Synaptic wiring motifs in posterior parietal cortex support decision-making.

The posterior parietal cortex exhibits choice-selective activity during perceptual decision-making tasks1-10. However, it is not known how this selective activity arises from the underlying synaptic connectivity. Here we combined virtual-reality behaviour, two-photon calcium imaging, high-throughput electron microscopy and circuit modelling to analyse how synaptic connectivity between neurons in the posterior parietal cortex relates to their selective activity. We found that excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity. In turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif. This motif was present even between neurons with activity peaks in different task epochs. We developed neural-circuit models of the computations performed by these motifs, and found that opponent inhibition between neural populations with opposite selectivity amplifies selective inputs, thereby improving the encoding of trial-type information. The models also predict that opponent inhibition between neurons with activity peaks in different task epochs contributes to creating choice-specific sequential activity. These results provide evidence for how synaptic connectivity in cortical circuits supports a learned decision-making task.

Preoperative Planning Software Does Not Accurately Predict Range of Motion in Reverse Total Shoulder Arthroplasty.

BACKGROUND: The purpose of this study was to determine whether preoperative planning software (PPS) accurately predicts clinical range of motion (ROM) in patients with reverse total shoulder arthroplasty 1 year postoperatively with preoperative and postoperative computed tomography (CT) scans. METHODS: This was a retrospective study of 16 reverse total shoulder arthroplasty patients with preoperative and postoperative (CT) scans obtained at least 1 year postoperatively. Clinical ROM was measured in abduction, external rotation at resting abduction, extension, and flexion at a minimum of 1 year postoperatively. All clinical measurements were obtained before generation of PPS ROM values. Using postoperative CT scans, the achieved implant component positions were quantified and then replicated in PPS on the preoperative CT scans. The preoperative predicted ROM was then recorded, both with and without osteophyte removal. Bland-Altman plots were generated within each motion comparing the differences between clinically measured motion and software-predicted motion. RESULTS: The variation in clinically measured ROM in abduction, external rotation at resting abduction, extension, and flexion were 118 ± 27 (65° to 180°), 33 ± 16 (10° to 75°), 56 ± 8 (50° to 65°), and 137 ± 25 (80° to 160°), respectively. Clinically measured motion differed greatly from PPS-predicted ROM, with mean differences of 33 ± 29 (-32 to 93) for abduction, 44 ± 25 (-38 to 57) for external rotation, 44 ± 25 (-35 to 65) for extension, and 54 ± 50 (-51 to 147) for flexion with no significant correlations between clinically measured and PPS-predicted ROM ( P > 0.05). With humeral or humeral and glenoid osteophyte resection, correlations for only flexion became significant ( P = 0.002 for both). CONCLUSION: The passive glenohumeral impingement-free ROM generated from PPS incompletely predicts clinically measured active humerothoracic ROM, possibly because of the unmeasured factors of soft-tissue tension, muscular strength, humeral torsion, resting scapular posture, and, most importantly, scapulothoracic motion. LEVEL OF EVIDENCE: IV.

Early single sport specialization does not improve pitching velocity, motion, strength, or utilization in high school baseball pitchers.

Background: The impact of single-sport specialization on performance and injury risk in youth and adolescent athletes remains debated. The purpose of this study was to determine the incidence of single-sport specialization and its association with pitch velocity, pitcher utilization, range of motion, strength, and injury history. Methods: High school pitchers in the Northeastern, Southeastern, Midwestern, and Western Regions of the United States were prospectively recruited. Prior to the season, pitchers were surveyed about their basic demographics, sport participation history, and injury history. At this timepoint, a standardized physical examination was performed and max pitch velocity was measured. They were then prospectively followed over the ensuing high school season, where pitch utilization and counts were followed and injuries were tracked. Results: Across the study, 115 pitchers were recruited, of whom 53% played baseball as their only sport and 47% played other sports. Single- position specialization within baseball was uncommon as 90% of athletes played positions other than pitcher. There were no differences in range of motion, strength, or pitch velocity between multisport athletes and single-sport specialists. Within the multisport group, 26% reported a history of injury, while 38% of the single-sport specialists reported a history of injury (P = .179). There were no significant differences in pitcher utilization between multisport athletes and single-sport specialists. Only a single prospective injury occurred in the 115 players. Conclusion: Although single-sport specialization is common, nearly half of all high school pitchers in this study were multisport athletes. While injury history was generally similar between the two groups, single-sport baseball players did not have the following: improved motion, increased strength, higher ball velocity, or greater pitching volumes during the high school baseball season compared to multisport athletes. Accordingly, single-sport specialization did not have a competitive advantage for these high school pitchers based on the performance factors studied. Further prospective studies are necessary to understand the association between single-sport specialization and injury risk in high school baseball players.

