bluuebunny/crossref_metadata_2025 huggingface dataset:
Midazolam and Ketamine Produce Distinct Neural Changes in Memory, Pain, and Fear Networks during Pain
Authors: Vogt Keith M. , Ibinson James W. , Smith C. Tyler , Citro Ally T. , Norton Caroline M. , Karim Helmet T. , Popov Vencislav , Mahajan Aman , Aizenstein Howard J. , Reder Lynne M. , Fiez Julie A.
Published: April 2021

Background

Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning.

Methods

In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d′ (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs.

Results

Recollection memory was reduced under midazolam (median [95% CI], d′ = 0.73 [0.43 to 1.02]) compared with saline (d′ = 1.78 [1.61 to 1.96]) and ketamine (d′ = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex.

Conclusions

Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories.

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What We Already Know about This Topic

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Evaluating the Correlation Between Nursing Practice and Electronic Nursing Records Using Importance-Performance Analysis
Authors: Park Hyunbong , Yu Soyoung , Lee Seon Heui
Published: April 2021

This study aimed to analyze the importance and performance of nursing task items in the standard guidelines for comprehensive nursing services and confirm whether they are reflected in the nursing records. A total of 120 nurses from three hospitals were surveyed for the importance-performance analysis of standard nursing services and their correlation with nursing records. The average scores for importance, performance, and correlation to nursing records were 3.65, 3.31, and 3.08, respectively, demonstrating a significant positive correlation. Regarding the correlation between nursing tasks and nursing records, spiritual and emotional assessment, mobilization, education and counseling, and escaping and suicide prevention items had moderately low scores. In the importance correlation to the nursing records of the task items matrix, 10 items in quadrant 1 were strengths. Conversely, in quadrant 2, suicide and escape prevention require critical areas for improvement. The other six items were low-priority items in quadrant 3, and the three items in quadrant 4 were hygiene, elimination, and nutrition, which required excessive effort. It is necessary to evaluate the electronic nursing records system periodically according to the nursing environment and modify and supplement the records if required.
Internet-delivered cognitive behavioral therapy for youth with functional abdominal pain: a randomized clinical trial testing differential efficacy by patient subgroup
Authors: Walker Lynn S. , Stone Amanda L. , Han Gloria T. , Garber Judy , Bruehl Stephen , Smith Craig A. , Anderson Julia , Palermo Tonya M.
Published: April 2021

Inconsistent results of psychological treatments for pediatric functional abdominal pain (FAP) may be due to heterogeneity of patients' pain-related psychological characteristics. This randomized controlled trial tested whether statistically derived patient subgroups (high pain dysfunctional [HPD], high pain adaptive [HPA], and low pain adaptive [LPA]) moderated response to cognitive behavior therapy (CBT) for adolescents with FAP and their parents (n = 278 dyads; patients were 66% female, mean [SD] age was 14.62 [1.88] years, and parents were 95% female). Randomization to Internet-delivered CBT vs Internet-delivered pain education (EDU) was stratified by patient subgroup. Follow-up assessments of gastrointestinal (GI) symptoms (primary outcome), abdominal pain, and pain interference were at midtreatment, posttreatment, 6 months, and 12 months. Data were analysed using linear mixed effects models. Significant treatment × subgroup × time interaction effects showed that patient subgroup significantly moderated the effect of treatment on GI symptoms (t[853 = −2.93, P = 0.003) and abdominal pain (t(844) = −2.14, P = 0.03) across the treatment period. Among HPD youth, those in CBT had significantly greater GI symptom reduction than those in EDU through posttreatment. By contrast, among HPA and LPA youth, symptom improvement did not differ by treatment condition. Furthermore, among all patients assigned to CBT, HPD youth demonstrated significantly greater reductions in GI symptoms compared with HPA and LPA youth and greater reductions in abdominal pain compared with LPA youth. All subgroups maintained symptom reductions throughout the follow-up period. Results suggest that subgrouping FAP patients may inform treatment allocation and optimize treatment response.
Noninvasive bladder testing of adolescent females to assess visceral hypersensitivity
Authors: Tu Frank F. , Hellman Kevin M. , Roth Genevieve E. , Dillane Katlyn E. , Walker Lynn S.
Published: April 2021

Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that could be performed readily on youth in early risk windows. Therefore, we evaluated the validity and reliability of a noninvasive bladder pain test in 124 healthy premenarchal females (median age 11, [interquartile range 11-12]), as previously studied in adult women. We explored whether psychosocial, sensory factors, and quantitative sensory test results were associated with provoked bladder pain and assessed the relation of bladder pain with abdominal pain history. Compared with findings in young adult females (age 21 [20-28]), results were similar except that adolescents had more pain at first sensation to void (P = 0.005) and lower maximum tolerance volume (P < 0.001). Anxiety, depression, somatic symptoms, and pain catastrophizing predicted provoked bladder pain (P's < 0.05). Bladder pain inversely correlated with pressure pain thresholds (r = −0.25, P < 0.05), but not with cold pressor pain or conditioned pain modulation effectiveness. Bladder pain was also associated with frequency of abdominal pain symptoms (r = 0.25, P = 0.039). We found strong retest reliability for bladder pain at standard levels of sensory urgency in 21 adolescents who attended repeat visits at 6 to 12 months (intraclass correlations = 0.88-0.90). Noninvasive bladder pain testing seems reproducible in adolescent females and may predict abdominal pain symptomatology. Confirmation of our findings and further investigation of the bladder test across menarche will help establish how visceral sensitivity contributes to the early trajectory of pelvic pain risk.
Efficacy and safety of single-dose DFN-15 for treatment of acute postsurgical dental pain: a randomized, double-blind, placebo-controlled study
Authors: Singla Neil , Bertoch Todd , Shenoy Srinivas , Munjal Sagar
Published: April 2021

