Batteryless wireless magnetostrictive Fe30Co70/Ni clad plate for human coronavirus 229E detection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been garnered increasing for its rapid worldwide spread. Each country had implemented city-wide lockdowns and immigration regulations to prevent the spread of the infection, resulting in severe economic consequences. Materials and technologies that monitor environmental conditions and wirelessly communicate such information to people are thus gaining considerable attention as a countermeasure. This study investigated the dynamic characteristics of batteryless magnetostrictive alloys for energy harvesting to detect human coronavirus 229E (HCoV-229E). Light and thin magnetostrictive Fe-Co/Ni clad plate with rectification, direct current (DC) voltage storage capacitor, and wireless information transmission circuits were developed for this purpose. The power consumption was reduced by improving the energy storage circuit, and the magnetostrictive clad plate under bending vibration stored a DC voltage of 1.9 V and wirelessly transmitted a signal to a personal computer once every 5 min and 10 s under bias magnetic fields of 0 and 10 mT, respectively. Then, on the clad plate surface, a novel CD13 biorecognition layer was immobilized using a self-assembled monolayer of -COOH groups, thus forming an amide bond with -NH2 groups for the detection of HCoV-229E. A bending vibration test demonstrated the resonance frequency changes because of HCoV-229E binding. The fluorescence signal demonstrated that HCoV-229E could be successfully detected. Thus, because HCoV-229E changed the dynamic characteristics of this plate, the CD13-modified magnetostrictive clad plate could detect HCoV-229E from the interval of wireless communication time. Therefore, a monitoring system that transmits/detects the presence of human coronavirus without batteries will be realized soon.

Early manipulation under anaesthesia for stiffness following total knee arthroplasty is associated with a greater gain in knee flexion.

PURPOSE: This study aimed to identify the risk factors for manipulation under anaesthesia (MUA) following total knee arthroplasty (TKA) and whether performing an 'early' MUA within 3 months leads to a greater improvement in range of motion. METHODS: Primary TKAs performed between 2013 and 2018 at three tertiary New Zealand hospitals were reviewed with a minimum follow-up of 1 year. Clinical details of patients who underwent MUA were reviewed to identify the knee flexion angle prior to and following MUA. Multivariate analysis identified the risk factors for undergoing MUA and compared flexion angles between 'early' (< 3 months) and 'late' MUA (> 3 months). RESULTS: A total of 7386 primary TKAs were analysed in which 131 underwent an MUA (1.8%). Patients aged < 65 years were two times more likely to undergo MUA compared to patients aged ≥ 65 years (2.5 versus 1.3%, p < 0.001; adjusted HR = 2.1, p < 0.001). There was no difference in the final flexion angle post-MUA between early and late MUA (104.7° versus 104.1°, p = 0.819). However, patients who underwent early MUA had poorer pre-MUA flexion (72.3° versus 79.6°, p = 0.012), and subsequently had a greater overall gain in flexion compared to those who underwent late MUA (mean gain 33.1° versus 24.3°, p < 0.001). CONCLUSION: Younger age was the only patient risk factor for MUA. Patients who underwent early MUA had similar post-MUA flexion, but had poorer pre-MUA flexion compared to those who underwent late MUA. Subsequently, a greater overall gain in flexion was achieved in those who underwent early MUA. LEVEL OF EVIDENCE: III.

Nonsteroidal Anti-Inflammatory Drugs and Oral Corticosteroids Mitigated the Risk of Arthrofibrosis After Total Knee Arthroplasty.