Revision Subpectoral Biceps Tenodesis Demonstrates a High Patient Satisfaction and Good Functional Outcomes.

Purpose: To clinically evaluate a subset of patients who underwent a revision subpectoral biceps tenodesis for a clinically failed proximal biceps tenodesis. Methods: This is a retrospective case series of patients with at least 2-year follow-up who had undergone a revision biceps tenodesis after clinical failure of a proximal biceps tenodesis between January 2008 and February 2020 by a single surgeon. Patients who underwent concomitant procedures, such as revision cuff repair, were excluded. Patients with a minimum of 2 years duration status postrevision subpectoral tenodesis were contacted for informed consent and outcome data, which included Simple Shoulder Test, American Shoulder and Elbow Surgeons score, visual analog scale for pain, and subjective reporting of arm weakness and satisfaction. Results: Fourteen patients were initially identified as meeting inclusion criteria with a minimum 2-year follow-up achieved for 11 of 14 patients (78.5% follow-up). The mean follow-up time was 8.1 years (range, 2.7-14.8 years). After the primary biceps tenodesis, a mean of 8.0 ± 9.6 months passed before the revision subpectoral biceps tenodesis was performed. The average postoperative active forward elevation and adducted external rotation were 159 ± 7° and 47 ± 17°, respectively. The mean ± standard deviation (range) follow-up American Shoulder and Elbow Surgeons score was 79 ± 23 (30-100), Simple Shoulder Test was 11 ± 2 (7-12), and visual analog scale for pain was 2.6 ± 2.8 (0-9). All 11 patients reported being satisfied with their operation and would elect to have the operation again. Conclusions: Revision subpectoral biceps tenodesis is a viable procedure for addressing patients with persistent pain following initial proximal biceps tenodesis. Although some persistent pain is common, revision subpectoral biceps tenodesis demonstrates a high patient satisfaction and good functional outcomes. Level of Evidence: Level IV, therapeutic case series.

Pneumomediastinum as a postinfectious complication of COVID-19 in paediatric patient.

An adolescent boy presented to the clinic with upper chest pain, anterior neck pain and difficulty swallowing 3 weeks following a COVID-19 infection. The pain started a few days before while participating in football practice. He reported no significant trauma or specific incidence when the pain began. His vital signs were stable and within normal limits. There was tenderness to palpation in the upper sternal area and low anterior neck. A chest X-ray was performed and was originally read by the primary care physician as unremarkable. This was followed by the official radiology read, which identified a spontaneous pneumomediastinum. A follow-up CT was confirmatory. The physician recommended rest and minimal activity, and the symptoms gradually resolved in 1 week. A follow-up 1 week after the initial visit revealed complete resolution by radiograph. One week later, a final set of radiographs confirmed sustained resolution of free air in the mediastinum. He was able to gradually return to normal activity.

Structured cerebellar connectivity supports resilient pattern separation.

The cerebellum is thought to help detect and correct errors between intended and executed commands1,2 and is critical for social behaviours, cognition and emotion3-6. Computations for motor control must be performed quickly to correct errors in real time and should be sensitive to small differences between patterns for fine error correction while being resilient to noise7. Influential theories of cerebellar information processing have largely assumed random network connectivity, which increases the encoding capacity of the network's first layer8-13. However, maximizing encoding capacity reduces the resilience to noise7. To understand how neuronal circuits address this fundamental trade-off, we mapped the feedforward connectivity in the mouse cerebellar cortex using automated large-scale transmission electron microscopy and convolutional neural network-based image segmentation. We found that both the input and output layers of the circuit exhibit redundant and selective connectivity motifs, which contrast with prevailing models. Numerical simulations suggest that these redundant, non-random connectivity motifs increase the resilience to noise at a negligible cost to the overall encoding capacity. This work reveals how neuronal network structure can support a trade-off between encoding capacity and redundancy, unveiling principles of biological network architecture with implications for the design of artificial neural networks.

Unsuccessful Chemical Immobilization of a Roan Antelope (Hippotragus equinus) Using a Premixed Medetomidine-Ketamine Combination.

We unsuccessfully attempted to safely chemically immobilize a roan antelope (Hippotragus equinus) with a premixed combination of medetomidine (5 mg/mL) and ketamine (150 mg/mL) for injury treatment. This dose (0.066 mg/kg medetomidine and 1.96 mg/kg ketamine) produced poor quality of immobilization, probably exacerbated by stimulation before completing induction.

Persistence of SARS-CoV-2 neutralizing antibodies longer than 13 months in naturally infected, captive white-tailed deer (Odocoileus virginianus), Texas.