The analgesic efficacy and safety of DFN-15, a new oral liquid formulation of celecoxib with more rapid absorption than the capsule, were evaluated in the treatment of acute pain in adult patients after dental surgery. In this randomized, double-blind, placebo-controlled, dose-ranging study, 120 otherwise healthy adults who underwent the extraction of bilateral impacted mandibular third molar teeth and experienced moderate to severe pain postsurgery were randomly assigned, in a 1:1:1:1 ratio, to receive one dose of either placebo or DFN-15 at 3 doses: 62.5, 125, and 250 mg. Participants were evaluated at prespecified time points over 8 hours after study drug administration, using several instruments, including the 11-point Numerical Pain Rating Scale, 5-point Pain Relief Scale, and 5-point Treatment Satisfaction Scale. Rescue analgesic (oxycodone / acetaminophen) was permitted. The primary endpoint was the summed pain intensity difference (SPID) over the 6-hour postdose period (SPID6), which was compared between each DFN-15 dose and placebo using analysis of covariance. Other assessments of pain relief, use of rescue medication, and safety were also analyzed. All 3 doses of DFN-15 were significantly superior to placebo in SPID6 (least square mean difference over placebo: −756.6, −1120.7, and −1355.1, P < 0.0001 for all comparisons). In addition, DFN-15 was generally superior to placebo in other endpoints, including reduction of pain intensity, speed and magnitude of pain relief, treatment satisfaction, and rescue medication use. DFN-15 was similar to placebo in the incidence of adverse events with no apparent dose-related effects.
Opioid prescribing in the U.S. Military Health System, 2014 to 2018: fewer prescriptions, fewer pills, and shorter treatment duration
Authors: Goldman Ashton H. , Johnson Daniel D. , Griffis Clare E. , Land Vaughn , Balazs George C.
Published: April 2021

Prescription opioids remain an important driver of the opioid crisis in the United States. The purpose of this study was to examine recent changes in opioid prescribing patterns in the Military Health System (MHS) which is a nationwide health system service active duty military personnel and civilian beneficiaries. All patients prescribed opioid analgesics by MHS providers and filled at MHS pharmacies between 2014 and 2018 were identified. Prescriptions were converted to oral morphine equivalents (OMEs) and categorized based on prescribing specialty and formulation. Total opioid prescription counts and opioid prescription counts weighted by the annual number of outpatient encounters for each specialty were calculated, as were total OMEs and daily OMEs per prescription. A total of 3,427,308 prescriptions were included. Primary care providers and surgeons wrote 47% and 29% of opioid prescriptions, respectively. Over the study period, there was a 56% decline in annual opioid prescriptions, 25% decline in median total OMEs, and a 57% decline in opioid prescriptions per patient encounter. The proportion of prescriptions written for >90 OMEs per day declined 21%. Declines in opioid prescriptions and quantities were observed in nearly all specialties over the study period. The results of this study suggest a broad-based shift towards less opioid prescribing.
Hemorrhagic pericardial tamponade in a peritoneal dialysis patient
Authors: Chou Yi-Hsin , Lin Ting-Yu , Tan Ann Charis , Chen Fan-Yu , Yu Wen-Chung , Lin Chih-Ching
Published: April 2021

Uremic pericarditis and pericardial effusion are possible complications among patients with end-stage renal disease. The accumulation of toxic metabolites may contribute to the pathogenesis of uremic pericarditis. Bleeding diathesis in peritoneal dialysis patients raises the risk of hemorrhagic pericardial tamponade, which is a fatal complication of peritoneal dialysis. We report a case of hemorrhagic pericardial tamponade who was nonadherent to peritoneal dialysis with initial presentation of hypotension and syncope. Transthoracic echocardiogram revealed septated, fibrinoid pericardial effusion and right ventricular diastolic compression. A massive bloody pericardial effusion was drained when he underwent the pericardial window procedure. There was a significant improvement both in his clinical condition and in the echocardiogram images after the procedure. Hemorrhagic pericardial tamponade occurs in uremic patients but is rarely seen in those undergoing peritoneal dialysis. Early diagnosis, immediate surgical drainage, and regular follow-up with echocardiography are crucial to achieve better prognoses in future similar clinical scenarios.
Differences in end-of-life care and outcomes in palliative consultation-eligible patients with and without do-not-resuscitate orders: A propensity score-matched study
Authors: Chang Julia Chia-Yu , Yang Che , Lai Li-Ling , Huang Hsien-Hao , Fan Ju-Sing , Lin Ming-Hwai , Hsu Teh-Fu , Yen David Hung-Tsang
Published: April 2021

Background:

The primary objective of palliative care, not synonymous with end-of-life (EOL) care, is to align care plans with patient goals, regardless of whether these goals include the pursuit of invasive, life-sustaining procedures, or not. This study determines the differences in EOL care, resource utilization, and outcome in palliative care consultation-eligible emergency department patients with and without do-not-resuscitate (DNR) orders.