BACKGROUND: The role of medications to prevent arthrofibrosis following total knee arthroplasty (TKA) remains unclear. We investigated the effect of common oral medications with reported antifibrotic properties on preventing arthrofibrosis and manipulation under anesthesia (MUA) following primary TKA. METHODS: Using our total joint registry, 9,771 patients (12,735 knees) who underwent TKA with cemented, posterior-stabilized, and metal-backed tibial components from 2000 to 2016 were identified. Arthrofibrosis, defined as range of motion (ROM) ≤90° for ≥12 weeks postoperatively or as ROM ≤90° requiring MUA, was diagnosed in 454 knees (4%) and matched 1:2 to controls. Mean age was 62 years (range, 19 to 87) and 57% were women. The majority of operative diagnoses were osteoarthritis. Perioperative use of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), oral corticosteroids, antihistamines, and nonsteroidal anti-inflammatory drugs (NSAIDs) were manually confirmed. Medication effect in preventing arthrofibrosis and MUA was assessed using adjusted multivariable analyses. Mean follow-up was 8 years (range, 2 to 20). RESULTS: Reduced risk of arthrofibrosis was associated with perioperative NSAID use (odds ratio (OR) 0.67, P = .045). A similar trend was observed with perioperative corticosteroids (OR 0.52, P = .098). Corticosteroids were associated with reduced risk of MUA (OR 0.26, P = .036), and NSAIDs trended towards reducing MUA (OR 0.69, P = .11). CONCLUSION: This investigation determined that perioperative NSAID use was associated with reduced risk of arthrofibrosis and trended towards reduced risk of subsequent MUA. Similarly, oral corticosteroids were associated with reduced risk of MUA and trended towards reduced risk of arthrofibrosis.

Pentylenetetrazol-induced seizures are followed by a reduction in the multiunitary activity of hippocampal CA1 pyramidal neurons in adult rats.

Pentylenetetrazol (PTZ) blocks the inhibitory action of GABA, triggering a Glu-mediated hyperexcitation of the dendritic spines in hippocampal CA1 pyramidal neurons that leads to the generation of epileptiform seizures. The aim of this work was to determine the effect of PTZ on the electrical activity of the hippocampal pyramidal neurons in male rats. Bipolar electrodes were implanted stereotaxically in the right and left hippocampal CA1 fields of adults, and PTZ (65 mg/kg) was administered i.p. Simultaneous recordings of the field activity and the firing rate (multiunitary activity, MUA) were analyzed at 10, 20, and 30 min post-administration of PTZ. Only rats that presented tonic-clonic seizures during the first 1-5 min after PTZ treatment were included in the study. The recordings of the field activity were analyzed in 4 frequency bands. In both the right and left hippocampal CA1 fields, the relative power corresponding to the slow waves (4-7 Hz) increased, while in the bands 13-30 Hz and 31-50 Hz, it decreased at 10, 20, and 30 min post-PTZ. MUA recordings were analyzed at four levels. The highest levels corresponded to larger amplitudes of the action potentials in the pyramidal neurons. The firing rates of the PTZ-treated rats did not differ from baseline but presented a significant decrement at 10, 20, and 30 min post-PTZ. The decreased firing rate of the hippocampal CA1 pyramidal neurons after PTZ treatment could be associated with plastic changes of dendritic spines along with some microenvironmental adaptations at synaptic level, after neuronal PTZ-mediated hyperexcitation.

Computing Extracellular Electric Potentials from Neuronal Simulations.

Measurements of electric potentials from neural activity have played a key role in neuroscience for almost a century, and simulations of neural activity is an important tool for understanding such measurements. Volume conductor (VC) theory is used to compute extracellular electric potentials stemming from neural activity, such as extracellular spikes, multi-unit activity (MUA), local field potentials (LFP), electrocorticography (ECoG), and electroencephalography (EEG). Further, VC theory is also used inversely to reconstruct neuronal current source distributions from recorded potentials through current source density methods. In this book chapter, we show how VC theory can be derived from a detailed electrodiffusive theory for ion concentration dynamics in the extracellular medium, and we show what assumptions must be introduced to get the VC theory on the simplified form that is commonly used by neuroscientists. Furthermore, we provide examples of how the theory is applied to compute spikes, LFP signals, and EEG signals generated by neurons and neuronal populations.

Arthroscopic capsular release versus manipulation under anaesthesia for treating frozen shoulder - a prospective randomised study.

