Pupillary constriction on stimulation of the parietal cortex-A novel finding.

Pupillary changes can be an important semiologic feature in focal epilepsy. Though the subcortical networks involving pupillomotor function have been described, cortical generators of pupillary dilation and constriction in humans are not well known. In this report, we describe a case of pupillary constriction occurring during seizures in a patient with drug resistant focal epilepsy. On stereoelectroencephalography, onset was noted within the posterior segment of the right intraparietal sulcus and direct cortical electrical stimulation of these electrode contacts reproduced pupillary constriction associated with habitual seizures. This is the first case report to describe ictal pupillary constriction during SEEG with confirmation of the cortical localization by direct cortical electrical stimulation. The posterior segment of the right intraparietal sulcus localization of pupillary constriction may aid in surgical evaluation patients with drug resistant focal epilepsy.

Isolated Palsy of the Anterior Interosseous Nerve to Flexor Pollicis Longus, Magnetic Resonance Imaging and Clinical Correlation: A Case Report.

CASE: Anterior interosseous nerve (AIN) palsy is an uncommon, though well-described, clinical entity. When isolated to the thumb, it can be confused with atraumatic rupture of the flexor pollicis longus (FPL) tendon. A 57-year-old man experienced atraumatic onset of difficulty flexing the distal interphalangeal thumb joint. Magnetic resonance imaging (MRI) demonstrated denervation edema of the FPL, suggesting atypical AIN palsy. Resolution of symptoms and MRI findings occurred concomitantly with nonoperative treatment. CONCLUSION: Atypical AIN palsy limited to the FPL is a rare clinical entity whose diagnosis can be supported with MRI. Here, we report a successful case of nonoperative management.

Brodie's abscess as a late complication of external fixation of the distal radius: A case report.

CASE: A 41-year-old male presented with an insidious onset of pain and swelling about the dorsal wrist, and was found to have a Brodie's abscess in the distal radius. The patient had a history of a distal radius fracture, treated with external fixation, nineteen years prior, which we believe contributed to the infection. The patient was treated surgically with abscess irrigation, debridement, bony curettage, bioactive glass S53P4 allograft, with concurrent antibiotic therapy. CONCLUSION: Brodie's abscesses can have atypical presentations, and a thorough history must be obtained from patients to identify any potential sources of infection.

Does Tranexamic Acid Reduce the Need for Hypotensive Anesthesia Within Orthognathic Surgery? A Retrospective Study.

Background: Tranexamic acid (TXA) is utilized frequently in orthognathic surgery to limit blood loss and improve surgical field visualization. This antifibrinolytic has been proven effective with use of concomitant hypotensive anesthesia. Despite proven efficacy, there is a recent push to avoid perioperative hypotensive anesthesia due to risks of organ hypoperfusion, cardiac ischemia and postoperative nausea. Aims: The aim is to study the efficacy and safety of utilizing TXA without controlled hypotensive anesthesia. Methods: The authors identified two cohorts of subjects that underwent bimaxillary orthognathic surgery both with and without TXA administration and compared operative and perioperative variables. A retrospective analysis was completed evaluating intraoperative MAP measurements in subjects treated both with and without TXA using descriptive and bivariate analysis. Results and conclusion: Sixty-three subjects met inclusion criteria. The TXA cohort experienced 11.5% less time under hypotensive anesthesia when compared to the group that did not receive TXA. Additionally, surgical length was decreased by more than 28 min when subjects received TXA. No subjects required a blood transfusion or experienced any TXA-related complications. Given the recommendations to limit hypotensive anesthesia perioperatively, TXA is a useful adjunct in orthognathic surgery to limit controlled hypotensive anesthesia.

Identifying characteristics and clinical conditions associated with hand grip strength in adults: the Project Baseline Health Study.

