bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Collagen Nerve Wrapping in a Rabbit Peripheral Neuropathy Model
Authors: Huddleston Hailey P. , Shah Neil V. , Kurtzman Joey S. , Dar Qurratul-Ain , Wang Hanbin , Carter John , Hayes Westley T. , Avoricani Alba , Dua Karan , Koehler Steven M.
Published: November 2021

Background:

Collagen nerve wraps (CNWs) theoretically allow for improved nerve gliding and decreased perineural scarring, and create a secluded environment to allow for nerve myelination and axonal healing. The goal of this study was to investigate the effect of CNWs on nerve gliding as assessed by pull-out strength and nerve changes in a rabbit model of peripheral neuropathy.

Methods:

Ten New Zealand rabbits were included. Sham surgery (control) was performed on left hindlimbs. To simulate compressive neuropathy, right sciatic nerves were freed of the mesoneurium, and the epineurium was sutured to the wound bed. Five rabbits were euthanized at 6 weeks [scarred nerve (SN); n = 5]. Neurolysis with CNW was performed in the remaining rabbits at 6 weeks (CNW; n = 5), which were euthanized at 22 weeks. Outcomes included peak pull-out force and histopathological markers of nerve recovery (axonal and Schwann cell counts).

Results:

The CNW group demonstrated significantly higher pull-out forces compared with the CNW sham control group (median: 4.40N versus 0.37N, P = 0.043) and a trend toward greater peak pull-out forces compared with the SN group (median: 4.40N versus 2.01N, P = 0.076). The CNW group had a significantly higher median Schwann cell density compared with the CNW control group (CNW: 1.30 × 10−3 cells/μm2 versus CNW control: 7.781 × 10−4 cells/μm2, P = 0.0431) and SN group (CNW: 1.30 × 10−3 cells/μm2 versus SN: 7.31 × 10−4 cells/μm2, P = 0.009). No significant difference in axonal density was observed between groups.

Conclusion:

Our findings suggest using a CNW does not improve nerve gliding, but may instead play a role in recruiting and/or supporting Schwann cells and their proliferation.
Modified Incision for Muscle-sparing Latissimus Dorsi to Increase Flap Perfusion in the Morbidly Obese
Authors: Schwartz Jean-Claude D.
Published: November 2021

The muscle-sparing latissimus dorsi flap relies on perforators from the descending branch of the thoracodorsal artery. Previous descriptions placed a transverse skin island independent of perforator location, as any design was thought to capture enough perforators to ensure flap survival. We have found this approach prone to complications when attempting breast reconstruction in obese patients who require large flap volumes. Although the most proximal perforators have the most reliable blood flow, inclusion of these perforators reduces the arc of rotation, as the flap would be close to the pivot point at the most cranial point of muscle division, leaving significant volume in the axilla. Here we describe a modified skin incision that includes all of the proximal perforators but also allows us free design of the skin island to harvest those areas of the back with maximal subcutaneous tissue and with enough distance from the pivot point to optimize arc of rotation.
Patient-Reported Problem Areas in Chronic Traumatic Brain Injury
Authors: Borgen Ida M. H. , Kleffelgård Ingerid , Hauger Solveig L. , Forslund Marit V. , Søberg Helene L. , Andelic Nada , Sveen Unni , Winter Laraine , Løvstad Marianne , Røe Cecilie
Published: November 2021

Objective:

The aims of this study were to (1) assess self-reported main problem areas reported by patients with traumatic brain injury (TBI) and their family members in the chronic phase, and (2) compare the self-prioritized problems with difficulties captured by questionnaires and neuropsychological screening through linking to the International Classification of Functioning, Disability and Health (ICF).

Setting:

Outpatient clinic at the Oslo University Hospital, Norway.

Participants:

In total, 120 patients with TBI were recruited, of whom, 78 had a participating family member. Eligibility criteria were a clinical TBI diagnosis with verified intracranial injury, living at home, aged 18 to 72 years, 2 years or more postinjury, and experiencing perceived TBI-related difficulties, reduced physical and mental health, or difficulties with participation in everyday life. Patients with severe psychiatric or neurological disorders or inability to participate in goal-setting processes were excluded.

Design:

Cross-sectional.

Main Measures:

Target Outcomes, that is, 3 main TBI-related problem areas reported by patients and family members, collected in a semistructured interview; standardized questionnaires of TBI-related symptoms, anxiety, depression, functioning, and health-related quality of life; neuropsychological screening battery.

Results:

Target Outcomes were related to cognitive, physical, emotional, and social difficulties. Target Outcomes were linked to 12 chapters and 112 distinct categories in the ICF, while standardized measures only covered 10 chapters and 28 categories. Some aspects of post-TBI adjustment were found to be insufficiently covered by the ICF classification, such as identity issues, lack of meaningful activities, and feeling lonely.