After identifying a captive herd of white-tailed deer in central Texas with >94% seroprevalence with SARS-CoV-2 neutralizing antibodies in September 2021, we worked retrospectively through archived serum samples of 21 deer and detected seroconversion of all animals between December 2020 and January 2021. We then collected prospective samples to conclude that the duration of persistence of neutralizing antibodies is at least 13 months for 19 (90.5%) of the animals, with two animals converting to seronegative after six and eight months. Antibody titres generally waned over this time frame, but three deer had a temporary 4- to 8-fold increases in plaque reduction neutralization test titres over a month after seroconversion; anamnestic response cannot be ruled out.

Improved management of pediatric obesity in the primary care setting through implementation of the healthy care for healthy kids obesity toolkit.

Pediatric obesity has become a major health care concern over the last several decades. This condition can lead to detrimental life-long physical and mental comorbidities. Pediatric primary care providers have a unique opportunity to both prevent and treat pediatric obesity in their clinics. However, discussing this topic with families can be uncomfortable and time consuming. Time efficient resources to educate and increase confidence are needed to improve the management of pediatric obesity. This quality improvement project integrated the Healthy Care for Healthy Kids by the National Institute for Children's Healthcare Quality (2014) into the electronic medical record at a pediatric primary care office in rural East Tennessee. This toolkit included handouts, management algorithms, and provider education for pediatric obesity. After an 8-week implementation period, improvements in lab draws and evaluation of a family''s readiness to change were noted. Overall, providers reported the toolkit was helpful and improved patient interaction. Currently, the clinic is still utilizing the integrated resources and handouts.

Safety and Efficacy of Nalbuphine, Medetomidine, and Azaperone for Immobilizing Aoudad (Ammotragus lervia).

We evaluated the safety and efficacy of nalbuphine (40 mg/mL), plus medetomidine (10 mg/mL), plus azaperone (10 mg/mL) under the premixed label NalMed-A. From January to March 2020, 10 aoudad (Ammotragus lervia) were immobilized via dart-gun for seven separate sampling periods for a total of 45 recorded individual immobilization events. Induction and reversal times with NalMed-A were 5.53±2.61 min and (following atipamezole administration) 5.08±2.43 min while previous studies with alpha-2 agonist-ketamine combinations gave median and average induction times of 4.6 min and 11.2 min using medetomidine-ketamine and xylazine-ketamine, respectively. Overall, NalMed-A adequately immobilized aoudad, with 13% incidence of hyperthermia and 2.22% mortality when delivered via dart.

High Seroprevalence of SARS-CoV-2 in White-Tailed Deer (Odocoileus virginianus) at One of Three Captive Cervid Facilities in Texas.

Free-ranging white-tailed deer (Odocoileus virginianus) across the United States are increasingly recognized for infection and transmission of SARS-CoV-2. Through a cross-sectional study of 80 deer at three captive cervid facilities in central and southern Texas, we provide evidence of 34 of 36 (94.4%) white-tailed deer at a single captive cervid facility seropositive for SARS-CoV-2 by neutralization assay (PRNT90), with endpoint titers as high as 1,280. In contrast, all tested white-tailed deer and axis deer (Axis axis) at two other captive cervid facilities were seronegative, and SARS-CoV-2 RNA was not detected in respiratory swabs from deer at any of the three facilities. These data support transmission among captive deer that cannot be explained by human contact for each infected animal, as only a subset of the seropositive does had direct human contact. The facility seroprevalence was more than double of that reported from wild deer, suggesting that the confined environment may facilitate transmission. Further exploration of captive cervids and other managed animals for their role in the epizootiology of SARS-CoV-2 is critical for understanding impacts on animal health and the potential for spillback transmission to humans or other animal taxa. IMPORTANCE As SARS-CoV-2 vaccine coverage of the human population increases and variants of concern continue to emerge, identification of the epidemiologic importance of animal virus reservoirs is critical. We found that nearly all (94.4%) of the captive white-tailed deer at a cervid facility in central Texas had neutralizing antibodies for SARS-CoV-2. This seroprevalence is over double than that which has been reported from free-ranging deer from other regions of the United States. Horizontal transmission among deer may be facilitated in confinement. Tracking new infections among wild and confined deer is critical for understanding the importance of animal reservoirs for both veterinary and human health.

Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy.

To investigate circuit mechanisms underlying locomotor behavior, we used serial-section electron microscopy (EM) to acquire a synapse-resolution dataset containing the ventral nerve cord (VNC) of an adult female Drosophila melanogaster. To generate this dataset, we developed GridTape, a technology that combines automated serial-section collection with automated high-throughput transmission EM. Using this dataset, we studied neuronal networks that control leg and wing movements by reconstructing all 507 motor neurons that control the limbs. We show that a specific class of leg sensory neurons synapses directly onto motor neurons with the largest-caliber axons on both sides of the body, representing a unique pathway for fast limb control. We provide open access to the dataset and reconstructions registered to a standard atlas to permit matching of cells between EM and light microscopy data. We also provide GridTape instrumentation designs and software to make large-scale EM more accessible and affordable to the scientific community.

