bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrin Hydrogels Prevent Contraction and Deliver Adipose Stem Cells to Debrided Deep Partial Thickness Burns for Accelerated Angiogenesis
Authors: Burmeister David M , Stone Randolph , Wrice Nicole L , Becerra Sandra C , Natesan Shanmugasundaram , Christy Robert J
Published: June 2021

Autografts for wound coverage often have limited availability, and result in donor site morbidities. Many different tissue engineering strategies have been explored to minimize and/or circumvent the need for grafting, however none have proven adequate. One promising technologyis PEGylated fibrin (PEG‐fibrin) hydrogels that have previously been shown to deliver adipose‐derived stem cells (ASCs) for enhanced angiogenesis. Here, we investigate the effectiveness of the combination of ASCs and PEG‐fibrin hydrogels in a porcine model of debrided burn wounds. We hypothesized that the scaffolding provided by PEG‐fibrin would mitigate the contraction seen upon meshing of autografts, while ASC delivery would accelerate wound healing. Deep‐partial thickness burns were created on the dorsum of anesthetized Yorkshire pigs, and subsequently debrided on post‐injury day 4. After debridement, wounds were treated with: split thickness skin grafts (STSG);meshed STSG at 1:1.5 (mSTSG); and mSTSG + PEG‐fibrin with ASCs at 0, 1×105,5×105, and 1×106 cells per 3cm diameter wound. Photographs and biopsies were taken on post‐burn days 10, 14, 21, and 42, with euthanasiaon post‐burn day 42. Excised tissue was processed for routine histopathology and western blot analysis. Treatment with mSTSG resulted in significantly more contraction of wounds (88.9 ± 5.6 % of original area) compared to those treated with STSG (109.3 ± 5.0% of original area) and mSTSG + PEG‐fibrin (110.6 ± 6.9% of original area) out to day 42 post‐burn. When ASCs were delivered to the wounds in PEG‐fibrin, the size of blood vessels counted via histopathology on day 10post‐injury increased in a dose dependent fashion. Furthermore, the size oxblood vessels significantly correlated with CD31 protein levels (r=0.69, P<0.0042). Surprisingly, there was no effect on reepithelialization of the wounds. The current report describes a dual‐action adjunct therapy to autografting which can be administered in situ. Specifically, PEG‐fibrin hydrogels act not only as scaffolding, which prevents the ensuing contraction after skin autografts are meshed but also as delivery vehicles for ASCs, which ultimately accelerate angiogenesis in a dose‐dependent fashion. This platform may be used to deliver other cell types or growth factors for accelerating wound closure and improving wound outcomes. The ultimate goal in investigating the combination of ASCs and PEG‐fibrin is to generate vascularized skin equivalents to for enhanced graft integration and reduced scarring.

Support or Funding Information

Medical Research and Materiel Command (MRMC) provided funding for this project.
Does Milk Portion Size or Energy Density Affect Preschool Children's Lunch Intake?
Authors: Kling Samantha MR , Roe Liane S , Rolls Barbara J
Published: June 2021

Government‐sponsored programs, such as the Child and Adult Care Food Program, recommend serving age‐appropriate portions of lower‐energy‐dense milk in order to moderate energy intake while promoting a nutrient‐dense diet. It is unclear, however, to what extent changes in milk portion size and energy density (ED) affect children's intake of both milk and the accompanying foods. To evaluate these recommendations, controlled studies are needed to determine if these factors influence children's intake of a meal served in their usual eating environment. Using a 2‐by‐2 crossover design, we investigated the influence of typical variations in milk portion size and ED on intake when milk was served with a standard lunch. Experimental meals were served once a week for 4 weeks in childcare classrooms and was consumed ad libitum by 125 children aged 3–5 y (67 boys and 58 girls). Across the 4 meals, unflavored milk was varied in portion size (9 fl. oz. or 6 fl.oz. [recommended]) and ED (3.25% full‐fat [0.61 kcal/g] or 1% low‐fat [0.42 kcal/g; recommended]). The foods served at the meal (chicken, pasta, broccoli, and bananas) were not varied. The results showed that serving the larger portion of milk increased milk energy intake by 20±3 kcal (27%; P<0.0001) compared to serving the smaller portion, but had no significant effect on food intake or meal energy intake. Serving higher‐ED milk increased milk energy intake by 31±2 kcal (44%) and decreased food energy intake by 26±6 kcal (10%) compared to serving lower‐ED milk (both P<0.0001). Thus, across all children, the change in milk ED did not influence total energy intake at the meal. The effects of milk portion size and ED were not influenced by most child characteristics, such as age, body size, and parent‐reported eating behaviors; however, the effect of milk ED on intake did differ significantly by sex. For boys, serving higher‐ED milk decreased food energy intake by 43±8 kcal (16%; P<0.0001) and did not affect total energy intake compared to serving lower‐ED milk. For girls, consuming more energy from the higher‐ED milk did not lead to a significant compensatory reduction in food energy intake and an additional 24±10 kcal (7%; P=0.03) was consumed over the entire meal. This suggests that boys, but not girls, adjusted their food energy intake in response to changes in ED of milk consumed with lunch. These results showed that serving larger portions of milk could promote milk intake without affecting total energy intake at a meal. However, the provision of lower‐ED milk is appropriate for preschool nutrition programs, since some children did not fully adjust their intake in response to higher‐ED milk and increased their lunch energy intake.