Low hand grip strength (HGS) is associated with several conditions, but its value outside of the older adult population is unclear. We sought to identify the most salient factors associated with HGS from an extensive list of candidate variables while stratifying by age and sex. We used data from the initial visit from the Project Baseline Health Study (N = 2502) which captured detailed demographic, occupational, social, lifestyle, and clinical data. We applied MI-LASSO using group methods to determine variables most associated with HGS out of 175 candidate variables. We performed analyses separately for sex and age (< 65 vs. ≥ 65 years). Race was associated with HGS to varying degrees across groups. Osteoporosis and osteopenia were negatively associated with HGS in female study participants. Immune cell counts were negatively associated with HGS for male participants ≥ 65 (neutrophils) and female participants (≥ 65, monocytes; < 65, lymphocytes). Most findings were age and/or sex group-specific; few were common across all groups. Several of the variables associated with HGS in each group were novel, while others corroborate previous research. Our results support HGS as a useful indicator of a variety of clinical characteristics; however, its utility varies by age and sex.

Measurable transitions during seizures in intracranial EEG: A stereoelectroencephalography and SPECT study.

OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.

Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation.

Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60 ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5 mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10 mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.

Structure of mavacamten-free human cardiac thick filaments within the sarcomere by cryoelectron tomography.

Heart muscle has the unique property that it can never rest; all cardiomyocytes contract with each heartbeat which requires a complex control mechanism to regulate cardiac output to physiological requirements. Changes in calcium concentration regulate the thin filament activation. A separate but linked mechanism regulates the thick filament activation, which frees sufficient myosin heads to bind the thin filament, thereby producing the required force. Thick filaments contain additional nonmyosin proteins, myosin-binding protein C and titin, the latter being the protein that transmits applied tension to the thick filament. How these three proteins interact to control thick filament activation is poorly understood. Here, we show using 3-D image reconstruction of frozen-hydrated human cardiac muscle myofibrils lacking exogenous drugs that the thick filament is structured to provide three levels of myosin activation corresponding to the three crowns of myosin heads in each 429Å repeat. In one crown, the myosin heads are almost completely activated and disordered. In another crown, many myosin heads are inactive, ordered into a structure called the interacting heads motif. At the third crown, the myosin heads are ordered into the interacting heads motif, but the stability of that motif is affected by myosin-binding protein C. We think that this hierarchy of control explains many of the effects of length-dependent activation as well as stretch activation in cardiac muscle control.

Tobacco-Specific Nitrosamines in Current Commercial Large Cigars, Cigarillos, and Little Cigars.

We measured levels of nitrosonornicotine (NNN) and 4-[methyl(nitroso)amino]-1-(3-pyridinyl)-1-butanone (NNK), the two most carcinogenic tobacco-specific nitrosamines, in the filler, binder, and wrapper of 50 cigars: 19 large cigars, 23 cigarillos, and 8 little cigars. The average NNN and NNK levels were 10.6 and 3.70 µg/g, respectively. These levels are 5- and 7-fold higher, respectively, than those of commercial cigarettes. The differences in NNN and NNK levels between cigars and cigarettes reflect differences in tobacco blends and tobacco treatments, such as fermentation. The average tobacco NNN and NNK levels of large cigars were 3- and 5-fold higher than those of cigarillos and little cigars, respectively. Large cigars also exhibited a significantly broader range of NNN and NNK than cigarillos and little cigars. The NNN and NNK levels in cigarillos are comparable to those of little cigars. These results are consistent with earlier studies finding that cigarillos and little cigars have similar tobacco blends with lower NNN and NNK content than large cigar tobacco blends.

Characterizing Acute Low Back Pain in a Community-Based Cohort.

Acute low back pain (LBP) is a common experience, however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, three acute LBP severity categorization definitions were used based on LBP frequency combined with either 1) pain impact frequency (impact-based) or 2) pain intensity (intensity-based), as well as LBP pain interference frequency (interference only-based) severity categories. The purpose of this manuscript is to describe and then compare these acute LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological. This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios for categorical variables and Hedges' g for continuous variables. Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. The interference-based category did not capture as much variability between acute LBP severity categories. This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute LBP. The robust differences observed between these categorization approaches suggest that how we define acute LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic LBP.

Prior Diagnosis of Opioid-Related Disorder Is Associated With Higher Medical Resource Utilization Following Primary Hip Arthroscopy: A National Database Study.