Methods:

This is a retrospective observational study. We consecutively enrolled all the acutely and critically ill emergency department patients eligible for palliative care consultation at the Taipei Veterans General Hospital, a 3000-bed tertiary hospital, from February 1 to July 31, 2018. The outcome measures included in-hospital mortality and EOL care of patients with and without DNR.

Results:

A total of 396 patients were included: 159 with and 237 without DNR. Propensity score matching revealed that patients with DNR had significantly shorter duration of hospital stay (404.4 ± 344.4 hours vs 505.2 ± 498.1 hours; p = 0.037), higher in-hospital mortality (54.1% vs 34.6%; p < 0.001), and lower total hospital expenditure (191 239 ± 177 962 NTD vs 249 194 ± 305 629 NTD; p = 0.04). Among patients with DNR, there were fewer deaths in the intensive care unit (30.2% vs 37.0%), more deaths in the hospice ward (16.3% vs 7.4%), more critical discharge to home (9.3% vs 7.4%), more endotracheal removals (3.1% vs 0%; p = 0.024), and more narcotics use (32.7% vs 22.1%; p = 0.018).

Conclusion:

The palliative care consultation-eligible emergency department patients with DNR compared with those without DNR experienced worse outcomes, greater pain control, more endotracheal extubations, shorter duration of hospital stay, more critical discharge to home, more hospice referrals, and 23.3% reduction in total expenditure. There were fewer deaths in the ICU among them as well.
The efficacy of periarticular injection intraoperatively for mini-open rotator cuff repair: A comparative study
Authors: Ma Hsuan-Hsiao , Huang Chung-Chin , Chang Ming-Chau , Chen Wei-Ming , Huang Tung-Fu
Published: April 2021

Background:

The optimal postoperative analgesia after open rotator cuff repair surgery remains unclear. This study compared the use of a multimodal pain regimen including periarticular injection (PAI), with a control condition. We hypothesized that PAI leads to decreased opioid consumption and lower pain scores.

Methods:

The perioperative analgesic regimen was standardized and implemented from January 1, 2017 to December 31, 2017. The PAI was administered from July 1, 2017 to December 31, 2017. The historical control group was enrolled from January 1, 2017 to June 30, 2017. The evaluation items included assessments of pain using a 10-point visual analog scale (VAS) before and after the mini-open rotator cuff repair and on postoperative days 1, 2, and 3. The dose of ketorolac suppository and its side effects were also evaluated.

Results:

The VAS score on the day of the operation was significantly low in the PAI group and less incidence of night pain. The time point of the rescue drug was longer in the PAI group than the control group (12.7 hours vs. 0.62 hours; p < 0.01). No cardiac or central nervous system toxicity was observed.

Discussion:

In our study, PAI in the shoulder after mini-open rotator cuff repair showed effective pain control on the day of the surgery, postponed the time of the first dosage of intravenous pain medication, and reduced the total dosage of the intravenous pain medication.
Beyond weight loss in nonalcoholic fatty liver disease: the role of carbohydrate restriction
Authors: Risi Renata , Tozzi Rossella , Watanabe Mikiko
Published: April 2021

Purpose of review

The low fat diet (LFD) is currently the first choice to treat nonalcoholic fatty liver disease (NAFLD) alongside with physical activity. However, low carbohydrate diets (LCDs) and ketogenic diets have gained attention lately, thanks to their favourable impact in reducing intrahepatic triglyceride content. We therefore aimed at providing an update on recent evidence evaluating the hepatoprotective effects of such dietary interventions.

Recent findings

Novel findings confirmed previous evidence by showing beneficial effects on liver fat content reduction for both LFDs and LCDs. The further restriction of carbohydrates to less than 50 g/day, usually leading to ketosis, confirmed to produce an improvement in NAFLD, with very low-calorie ketogenic diets possibly proving particularly beneficial thanks to the significant weight loss that can be obtained.

Most of the latest evidence shows that carbohydrate restriction plays a fundamental role in the modulation of lipid metabolism leading to similar efficacy in improving NAFLD compared with LFDs. The hepatoprotective role of carbohydrate restriction appears to be boosted when ketogenesis is induced, when the total calorie intake is extremely reduced, or, possibly, when dietary interventions have reduced content in free sugars, making such interventions valuable tools to deal with NAFLD.
Multisystem inflammatory syndrome in children: a microcosm of challenges and opportunities for translational bioinformatics in pediatric research
Authors: Murphy Jones Lara , Khatri Purvesh
Published: April 2021

Purpose of review

Despite significant progress in our understanding and clinical management of multisystem inflammatory syndrome in children (MIS-C), significant challenges remain. Here, we review recently published studies on the clinical diagnosis, risk stratification, and treatment of MIS-C, highlighting key gaps in research progress that are a microcosm for challenges in translational pediatric research. We then discuss potential solutions in the realm of translational bioinformatics.