Conclusion:

The Target Outcomes approach is a useful assessment method in a population with chronic TBI. The standardized questionnaires capture the spectrum of problems, whereas the Target Outcomes approach captures the prioritized individual problems hindering everyday life after TBI. While the standardized measures are an irreplaceable part of the assessment, Target Outcomes ensures patient involvement and may help clinicians better tailor relevant rehabilitation efforts.
CLINICAL ASSOCIATIONS AND PROGNOSTIC IMPLICATIONS OF REPAIR TISSUE PROLIFERATION IN EYES WITH RETINAL PIGMENT EPITHELIUM TEARS
Authors: Cicinelli Maria V. , Rabiolo Alessandro , Montesano Giovanni , Marchese Alessandro , Barresi Costanza , Introini Ugo , Parodi Maurizio B. , Bandello Francesco
Published: November 2021

Purpose:

To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up.

Methods:

Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models.

Results:

Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: −0.042 mm2/month; P = 0.001) and female gender (estimate: −0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = −0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008).

Conclusion:

Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.
UVEAL MELANOMA PRESENTING AS HEPATIC METASTASIS IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS
Authors: Evans William I. , Wilson Matthew W. , Bahrami Armita , Pappo Alberto S. , Hoehn Mary E.
Published: November 2021

Purpose:

To report an atypical case of occult uveal melanoma in a patient with oculodermal melanocytosis that first presented with symptoms of hepatic metastasis.

Methods:

A previously healthy 16-year-old boy with noted ocular hyperpigmentation developed abdominal pain and vomiting and was found to have a hepatic mass consistent with a metastatic lesion from an occult uveal melanoma.

Results:

On examination, the patient's visual acuity was 20/20, and pupils were reactive without an afferent pupillary defect in both eyes. Examination of the left eye revealed normal findings. In the right eye, conjunctiva was freely moving over hyperpigmented sclera. Dilated fundus examination demonstrated a hyperpigmented, minimally elevated, choroidal mass in the right eye. Results of fundus autofluorescence, IV fluorescein angiography, spectral-domain optical coherence tomography, and ultrasonography were suspicious for uveal melanoma. Genetic testing of the hepatic mass was positive for BAP1, confirming that the metastasis originated as uveal melanoma rather than cutaneous or intracranial melanoma. Magnetic resonance imaging of the brain and orbits showed negative impression for intracranial lesions. A PET scan revealed numerous additional metastatic lesions, and the patient was referred to palliative care.

Conclusion:

Patients with oculodermal melanocytosis are at an increased risk for both uveal melanoma and subsequent metastasis, and frequent monitoring should be performed because treatment options for metastatic uveal melanoma are limited.
Deep Anterior Lamellar Keratoplasty: Current Status and Future Directions
Authors: Yu Angeli Christy , Spena Rossella , Pellegrini Marco , Bovone Cristina , Busin Massimo
Published: November 2021

Deep anterior lamellar keratoplasty (DALK) involves selective replacement of diseased corneal stroma while preserving normal healthy endothelium. Despite several well-recognized advantages, the uptake of DALK has remained sluggish with an adoption rate that has plateaued over the past decade. Misconceptions such as the rarity of complications of penetrating keratoplasty, lack of standardization of the DALK technique, and limited substantial benefit in visual and refractive outcomes are frequently cited as arguments against performing DALK. This brief review discusses the recent findings that refute these perceived barriers; describes contemporary techniques, tools, and modifications in the surgical approach; and evaluates the evidence regarding the clinical outcomes of DALK.
Ultrasound-Enhanced Transcorneal Drug Delivery for Treatment of Fungal Keratitis
Authors: Allison Claire , Cellum Blake , Karpinecz Bianca , Nasrallah Fadi , Zderic Vesna
Published: November 2021

Purpose:

Transcorneal drug delivery is hindered by ocular physical and biochemical properties, such as tear production, the epithelial layer of the cornea, and blinking. The aim of this study was to determine whether ultrasound can be applied to increase the transcorneal drug delivery of natamycin used in the treatment of fungal keratitis without dangerously overheating the surrounding ocular tissues.

Methods:

To verify the safety of various sets of ultrasound parameters, modeling studies were conducted using OnScale, an ultrasonic wave modeling software. Ultrasound parameters determined optimal for ocular tissue safety were used in a laboratory setting in a jacketed Franz diffusion cell setup. Histological images of the cross-section of the corneas used in experiments were examined for cell damage under a microscope.

Results:

Increases in transcorneal drug delivery were seen in every treatment parameter combination when compared with the sham treatment. The highest increase was 4.0 times for 5 minutes of pulsed ultrasound at a 25% duty cycle and a frequency of 400 kHz and an intensity of 0.5 W/cm2 with statistical significance (P < 0.001). Histological analysis revealed structural damage only in the corneal epithelium, with most damage being at the epithelial surface.

Conclusions:

This study suggests that ultrasound is a safe, effective, and minimally invasive treatment method for enhancing the transcorneal drug delivery of natamycin. Further research is needed into the long-term effects of ultrasound parameters used in this study on human ocular tissues.
Remote Surgeon Virtual Presence: A Novel Telementoring Method for Live Surgical Training
Authors: Din Nizar , Chan Clara C. , Cohen Eyal , Iovieno Alfonso , Dahan Amit , Rootman David S. , Litvin Gilad
Published: November 2021

Purpose:

We describe the first known use of telementoring in corneal surgery and technology combining a 3-dimensional microscope system, 5G live streaming technology, group chat software, and a virtual reality headset for intercontinental surgical supervision.