PURPOSE: To compare adverse events, medical resource utilization, prescribing patterns, and revision surgery rates of patients with opioid-related disorders (ORDs) undergoing primary hip arthroscopy against a propensity-matched group with no opioid-related disorders (NORDs). METHODS: The TriNetX database was queried between January 2015 and December 2020 using International Classification of Diseases, 10th Revision and Current Procedural Terminology codes to identify patients undergoing primary hip arthroscopy between ages 18 and 70 years. The ORD cohort was propensity matched in a 1:1 ratio to NORD patients based on age, sex, alcohol-related disorders, heart disease, hypertension, metabolic disorders, anxiety disorders, major depressive disorder, diabetes mellitus, and antidepressant prescriptions. Postoperative rates of adverse events and medical resources were compared within 90 days of procedure, prescriptions were compared within 1 year, and revision surgery was compared within 2 years. RESULTS: A total of 809 ORD patients were propensity matched in a 1:1 ratio to NORD patients. Postoperative adverse events were similar between groups (P = .693). Rates of revision arthroscopy were also similar for both ORD (9.3%) and NORD (8.0%) cohorts (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.83-1.66; P = .377). ORD patients received care from the emergency department, inpatient admission, outpatient visit, and physical therapy evaluations at higher rates. The ORD cohort received a greater amount of new opioid (OR, 2.66; 95% CI, 2.17-3.26; P < .0001) and antidepressant prescriptions (OR, 1.58; 95% CI, 1.26-1.97; P < .0001) compared to NORD patients within 1 year of surgery. CONCLUSIONS: ORD patients demonstrated similar rates of adverse events and revision surgery when compared to a propensity-matched group of NORD patients undergoing primary hip arthroscopy. However, ORD patients experienced increased rates of emergency department visits and hospitalizations and were prescribed higher rates of opioid and antidepressant prescriptions. LEVEL OF EVIDENCE: Level III, cohort study.

Seventeen-Year National Pain Prevalence Trends Among U.S. Military Veterans.

U.S. military veterans experience higher pain prevalence than nonveterans. However, it is unclear how the disparities in pain prevalence have changed over time because previous trend studies are limited to veterans using the Veterans Health Administration. This repeated cross-sectional study aimed to characterize pain prevalence trends in the overall population of U.S. veterans compared to nonveterans, using nationally representative data. We analyzed 17 years of data from the National Health Interview Survey (2002-2018), with a mean annual unweighted sample of 29,802 U.S. adults (total unweighted n = 506,639) and mean annual weighted population of 229.7 million noninstitutionalized adults. The weighted proportion of veterans ranged from 11.48% in 2002 (highest) to 8.41% in 2017 (lowest). We found that veterans experience a similar or higher prevalence of pain than nonveterans across the study period, except for severe headaches or migraine and facial pain. Pain prevalence among veterans increased over time, with a higher rate of increase compared to nonveterans for all pain variables. From 2002 to 2018, there was an absolute increase (95% confidence interval) in pain prevalence among veterans (severe headache or migraine: 2.0% [1.6-2.4%]; facial pain: 1.9% [1.4-2.4%]; neck pain: 4.7% [4.1-5.2%]; joint pain: 11.4% [10.8-11.9%]; low back pain: 10.3% [9.5-11.1%]; any pain: 10.0% [9.6-10.4%]; and multiple pains: 9.9% [9.2-10.6%]). The continued pain prevalence increase among veterans may have implications for health care utilization, highlighting the need for improved pain prevention and care programs for this population with a disproportionate pain burden. PERSPECTIVE: This article uses routinely-collected cross-sectional data that are nationally representative of U.S. adults to present changes in pain prevalence among military veterans compared to nonveterans. The findings underscore the need for improved prevention and pain care programs for veterans, who experienced a widening disproportionate pain burden from 2002 to 2018.

Zone I Revision Finger Amputations Performed in the Emergency Department Compared With Those Performed in the Operating Room.