Recent findings

Current case definitions are inconsistent and do not capture the underlying pathophysiology of MIS-C, which remains poorly understood. Although overall mortality is low, some patients rapidly decompensate, and a test to identify those at risk for severe outcomes remains an unmet need. Treatment consists of various combinations of immunoglobulins, corticosteroids, and biologics, based on extrapolated data and expert opinion, while the benefits remain unclear as we await the completion of clinical trials.

The small size and heterogeneity of the pediatric population contribute to unmet needs because of financial and logistical constraints of the current research infrastructure focused on eliminating most sources of heterogeneity, leading to ungeneralizable results. Data sharing and meta-analysis of gene expression shows promise to accelerate progress in the field of MIS-C as well as other childhood diseases beyond the current pandemic.
Emergency Physician Perceptions of Electronic Health Record Usability and Safety
Authors: Pruitt Zoe M. , Howe Jessica L. , Hettinger Aaron Z. , Ratwani Raj M.
Published: April 2021

Objectives

Despite requirements for electronic health record (EHR) vendor usability testing, usability challenges persist, contributing to patient safety concerns. We sought to identify emergency physicians’ perceived EHR usability and safety strengths and shortcomings across major EHR vendor products.

Methods

Fifty-five emergency physicians from 4 different hospitals were interviewed. The interviews were qualitatively analyzed, and physician comments were aligned with a usability taxonomy to identify emerging themes by vendor and hospital.

Results

Of the 194 comments about usability, the 3 most commonly discussed usability topics were Workflow Support (33.5% of comments), Visual Display (20.1%), and Data Entry (14.4%). Electronic health record usability strengths were centered on Visual Display, and the most common shortcoming was the lack of Workflow Support. Fourteen cross-hospital/cross-vendor themes, 6 vendor-specific themes, and 4 hospital-specific themes were identified.

Conclusions

Usability shortcomings that spanned across hospitals and vendors may suggest a need for more applied research and improved design to resolve these issues. Shortcomings that are localized to a specific product or hospital may be due to customization and may be addressable by learning from other organizations.
Influence of Orthognathic Surgery on Oral Health and Quality of Life
Authors: Tüz Hakan Hifzi , Ergezen Ezgi , Meral Salih Eren , Ekmekcioglu Aylin , El Hakan
Published: April 2021

Orthognathic surgery is a common treatment modality for moderate to severe dentofacial deformities. This study aimed to determine the early postoperative changes in quality of life (QoL) after orthognathic surgery.

Twenty patients were evaluated preoperatively (T0), postoperatively after 1 month (T1), and postoperatively after 3 months (T2). Short Form Oral Health Impact Profile and Orthognathic Quality of life Questionnaire were used as generic oral health-related and condition-specific QoL measures.

Oral Health Impact Profile -14 and Orthognathic Quality of life Questionnaire scores significantly decreased from T0-T2. Physical pain, psychological disability, social disability, and handicap scores significantly decreased during this interval. Facial esthetic, function, awareness of facial deformity, and social aspects of deformity were also found to significantly improve. No significant difference was found between age groups; female patients had significantly greater preoperative Oral Health Impact Profil-14 scores than did male patients.

Orthognathic surgery not only enhances the skeletal and facial relations, but also has significant positive effects on the patients’ QoL, oral health, and psychological status.
Surgical Burr-Assisted Lateral Osteotomy Technique in Septorhinoplasty
Authors: Aysel Abdulhalim , Karatan Berrak , Müderris Togay
Published: April 2021

Achieving aesthetic and functional results in rhinoplasty requires meticulous techniques, and postoperative edema, ecchymosis, and pain can deteriorate the desired outcomes. Different osteotomy techniques are defined to have optimal outcomes while reducing edema, ecchymosis, and pain. In this study, the authors compared conventional and power-assisted surgical burr osteotomy techniques in terms of early postoperative complications. Patients who underwent primary open septorhinoplasty were included in the study and were divided into 2 groups. The first group had lateral endonasal osteotomy with conventional guided osteotomes, and the second group had lateral osteotomy with surgical round burr. Edema and ecchymosis scoring systems were used on the postoperative first, third, and seventh day to evaluate postoperative edema and ecchymosis, and the visual analog scale was used to evaluate pain severity on the postoperative period. Out of 70 patients who had undergone septorhinoplasty, 36 received conventional osteotomy and 34 received surgical round burr osteotomy. Periorbital ecchymosis scores were significantly lower in the second group on the postoperative first, third, and seventh days. The periorbital edema scores were significantly lower in the second group on the first postoperative day but no difference was found between postoperative days 3 and 7. Also, the pain scores were significantly lower in the second group. Osteotomy with surgical round burr yields less ecchymosis, edema, and pain in the early postoperative period than conventional osteotomy in primary septorhinoplasty patients.
Prospective Cross-Sectional Study of Repeatability of Peripapillary Capillary Density Measurement Using Optical Coherence Tomography Angiography in Eyes With Optic Nerve and Retinal Vascular Pathology
Authors: Vu Alexander F. , Alber Susan A. , Chang Melinda Y. , Park Susanna S.
Published: April 2021

Background:

Optical coherence tomography angiography (OCTA) is a new noninvasive imaging modality that provides high resolution images of the optic nerve head and peripapillary retinal capillary vasculature which can be affected by optic nerve or retinal pathologies. High repeatability of peripapillary capillary density measurement using OCTA has been demonstrated in normal eyes and eyes with glaucoma. The purpose of our study was to quantify the repeatability of peripapillary capillary density measurement using OCTA in both normal eyes and eyes with optic atrophy, optic disc edema, and retinal vasculopathy.