Methods:

Three surgeons in Toronto were proctored by a surgeon in Israel in the implantation of a novel keratoprosthesis device (CorNeat KPro; Ra'anana, Israel) into cadaver eyes. In Toronto, the NGENUITY platform (Alcon) transmitted high-definition, 3-dimensional images to the proctor in Israel who viewed the live video through a GOOVIS Virtual Reality headset with subsecond latency. This was made possible by the LiveU technology (Hackensack, NJ), which is a portable device to increase the bandwidth of transmission. The primary outcome was the successful completion of CorNeat KPro implantation. After each procedure, all surgeons completed a Likert scale questionnaire that assessed opinions on telementoring.

Results:

All participants implanted the CorNeat KPro device. There was significant satisfaction reported. A total cumulative score from the questionnaire was 149 of 150 from the operating surgeons, with a score of 135 of 150 by the proctor. All felt that there was excellent AV quality with no lag time and recommended the technology.

Conclusions:

Telementoring is a promising tool that can traverse large distances for ophthalmic education.
Indications for surgical management of retained lens fragments
Authors: Salabati Mirataollah , Mahmoudzadeh Raziyeh , Wakabayashi Taku , Hinkle John W. , Ho Allen C.
Published: November 2021

Purpose of review

Retained lens fragments are a relatively rare occurrence after cataract surgery. While no definite guidelines for the surgical management or timing of surgery of this complication exist, surgery is indicated for patients with large lens fragments, persistent inflammation, secondary glaucoma, corneal edema, retinal tears or detachments, and associated endophthalmitis. The aim of this review is to summarize the current surgical management of retained lens material.

Recent findings

The Intelligent Research in Sight registry database of 2.26 million patients who underwent cataract surgery in the US indicated that 0.18% (1 in 563) had secondary removal of retained lens fragments in the anterior chamber in the operating room within 1 year of the original cataract surgery. The risk of returning to the operating room for retained lens material removal was greater among men, smokers, patients with Medicaid or military insurance, and those who had complex cataract surgery. Medical management with topical corticosteroids or observation may be considered for small lens fragments, but surgical removal remains the mainstay of the treatment for large lens fragments.

Retained lens fragments following cataract surgery may result in various vision-threatening complications. Understanding the risk factors, diagnosis, and surgical management of retained lens fragments are critical to preserving good visual outcomes. Vitrectomy is effective in patients with posterior nuclear fragments, retinal detachment, endophthalmitis, or uncontrolled glaucoma not responding to medical management. The best timing for surgery for retained lens fragments should be further investigated in a prospective study.
Bilateral Acute Retinal Necrosis From Ocular Syphilis in a Nonimmunocompromised Patient
Authors: Jumah Ammar , Joshi Seema , Nair Sashi , AlAttal Sara , Jumah Fareed , Eltous Lara , Zervos Marcus
Published: November 2021

Acute retinal necrosis (ARN) is an inflammatory condition of the eye usually caused by viral infection, predominantly herpes simplex virus or varicella-zoster virus. More rarely, noninfectious conditions or infection with other viral and nonviral pathogens can lead to ARN. Onset of disease, which may occur unilaterally or bilaterally, is usually rapid and characterized by a range of symptoms, including pain of eye movement, eye redness, light sensitivity, impaired vision, and narrowing of the visual field. While infectious ARN may develop in otherwise healthy individuals, those who are immunocompromised may be more susceptible to this eye pathology, especially patients who are infected with HIV. Left untreated, ARN can lead to permanent vision loss; thus, rapid identification of the specific etiology of ARN is crucial for implementing appropriate therapies. However, infection with rare pathogens in patients who are at risk for common causes of ARN can complicate diagnosis and treatment, highlighting the need for physicians to know the full range of possible etiologies for the differential diagnosis. We present a case of bilateral ARN in an immunocompetent woman who was infected with genital herpes simplex virus 2, and therefore at high risk of viral infection, but whose ARN was an example of ocular syphilis caused by the bacterial pathogen Treponema pallidum. A review of the literature on ocular syphilis is also discussed.
Immersion ultrasound biometry vs optical biometry
Authors: Cooke David L. , Waldron Rhonda , Savini Giacomo , Riaz Kamran M. , Taroni Leonardo , Murphy David A. , Guaraldi Fabio
Published: November 2021

Purpose:

To compare axial length (AL) measurements obtained by optical biometry (OB) and immersion ultrasound (iUS) to investigate the agreement between the 2 techniques and how to use OB constants for eyes with AL by iUS.

Setting:

Multicenter study.

Design:

Retrospective observational case series.

Methods:

Agreement between OB and iUS ALs was investigated in 4 subsets. Also, in a test database, the prediction error (PE) for iUS AL was assessed with 4 methods: (1) data-optimized constants; (2) user group for laser interference biometry (ULIB) constants with iUS biometry; (3) with recalibrated AL; and (4) ULIB A-constant − 0.23.

Results:

A Combined 1970 eyes were measured with both OB and iUS biometry. OB mean AL was 0.0873 mm longer than iUS AL. The latter was made equivalent to OB ALs with this equation: Recalibrated iUS AL = 1.0228 × iUS AL − 0.4556. In a fifth database (n = 1079) with OB AL measurements only, after AL was artificially shortened by 0.0873 mm, the original A-constant had to be reduced by 0.23 to maintain a zero PE. In a sixth database (n = 127) with iUS AL, the original ULIB A-constant provided the poorest outcomes. Using either recalibrated iUS AL or ULIB A-constant − 0.23 zeroed out the mean PE and achieved the lowest median absolute error.