Support or Funding Information

USDA NIFA Grant 2011‐67001‐30117 and National Institutes of Health Grant DK082580.
INSIGHT Study Parenting Intervention to Prevent Childhood Obesity Improves Patterns of Dietary Exposures in Infants
Authors: Hohman Emily E , Savage Jennifer S , Paul Ian M , Birch Leann L
Published: June 2021

Composition of the infant diet changes rapidly throughout the first year of life, and caregiver decisions on when to introduce foods and what to feed an infant vary. Early dietary patterns have been associated with differing risk for obesity as well as food preferences and intake later in childhood. The objectives of this analysis were to 1) identify patterns of milk and complementary feeding among 40 week old infants participating in the INSIGHT study, an ongoing randomized, controlled trial designed to prevent childhood obesity, and 2) determine whether infants in the parenting intervention group consumed a wider variety of age‐appropriate, nutrient dense foods than control infants. Primiparous mother‐newborn dyads (n=291) were randomized to parenting intervention or a safety control group 2 weeks after birth. The parenting curriculum, built around a framework of responsive parenting in the domains of feeding, sleep, emotional/social regulation, and active social play, or a child safety control curriculum, was delivered at nurse home visits at 3, 16, 28, and 40 weeks after birth. Feeding guidance included messaging on responsive feeding, delayed introduction of solids, repeated exposure to novel foods, and age‐appropriate foods and portion sizes. Infant dietary intake was assessed by food frequency questionnaire at 40 weeks. Latent class analysis was used to identify patterns of dietary exposure encompassing both milk feeding type (formula vs. breast) and solid foods at 40 weeks. Dietary pattern class membership at 40 weeks was used to predict child weight outcomes measured at 1 year. Similar to previous work, five distinct patterns of dietary exposures were identified: 1) “Breastfed, Fruits and Vegetables (BFV)”, 2) “Breastfed, Low Variety (BLV)”, 3) “Formula, Fruits and Vegetables (FFV)”, 4) “Formula, Low Variety (FLV)”, and 5) “Formula, High Energy Density (FHED)”. Class membership probabilities differed between the control and parenting groups (p=0.002). A greater percentage of infants in the parenting group than control were predicted to be in the BFV and FFV classes (60.5% vs 38.5%, p=0.0004), classes characterized by higher fruit and vegetable intake and low intake of high energy‐dense foods. Among formula fed infants, a greater percentage of infants in the parenting group than control were predicted to be in the FFV class rather than the FLV or FHED classes (47.5% vs 19.0% of formula fed infants, p=0.0001). At 1 year, children in the FLV class had significantly higher average weight‐for‐length percentile than those in the BFV class (p=0.04). These results suggest that the parenting intervention improved patterns of dietary intake in 40 week‐old infants, particularly those being fed formula, by increasing fruit and vegetable intake, which may reduce later risk of obesity.

Support or Funding Information

NIDDK R01DK088244 and The Childhood Obesity Training Grant #2011‐67001‐30117 from USDA
Adherence Monitoring Tool for Controlled Feeding Studies
Authors: Burnett Dustin J , Peerson Janet M , Miller Beverly , Welch Lucas C , Witbracht Megan G , Krishnan Sridevi , Keim Nancy L
Published: June 2021

Objective

To devise a dietary adherence monitoring tool for use in controlled human feeding trials involving free‐living study participants.

Methods

A scoring tool was devised to measure and track dietary adherence for an 8‐wk randomized trial evaluating the effects of two different dietary patterns on metabolic health outcomes. One dietary pattern is based on the 2010 Dietary Guidelines for Americans; and the other using recent dietary intake data from the What We Eat In America (WWEIA) National survey. In our trial, all foods and beverages are provided to the study participants. The scoring system is a modified version of that used in the Dietary Approaches to Stop Hypertension (DASH) feeding study. Study volunteers maintain detailed daily food logs that are used to score their adherence in these categories. These scores are then adjusted using weigh‐backs of foods not consumed, when a discrepancy between self‐report and weigh backs arise. Adherence scores are assigned on a daily basis to four categories: 1) adherence to the provided study foods (SF), 2) intake of non‐study foods (NSF), 3) intake of coffee or tea that was not provided (C/T), and 4) addition of salt, pepper, herbs or other spices (S/P/S). A score of 0 indicates complete adherence in all categories. For the study and non‐study food categories, scores of 1, 2 or 3 represent deviations of <1, 1–2.9, or ≥ 3 servings/d. In the C/T or S/P/S categories, scores of 1 indicate that these items were added by the participant. A Wilcoxon's signed‐rank test was used to compare the difference in adherence between SF and NSF.

Results

Scores for the first ten participants suggest that deviations from adhering to eating all of the study foods (0.6 ± 1.0) were greater than deviations from eating non‐study foods (0.1 ± 0.5) (p=0.002). There were only a total of 10 reported instances of C/T deviations and 4 of S/P/S deviations during the full 8‐wk study for these ten participants.

Conclusions

The scoring tool enables us to closely follow free‐living participants on a daily basis in controlled feeding trials and has the potential to improve adherence while the volunteer is actively enrolled in the study. In our study, this scoring tool will be paired with additional objective checks of adherence, including measurements of body weight and urinary nitrogen, sodium and potassium to more fully characterize dietary adherence.