PURPOSE: Arthroscopic capsular release (ACR) and Manipulation under anaesthesia(MUA) have been widely used in the treatment of frozen shoulder (FS). However, there is only limited Level-I evidence to prefer ACR over MUA. The purpose of our study was to conduct a randomised trial comparing ACR versus MUA to assess the difference in outcome, complications and cost-effectiveness of both procedures. METHODS: From May 2020 to June 2021, patients presenting with FS were randomised into two groups ACR (n = 44) and MUA (n = 41). Patients with arthritis, full-thickness cuff tears, history of trauma/previous surgery around the shoulder were excluded from the study. Range of movement (ROM), pain grading using visual analogue scale (VAS), functional scores- UCLA, CONSTANT and EuroQol-5D scores were measured pre-operatively and post-operatively. MRI was done at three weeks post-operatively for screening complications of either procedure. Quality-adjusted life years (QALY) was used for cost-analysis. RESULTS: Post-operatively, patients had significant improvement in pain, ROM and functional scores in both groups (P < 0.001) with no significant difference between groups at 24 weeks of follow-up. Diabetic patients undergoing ACR had lesser improvement in abduction and external rotation when compared to non-diabetic patients. Labral tears in MUA group and bone bruises in ACR group were the most common complications noted on the post-operative MRI. For ACR cost per QALY gained was 896 USD while that for MUA was 424 USD. CONCLUSION: Both ACR and MUA resulted in good improvement in pain and shoulder function. Good outcomes, simple technique and better cost-effectiveness would still make MUA an attractive option over ACR for treating FS.

Highly selective and sensitive sandwich immunosensor platform modified with MUA-capped GNPs for detection of spike Receptor Binding Domain protein: A precious marker of COVID 19 infection.

A label-free electrochemical biosensing system as a suitable analysis technique for COVID 19 specific spike receptor-binding domain protein (RBD) was developed with an aim to facilitate the diagnosis of coronavirus. A novel production procedure for the fabrication of gold nanoparticles (GNPs)-capped 11-mercaptoundecanoic acid (MUA) modified bioelectrode was presented and its application potential for RBD biosensing was examined. The bioelectrode fabrication protocol was based on covalent ester linking formation between hydroxylated ITO electrode and GNPs-capped MUA (GNPs@MUA) with carboxyl ends. For this aim, spherical GNPs were prepared and characterized with scanning-transmission electron microscopy (S-TEM), UV-vis, and Raman spectroscopy. The synthesized GNPs were functionalized with MUA yielding Au-S bonds. Then, covalent immobilization of anti-RBD antibodies on the GNPs@MUA was performed with the help of carbodiimide coupling chemistry. The assembly processes of GNPs@MUA, anti-RBD antibodies and RBD antigens were characterized electrochemical, chemical and morphological techniques. GNPs@MUA was used as immobilization environment and provided the most effective surface design for target immunosensor. The resulting immunosensor is further applied to the impedimetric detection of RBD and it displayed a linear response to RBD antigen in the linear range of 0.002-100 pg mL-1 with a limit of detection of 0.577 fg mL-1 and sensitivity of 0.238 kohmpgmL-1 cm-2. The fabricated immunosensor had a good repeatability, long storage, stability and a reusable property after simple regeneration process. Furthermore, it was successfully employed for selective determination of RBD in artificial nasal secretion samples.

Acquired Idiopathic Stiffness After Contemporary Total Knee Arthroplasty: Incidence, Risk Factors, and Results Over 25 Years.

BACKGROUND: Acquired idiopathic stiffness (AIS) remains a common failure mode of contemporary total knee arthroplasties (TKAs). The present study investigated the incidence of AIS and manipulation under anesthesia (MUA) at a single institution over time, determined outcomes of MUAs, and identified risk factors associated with AIS and MUA. METHODS: We identified 9771 patients (12,735 knees) who underwent primary TKAs with cemented, modular metal-backed, posterior-stabilized implants from 2000 to 2016 using our institutional total joint registry. Mean age was 68 years, 57% were female, and mean body mass index was 33 kg/m2. Demographic, surgical, and comorbidity data were investigated via univariate Cox proportional hazard models and fit to an adjusted multivariate model to access risk for AIS and MUA. Mean follow-up was 7 years. RESULTS: During the study period, 456 knees (3.6%) developed AIS and 336 knees (2.6%) underwent MUA. Range of motion (ROM) increased a mean of 34° after the MUA; however, ROM for patients treated with MUA was inferior to patients without AIS at final follow-up (102° vs 116°, P < .0001). Significant risk factors included younger age (HR 2.3, P < .001), increased tourniquet time (HR 1.01, P < .001), general anesthesia (HR 1.3, P = .007), and diabetes (HR 1.5, P = .001). CONCLUSION: Acquired idiopathic stiffness has continued to have an important adverse impact on the outcomes of a subset of patients undergoing primary TKAs. When utilized, MUA improved mean ROM by 34°, but patients treated with MUA still had decreased ROM compared to patients without AIS. Importantly, we identified several significant risk factors associated with AIS and subsequent MUA. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Developmental excitatory-to-inhibitory GABA polarity switch is delayed in Ts65Dn mice, a genetic model of Down syndrome.