Finger amputations are commonly encountered. These may be revised in the emergency department (ED) or the operating room (OR). Previous studies have demonstrated the cost-effectiveness associated with procedures performed in the ED. Patient outcomes have not been described. We retrospectively reviewed patients who presented to our level 1 trauma center with a traumatic partial or complete finger amputation through flexor tendon zone I. All were treated with revision amputation performed in either the ED or the OR between January 2012 and December 2017. A total of 172 patient charts were included. Ninety-three of the revision amputations were performed in the ED, while 79 were performed in the OR. There was no difference in age, race, sex, having a manual labor job, medical comorbidities, or mechanism of injury between the groups. Compared with procedures performed in the ED, procedures performed in the OR had a higher rate of delayed healing, a longer stay in the hospital, and a higher referral to therapy postoperatively. Length of follow-up and number of follow-up visits were not statistically different based on location of procedure. There was no difference in post-procedural infection rate or need for revision procedure between the groups. Our data support the efficacy of performing revision amputation procedures in the ED. Recorded patient complications and subsequent treatment after revision amputations performed in the ED vs the OR were comparable. Those performed in the ED potentially decrease the burden placed on the patient and the health care system. [Orthopedics. 202x;4x(x):xx-xx.].

Cutaneous Sarcoidosis in Bilateral Carpal Tunnel Release Scars: A Case Report.

CASE: A 58-year-old woman with a history of systemic sarcoidosis, 2 years in remission, presented 6 years after bilateral carpal tunnel release with a 3-month history of nodularity, erythema, and tenderness to her bilateral incisions. Histopathology demonstrated noncaseating granulomas without evidence of foreign material or organisms, consistent with infiltrative scar sarcoidosis. Treatment included 4 intralesional corticosteroid injections over 5 months, with progressive resolution of symptoms and no evidence of systemic sarcoidosis reoccurrence. CONCLUSION: Sarcoidosis should be considered when presented with a cutaneous lesion in association with an incisional scar, either as primary presentation or as disease recurrence.

Structure of the Drosophila melanogaster Flight Muscle Myosin Filament at 4.7 Å Resolution Reveals New Details of Non-Myosin Proteins.

Striated muscle thick filaments are composed of myosin II and several non-myosin proteins which define the filament length and modify its function. Myosin II has a globular N-terminal motor domain comprising its catalytic and actin-binding activities and a long α-helical, coiled tail that forms the dense filament backbone. Myosin alone polymerizes into filaments of irregular length, but striated muscle thick filaments have defined lengths that, with thin filaments, define the sarcomere structure. The motor domain structure and function are well understood, but the myosin filament backbone is not. Here we report on the structure of the flight muscle thick filaments from Drosophila melanogaster at 4.7 Å resolution, which eliminates previous ambiguities in non-myosin densities. The full proximal S2 region is resolved, as are the connecting densities between the Ig domains of stretchin-klp. The proteins, flightin, and myofilin are resolved in sufficient detail to build an atomic model based on an AlphaFold prediction. Our results suggest a method by which flightin and myofilin cooperate to define the structure of the thick filament and explains a key myosin mutation that affects flightin incorporation. Drosophila is a genetic model organism for which our results can define strategies for functional testing.

The cryo-EM 3D image reconstruction of isolated Lethocerus indicus Z-discs.

The Z-disk of striated muscle defines the ends of the sarcomere, which repeats many times within the muscle fiber. Here we report application of cryoelectron tomography and subtomogram averaging to Z-disks isolated from the flight muscles of the large waterbug Lethocerus indicus. We use high salt solutions to remove the myosin containing filaments and use gelsolin to remove the actin filaments of the A- and I-bands leaving only the thin filaments within the Z-disk which were then frozen for cryoelectron microscopy. The Lethocerus Z-disk structure is similar in many ways to the previously studied Z-disk of the honeybee Apis mellifera. At the corners of the unit cell are positioned trimers of paired antiparallel F-actins defining a large solvent channel, whereas at the trigonal positions are positioned F-actin trimers converging slowly towards their (+) ends defining a small solvent channel through the Z-disk. These near parallel F-actins terminate at different Z-heights within the Z-disk. The two types of solvent channel in Lethocerus are similar in size compared to those of Apis which are very different in size. Two types of α-actinin crosslinks were observed between oppositely oriented actin filaments. In one of these, the α-actinin long axis is almost parallel to the F-actins it crosslinks. In the other, the α-actinins are at a small but distinctive angle with respect to the crosslinked actin filaments. The utility of isolated Z-disks for structure determination is discussed.