Methods:

This prospective cross-sectional study enrolled 31 patients (59 eyes) including 16 eyes with optic nerve pathology (7 with disc edema from papilledema and 9 with optic atrophy), 35 eyes with retinal vascular disease, and 8 normal eyes. All eyes were imaged twice (30 minutes apart) with the Optovue AngioVue OCTA instrument to obtain 4.5 × 4.5 mm peripapillary scans. Scans were considered good quality if signal strength was 6 or greater. The OCTA parameters obtained include the radial peripapillary capillary (RPC) density of the whole disc, inside the disc, peripapillary region, and the 4 quadrants of the disc (superior, nasal, inferior, and temporal). A Student's t test was used to compare means. Intraclass correlation coefficient (ICC) was calculated to measure repeatability.

Results:

Repeatability of RPC density measurements for all regions analyzed demonstrated good to excellent repeatability for the whole cohort {ICC for the whole image was 0.915 (95% confidence interval [CI] = 0.855–0.951)}; ICC for the peripapillary region was 0.945 (95% CI = 0.905–0.969). In the subset of eyes with good image quality (i.e., signal strength ≥ 6), ICC was slightly higher for all regions, with excellent repeatability of the peripapillary region (ICC was 0.971 [95% CI = 0.943–0.986]). Conversely, for eyes with poor image quality scans (i.e., signal strength < 6), ICC was lower, corresponding to moderate to good repeatability for most parameters. For the subset of eyes with optic atrophy, disc edema from papilledema or retinal vasculopathy, all had good to excellent repeatability of the vessel density of the entire disc (ICC values were 0.954 [95% CI = 0.804–0.990], 0.921 [95% CI = 0.711–0.982], and 0.895 [95% CI = 0.788–0.951, respectively]) and of the peripapillary region (ICC values were 0.980 [95% CI = 0.904–0.996], 0.966 [95% CI = 0.854–0.993], and 0.916 [95% CI = 0.827–0.961], respectively).

Conclusions:

The peripapillary capillary density measurement obtained using a commercial OCTA instrument is highly repeatable in eyes with optic nerve atrophy, disc edema from papilledema, or retinal vasculopathy.
Isolated Oculomotor Neuritis After Dengue Fever
Authors: Bhate Manjushree , Ponnaganti Sandeep
Published: April 2021

We report a rare case of isolated partial left III cranial nerve palsy due to inflammatory oculomotor neuritis after dengue fever with unique neuro-imaging findings of enhancement seen along the entire course of the oculomotor nerve.
The “Eyelet Sign” as an MRI Clue for Inflammatory Brown Syndrome
Authors: Fierz Fabienne C. , Landau Klara , Kottke Raimund , Wichmann Werner , Sturm Veit , Weber Konrad P. , Gerth-Kahlert Christina
Published: April 2021

Background:

Brown syndrome is characterized by a restrictive elevation deficit of the affected eye in adduction. Besides the well-known congenital form, different acquired etiologies including inflammation, trauma, and surgery may prevent the superior oblique (SO) tendon from gliding freely through the trochlea on attempted upgaze. We present MRI findings in pediatric and adult patients with inflammatory acquired Brown syndrome.

Methods:

Retrospective review of clinical and MRI findings of 6 patients (4 children: median age 8.4 years [range 6.1–8.7]; 2 adults: age 46.4 and 51.1 years). Median follow-up was 23 months (range 1–52).

Results:

In all 6 patients, orbital MRI demonstrated inflammatory changes of the SO tendon–trochlea complex. A striking feature was circumferential contrast enhancement of the trochlea with central sparing where the tendon passes, reminiscent of an eyelet. In all cases, the motility restriction improved either spontaneously or with systemic anti-inflammatory treatment. Although both adult patients had a history of known seronegative spondyloarthritis, there was no associated systemic condition in the children in our series.

Conclusions:

Both in children and in adults, MRI can provide evidence of inflammatory changes located at the trochlea–tendon complex in acquired Brown syndrome here referred to as the “eyelet sign,” which may be helpful in confirming the clinical diagnosis and guide appropriate treatment.
Cognitive Performance of Patients With Multiple Sclerosis and Optic Neuritis at Presentation
Authors: Leshno Ari , Sagiv Oded , Aloni Roy , Skaat Alon , Achiron Anat , Huna-Baron Ruth
Published: April 2021

Background:

Cognitive dysfunction is common among patients with multiple sclerosis (MS), but the effect of coexisting optic neuritis (ON) at the first presentation of multiple sclerosis on the course of cognitive decline is unknown. The purpose of this study was to assess whether ON at presentation has any effect on the progression of cognitive decline in MS.