Down syndrome (DS) is the most frequent genetic cause of developmental abnormalities leading to intellectual disability. One notable phenomenon affecting the formation of nascent neural circuits during late developmental periods is developmental switch of GABA action from depolarizing to hyperpolarizing mode. We examined properties of this switch in DS using primary cultures and acute hippocampal slices from Ts65Dn mice, a genetic model of DS. Cultures of DIV3-DIV13 Ts65Dn and control normosomic (2 N) neurons were loaded with FURA-2 AM, and GABA action was assessed using local applications. In 2 N cultures, the number of GABA-activated cells dropped from ~100% to 20% between postnatal days 3-13 (P3-P13) reflecting the switch in GABA action polarity. In Ts65Dn cultures, the timing of this switch was delayed by 2-3 days. Next, microelectrode recordings of multi-unit activity (MUA) were performed in CA3 slices during bath application of the GABAA agonist isoguvacine. MUA frequency was increased in P8-P12 and reduced in P14-P22 slices reflecting the switch of GABA action from excitatory to inhibitory mode. The timing of this switch was delayed in Ts65Dn by approximately 2 days. Finally, frequency of giant depolarizing potentials (GDPs), a form of primordial neural activity, was significantly increased in slices from Ts65Dn pups at P12 and P14. These experimental evidences show that GABA action polarity switch is delayed in Ts65Dn model of DS, and that these changes lead to a delay in maturation of nascent neural circuits. These alterations may affect properties of neural circuits in adult animals and, therefore, represent a prospective target for pharmacotherapy of cognitive impairment in DS.

Sex differences in circadian timing systems: implications for disease.

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.

Effects of neural synchrony on surface EEG.

It has long been assumed that the surface electroencephalography (EEG) signal depends on both the amplitude and spatial synchronization of underlying neural activity, though isolating their respective contribution remains elusive. To address this, we made simultaneous surface EEG measurements along with intracortical recordings of local field potentials (LFPs) in the primary visual cortex of behaving nonhuman primates. We found that trial-by-trial fluctuations in EEG power could be explained by a linear combination of LFP power and interelectrode temporal synchrony. This effect was observed in both stimulus and stimulus-free conditions and was particularly strong in the gamma range (30-100 Hz). Subsequently, we used pharmacological manipulations to show that neural synchrony can produce a positively modulated EEG signal even when the LFP signal is negatively modulated. Taken together, our results demonstrate that neural synchrony can modulate EEG signals independently of amplitude changes in neural activity. This finding has strong implications for the interpretation of EEG in basic and clinical research, and helps reconcile EEG response discrepancies observed in different modalities (e.g., EEG vs. functional magnetic resonance imaging) and different spatial scales (e.g., EEG vs. intracranial EEG).

Postoperative Continuous Passive Motion Does Not Improve the Range of Movement Achieved After Manipulation Under Anesthetic for Stiffness in Total Knee Replacement.

Background: Stiffness is a common complication following total knee arthroplasty. Manipulation under anesthesia (MUA) is an intervention that can potentially improve range of motion (ROM). Continuous passive motion (CPM) therapy has been utilized to enhance post-MUA ROM, but its effectiveness remains debated. This study assesses whether CPM therapy after MUA results in superior ROM outcomes compared to MUA alone. Methods: A retrospective analysis included patients undergoing MUA for stiff primary total knee arthroplasty between 2017 and 2022. Demographics and ROM data were collected. Patients were in 2 groups: those who received inpatient CPM post-MUA and those who received day-case MUA alone. Complications and further interventions were noted. Results: Of 126 patients, 39 underwent MUA only (day-case group), and 87 received CPM and MUA (inpatient group). Mean preoperative ROM was 69.4° (standard deviation [SD]:18.0°) and 73.9° (SD: 18.1°) for inpatient and day-case groups, respectively. Mean post-MUA ROM improved by 39.4° (SD: 17.7°) and 25.5° (SD: 11.1°) inpatient groups and day-case, respectively. The mean percentage of ROM gained at MUA maintained at final follow-up was 63.7% (40.8%) and 67.0% (47.5%) inpatient and day-case groups, respectively. Conclusions: This study found no advantage in the routine use of CPM post-MUA for stiff total knee replacement patients, suggesting it may not provide sustained ROM improvements compared to MUA alone. Cost-effectiveness and patient selection merit further investigation.