Support or Funding Information

Supported by National Dairy Council, Campbell Soup Company, and the USDA project number #2032‐51530‐022
A Validation of Automated Self‐Administered 24‐Hour Dietary Recalls(ASA24) Relative to Interviewer‐Administered Recalls using the Nutrition Data System for Research (NDSR)
Authors: Mitchell Diane C , Cheng Feon W , Still Christopher D , Jensen Gordon L
Published: June 2021

Introduction

The ASA24, an innovative internet‐based tool widely used by researchers, may be a valid and reliable alternative in research when cost or time constraints do not allow for telephone 24‐hr dietary recalls or when food frequency data is insufficient for the level of detail needed. Few studies have been conducted to evaluate, validate or test the feasibility and cost‐effectiveness of the ASA24 relative to standard methods in different populations. Our objective was to assess the relative validity of the ASA24 in middle aged adults residing in rural Pennsylvania.

Methods

Adult men (n= 60) and women (n= 108) 50–65 years of age (mean age 57 ± 4.5 yrs.) were recruited and randomly assigned using a cross‐over design to complete both the internet‐based ASA24 and telephone interviewer‐administered NDSR assessments. Participants were either emailed or called on randomly selected, unannounced days to complete 1 weekend and 2 weekdays of intake. Of the 181 participants who were recruited, 3 participants dropped, 9 (5%) did not complete the ASA24 and 1 did not complete the NDSR assessments leaving 168 participants with complete assessments for both methods. Relative validity was assessed by Spearman correlation for energy and energy adjusted and deattenuated correlations for nutrients and food groups.

Results

The ASA24 yielded higher energy intakes (1966 vs. 1853 kcal) with a correlation of 0.67. Correlations were higher for women (r=0.58) than men (r=0.48). Correlations coefficients for nutrients ranged from 0.21 to 0.84 for all nutrients examined. Correlations were lowest for polyunsaturated fat (r=0.21) and for zinc (r=0.33) and highest for fiber (r=0.84), vitamin A (r=0.80), magnesium (r=0.84), vitamin C (r=0.78) and potassium (r=0.78). For food groups correlations were highest for whole fruit (r=0.99) and total fruit (r=0.92) and lowest for total protein foods (r=0.48), total grains (r =0.61), and vegetables (r=0.66).

Conclusion

This study provides inconclusive evidence of the validity of the ASA24 relative to standard telephone methods with relatively high correlations for some nutrients and food groups and low correlations for others. The use of the ASA24 may largely depend on specific research questions and on nutrient and food outcomes of interest. Further research will improve our understanding of the validity of ASA24 and its role in replacing standard interviewer‐administered methods.

Support or Funding Information

Supported by the United States Department of Agriculture, #8050‐51530‐012‐01A.
Development of a Shared Decision-Making Tool for Adolescents With Scoliosis to Decide Between Observation Versus Fusion Surgery
Authors: Ifelayo Oluwatomilona I. , Brito Juan P. , Hargraves Ian G. , Larson A. Noelle
Published: June 2021

Background:

Adolescent patients with moderate to severe idiopathic scoliosis who have completed their skeletal growth face a significant choice in their treatment path: watchful waiting or spinal fusion. Shared decision making (SDM) assists patients and clinicians to find treatments that make intellectual, practical and emotional sense. Our objective was to develop a tool that supports SDM for patients with scoliosis and their families.

Methods:

We used a user-centered design approach that included collaboration between patients, surgeons and SDM experts, observation of clinician encounters, and literature review. We focused on adolescent idiopathic scoliosis patients 13 or more years of age with less than 1 year of growth remaining (Risser stage 3 or greater) and curves between 40 and 65 degrees.

Results:

We included 22 patients, and collected 22 video recordings. From these videos, we identified salient patient priorities for decision making including treatment benefits, surgical complications, pain, scheduling and recovery, and cost. For each theme, we conducted a focused review to obtain the best estimate of effect. Then, an expert SDM designer developed an electronic prototype called Scoliosis Choice.

Conclusions:

The initial prototype of the scoliosis SDM was finalized and is currently being field tested in clinic. Scoliosis Choice may help patients and surgeons better understand the potential risks and benefits of spinal fusion vs. observation for scoliosis treatment and improve validated measures of quality in patient-parent-surgeon communication.
Has the Threshold for Epiphysiodesis Versus Lengthening Changed in the Era of Magnetically Controlled Nails?
Authors: Nichols L. Reid Boyce
Published: June 2021

Introduction:

Limb length discrepancy (LLD) is common in both the pediatric and adult population. Length inequalities can be due to a multitude of etiologies including congenital, developmental, and acquired causes. There has been little consensus on the morbidity of LLD and, as a result, the threshold necessary for treatment of LLD to prevent morbidity. Advances in magnetically controlled lengthening devices achieve greater accuracy and patient satisfaction and create an opportunity to lower the threshold for limb lengthening.