Methods:

Historical cohort study. We retrospectively compared the cognitive performance of patients with relapsing-remitting MS with and without ON at the time of MS diagnosis. Subjects were included if cognitive test results were available both at baseline and after at least 36 months from presentation and grouped based on the presence (MS-ON) or absence (MS-non-ON) of optic neuritis at presentation.

Results:

One hundred seventy consecutive subjects with MS were found suitable, with a 1:2 male:female ratio and a mean age at diagnosis of 33.0 ± 10.9 years. Forty-six patients (27.1%) presented with ON. No significant differences were found in cognitive performance at onset between the 2 groups. Both groups had a similar follow-up duration. The prevalence of cognitive decline in the general score was significantly higher in the MS-ON group compared with the MS-non-ON group (6.5% vs 0%, respectively; P < 0.001), as well as in the attention (8.7% vs 1.6%; P = 0.046) and the executive function (17.4% vs 2.4%; P = 0.001) domains.

Conclusions:

Optic neuritis at presentation of MS is associated with a higher prevalence of cognitive decline over time. Potential benefit of early intervention to prevent cognitive decline may be warranted.
Optic Nerve Aplasia
Authors: Saffren Brooke D. , Yassin Shaden H. , Geddie Brooke E. , de Faber Jan Tjeerd H. N. , Blieden Lauren S. , Bhate Manjushree , Gamio Susana , Rutar Tina , Levin Alex V.
Published: April 2021

Objective:

Optic nerve aplasia (ONA) is a rare ocular anomaly. We report ophthalmologic, systemic, and genetic findings in ONA.

Methods:

Patients were identified through an International Pediatric Ophthalmology listserv and from the practice of the senior author. Participating Listserv physicians completed a data collection sheet. Children of all ages were included. Neuroimaging findings were also recorded.

Results:

Nine cases of ONA are reported. Patients' ages ranged from 10 days to 2 years (median 9 months). Seven cases were bilateral. All patients had absence of the optic nerve and retinal vessels in the affected eye or eyes. Ophthalmologic findings included glaucoma, microcornea, persistent pupillary membrane, iris coloboma, aniridia, retinal dysplasia, retinal atrophy, chorioretinal coloboma, and persistent fetal vasculature. Systemic findings included facial dysmorphism, cardiac, genitourinary, skeletal, and developmental defects. A BCOR mutation was found in one patient. One patient had rudimentary optic nerves and chiasm on imaging.

Conclusion:

ONA is a unilateral or bilateral condition that may be associated with anomalies of the anterior or posterior segment with or without systemic findings. Rudimentary optic nerve on neuroimaging in one case suggests that ONA is on the continuum of optic nerve hypoplasia.
Full-length Genome of aOgataea polymorphastrain CBS4732ura3Δ reveals large duplicated segments in subtelomeric regions
Authors: Chang Jia , Bei Jinlong , Shao Qi , Wang Hemu , Fan Huan , Yau Tung On , Bu Wenjun , Ruan Jishou , Wei Dongsheng , Gao Shan
Published: April 2021

Background

Currently, methylotrophic yeasts (e.g.,Pichia pastoris, Ogataea polymorpha, andCandida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genusOgataea, most research is focused on three basicO. polymorphastrains—CBS4732, NCYC495, and DL-1. However, the relationship between CBS4732, NCYC495, and DL-1 remains unclear, as the genomic differences between them have not be exactly determined without their high-quality complete genomes. As a nutritionally deficient mutant derived from CBS4732, theO. polymorphastrain CBS4732ura3Δ (named HU-11) is being used for high-yield production of several important proteins or peptides. HU-11 has the same reference genome as CBS4732 (noted as HU-11/CBS4732), because the only genomic difference between them is a 5-bp insertion.

Results

In the present study, we have assembled the full-length genome ofO. polymorphaHU-11/CBS4732 using high-depth PacBio and Illumina data. Long terminal repeat (LTR) retrotransposons, rDNA, 5’ and 3’ telomeric, subtelomeric, low complexity and other repeat regions were curated to improve the genome quality. Particularly, we detected large duplicated segments (LDSs) in the subtelomeric regions and exactly determined all the structural variations (SVs) between CBS4732 and NCYC495.

New findings mainly include

(1) the genomic differences between HU-11/CBS4732 and NCYC495 include single nucleotide polymorphisms, small insertions and deletions, and only three SVs; (2) six genes were incorporated into CBS4732 fromCyberlindnera jadiniiby horizontal gene transfer and may bring HU-11/CBS4732 new biological functions or physiological properties; (3) many recombination events may have occurred on chromosome 4 and 5 of CBS4732 and NCYC495’ ancestors and two large segments were acquired by CBS4732 and NCYC495 from chromosome 6 andC. jadiniiduring recombination, respectively; and (4) the genome expansion in methylotrophic yeasts is mainly driven by large segment duplication in subtelomeric regions.