Peripheral administration of a κ-opioid receptor agonist nalfurafine inactivates gonadotropin-releasing hormone pulse generator activity in goats.

Neurons co-expressing kisspeptin, neurokinin B, and dynorphin A (KNDy neurons), located in the arcuate nucleus (ARC) of the hypothalamus, are indicated to be the gonadotropin-releasing hormone (GnRH) pulse generator. Dynorphin A is reported to suppress GnRH pulse generator activity. Nalfurafine is a selective agonist of the κ-opioid receptor (KOR), a receptor for dynorphin A, clinically used as an anti-pruritic drug. This study aimed to evaluate the effects of nalfurafine on GnRH pulse generator activity and luteinizing hormone (LH) pulses using female goats. Nalfurafine (0, 2, 4, 8, or 16 µg/head) was intravenously injected into ovariectomized Shiba goats. The multiple unit activity (MUA) in the ARC area was recorded, and plasma LH concentrations were measured 2 and 48 h before and after injection, respectively. The MUA volley interval during 0-2 h after injection was significantly increased in the nalfurafine 8 and 16 µg groups compared with the vehicle group. In 0-2 h after injection, the number of LH pulses was significantly decreased in the nalfurafine 8 and 16 µg groups, and the mean and baseline LH were significantly decreased in all nalfurafine-treated groups (2, 4, 8, and 16 µg) compared with the vehicle group. These results suggest that nalfurafine inhibits the activity of the GnRH pulse generator in the ARC, thus suppressing pulsatile LH secretion. Therefore, nalfurafine could be used as a reproductive inhibitor in mammals.

Prussian blue nanoparticles as nanocargoes for delivering DNA drugs to cancer cells.

We studied the use of Prussian blue nanoparticles (PBNPs) as novel nanocarriers for sending DNA drugs into cancer cells. 11-mercaptoundecanoic acid (MUA) was used to functionalize the surfaces of PBNPs (nanocubes with an average dimension of 75 nm) for subsequent covalent grafting of a 33-mer DNA drug with a FAM reporter at the 3' end. The PBNPs synthesis and DNA drug conjugation were characterized by transmission electron microscopy (TEM) and Fourier-transform infrared absorption (FTIR), respectively. The drug was a decoy oligodeoxynucleotide (dODN) that inhibits the signal transducer and activator of transcription 3 (STAT3). The DNA-PBNPs drug (dODN@MUA-PBNPs) was delivered into human prostate carcinoma 22rv1 cells by endocytosis in vitro as confirmed by confocal fluorescence microscopy. MTT cell viability assays were carried out to assess the effect of the DNA-PBNPs drug. The results showed that the dODN molecules were successfully conjugated to the MUA modified PBNPs via amide and/or disulfide bond formation and could thus be successfully delivered into the cancer cells. The control experiments showed that the unconjugated dODN molecules were not able to enter the cancer cells no matter whether non-functionalized PBNPs were present or not. It was also found that the DNA-PBNPs drugs were internalized and then distributed homogeneously throughout the cell, including cytoplasmic and nucleic regions, after endocytosis. The cancer cell-killing ability increased with the amount of dODN conjugated on PBNPs and the dosage of DNA-PBNPs drug internalized.

Electrophysiological characteristics of CM-pf in diagnosis and outcome of patients with disorders of consciousness.