Discussion:

Asymptomatic LLD is relatively common in both pediatric and adult populations. Only ~10% of the population has equal leg length. LLD of <5 cm may lead to long-term morbidities such as scoliosis, lower back pain, gait abnormalities, stress on hip or knee joint, and lower extremity symptomatic versus asymptomatic osteoarthritis. The teaching in most orthopaedic textbooks is to adjust the shoe if symptomatic for discrepancies up to 2 cm; consider an orthotic, epiphysiodesis, or skeletal shortening for 2.5 to 5 cm; and possible limb reconstruction for >5 cm. The assumption is that there are no long-term consequences of mild LLD. However, data in recent literature show that small discrepancies may contribute to pathologic changes such as pain, gait abnormalities, and osteoarthritis. Major advances have been made in limb lengthening over the past 40 years. The increased accuracy and superior patient satisfaction of the magnetically controlled lengthening nail versus external fixation methods argue for including lengthening for LLD of <5 cm.

Conclusion:

If mild LLD can cause long-term pathology, it is important to counsel families on the full range of options for limb equalization no matter the size of the discrepancy. The evolution in technology and understanding of limb lengthening has provided additional safe surgical options. Therefore, the historic treatment protocol for addressing limb differences may need to include lengthening for smaller discrepancies even <2 cm.
Orthopaedic Problems in 35 Patients With Organic Acid Disorders
Authors: Prasad Niyathi , Gottlich Caleb , Nhan Derek , Hamosh Ada , Sponseller Paul D.
Published: June 2021

Introduction:

Organic acid disorders (OADs) are a subset of inborn errors of metabolism that result in a toxic accumulation of organic acids in the body, which can lead to metabolic derangements and encephalopathy. Patients with these disorders are managed by a team of biochemical geneticists and metabolic nutritionists. However, subspecialists such as neurologists and orthopaedic surgeons are often needed to help manage the sequelae of the metabolic derangements. The breadth of orthopaedic sequelae of these disease states is poorly understood. Herein, we describe orthopaedic problems associated with 5 types of OAD most commonly seen at our institution: maple syrup urine disease, methylmalonic aciduria, propionic aciduria, pyruvate dehydrogenase deficiency, and glutaric aciduria type 1.

Methods:

We retrospectively reviewed medical records of 35 patients with an OAD who were seen at our academic tertiary care center from May 1999 to May 2020. Patients were grouped into cohorts according to OAD type and analyzed for orthopaedic presentations of hip, knee, or foot disorders, presence and severity of scoliosis, history of fracture, movement disorders, and osteopenia/osteoporosis.

Results:

Of the 35 patients, 13 had maple syrup urine disease, 12 had methylmalonic aciduria, 4 had propionic aciduria, 4 had pyruvate dehydrogenase deficiency, and 2 had glutaric aciduria type 1. Associated orthopaedic problems included spasticity causing neuromuscular scoliosis and/or hip subluxation or dislocation (10 patients), fractures (7 patients), and osteopenia/osteoporosis (7 patients). Overall, 22 of 35 patients had some orthopaedic condition.

Conclusions:

Most in this cohort of patients with OAD also had an orthopaedic abnormality. It is important for physicians treating these patients to understand their propensity for musculoskeletal problems. When treating patients with OAD, it is important to initiate and maintain communication with specialists in several disciplines and to develop collaborative treatments for this unique population.

Level of Evidence:

Level IV—prognostic study.
Screw Malposition: Are There Long-term Repercussions to Malposition of Pedicle Screws?
Authors: Amaral Terry D. , Hasan Sayyida , Galina Jesse , Sarwahi Vishal
Published: June 2021

Background/Introduction:

Pedicle screws have long been part of the continued advancements in spine surgery. Despite the many techniques that have been devised for their safe placement, malposition of screws continues to occur. Studies have evaluated the possible safe limits of screw malposition, and have given some insight on anatomic variation in spinal deformity. Review of the literature reveals several cases of deleterious long-term sequelae of malpositioned screws.

Discussion:

With the current experience, proposed recommendations are provided to detect and avoid the potential long-term sequelae. Though the literature has helped to define possible concerning screws, there are no good studies predicting long-term risk.

Conclusion:

Improvements in technology and techniques, advancements in intraoperative confirmation and postoperative surveillance, studies that assist risk stratification, and expert consensus evaluations will help guide surgeons in their decision for addressing misplaced screws.
Early Experience with External Negative Pressure Delay in Free Anterolateral Thigh Perforator Flap Reconstruction
Authors: Brown Ciara A. , Ghareeb Paul A.
Published: June 2021

Negative pressure therapy has been utilized in the treatment of open and closed wounds to increase blood flow and improve wound healing. More recently, external negative pressure has been shown to induce a noninvasive delay phenomenon in animal models by increasing vessel size and density within a planned flap, leading to improvement in flap survival. Although successful in animal models, this new method of delay has not been demonstrated in clinical practice. We present our initial experience with preoperative external negative pressure delay of free anterolateral thigh flaps in upper extremity reconstruction to detail the technique and safety profile of this innovative new technique. External negative pressure delay has the potential to provide results similar to those of traditional surgical delay, while being cost effective, safer, and more convenient for patients. More research is needed to investigate the clinical benefit and cost effectiveness of external negative pressure delay.
Comparing Plastic Surgeon Operative Time for DIEP Flap Breast Reconstruction: 2-stage More Efficient than 1-stage?
Authors: Issa Christopher J. , Lu Stephen M. , Boudiab Elizabeth M. , DeSano Jeffrey , Sachanandani Neil S. , Powers Jeremy M. , Chaiyasate Kongkrit
Published: June 2021

Background:

The deep inferior epigastric perforator flap for breast reconstruction is associated with lengthy operative times that remain an issue for plastic surgeons today. The main objective of this study was to determine if a 2-stage deep inferior epigastric perforator flap reconstruction resulted in a shorter total plastic surgeon operative time compared with an immediate reconstruction.