Conclusions

The present study preliminarily revealed the complex relationship between CBS4732, NCYC495, and DL-1. The new findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications ofO. polymorphaCBS4732, NCYC495, DL-1, and their derivative strains. The full-length genome of theO. polymorphastrain HU-11/CBS4732 should be included into the NCBI RefSeq database for future studies ofOgataeaspp..
A variable-rate quantitative trait evolution model using penalized-likelihood
Authors: Revell Liam J.
Published: April 2021

In recent years it has become increasingly popular to use phylogenetic comparative methods to investigate heterogeneity in the rate or process of quantitative trait evolution across the branches or clades of a phylogenetic tree. Here, I present a new method for modeling variability in the rate of evolution of a continuously-valued character trait on a reconstructed phylogeny. The underlying model of evolution is stochastic diffusion (Brownian motion), but in which the instantaneous diffusion rate (σ2)alsoevolves by Brownian motion on a logarithmic scale. Unfortunately, it’s not possible to simultaneously estimate the rates of evolution along each edge of the treeandthe rate of evolution ofσ2itself using Maximum Likelihood. As such, I propose a penalized-likelihood method in which the penalty term is equal to the log-transformed probability density of the rates under a Brownian model, multiplied by a ‘smoothing’ coefficient,λ, selected by the user.λdetermines the magnitude of penalty that’s applied to rate variation between edges. Lower values ofλpenalize rate variation relatively little; whereas largerλvalues result in minimal rate variation among edges of the tree in the fitted model, eventually converging on a single value ofσ2for all of the branches of the tree. In addition to presenting this model here, I have also implemented it as part of myphytoolsR package in the functionmultirateBM. Using different values of the penalty coefficient,λ, I fit the model to simulated data with: Brownian rate variation among edges (the model assumption); uncorrelated rate variation; rate changes that occur in discrete places on the tree; and no rate variation at all among the branches of the phylogeny. I then compare the estimated values ofσ2to their known true values. In addition, I use the method to analyze a simple empirical dataset of body mass evolution in mammals. Finally, I discuss the relationship between the method of this article and other models from the phylogenetic comparative methods and finance literature, as well as some applications and limitations of the approach.
The critical role of natural history museums in advancing eDNA for biodiversity studies: a case study with Amazonian fishes
Authors: de Santana C. David , Parenti Lynne R. , Dillman Casey B. , Coddington Jonathan A. , Bastos D. A. , Baldwin Carole C. , Zuanon Jansen , Torrente-Vilara Gislene , Covain Raphaël , Menezes Naércio A. , Datovo Aléssio , Sado T. , Miya M.
Published: April 2021

Ichthyological surveys have traditionally been conducted using whole-specimen, capture-based sampling with varied, but conventional fishing gear. Recently, environmental DNA (eDNA) metabarcoding has emerged as a complementary, and possible alternative, approach to whole-specimen methodologies. In the tropics, where much of the diversity remains undescribed, vast reaches continue unexplored, and anthropogenic activities are constant threats; there have been few eDNA attempts for ichthyological inventories. We tested the discriminatory power of eDNA using MiFish primers with existing public reference libraries and compared this with capture-based methods in two distinct ecosystems in the megadiverse Amazon basin. In our study, eDNA provided an accurate snapshot of the fishes at higher taxonomic levels and corroborated its effectiveness to detect specialized fish assemblages. Some flaws in fish metabarcoding studies are routine issues addressed in natural history museums. Thus, by expanding their archives to include eDNA and adopting a series of initiatives linking collection-based research, training and outreach, natural history museums can enable the effective use of eDNA to survey Earth’s hotspots of biodiversity before taxa go extinct. Our project surveying poorly explored rivers and using DNA vouchered archives to build metabarcoding libraries for Neotropical fishes can serve as a model of this protocol.
Drug metabolic activity is a critical cell-intrinsic determinant for selection of hepatocytes during long-term culture
Authors: Akiyama Saeko , Saku Noriaki , Miyata Shoko , Ite Kenta , Toyoda Masashi , Kimura Tohru , Kuroda Masahiko , Nakazawa Atsuko , Kasahara Mureo , Nonaka Hidenori , Kamiya Akihide , Kiyono Tohru , Kobayshi Toru , Murakami Yasufumi , Umezawa Akihiro
Published: April 2021

Hepatocytes can be used to study the pathogenesis of liver diseases and drug discovery research. Human hepatocytes are, however, hardly expandable in vitro making it difficult to secure large numbers of cells from one donor. In this study, we aimed to establish an in vitro long-term culture system that enables stable proliferation and maintenance of human hepatocytes to ensure a constant supply. We purified human hepatocytes by selection with cytocidal puromycin, and cultured them for more than 60 population doublings over a span of more than 350 days. These results show that this simple culture system with usage of the cytocidal antibiotics enables efficient hepatocyte proliferation and is an effective method for generating a stable supply of hepatocytes for drug discovery research at a significant cost reduction.
A new species of the genusEuphlyctis(Anura: Dicroglossidae) from West Bengal, India
Authors: Bhakat Somnath , Bhakat Soumendranath
Published: April 2021

A new species of green frog of the genusEuphlyctisFitzinger, 1843 is described from West Bengal, a state of eastern India. A robust frog, SVL of male 86mm and that of female 132mm. The species is diagnosed by the presence of following characters: green dorsum and female with a greenish white mid-dorsal line, tibiotarsal articulation reaches eye, male with two vocal sac openings at the junction of jaw, female is larger than male though body parameters is proportionately longer in male, nostril snout length 3.45% of SVL, nostril much closer to snout tip than eye, units of hind limb i. e. thigh, shank and foot are almost equal in length, relative length of finger: II < IV < I < III.