BACKGROUND: Deep brain stimulation (DBS) in the centromedian-parafascicular complex (CM-pf) has been reported as a potential therapeutic option for disorders of consciousness (DoC). However, the lack of understanding of its electrophysiological characteristics limits the improvement of therapeutic effect. OBJECTIVE: To investigate the CM-pf electrophysiological characteristics underlying disorders of consciousness (DoC) and its recovery. METHODS: We collected the CM-pf electrophysiological signals from 23 DoC patients who underwent central thalamus DBS (CT-DBS) surgery. Five typical electrophysiological features were extracted, including neuronal firing properties, multiunit activity (MUA) properties, signal stability, spike-MUA synchronization strength (syncMUA), and the background noise level. Their correlations with the consciousness level, the outcome, and the primary clinical factors of DoC were analyzed. RESULTS: 11 out of 23 patients (0/2 chronic coma, 5/13 unresponsive wakefulness syndrome/vegetative state (UWS/VS), 6/8 minimally conscious state minus (MCS-)) exhibited an improvement in the level of consciousness after CT-DBS. In CM-pf, significantly stronger gamma band syncMUA strength and alpha band normalized MUA power were found in MCS- patients. In addition, higher firing rates, stronger high-gamma band MUA power and alpha band normalized power, and more stable theta oscillation were correlated with better outcomes. Besides, we also identified electrophysiological properties that are correlated with clinical factors, including etiologies, age, and duration of DoC. CONCLUSION: We provide comprehensive analyses of the electrophysiological characteristics of CM-pf in DoC patients. Our results support the 'mesocircuit' hypothesis, one proposed mechanism of DoC recovery, and reveal CM-pf electrophysiological features that are crucial for understanding the pathogenesis of DoC, predicting its recovery, and explaining the effect of clinical factors on DoC.

Use of Online Newborn Screening Educational Resources for the Education of Expectant Parents: An Improvement in Equity.

Educating parents about the newborn screening (NBS) process is critical in ensuring that families are aware of their child's NBS, which could contribute to better outcomes for the baby and experiences for the family. Successful education efforts result in expecting parents understanding the importance of NBS, feeling comfortable with the NBS process, and being aware of their choices after NBS is complete. Educating parents prenatally is challenging for many NBS programs for a variety of reasons. The COVID-19 pandemic added additional barriers to NBS programs' ability to educate parents prenatally about NBS. By initiating a department-wide partnership among other programs with a similar target audience, Michigan's NBS Program was able to host a virtual baby fair. Since the inaugural event, Michigan's NBS Program has hosted seven virtual fairs with 15 participating programs. A total of 692 participants registered for the baby fair and received a resource packet, over 157 participants joined one of the live presentations, and 211 have viewed the YouTube videos of recorded fairs. Virtual baby fairs are a cost-effective and convenient approach to education that could be implemented in any NBS program to educate parents prenatally about NBS.

Parental acceptability of pediatric forearm manipulations in a UK district hospital emergency department.

Purpose: Pediatric forearm fractures are a common presentation to Accident and Emergency departments. Standard treatment for the majority of these is manipulation under sedation within the department, followed by cast application. Concerns have been raised about the acceptability of such interventions, and reluctance to perform these procedures has led to increased admissions and manipulations performed under general anesthetic. Methods: A prospective case series of all pediatric patients with forearm fractures who underwent a manipulation under sedation in the Accident and Emergency department was collected over 12 months. All parents were invited to complete an acceptability questionnaire, adapted from the Swedish Pyramid Questionnaire for Treatment, based on their experiences. Results: A total of 77 patients were included and their parents were asked to complete a Swedish Pyramid Questionnaire of Treatment. Forty-four parents (55%) agreed to fill out the questionnaire. Patient demographics and fracture characteristics were compared between the group that responded and those that did not, with no significant differences. Average level of satisfaction was 9.4/10 (range = 7-10). 98% of respondents were satisfied with the level of analgesia provided, but only 86% with the timeliness of administration. Conclusion: This parent-focused evaluation of treatment confirms high levels of parental satisfaction with the management of pediatric forearm fractures in Accident and Emergency, with regard to care, analgesia, and information. It provides insights about parental concern relating to the injury and their anxiety as information useful to further improving care, a template for assessing quality improvement and should be considered as part of further studies in this field. Level of evidence: Level IV case series.

Understanding rates, risk factors, and complications associated with manipulation under anesthesia after total knee arthroplasty (TKA): An analysis of 100,613 TKAs.