Methods:

A retrospective chart review was conducted on all patients who underwent deep inferior epigastric perforator flap breast reconstruction from February 2013 to July 2020 by the senior author. Patient demographics, medical comorbidities, mastectomy characteristics, expander placement, reconstructive procedures, operative time, and complications were tabulated.

Results:

The study included a total of 128 patients. For immediate/1-stage flap reconstruction, average operative times for the plastic surgeon were 427.0 minutes for unilateral procedures, and 506.3 minutes for bilateral procedures. For delayed/2-stage reconstruction, average combined plastic surgeon operative times were 351.1 minutes for unilateral expander followed by flap reconstruction (75.9 minutes shorter than immediate unilateral, P = 0.007), and 464.8 minutes for bilateral reconstruction (41.5 minutes shorter than immediate bilateral, P = 0.04). Total patient time under anesthesia was longer for 2-staged bilateral reconstruction (P = 0.0001), but did not differ significantly for unilateral reconstruction. Complications between immediate and delayed groups were not significantly different.

Conclusions:

We found that staged reconstruction over 2 procedures resulted in a significant reduction in operative time for the plastic surgeon for both unilateral and bilateral reconstruction. With amenable breast surgeons and patients, the advantages of controlling scheduling and the operating room may encourage plastic surgeons to consider performing free flap reconstruction in a delayed fashion.
Spare Parts Surgery with a Free Posterior Interosseous Artery Perforator Flap for Thumb Tip
Authors: Kamei Wataru , Murakami Masami , Nakamoto Kan , Osa Nagisa , Niimi Yosuke , Sakurai Hiroyuki
Published: June 2021

Replantation is an ideal method for treating fingertip amputation. However, in some cases, replantation is known to be a challenging issue. This report described a successful thumb tip reconstruction performed with bone and nail bed salvaged as spare parts, and a free posterior interosseous artery perforator (PIAP) flap. A 75-year-old man accidentally amputated his left thumb with an electric saw, and emergency replantation was started under brachial plexus block. However, the distal stump of digital artery was unable to be identified, forcing the initial plan to change to flap reconstruction. After vascular anastomosis, complex tissue containing nail bed and side nail fold was grafted on the adipofascial tissue of PIAP flap. Both PIAP flap and the complex tissue survived completely. At 12 months after surgery, only a slight deformity in the nail plate was observed. Spare parts surgery is a surgical procedure effectively salvaging and utilizing tissue that is going to be discarded in severe limb trauma. This idea can be applied to treatment for the finger amputation. In this case, replantation would be difficult in the thumb tip amputation, so spare parts surgery was performed with a PIAP flap. The innervated PIAP flap is reported, including the posterior antebrachial cutaneous nerve. In this case, the cutaneous nerve was able to be identified, neurorrhaphy was performed, and sufficient sensory recovery was obtained. Surgical procedure with PIAP flaps was found to be a useful method for immediate reconstruction with salvaged spare parts after fingertip replantation was considered to be difficult intraoperatively.
Enterovirus-A71 Rhombencephalitis Outbreak in Catalonia: Characteristics, Management and Outcome
Authors: Wörner Núria , Rodrigo-García Rocío , Antón Andrés , Castellarnau Ester , Delgado Ignacio , Vazquez Èlida , González Sebastià , Mayol Lluís , Méndez Maria , Solé Eduard , Rosal Jaume , Andrés Cristina , Casquero Alejandro , Lera Esther , Sancosmed Mónica , Campins Magda , Pumarola Tomàs , Rodrigo Carlos
Published: June 2021

Background:

Between April and June 2016, an outbreak of rhombencephalitis (RE) caused by enterovirus (EV) A71 was detected in Catalonia, Spain—the first documented in Western Europe. The clinical characteristics and outcome of patients with this condition differed from those reported in outbreaks occurring in Southeast Asia.

Methods:

Observational, multicenter study analyzing characteristics, treatment and outcome of patients with EV-A71 rhombencephalitis diagnosed in 6 publicly funded hospitals within the Catalonian Health Institute. A review of clinical characteristics, diagnosis, treatment and outcome of these patients was conducted.

Results:

Sixty-four patients met the clinical and virologic criteria for rhombencephalitis caused by EV-A71. All patients had symptoms suggesting viral disease, mainly fever, lethargy, ataxia and tremor, with 30% of hand-foot-mouth disease. Intravenous immunoglobulin therapy was given to 44/64 (69%) patients and methylprednisolone to 27/64 (42%). Six patients (9%) required pediatric intensive care unit admission. Three patients had acute flaccid paralysis of 1 limb, and another had autonomic nervous system (ANS) dysfunction with cardiorespiratory arrest. Outcome in all patients (except the patient with hypoxic-ischemic encephalopathy) was good, with complete resolution of the symptoms.

