyperprolactinemia. Although symptomatic hyperprolactinemia is among the well-described adverse reactions of antipsychotic agents, it may also be reported with the use of selective serotonin reuptake inhibitors. Hereby, we present a case of sertraline-related hyperprolactinemic amenorrhea in an adolescent. Amenorrhea occurred 2 months after starting sertraline, and menstrual cycle restored after stopping the treatment.
Video Game-Induced Theta Rhythm
Authors: Sener Ugur , McKay Jake H. , Feyissa Anteneh M. , Tatum William O.
Published: March 2019

Smartphones and other personal electronic devices present novel cortical processing tasks with potential for identification of novel EEG waveforms. A 17-year-old patient with epilepsy manifested as recurrent myoclonic seizures, absence seizures, and a single generalized tonic–clonic seizure was hospitalized to undergo video-EEG monitoring for seizure quantification and classification of the epilepsy syndrome. During the monitoring session, a frontocentral predominant 5 to 6 Hz theta rhythm was identified only when the patient was actively texting or playing a video game on his smartphone. Previously, patients with focal epilepsy have been found to have a frontocentral theta rhythm on EEG while texting on mobile devices. We report similar EEG findings in a patient with genetic generalized epilepsy during smartphone gaming to expand the population and triggers for this theta waveform. Given the young age and type of epilepsy, we suggest that the waveform represents the EEG manifestation of the attention–visuomotor pathway that is stimulus independent.
Multiple Point Stimulation MUNE in ALS: Toward a Faster Modification
Authors: Oliveira Santos Miguel , Jacobsen Anna Bystrup , Tankisi Hatice
Published: March 2019

Purpose:

Multiple point stimulation is a well-established motor unit number estimate method that can be used in all EMG machines, but it is time-consuming. We investigated whether a faster modification of multiple point stimulation using five surface motor unit action potentials (sMUAP) had similar reproducibility, sensitivity, and specificity as 10.

Methods:

Twenty-two motor neuron disease patients and 20 healthy controls were prospectively examined by two physicians twice in the thenar muscles.

Results:

A total of 168 multiple point stimulation motor unit number estimate recordings were obtained. Mean motor unit number estimate was significantly lower in patients in contrast to the controls, whether using 5 (53 ± 55 [1–170] vs. 150 ± 64 (51–325), P < 0.001] or 10 sMUAP [52 ± 51 (1–162) vs. 151 ± 50 (75–274), P < 0.001]. No significant differences (P > 0.05) were found between mean motor unit number estimate obtained from 5 or 10 sMUAP in both patients and controls. Intra-rater coefficient of variation (CV) for patients (17% vs. 15%) and controls (16% vs. 13%) and inter-rater coefficient of variation for patients (25% vs. 24%) did not differ between five and 10 sMUAP (P > 0.05), whereas interrater coefficient of variation was higher for five sMUAP in controls (21% vs. 16%, P = 0.004). An excellent intraclass correlation coefficient (≥0.78) was found, sampling either 5 or 10 sMUAP, for both groups. Receiver operating characteristic curves collecting 5 or 10 sMUAP showed excellent accuracy in distinguishing between patients and controls.

Conclusions:

The faster modification of Multiple point stimulation by sampling five sMUAP had similar reproducibility, sensitivity, and specificity as 10 and may be suggested in future research and clinical practice.
Competition is crucial for social comparison processes in long-tailed macaques
Authors: Keupp Stefanie , Titchener Rowan , Bugnyar Thomas , Mussweiler Thomas , Fischer Julia
Published: March 2019

Humans modulate their self-evaluations and behaviour as a function of conspecific presence and performance. In this study, we tested for the presence of human-like social comparison effects in long-tailed macaques (Macaca fascicularis). The monkeys' task was to extract food from an apparatus by pulling drawers within reach and we measured latency between drawer pulls. Subjects either worked on the task with a partner who could access the apparatus from an adjacent cage, worked in the absence of a conspecific but with food moving towards the partner's side or worked next to a partner who was denied apparatus access. We further manipulated partner performance and competitiveness of the set-up. We found no indication that long-tailed macaques compare their performance to the performance of conspecifics. They were not affected by the mere presence of the partner but they paid close attention to the partner's actions when they were consequential for food availability. If social comparison processes are present in long-tailed macaques, the present study suggests they may only manifest in situations involving direct competition and would thus be different from social comparisons in humans, which manifest also in the absence of direct competition, for example in evaluative contexts.
Digit ratio predicts the number of lifetime recruits in female collared flycatchers
Authors: Nagy Gergely , Garamszegi László Zsolt , Hegyi Gergely , Herényi Márton , Laczi Miklós , Rosivall Balázs , Szöllősi Eszter , Török János
Published: March 2019