Conclusions:

AL measurements by iUS can be used with ULIB constants for OB by subtracting 0.23 from the A-constant; alternatively, the iUS AL may be recalibrated. The recalibrated iUS AL should be treated as AL measurements obtained by OB. It is longer than iUS AL in long eyes.
Home-based noninvasive pelvic floor muscle training device to assist women in performing Kegel exercise in the management of stress urinary incontinence
Authors: Horng Huann-Cheng , Chao Wei-Ting , Chen Jui-Fa , Chang Chia-Pei , Wang Peng-Hui , Chang Po-Lun
Published: November 2021

Background:

Stress urinary incontinence (SUI) is a major health problem affecting approximately 50% of the female population over 45 years of age. We evaluated the therapeutic effects of a home-based non-invasive wireless sensor pelvic floor muscle training (PFMT) device with assisted Kegel exercise for SUI.

Methods:

We included 60 women 40 to 60 years of age who were diagnosed with urodynamic SUI (mean pad test, 10.52 g). The PFMT device applicator was clamped on the upper inner thigh, and the patients could self-train at home. The signal was recorded and delivered to a 3G/4G smartphone via Bluetooth, which also allows guided feedback via the smartphone’s voice. To evaluate the therapeutic effect, all patients completed the following questionnaires: a 3-day bladder diary, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the Urogenital Distress Inventory-Short Form, and the Incontinence Impact Questionnaire-7 (IIQ-7). One-hour pad test measurements were performed before the test (M0) and at 1 (M1), 2 months (M2), and 3 months (M3) after the PFMT device-assisted Kegel exercise.

Results:

The 1-hour pad test and the scores of the ICIQ-SF, UDI-6, and IIQ-7 questionnaires were improved at M1, M2, and M3, compared with the M0 values. The mean value of the post-voiding residual urine (PVR) significantly decreased at M2 and M3. The subjective and objective improvement rates at M3 were 80% and 72%, respectively.

Conclusion:

The data demonstrated that 3 months of Kegel exercise assisted with a home-based PFMT device improved the number and severity of episodes, PVR, and quality of life in patients with SUI, suggesting that this device might serve as an alternative non-invasive therapy for mild and moderate SUI.
Kenyan HIV Clinics With Youth-Friendly Services and Trained Providers Have a Higher Prevalence of Viral Suppression Among Adolescents and Young Adults: Results From an Observational Study
Authors: Wilson Kate , Onyango Alvin , Mugo Cyrus , Guthrie Brandon , Slyker Jennifer , Richardson Barbra , John-Stewart Grace , Inwani Irene , Bukusi David , Wamalwa Dalton , Kohler Pamela
Published: November 2021

Sustained viral suppression in adolescents and young adults living with HIV (AYALWH) is necessary for epidemic control. We evaluated facility and individual correlates of viral suppression using programmatic data from AYALWH between ages 10 and 24 years at 24 HIV clinics in Kenya. Binomial regression was used to evaluate correlates of viral load (VL) suppression (<1,000 copies/ml). Of 5,316 AYALWH on antiretroviral therapy ≥6 months, 2,081 (39%) had VLs available in the medical record, of which 76% were virally suppressed. In multivariable analyses, antiretroviral therapy initiation among AYALWH older than 10 years was associated with higher viral suppression than initiation younger than 10 years (adjusted risk ratio [aRR] 10–14 = 1.03, 95% confidence interval [CI] 0.97–1.10; aRR 15–19 = 1.30, 95% CI 1.19–1.41; aRR 20–24 = 1.43, 95% CI 1.24–1.63). Facilities with both youth-friendly services (YFS) and trained providers had significantly higher VL suppression compared with facilities without YFS or trained providers (adjusted odds ratio: 2.07, 95% CI: 1.71–2.52). Viral suppression remains suboptimal among AYALWH. YFS and trained providers plus greater use of VL data may help increase viral suppression among AYALWH.
Occupational Differences in Deaths of Despair in the United States, Using Data From the Using the National Occupational Mortality Surveillance System
Authors: Rayhall Cherish , Hawkins Devan
Published: November 2021

Objective: :

To assess occupational differences in proportional mortality ratios (PMRs) and trends in these PMRs due to the deaths of despair in the United States.

Methods: :

PMRs for deaths due to drug overdoses, suicide, and alcoholic liver disease were obtained from the National Occupational Mortality Surveillance system. Data came from various states for the years 1985 to 1998, 1999, 2003 to 2004, and 2007 to 2014.

Results: :

Occupations with the highest risk for deaths of despair included construction; architects; and food preparation and service. Occupations with the highest increases in deaths due to deaths of despair included personal care and service and home aides.