Conclusions:

During the 2016 outbreak, rhombencephalitis without ANS symptoms was the predominant form of presentation and most patients showed no hand-foot-mouth disease. These findings contrast with those of other patient series reporting associated ANS dysfunction (10%–15%) and hand-foot-mouth disease (60%–80%). Complete recovery occurred in almost all cases. In light of the favorable outcome in untreated mild cases, therapies for this condition should be reserved for patients with moderate-severe infection. The main relevance of this study is to provide useful information for setting priorities, management approaches and adequate use of resources in future EV-A71 associated rhombencephalitis outbreaks.
Rationale of Therapeutic Plasma Exchange as Rescue Immunomodulatory Treatment for MIS-C With Multiorgan Failure
Authors: Díaz Franco , Cores Camila , Atenas Omar , Rodríguez Nicolás , Bustos Raúl , Cruces Pablo
Published: June 2021

Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection is an infrequent and poorly understood illness. It can present as severe multiorgan failure in children, potentially lethal. Immunomodulation is the empiric treatment because a dysregulated immune response is the primary pathophysiologic mechanism. We present an infant with severe MIS-C, refractory to usual treatment, successfully treated with plasmapheresis.
Effects of joint and nerve mobilisation on neuroimmune responses in animals and humans with neuromusculoskeletal conditions: a systematic review and meta-analysis
Authors: Lutke Schipholt Ivo J. , Coppieters Michel W. , Meijer Onno G. , Tompra Nefeli , de Vries Rob B. M. , Scholten-Peeters Gwendolyne G. M.
Published: June 2021

Several animal and human studies revealed that joint and nerve mobilisations positively influence neuroimmune responses in neuromusculoskeletal conditions. However, no systematic review and meta-analysis has been performed. Therefore, this study aimed to synthesize the effects of joint and nerve mobilisation compared with sham or no intervention on neuroimmune responses in animals and humans with neuromusculoskeletal conditions. Four electronic databases were searched for controlled trials. Two reviewers independently selected studies, extracted data, assessed the risk of bias, and graded the certainty of the evidence. Where possible, meta-analyses using random effects models were used to pool the results. Preliminary evidence from 13 animal studies report neuroimmune responses after joint and nerve mobilisations. In neuropathic pain models, meta-analysis revealed decreased spinal cord levels of glial fibrillary acidic protein, dorsal root ganglion levels of interleukin-1β, number of dorsal root ganglion nonneuronal cells, and increased spinal cord interleukin-10 levels. The 5 included human studies showed mixed effects of spinal manipulation on salivary/serum cortisol levels in people with spinal pain, and no significant effects on serum β-endorphin or interleukin-1β levels in people with spinal pain. There is evidence that joint and nerve mobilisations positively influence various neuroimmune responses. However, as most findings are based on single studies, the certainty of the evidence is low to very low. Further studies are needed.
Magnetoencephalography reveals increased slow-to-fast alpha power ratios in patients with chronic pain
Authors: Witjes Bart , Baillet Sylvain , Roy Mathieu , Oostenveld Robert , J.P.M. Huygen Frank , C. de Vos Cecile
Published: June 2021

Introduction:

Objective disease markers are a key for diagnosis and personalized interventions. In chronic pain, such markers are still not available, and therapy relies on individual patients' reports. However, several pain studies have reported group-based differences in functional magnetic resonance imaging, electroencephalography, and magnetoencephalography (MEG).

Objectives:

We aimed to explore spectral differences in resting-state MEG brain signals between patients with chronic pain and pain-free controls and to characterize the cortical and subcortical regions involved.

Methods:

We estimated power spectral density over 5 minutes of resting-state MEG recordings in patients with chronic pain and controls and derived 7 spectral features at the sensor and source levels: alpha peak frequency, alpha power ratio (power 7–9 Hz divided by power 9–11 Hz), and average power in theta, alpha, beta, low-gamma, and high-gamma bands. We performed nonparametric permutation t tests (false discovery rate corrected) to assess between-group differences in these 7 spectral features.

Results:

Twenty-one patients with chronic pain and 25 controls were included. No significant group differences were found in alpha peak frequency or average power in any frequency band. The alpha power ratio was significantly higher (P < 0.05) in patients with chronic pain at both the sensor and brain source levels. The brain regions showing significantly higher ratios included the occipital, parietal, temporal and frontal lobe areas, insular and cingulate cortex, and right thalamus.

Conclusion:

The alpha power ratio is a simple, promising signal marker of chronic pain, affecting an expansive range of cortical and subcortical regions, including known pain-processing areas.
Dissociative and analgesic properties of ketamine are independent and unaltered by sevoflurane general anesthesia
Authors: Hahm Eunice Y. , Chamadia Shubham , Locascio Joseph J. , Pedemonte Juan C. , Gitlin Jacob , Mekonnen Jennifer , Ibala Reine , Ethridge Breanna R. , Colon Katia M. , Qu Jason , Akeju Oluwaseun
Published: June 2021

Introduction:

Ketamine, an anesthetic adjunct, is routinely administered as part of a balanced general anesthetic technique. We recently showed that the acute analgesic and dissociation properties of ketamine are separable to suggest that distinct neural circuits underlie these states.

Objective:

We aimed to study whether this finding is robust to the substantial neural circuit alterations associated with general anesthesia.