The early environment in which an organism grows can have long-lasting impacts on both its phenotype and fitness. However, assessing this environment comprehensively is a formidable task. The relative length of the second to the fourth digit (2D : 4D) is a broadly studied skeletal trait that is fixed for life during ontogeny. 2D : 4D has been shown to indicate various early effects including the perinatal steroid milieu in both humans and non-human animals. However, the fitness relevance of the early effects indicated by 2D : 4D remains unknown. Here, we investigated hindlimb 2D : 4D and measures of lifetime performance in wild collared flycatcher (
Ficedula albicollis
) females. We found that females with higher 2D : 4D had a greater number of recruiting offspring to the breeding population. This was the case despite the fact that such females did not lay more eggs or breed more frequently during their reproductive life. Our results support the suggestion that 2D : 4D, known to be a retrospective marker of perinatal development, positively associates with female quality in the collared flycatcher.
Sir Patrick Bateson FRS. 31 March 1938—1 August 2017
Authors: Laland Kevin N. , Rose Steven
Published: March 2019

Patrick Bateson made outstanding contributions to the study of animal behaviour over a 50-year period, a field in which he was regarded as a world leader. His research involved analyses of the development, causal mechanisms, function and evolution of behaviour, and combined work in the experimental laboratory with observations of the natural behaviour of animals and theoretical analyses. With particular expertise on behavioural development, Bateson made seminal contributions to several topics, including filial imprinting, mate choice, developmental plasticity, the roles of behaviour and development in evolution, animal welfare and animal play. His research on imprinting in birds pioneered new methods, set new standards for behavioural research and shed new light on the interplay of internal and external factors during behavioural development. Recognizing that a complete understanding of behaviour requires investigation at a number of levels, Bateson's interactionist perspective led him to be highly critical of reductionism and of simple-minded use of terms such as ‘instinct’ and ‘innate’. Bateson published several influential books and well over 300 scientific articles, including a substantial number in flagship journals such as
Nature
and
Science
. His contribution to science was recognized with many honours, including a knighthood, the Frink Medal of the Zoological Society of London and the Distinguished Animal Behaviorist Career Award of the Animal Behavior Society. Bateson was also provost of Kings College Cambridge, president of the Zoological Society of London and biological secretary and vice-president of the Royal Society. A leading public intellectual in the early part of the twenty-first century, Bateson brought leadership and balanced judgement to many difficult issues, including the use of animals in medical research, dog breeding and hunting.
Mechanical regulation of bone formation and resorption around implants in a mouse model of osteopenic bone
Authors: Li Zihui , Betts Duncan , Kuhn Gisela , Schirmer Michael , Müller Ralph , Ruffoni Davide
Published: March 2019

Although mechanical stimulation is considered a promising approach to accelerate implant integration, our understanding of load-driven bone formation and resorption around implants is still limited. This lack of knowledge may delay the development of effective loading protocols to prevent implant loosening, especially in osteoporosis. In healthy bone, formation and resorption are mechanoregulated processes. In the intricate context of peri-implant bone regeneration, it is not clear whether bone (re)modelling can still be load-driven. Here, we investigated the mechanical control of peri-implant bone (re)modelling with a well-controlled mechanobiological experiment. We applied cyclic mechanical loading after implant insertion in tail vertebrae of oestrogen depleted mice and we monitored peri-implant bone response byin vivomicro-CT. Experimental data were combined with micro-finite element simulations to estimate local tissue strains in (re)modelling locations. We demonstrated that a substantial increase in bone mass around the implant could be obtained by loading the entire bone. This augmentation could be attributed to a large reduction in bone resorption rather than to an increase in bone formation. We also showed that following implantation, mechanical regulation of bone (re)modelling was transiently lost. Our findings should help to clarify the role of mechanical stimulation on the maintenance of peri-implant bone mass.
Theoretical investigation of stochastic clearance of bacteria: first-passage analysis
Authors: Teimouri Hamid , Kolomeisky Anatoly B.
Published: March 2019

Understanding mechanisms of bacterial eradication is critically important for overcoming failures of antibiotic treatments. Current studies suggest that the clearance of large bacterial populations proceeds deterministically, while for smaller populations, the stochastic effects become more relevant. Here, we develop a theoretical approach to investigate the bacterial population dynamics under the effect of antibiotic drugs using a method of first-passage processes. It allows us to explicitly evaluate the most important characteristics of bacterial clearance dynamics such as extinction probabilities and extinction times. The new meaning of minimal inhibitory concentrations for stochastic clearance of bacterial populations is also discussed. In addition, we investigate the effect of fluctuations in population growth rates on the dynamics of bacterial eradication. It is found that extinction probabilities and extinction times generally do not correlate with each other when random fluctuations in the growth rates are taking place. Unexpectedly, for a significant range of parameters, the extinction times increase due to these fluctuations, indicating a slowing in the bacterial clearance dynamics. It is argued that this might be one of the initial steps in the pathway for the development of antibiotic resistance. Furthermore, it is suggested that extinction times is a convenient measure of bacterial tolerance.
Public questions spur the discovery of new bacterial species associated with lignin bioconversion of industrial waste
Authors: Mathews Stephanie L. , Epps Mary Jane , Blackburn R. Kevin , Goshe Michael B. , Grunden Amy M. , Dunn Robert R.
Published: March 2019