Conclusions: :

Identifying occupations with elevated risk factors for deaths of despair makes it possible to focus interventions on these occupations. Occupational hazards and exposures may increase risk to deaths of despair for specific workers.
Prevalence, Clinical Characteristics, and Self-Reported Treatment of Exercise-Associated Muscle Cramping Differ Between 21.1- and 56-Km Running Race Entrants—SAFER XXII
Authors: de Jager Izaan , Schwellnus Martin , Viljoen Carel , Korkie Elzette , Sewry Nicola , Swanevelder Sonja , Jordaan Esme
Published: November 2021

Objective:

To determine whether the lifetime prevalence and clinical characteristics of exercise-associated muscle cramping (EAMC) differ between runners entering a 21.1- versus 56-km road race.

Design:

Cross-sectional study

Setting:

The 2012 to 2015 Two Oceans Marathon races (21.1 and 56 km), South Africa.

Participants:

Participants were consenting race entrants (21.1 km = 44 458; 56 km = 26 962) who completed an online prerace medical screening questionnaire.

Independent Variable:

A history of EAMC.

Main Outcome Measures:

The main outcome variables were lifetime prevalence (%) and clinical characteristics (muscle groups affected, timing of occurrence, severity, frequency of serious EAMC, and self-reported treatment) of a history of EAMC. Differences between 56- and 21.1-km race entrants were explored (relative risk [RR]).

Results:

The lifetime prevalence of EAMC was 12.8%, which was higher in 56- (20.0%; 95% CI 19.5-20.6) versus 21.1-km race entrants (8.5%; 8.2-8.8) (P = 0.0001). In all entrants, the fourth quarter was the most common onset (46.4%), calf muscles were the most commonly affected (53.1%), and most EAMCs were of mild-to-moderate severity (95%). In 56- versus 21.1-km entrants, hamstring (RR = 1.7; 1.5-1.9) and quadriceps muscle groups (RR = 1.5; 1.3-1.7) were more frequently affected (P = 0.0001), the onset of EAMC during racing was less common in the first quarter (RR = 0.3; 0.2-0.4) (P = 0.0001), and serious EAMC was more frequent (RR = 1.6; 1.4-1.9) (P = 0.0001).

Conclusions:

In 56- versus 21.1-km runners, a history of EAMC is 2 times more frequent and muscle groups affected, onset in a race, and severity of EAMC differed. The lifetime prevalence was lower than previously reported in other events. Risk factors associated with EAMC may differ between entrants for different race distances.
Impact of Age on Emergency Resource Utilization and Outcomes in Pediatric and Young Adult Patients Supported with a Ventricular Assist Device
Authors: Edwards Jonathan J. , Edelson Jonathan B. , Mondal Antara , Katcoff Hannah , Reza Nosheen , Griffis Heather , Burstein Danielle S. , Wittlieb-Weber Carol A. , O’Connor Matthew J. , Rossano Joseph W. , Ravishankar Chitra , Mascio Christopher , Birati Edo Y. , Lin Kimberly Y.
Published: November 2021

There are minimal data describing outcomes in ambulatory pediatric and young adult ventricular assist device (VAD)-supported patient populations. We performed a retrospective analysis of encounter-level data from 2006 to 2017 Nationwide Emergency Department Sample (NEDS) to compare emergency department (ED) resource utilization and outcomes for pediatric (≤18 years, n = 494) to young adult (19–29 years, n = 2,074) VAD-supported patient encounters. Pediatric encounters were more likely to have a history of congenital heart disease (11.3% vs. 4.8%). However, Pediatric encounters had lower admission/transfer rates (37.8% vs. 57.8%) and median charges ($3,334 (IQR $1,473–$19,818) vs. $13,673 ($3,331–$45,884)) (all p < 0.05). Multivariable logistic regression modeling revealed that age itself was not a predictor of admission, instead high acuity primary diagnoses and medical complexity were: (adjusted odds ratio; 95% confidence intervals): cardiac (3.0; 1.6–5.4), infection (3.4; 1.7–6.5), bleeding (3.9; 1.7–8.8), device complication (7.2; 2.7–18.9), and ≥1 chronic comorbidity (4.1; 2.5–6.7). In this largest study to date describing ED resource use and outcomes for pediatric and young adult VAD-supported patients, we found that, rather than age, high acuity presentations and comorbidities were primary drivers of clinical outcomes. Thus, reducing morbidity in this population should target comorbidities and early recognition of VAD-related complications.
A Visual Task-Based Assessment of Theory of Mind and Social Perception Within Bipolar Disorder
Authors: Aidelbaum Robert , Goghari Vina
Published: November 2021

Evidence suggests that theory of mind (TOM) and social perception (SP) may be impaired within bipolar disorder (BD). However, it remains unclear whether these deficits are facet specific and predictive of functioning. This study assessed the manifestation of TOM and SP in a BD sample. Twenty-six individuals diagnosed with BD and 25 controls were recruited and assessed for TOM, SP, and functioning. Whereas differences were observed regarding functional outcome, differences were not observed regarding social cognitive performance, regardless of facet. Correlations between social cognitive and functional outcome domains were nonsignificant, whereas significant associations were observed between the social cognitive measures. Results suggest that despite functional differences, TOM and SP, independent of facet assessed, seem preserved within the BD sample. Although evidence was not provided supporting the utility of TOM and SP in the prediction of functional outcome, evidence supports the possible dependence of these social cognitive domains on shared underlying processes.
Physical Activity Spaces Not Effective against Socioeconomic Inequalities in Myopia Incidence: The Generation R Study
Authors: Enthoven Clair A. , Mölenberg Famke J. M. , Tideman J. Willem L. , Polling Jan Roelof , Labrecque Jeremy A. , Raat Hein , van Lenthe Frank J. , Klaver Caroline C. W.
Published: November 2021

SIGNIFICANCE

Our findings show that non-Dutch background, lower maternal education, and lower net household income level may be new risk factors for myopia development in the Netherlands. Newly introduced physical activity spaces may not be effective enough in increasing outdoor exposure in children to reduce eye growth.