Methods:

We conducted a single-site, open-label, randomized controlled, cross-over study of sevoflurane and sevoflurane-plus-ketamine (SK) general anesthesia in healthy subjects (n = 12). Before and after general anesthesia, we assessed precalibrated cuff pain intensity and nociceptive pain quality as well as dissociation using the Clinician-Administered Dissociative States Scale (CADSS). For statistical inference, we ran a variation of backward elimination repeated-measures analysis of covariance. Models with CADSS as a covariate term were used to assess whether dissociation mediated the effect of ketamine on pain intensity and quality.

Results:

Sevoflurane-plus-ketamine general anesthesia was associated with a significant (P = 0.0002) pain intensity decline of 3 (SE, 0.44). There was an order effect for dissociation such that SK was associated with a significant (P = 0.0043) CADSS increase of 17.8 (3.2) when the SK treatment came first. When the pain intensity model was reanalyzed with CADSS as an additional covariate, the effect of CADSS was not significant. These results were also conserved for pain quality.

Conclusions:

Our findings suggest that the analgesic and dissociation properties of ketamine remain separable despite general anesthesia. Thus, ketamine may be used as a probe to advance our knowledge of dissociation independent pain circuits.
MRI of Sinonasal Malignancies
Authors: Famuyide Akinrinola , Juliano Amy , Moonis Gul
Published: June 2021

Sinonasal cavity is an important subsite in head and neck tumors. There are a myriad of malignancies that present within this area. Adequate staging for treatment planning requires multimodality evaluation. Magnetic resonance imaging (MRI) forms an important component in the evaluation of sinonasal tumors. We sought to review the most common sinonasal tumors, including sinonasal anatomy, clinical features, and common imaging features. A literature review was performed to evaluate common sinonasal tumors. Owing to the different tissue types within the sinonasal cavity, there are multiple different tumor pathologies within the sinonasal compartment. Most present in adults although some present in the young. Many of these tumor types have imaging overlaps, although some have a characteristic appearance. MRI can aid in soft tissue delineation, evaluation of multicompartmental extension, intracranial spread, and perineural spread. Sinonasal tumors are a heterogeneous group for which soft tissue delineation via MRI forms an important role in ensuring adequate treatment planning to improve outcomes, decreasing morbidity, and improve functional outcomes.
Doing Great With DOTATATE
Authors: Zlochower Avraham B. , Steinklein Jared M.
Published: June 2021

Sinonasal tumors are relatively rare and radiographically challenging to evaluate due to their wide variety of pathologies and imaging features. However, sinonasal tumors possessing somatostatin receptor overexpression have the benefit of utilizing a multimodality anatomic and functional imaging for a more comprehensive evaluation. This is particularly evident with esthesioneuroblastoma, with computed tomography and magnetic resonance imaging defining the anatomic extent of the tumor, whereas somatostatin receptor imaging, particularly with gallium-68 DOTATATE positron emission tomography/computed tomography, is used to assess the presence of metastatic disease for staging purposes as well as in the surveillance for tumor recurrence. In addition, areas which accumulate gallium-68 DOTATATE are potentially amenable to treatment with peptide receptor radionuclide therapy. In this manner, a combined approach of anatomic and functional imaging is critical for optimal imaging evaluation and treatment strategy of patients with sinonasal tumors.
Electric demand response and bounded rationality: mean-field control for large populations of heterogeneous bounded-rational agents
Authors: Marín Radoszynski Andrea , Pinson Pierre
Published: June 2021

The increased penetration of renewable energy sources into existing power systems induces challenges in supply–demand balancing. Demand-side flexibility is seen as an option to accommodate variability and limited predictability from renewable energy generation. Heat pumps at residential level, if well coordinated, can be one of those flexibility sources. The complexity involved is high though, since their coordinated operation combines control, population effects and the fact agents may actually not behave as rational decision-makers. We describe here a coordinated control framework that accounts for those aspects altogether. Decentralized model predictive control for large populations of heterogeneous agents is employed. As the cost to be minimized is affected by the population behaviour as a whole through the electricity price, the decentralized control is re-thought as a mean-field game. Existence and uniqueness of a Nash equilibrium are discussed while the Picard–Banach algorithm is used as a solution approach. It is extended to the case of bounded-rational agents. The impact on system dynamics of modelling agents as bounded rational is illustrated through numerical simulations.

This article is part of the theme issue ‘The mathematics of energy systems’.
Welfare-maximizing transmission capacity expansion under uncertainty
Authors: Wogrin S. , Tejada-Arango D. , Downward A. , Philpott A.B.
Published: June 2021

We apply the JuDGE optimization package to a multistage stochastic leader–follower model that determines a transmission capacity expansion plan to maximize expected social welfare of consumers and producers who act as Cournot oligopolists in each time period. The problem is formulated as a large-scale mixed integer programme and applied to a 5-bus instance over scenario trees of varying size. The computational effort required by JuDGE is compared with solving the deterministic equivalent mixed integer programme using a state-of-the-art integer programming package.