BACKGROUND: Considering the growing adoption of technology-assisted total knee arthroplasties (TKA), previous database studies evaluating post-operative stiffness may be outdated. The present study aimed to: (1) evaluate the incidence of manipulation under anesthesia (MUA) after primary TKA; (2) determine independent risk factors for MUA; and (3) assess complications after MUA. METHODS: Primary TKAs, with at least 6-month follow-up, were identified from the Florida State Inpatient Database (January 2016-June 2018) and linked to outpatient records from the Florida State Ambulatory Surgery and Services Database. Multivariable regression analyses were performed to compare patient factors and complications (e.g., mechanical, non-mechanical, infectious) associated with MUA, while adjusting for baseline demographics, comorbidities, use of robotic- and computer-technologies, time to MUA (0-3, 3-12, or >12 months), and need for repeat MUA (one-time vs >1). RESULTS: The MUA rate was 2.8% (2821 of 100,613). Being younger, a woman, Black or Hispanic; having private or self-pay insurance; and conventional TKA were associated with significantly higher odds of undergoing MUA. Higher rates of mechanical complications and acute posthemorrhagic anemia were observed in the MUA cohort. Time to MUA, repeat MUA, and baseline demographics were not associated with complication rates among the MUA cohort. CONCLUSION: Overall, 1 in 36 patients underwent MUA after primary TKA. Several non-modifiable patient characteristics, such as Black or Hispanic race, female sex, and younger age were associated with an increased risk of MUA. However, technology-assisted TKA might help to decrease the risk of MUA.

Neural modulations in the auditory cortex during internal and external attention tasks: A single-patient intracranial recording study.

Brain sensory processing is not passive, but is rather modulated by our internal state. Different research methods such as non-invasive imaging methods and intracranial recording of the local field potential (LFP) have been used to study to what extent sensory processing and the auditory cortex in particular are modulated by selective attention. However, at the level of the single- or multi-units the selective attention in humans has not been tested. In addition, most previous research on selective attention has explored externally-oriented attention, but attention can be also directed inward (i.e., internal attention), like spontaneous self-generated thoughts and mind-wandering. In the present study we had a rare opportunity to record multi-unit activity (MUA) in the auditory cortex of a patient. To complement, we also analyzed the LFP signal of the macro-contact in the auditory cortex. Our experiment consisted of two conditions with periodic beeping sounds. The participants were asked either to count the beeps (i.e., an "external attention" condition) or to recall the events of the previous day (i.e., an "internal attention" condition). We found that the four out of seven recorded units in the auditory cortex showed increased firing rates in "external attention" compared to "internal attention" condition. The beginning of this attentional modulation varied across multi-units between 30-50 msec and 130-150 msec from stimulus onset, a result that is compatible with an early selection view. The LFP evoked potential and induced high gamma activity both showed attentional modulation starting at about 70-80 msec. As the control, for the same experiment we recorded MUA activity in the amygdala and hippocampus of two additional patients. No major attentional modulation was found in the control regions. Overall, we believe that our results provide new empirical information and support for existing theoretical views on selective attention and spontaneous self-generated cognition.

MuA-based Molecular Indexing for Rare Mutation Detection by Next-Generation Sequencing.

Detection of low-frequency mutations in cancer genomes or other heterogeneous cell populations requires high-fidelity sequencing. Molecular barcoding is one of the key technologies that enables the differentiation of true mutations from errors, which can be caused by sequencing or library preparation processes. However, current approaches where barcodes are introduced via primer extension or adaptor ligation do not utilize the full power of barcoding, due to complicated library preparation workflows and biases. Here we demonstrate the remarkable tolerance of MuA transposase to the presence of multiple replacements in transposon sequence, and explore this unique feature to engineer the MuA transposome complex with randomised nucleotides in 12 transposon positions, which can be introduced as a barcode into the target molecule after transposition event. We applied the approach of Unique MuA-based Molecular Indexing (UMAMI) to assess the power of rare mutation detection by shortgun sequencing on the Illumina platform. Our results show that UMAMI allows detection of rare mutations readily and reliably, and in this paper we report error rate values for the number of thermophilic DNA polymerases measured by using UMAMI.