PURPOSE

The aims of this study were to evaluate socioeconomic inequalities in myopia incidence, eye growth, outdoor exposure, and computer use and to investigate if newly introduced physical activity spaces can reduce eye growth in school-aged children.

METHODS

Participants (N = 2643) from the Dutch population–based birth cohort Generation R were examined at ages 6 and 9 years. Socioeconomic inequalities in myopia incidence, eye growth, and lifestyle were determined using regression analyses. Information on physical activity spaces located in Rotterdam was obtained. Differences in eye growth between those who became exposed to new physical activity spaces (n = 230) and those nonexposed (n = 1866) were evaluated with individual-level fixed-effects models.

RESULTS

Myopia prevalence was 2.2% at age 6 years and 12.2% at age 9 years. Outdoor exposure was 11.4 h/wk at age 6 years and 7.4 h/wk at age 9 years. Computer use was 2.1 h/wk at age 6 years and 5.2 h/wk at age 9 years. Myopia incidence was higher in children with non-Dutch background, and families with lower household income and lower maternal education (odds ratio [OR], 1.081 [95% confidence interval, 1.052 to 1.112]; OR, 1.035 [95% confidence interval, 1.008 to 1.063]; OR, 1.028 [95% confidence interval, 1.001 to 1.055], respectively). Children living <600 m of a physical activity space did not have increased outdoor exposure, except those from families with lower maternal education (β = 1.33 h/wk; 95% confidence interval, 0.15 to 2.51 h/wk). Newly introduced physical activity spaces were not associated with reduction of eye growth.

CONCLUSIONS

Children from socioeconomically disadvantaged families became more often myopic than those from socioeconomically advantaged families. We did not find evidence that physical activity spaces protect against myopia for the population at large, but subgroups may benefit.
Feasibility of Aortic Annular Measurements Using Noncontrast-Enhanced Cardiac Computed Tomography in Preprocedural Evaluation of Transcatheter Aortic Valve Replacement: A Comparison With Contrast-Enhanced Computed Tomography
Authors: Suh Young Joo , Lee Sak , Hong Geu-Ru , Ko Young-Guk , Hong Myeong-Ki , Kim Young Jin
Published: November 2021

Objective

Noncontrast-enhanced (NCE) cross-sectional images other than contrast-enhanced (CE)-computed tomography (CT) may be necessary for annular sizing before transcatheter aortic valve replacement (TAVR), because of the risk of contrast-induced nephropathy. We aimed to investigate the feasibility of aortic annular measurements using NCE-CT in TAVR candidates by comparing them with CE-CT measurements.

Methods

We retrospectively enrolled 46 patients who underwent CT for the purpose of pre-TAVR evaluation (17 men; mean age, 82.3 ± 5.0 years). On CE and NCE examination, measurements of the average diameter and perimeter of aortic annulus were performed by 2 observers, and coronary ostial heights were measured. Differences in annular parameters and coronary ostial heights between NCE and CE examinations were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs).

Results

Aortic annulus measurement values were significantly larger in the NCE examinations compared with those in the CE examinations according to both readers (mean differences of 0.8 mm for the average diameter and 2.1 mm for the perimeter according to observer 1, and 1.1 mm for the average diameter and 3.4 mm for the perimeter according to observer 2; ICC, 0.771–0.923). The mean difference between coronary ostial height measurement on NCE and CE examination was 0.6 mm for left coronary ostium (ICC, 0.795) and 0.7 mm for right coronary ostium (ICC, 0.802). No case showed disagreement between NCE and CE examinations for hypothetical valve sizing.

Conclusions

Noncontrast-enhanced cardiac CT examination may be feasible for aortic annular measurements before TAVR and provides comparable measurement values to CE examination.
Temporomandibular Disorder Patients Benefit From Intramuscular Botulinum Toxin Type a Injections
Authors: Oksanen Erkka , Männistö Ville , Kormi Eeva , Vallioniemi Hanna , Suojanen Juho
Published: November 2021

Purpose:

The aim of this study was to analyze the clinical outcome of the use of botulinum toxin type A (BTX) intramuscular injections to the head and neck, particularly the masticatory muscles of patients with temporomandibular disorder (TMD).

Methods:

The medical records of all patients who had received intramuscular BTX injections between 2005 and 2018 at Päijät- Häme Central Hospital, Lahti, Finland were analyzed retrospectively. Gender, age, previous medical history, number of injections, injection areas, and therapeutic results were collected and analyzed. The outcome was divided into three categories based on the patients’ subjective reports: not beneficial, beneficial, and highly beneficial.