This article is part of the theme issue ‘The mathematics of energy systems’.
Insight into phenotypic and genotypic differences between vaginal Lactobacillus crispatus BC5 and Lactobacillus gasseri BC12 to unravel nutritional and stress factors influencing their metabolic activity
Authors: Costantini Paolo Emidio , Firrincieli Andrea , Fedi Stefano , Parolin Carola , Viti Carlo , Cappelletti Martina , Vitali Beatrice
Published: June 2021

The vaginal microbiota, normally characterized by lactobacilli presence, is crucial for vaginal health. Members belonging to

L. crispatus

and

L. gasseri

species exert crucial protective functions against pathogens, although a total comprehension of factors that influence their dominance in healthy women is still lacking. Here we investigated the complete genome sequence and comprehensive phenotypic profile of

L. crispatus

strain BC5 and

L. gasseri

strain BC12, two vaginal strains featured by anti-bacterial and anti-viral activities. Phenotype microarray (PM) results revealed an improved capacity of BC5 to utilize different carbon sources as compared to BC12, although some specific carbon sources that can be associated to the human diet were only metabolized by BC12, i.e. uridine, amygdalin, tagatose. Additionally, the two strains were mostly distinct in the capacity to utilize the nitrogen sources under analysis. On the other hand, BC12 showed tolerance/resistance towards twice the number of stressors (i.e. antibiotics, toxic metals etc.) with respect to BC5. The divergent phenotypes observed in PM were supported by the identification in either BC5 or BC12 of specific genetic determinants that were found to be part of the core genome of each species. The PM results in combination with comparative genome data provide insights into the possible environmental factors and genetic traits supporting the predominance of either

L. crispatus

BC5 or

L. gasseri

BC12 in the vaginal niche, giving also indications for metabolic predictions at the species level.
Revealing public opinion towards COVID-19 vaccines with Twitter Data in the United States: a spatiotemporal perspective
Authors: Hu Tao , Wang Siqin , Luo Wei , Zhang Mengxi , Huang Xiao , Yan Yingwei , Liu Regina , Ly Kelly , Kacker Viraj , She Bing , Li Zhenlong
Published: June 2021

Background

The COVID-19 pandemic has imposed a large, initially uncontrollable, public health crisis both in the US and across the world, with experts looking to vaccines as the ultimate mechanism of defense. The development and deployment of COVID-19 vaccines have been rapidly advancing via global efforts. Hence, it is crucial for governments, public health officials, and policy makers to understand public attitudes and opinions towards vaccines, such that effective interventions and educational campaigns can be designed to promote vaccine acceptance.

Objective

The aim of this study is to investigate public opinion and perception on COVID-19 vaccines by investigating the spatiotemporal trends of their sentiment and emotion towards vaccines, as well as how such trends relate to popular topics on Twitter in the US.

Methods

We collected over 300,000 geotagged tweets in the US from March 1, 2020 to February 28, 2021. We examined the spatiotemporal patterns of public sentiment and emotion over time at both national and state scales and identified three phases along the pandemic timeline with the significant changes of public sentiment and emotion, further linking to eleven key events and major topics as the potential drivers to induce such changes via cloud mapping of keywords and topic modelling.

Results

An increasing trend of positive sentiment in parallel with the decrease of negative sentiment are generally observed in most states, reflecting the rising confidence and anticipation of the public towards vaccines. The overall tendency of the eight types of emotion implies the trustiness and anticipation of the public to vaccination, accompanied by the mixture of fear, sadness and anger. Critical social/international events and/or the announcements of political leaders and authorities may have potential impacts on the public opinion on vaccines. These factors, along with important topics and manual reading of popular posts on eleven key events, help identify underlying themes and validate insights from the analysis.

Conclusions

The analyses of near real-time social media big data benefit public health authorities by enabling them to monitor public attitudes and opinions towards vaccine-related information in a geo-aware manner, address the concerns of vaccine skeptics and promote the confidence of individuals within a certain region or community, towards vaccines.
A Systematic Review and Meta-Analysis of the Mental Health Symptoms during the Covid-19 Pandemic in Southeast Asia
Authors: Pappa Sofia , Chen Jiyao , Barnet Joshua , Chang Anabel , Dong Rebecca Kechen , Xu Wen , Yin Allen , Chen Bryan Z. , Delios Andrew , Chen Richard Z. , Miller Saylor , Wan Xue , Zhang Stephen X.
Published: June 2021

Aims

The Covid-19 pandemic has had a substantial impact on the mental health of the general public and high-risk groups worldwide. Due to its proximity and close links to China, Southeast Asia was one of the first regions to be affected by the outbreak. The aim of this systematic review was to evaluate the prevalence of anxiety, depression and insomnia in the general adult population and healthcare workers (HCWs) in Southeast Asia during the course of the first year of the pandemic.

Methods

Several literature databases were systemically searched for articles published up to February 2021 and two reviewers independently evaluated all relevant studies using pre-determined criteria. The prevalence rates of mental health symptoms were calculated using a random-effect meta-analysis model.

Results

In total, 32 samples from 25 studies with 20,352 participants were included. Anxiety was assessed in all 25 studies and depression in 15 studies with pooled prevalence rates of 22% and 16% respectively. Only two studies assessed insomnia, which was estimated at 19%. The prevalence of anxiety and depression was similar amongst frontline HCWs (18%), general HCWs (17%), and students (20%) whilst being noticeably higher in the general population (27%).

Conclusions

This is the first systematic review to investigate the mental health impact of the Covid-19 pandemic in Southeast Asia. A considerable proportion of the general population and HCWs reported mild to moderate symptoms of anxiety and depression; the pooled prevalence rater, however, remain significantly lower than those reported in other areas such as China and Europe.