A citizen science project found that the greenhouse camel cricket (
Diestrammena asynamora
) is common in North American homes. Public response was to wonder ‘what good are they anyway?’ and ecology and evolution guided the search for potential benefit. We predicted that camel crickets and similar household species would likely host bacteria with the ability to degrade recalcitrant carbon compounds. Lignocellulose is particularly relevant as it is difficult to degrade yet is an important feedstock for pulp and paper, chemical and biofuel industries. We screened gut bacteria of greenhouse camel crickets and another household insect, the hide beetle (
Dermestes maculatus
) for the ability to grow on and degrade lignocellulose components as well as the lignocellulose-derived industrial waste product black liquor. From three greenhouse camel crickets and three hide beetles, 14 bacterial strains were identified that were capable of growth on lignocellulosic components, including lignin.
Cedecea lapagei
was selected for further study due to growth on most lignocellulose components. The
C. lapagei
secretome was identified using LC/MS/MS analysis. This work demonstrates a novel source of lignocellulose-degrading bacteria and introduces an effective workflow to identify bacterial enzymes for transforming industrial waste into value-added products. More generally, our research suggests the value of ecologically guided discovery of novel organisms.
Social flocculation in plant–animal worms
Authors: Worley Alan , Sendova-Franks Ana B. , Franks Nigel R.
Published: March 2019

Individual animals can often move more safely or more efficiently as members of a group. This can be as simple as safety in numbers or as sophisticated as aerodynamic or hydrodynamic cooperation. Here, we show that individual plant–animal worms (
Symsagittifera roscoffensis
) can move to safety more quickly through flocculation. Flocs form in response to turbulence that might otherwise carry these beach-dwelling worms out to sea. They allow the worms to descend much more quickly to the safety of the substrate than single worms could swim. Descent speed increases with floc size such that larger flocs can catch up with smaller ones and engulf them to become even larger and faster. To our knowledge, this is the first demonstration of social flocculation in a wild, multicellular organism. It is also remarkable that such effective flocculation occurs where the components are comparatively large multicellular organisms organized as entangled ensembles.
Deep eutectic solvent for an expeditious sono-synthesis of novel series of
bis
-quinazolin-4-one derivatives as potential anti-cancer agents
Authors: Ahmed Arafa Wael Abdelgayed
Published: March 2019

To produce a new category of anti-cancer compounds, a facile and environmentally sustainable method for preparing diversified
bis
-quinazolinones was demonstrated using recyclable deep eutectic solvent (DES) under ultrasonic irradiation. The reactions were performed smoothly with a wide scope of substrates affording the desired derivatives in good-to-excellent yields under an atom-economical pathway. Particularly, halogen substituents that are amenable for further synthetic elaborations are well tolerated. Furthermore, the ‘greenness’ of the protocol was assessed within the scope of several green metrics and found to display an excellent score in the specified parameters. Cytotoxic activity of all novel
bis
-quinazolinones was investigated utilizing two cancer cell lines: breast (MCF-7) and lung (A549) cell lines and their IC
50
values were determined. Most of the prepared derivatives displayed fascinating inhibitory activity with IC
50
values in a low micromolar range. Remarkably, the derivative
7e
[3,3'-(sulfonyl
bis
(4,1-phenylene))
bis
(2-methyl-6-nitroquinazolin-4(3
H
)-one)] showed superior potency against MCF-7 and A549 cancer cell lines, with IC
50
values of 1.26 µM and 2.75 µM, respectively. Moreover, this derivative was found to have low toxicity to the normal breast cell line (MCF-10A) and could serve as a promising lead candidate for further development.
Evidence to support common application switching behaviour on smartphones
Authors: Turner Liam D. , Whitaker Roger M. , Allen Stuart M. , Linden David E. J. , Tu Kun , Li Jian , Towsley Don
Published: March 2019

We find evidence to support common behaviour in smartphone usage based on analysis of application (app) switching. This is an overlooked aspect of smartphone usage that gives additional insight beyond screen time and the particular apps that are accessed. Using a dataset of usage behaviour from 53 participants over a six-week period, we find strong similarity in the structure of networks built from app switching, despite diversity in the apps used, and the volume of app switching. App switch networks exhibit small-world, broad-scale network features, with a rapid popularity decay, suggesting that preferential attachment may drive next-app decision-making.