Results:

A total of 68 patients had received intramuscular BTX injections in our unit for TMD symptoms. Clinical effectiveness could be analyzed from 63 patients. Overall, 87% of them reported fävorable outcomes. 8 (13%) reported BTX injections as not beneficial, 15 (24%) as beneficial, and 40 patients (63%) as highly beneficial.

Most patients had already received conventional treatment with an occlusal splint (93%) combined with pain medication (60%) in the primary care units before they were referred to our hospital.

There were 59 (83%) female patients, and they responded better to BTX therapy than the male patients: 91% versus 57% (P value = 0.04). Average age at the first BTX injection visit was 44.6 years (range 17.8–77.2). Most commonly (65%), BTX was divided bilaterally to the masseter and temporalis muscles.

Conclusions:

BTX injections had good therapeutic outcomes for our TMD patients. However, most patients require multiple injection visits.
A Novel Method for Correction of the Tethered and Contracted Facial Scars: The Three-Dimensional Subcutaneous Z-Plasty
Authors: Demir Can Ilker , Yaşar Emrah Kağan , Alagöz Murat Şahin
Published: November 2021

Objective:

Scar revision is 1 of the basic surgery in the field of plastic and reconstructive surgery. The classic treatment of the scar is excision scarless tissue, wide undermining and suture by planes. This method has had unsatisfying results on contracted and tethered scars. The aim of this study is to present the three-dimensional subcutaneous z-plasty technique for correction of tethered facial scars without scar lengthening.

Materials and Methods:

Twenty tethered scars were corrected using this technique. All scars were located on the face. Objectively, the final result was evaluated by using the Stony Brook Scar Evaluation Scale. Subjectively, patients’ overall satisfaction was assessed 1 year after the surgical operation. In addition, the information on the age, gender, etiology, scar location, scar length, type of anesthesia, and follow-up period were examined.

Results:

This procedure was used in nineteen patients (8 males and eleven females). The mean follow-up period was 15.3 months. There was a mean increase of 2.85 points increase in the Stony Brook Scar Evaluation Scale value. The overall success rates for the procedure, as assessed by the patients, were: very satisfied in 12 patients, satisfied in 5 patients, and slightly satisfied in 2 patients. One patient had minimal wound dehiscence. No complications including hypertrophic scar, infection, hematoma, and suture reaction were observed in any patients.

Conclusions:

The three-dimensional subcutaneous z-plasty technique is a procedure that uses only basic plastic surgery principles. It offers a good solution for the correction of tethered and contracted scars without recurrence. This technique combines the advantages of elliptical excision and z-plasty by enabling the augmentation of the depressed area without extending the scar length.
Difference in the ascending reticular activating system between vegetative and minimally conscious states following traumatic brain injury
Authors: Jang Sung Ho , Kim Seong Ho , Kim Jae Woon , Lee Han Do , Cho Min Kyeong
Published: November 2021

Objectives

We investigated differences in the ascending reticular activating system (ARAS) between vegetative state (VS) and minimally conscious state (MCS) in patients with traumatic brain injury (TBI) by using diffusion tensor tractography.

Methods

We recruited TBI patients and normal subjects. We reconstructed the lower ARAS and five parts of upper ARAS [prefrontal cortex (PFC), premotor cortex, primary motor cortex, primary somatosensory cortex, and posterior parietal cortex].

Results

Significant differences were observed in the fractional anisotropy (FA) and fiber number (FN) values of the five parts of upper ARAS between the VS and control groups and between the MCS and control groups (P < 0.05), but no differences were detected in the lower ARAS (P > 0.05). The FA and FN values of the PFC in the upper ARAS were significantly different between the VS and MCS groups (P < 0.05). No other significant differences in FA and FN values were detected among the other segments of the upper ARAS or in the lower ARAS (P > 0.05).

Conclusion

The results indicate that the prefrontal portion of the upper ARAS is the critical area for distinguishing between VS and MCS in patients with TBI.
Parent-of-origin effects in the UK Biobank
Authors: Hofmeister R. J. , Rubinacci S. , Ribeiro D. M. , Kutalik Z. , Buil A. , Delaneau O.
Published: November 2021

Identical genetic variations can have different phenotypic effects depending on their parent of origin (PofO). Yet, studies focussing on PofO effects have been largely limited in terms of sample size due to the need of parental genomes or known genealogies. Here, we used a novel probabilistic approach to infer PofO of individual alleles in the UK Biobank that does not require parental genomes nor prior knowledge of genealogy. Our model uses Identity-By-Descent (IBD) sharing with second- and third-degree relatives to assign alleles to parental groups and leverages chromosome X data in males to distinguish maternal from paternal groups. When combined with robust haplotype inference and haploid imputation, this allowed us to infer the PofO at 5.4 million variants genome-wide for 26,393 UK Biobank individuals. We used this large dataset to systematically screen 59 biomarkers and 38 anthropomorphic phenotypes for PofO effects and discovered 101 significant associations, demonstrating that this type of effects contributes to the genetics of complex traits. Notably, we retrieved well known PofO effects, such as the MEG3/DLK1 locus on platelet count, and we discovered many new ones at loci often unsuspected of being imprinted and, in some cases, previously thought to harbour additive associations.
Octopamine drives honeybee thermogenesis
Authors: Kaya-Zeeb Sinan , Engelmayer Lorenz , Bayer Jasmin , Bähre Heike , Seifert Roland , Scherf-Clavel Oliver , Thamm Markus
Published: November 2021