The new species is compared with existing eight species of the genusEuphlyctis.
Multiview tiling light sheet microscopy for 3D high resolution live imaging
Authors: Aakhte Mostafa , Müller H.-Arno J.
Published: April 2021

Light sheet or selective plane illumination microscopy (SPIM) is ideally suited forin totoimaging of living specimens at high temporal-spatial resolution. In SPIM, the light scattering that occurs during imaging of opaque specimens brings about limitations in terms of resolution and the imaging field of view. To ameliorate this shortcoming, the illumination beam can be engineered into a highly confined light sheet over a large field of view and multi-view imaging can be performed by applying multiple lenses combined with mechanical rotation of the sample. Here, we present a Multiview tiling SPIM (MT-SPIM) that combines the Multi-view SPIM (M-SPIM) with a confined, multi-tiled light sheet. The MT-SPIM provides high-resolution, robust and rotation-free imaging of living specimens. We applied the MT-SPIM to image nuclei and Myosin II from the cellular to subcellular spatial scale in earlyDrosophilaembryogenesis. We show that the MT-SPIM improves the axial-resolution relative to the conventional M-SPIM by a factor of two. We further demonstrate that this axial resolution enhancement improves the automated segmentation of Myosin II distribution and of nuclear volumes and shapes.
Eukaryotic ribosome recognizes 3′ context and stimulates stop codon readthrough
Authors: Sokolova Elizaveta , Egorova Tatiana , Shuvalov Alexey , Alkalaeva Elena
Published: April 2021

It is known that the nucleotide context surrounding stop codons significantly affects the efficiency of translation termination. In eukaryotes, various 3′ contexts have been described that are unfavourable for translation termination; however, the exact molecular mechanism that mediates their effect remains unknown. In this study, we used a reconstituted mammalian translation system to examine the efficiency of stop codons in different contexts, including several previously described weak 3′ stop codon contexts. Our results revealed that ribosomes can independently recognize certain contexts and ignore stop codons that are followed by these sequences. Moreover, the efficiency of translation termination at the weak 3′ contexts was almost equal to the one at the standard context. We propose that weak 3′ contexts interact with the 18S rRNA provoking a conformational change in the U-turn-like structure of the stop codon in the A site of ribosome. This change makes incorporation of the near-cognate tRNA more preferable than recognition of the stop codon by the release factors and increases readthrough.
Bacteriophage λ RexA and RexB Functions Assist the Transition from Lysogeny to Lytic Growth
Authors: Thomason Lynn C. , Schiltz Carl J. , Court Carolyn , Hosford Christopher J. , Adams Myfanwy C. , Chappie Joshua S. , Court Donald L.
Published: April 2021

The CI and Cro repressors of bacteriophage λ create a bistable switch between lysogenic and lytic growth. In λ lysogens, CI repressor expressed from thePRMpromoter blocks expression of the lytic promotersPLandPRto allow stable maintenance of the lysogenic state. When lysogens are induced, CI repressor is inactivated and Cro repressor is expressed from the lyticPRpromoter. Cro repressor blocksPRMtranscription and CI repressor synthesis to ensure that the lytic state proceeds. RexA and RexB proteins, like CI, are expressed from thePRMpromoter in λ lysogens; RexB is also expressed from a second promoter,PLIT, embedded inrexA.Here we show that RexA binds CI repressor and assists the transition from lysogenic to lytic growth, using both intact lysogens and defective prophages with reporter genes under control of the lyticPLandPRpromoters. Once lytic growth begins, if the bistable switch does return to the immune state, RexA expression lessens the probability that it will remain there, thus stabilizing the lytic state and activation of the lyticPLandPRpromoters. RexB modulates the effect of RexA and may also help establish phage DNA replication as lytic growth ensues.
Synchronization of iPS-derived cardiomyocytes to visitor heartbeat in an interactive museum exhibit
Authors: Perez-Bermejo Juan A. , Reisman Samuel J. , Ma Joyce , Cerrito Chris , Conklin Bruce R. , Yu Kristina
Published: April 2021

Science museums play an important role in science education, both engaging the public with science concepts and building support for scientific research. Designing museum exhibits to meet increasing public interests in the life sciences is particularly important, yet remains challenging. In this report we describeGive Heart Cells a Beat, a permanent interactive science exhibit that allows museum visitors to synchronize the beating of live stem cell-derived cardiomyocytes to their own heart rate in real-time. Evaluation with museum visitors reveals that the exhibit engaged the public with the specimen and prompted curiosity in heart biology and, to a lesser degree, stem cells and electrophysiology.Give Heart Cells a Beatis the product of a close collaboration between a museum and a research laboratory, and, to our knowledge, the first example of the use of live human heart cells in an interactive exhibit. We hope this exhibit will serve as an example for the implementation of stem cell technology in the field of informal science education and encourage others to pursue close working relationships between academia and public science venues such as museums.