Treatment of Brooke-Spiegler Syndrome Trichoepitheliomas with Erbium: Yttrium-Aluminum-Garnet Laser: A Case Report and Review of the Literature.

Patients with Brooke-Spiegler Syndrome (BSS) can present with benign cylindromas, spiradenomas, spiradenocylindromas, and trichoepithelioma. Therapy options include excision, electrocautery, CO2 laser ablation, dermabrasion, and radiofrequency. Here, we present a patient with BSS with multiple trichoepitheliomas who was successfully treated with erbium:yttrium-aluminum-garnet (YAG) laser therapy and review similar cases of BSS treated with a YAG laser modality.

Dense neuronal reconstruction through X-ray holographic nano-tomography.

Imaging neuronal networks provides a foundation for understanding the nervous system, but resolving dense nanometer-scale structures over large volumes remains challenging for light microscopy (LM) and electron microscopy (EM). Here we show that X-ray holographic nano-tomography (XNH) can image millimeter-scale volumes with sub-100-nm resolution, enabling reconstruction of dense wiring in Drosophila melanogaster and mouse nervous tissue. We performed correlative XNH and EM to reconstruct hundreds of cortical pyramidal cells and show that more superficial cells receive stronger synaptic inhibition on their apical dendrites. By combining multiple XNH scans, we imaged an adult Drosophila leg with sufficient resolution to comprehensively catalog mechanosensory neurons and trace individual motor axons from muscles to the central nervous system. To accelerate neuronal reconstructions, we trained a convolutional neural network to automatically segment neurons from XNH volumes. Thus, XNH bridges a key gap between LM and EM, providing a new avenue for neural circuit discovery.

Radiofrequency Therapy and Noncosmetic Cutaneous Conditions.

BACKGROUND: The need for noninvasive methods in treatment of cutaneous disease has continued to evolve exponentially. Amidst the search for technologies, radiofrequency (RF) has proven efficacious in numerous skin disease processes. Although RF is well known for its cosmetic utility, its mechanism is valued in the treatment of many noncosmetic cutaneous conditions of various etiologies. OBJECTIVE: To identify and describe studies in which RF was used to treat noncosmetic skin conditions and to explore the potential of this modality for further application in dermatologic diseases. MATERIALS AND METHODS: The PubMed database was used to find relevant articles. RESULTS: This search strategy yielded 54 articles that met the eligibility criteria. Noncosmetic indications discussed in these articles include varicose veins (n = 10,550), lymphangioma circumscriptum (n = 72), cutaneous neoplasms (n = 42), cutaneous leishmaniasis (n = 743), acne and acne scarring (n = 158), non-acne scarring (n = 43), primary axillary hyperhidrosis (n = 76), and acute and chronic wounds (n = 94). CONCLUSION: Treatment with RF is an effective, generally noninvasive modality with a relatively short postprocedure recovery time and little potential for severe adverse effects in the treatment of several cutaneous conditions. Further clinical studies would prove useful to assess the efficacy and cost-effectiveness of this treatment.

Systematic review of anti-drug antibodies of IL-17 inhibitors for psoriasis.

Three main biologics target the IL-17 pathway; these include secukinumab, ixekizumab, brodalumab, all of which are approved for treatment of moderate-to-severe plaque psoriasis. We performed a systematic review of the literature to determine if IL-17 inhibitors are prone to develop anti-drug antibodies (ADA) and how efficacy of treatment is influenced. A total of 14 papers were reviewed. Only one secukinumab trial detected treatment-emergent ADA in 4 out of 996 (0.41%) patients during the 52-week treatment period. Two of these patients (1 on 150-mg retreatment as needed and 1 on 150-mg fixed interval) were found to have neutralizing antibodies; however, they were not associated with decreased efficacy. One paper reported ADAs against ixekizumab. One out of 1150 (9%) developed titers to ixekizumab after receiving 160-mg-loading dose followed by 80 mg every 2 weeks. Nineteen out of 1150 (1.7%) developed high titer (>1:1280) which impacted clinical outcomes. Three studies did detect ADA against brodalumab; however, none were neutralizing. It is difficult to draw a conclusion from our findings given the variability in ADA development. Most trials did not develop ADA, and if they did, the majority of the time they were not neutralizing. Only ixekizumab showed decreased efficacy, but no increased adverse events in cases with neutralizing ADA.