In times of environmental change species have two options to survive: they either relocate to a new habitat or they adapt to the altered environment. Adaptation requires physiological plasticity and provides a selection benefit. In this regard, the Western honeybee (Apis mellifera) protrudes with its thermoregulatory capabilities, which enables a nearly worldwide distribution. Especially in the cold, shivering thermogenesis enables foraging as well as proper brood development and thus survival. In this study, we present octopamine signaling as a neurochemical prerequisite for honeybee thermogenesis: we were able to induce hypothermia by depleting octopamine in the flight muscles. Additionally, we could restore the ability to increase body temperature by administering octopamine. Thus we conclude, that octopamine is necessary and sufficient for thermogenesis. Moreover, we show that these effects are mediated by β octopamine receptors. The significance of our results is highlighted by the fact the respective receptor genes underlie enormous selective pressure due to adaptation to cold climates. Finally, octopamine signaling in the service of thermogenesis might be a key strategy to survive in a changing environment.
GAPDH cooperativity mediates drug resistance and metabolism in Plasmodium fal-ciparum malaria parasites
Authors: Jezewski Andrew J. , Guggisberg Ann M. , Hodge Dana M. , Ghebremichael Naomi , McLellan Lisa K. , Odom John Audrey R.
Published: November 2021

Efforts to control the global malaria health crisis are undermined by antimalarial resistance. Iden-tifying mechanisms of resistance will uncover the underlying biology of the Plasmodium falciparum malaria parasites that allow evasion of our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor of plastidial isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway. We have thus identified an unusual metabolic regulation scheme in the malaria parasite through the essential glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Two parallel genetic screens converged on independent but functionally analogous resistance alleles in GAPDH. Metabolic profiling of FSM-resistant gapdh mutant parasites indicates that neither of these mutations disrupt overall glycolytic output. While FSM-resistant GAPDH variant proteins are catalytically active, they have reduced assembly into the homotetrameric state favored by wild-type GAPDH. Disrupted oligomerization of FSM-resistant GAPDH variant proteins is accompanied by altered enzymatic cooperativity and reduced susceptibility to inhibition by free heme. Together, our data identifies a new genetic biomarker of FSM-resistance and reveals the central role of GAPDH cooperativity in MEP pathway control and antimalarial sensitivity.
Efficient transformation and genome editing of watermelon assisted by genes that encode developmental regulators
Authors: Pan Wenbo , Cheng Zhentao , Han Zhiguo , Yang Hong , Zhang Wanggen , Zhang Huawei
Published: November 2021

Abstruct

The Cucurbitaceae contains multiple species of important food plants. But most of them are difficult to be genetically transformed. Watermelon is one of the most important fruit species of Cucurbitaceae, and it is a model horticulture crops. Its low transgenic efficiency is the major bottleneck in functional genome research and genome editing-based breeding. Here, with the help of genes that encode developmental regulators (DRs), in particular AtGRF5, and an appropriate Agrobacterium strain (GV3101), we have significantly increased the transformation efficiency of watermelon to about 25%, which is a 40-fold increase compared with a traditional vector. AtGRF5-mediated transformation increased the number of transformable watermelon genotypes without causing obvious side effects. Moreover, when applying this strategy to CRISPR/Cas9-mediated genome editing, clpds knockout mutants were generated in the T0 generation. Our results show that AtGRF5 is a powerful and robust tool to effectively create transgenic plants or knockout mutations in watermelon. Similar strategies using DRs might also be able to overcome the transformation barriers in many other Cucurbitaceae species.
Discrete-to-analog signal conversion in human pluripotent stem cells
Authors: Prochazka Laura , Michaels Yale S. , Lau Charles , Siu Mona , Yin Ting , Wu Diana , Jang Esther , Jones Ross D. , Vázquez-Cantú Mercedes , Gilbert Penney M. , Kaul Himanshu , Benenson Yaakov , Zandstra Peter W.
Published: November 2021

During development, state transitions are coordinated through changes in the identity of molecular regulators in a cell state- and dose specific manner. The ability to rationally engineer such functions in human pluripotent stem cells (hPSC) will enable numerous applications in regenerative medicine. Herein we report the generation of synthetic gene circuits that can detect a discrete cell state, and upon state detection, produce fine-tuned effector proteins in a programmable manner. Effectively, these gene circuits convert a discrete (digital-like) cell state into an analog signal by merging AND-like logic integration of endogenous miRNAs (classifiers) with a miRNA-mediated output fine-tuning technology (miSFITs). Using an automated miRNA identification and model-guided circuit optimization approach, we were able to produce robust cell state specific and graded output production in undifferentiated hPSC. We further finely controlled the levels of endogenous BMP4 secretion, which allowed us to document the effect of endogenous factor secretion in comparison to exogenous factor addition on early tissue development using the hPSC-derived gastruloid system. Our work provides the first demonstration of a discrete-to-analog signal conversion circuit operating in living hPSC, and a platform for customized cell state-specific control of desired physiological factors, laying the foundation for programming cell compositions in hPSC-derived tissues and beyond.

Graphical Abstract