The Effect of Anticoagulant and Antiplatelet Medications on Wide-Awake Hand Surgery: An Analysis of 2,162 Cases.

PURPOSE: The purpose of the study was to determine if perioperative prescription anticoagulant (AC) or antiplatelet (AP) medication use increases the rate of revision surgeries or complications following wide-awake hand surgery performed under local anesthesia. METHODS: All patients who underwent outpatient wide-awake hand surgery under local anesthesia without a tourniquet by two fellowship-trained orthopedic hand surgeons at a single academic practice over a 3-year period were included. Prescription history was reviewed to determine if any prescriptions were filled for an AC/AP drug within 90 days of surgery. All cases requiring revision were identified. Office notes were reviewed to determine postoperative complications and/or postoperative antibiotics prescribed for infection concerns. The number of revisions, complications, and postoperative antibiotic prescriptions were compared between patients who did, and did not, use perioperative AC/AP drugs. RESULTS: A total of 2,162 wide-awake local anesthesia surgeries were included, and there were 128 cases (5.9%) with perioperative AC/AP use. Of the 2,162 cases, 19 cases required revision surgery (18 without AC/AP use and one with AC/AP use). Postoperative wound complications occurred in 42 patients (38 without AC/AP use and four with AC/AP use). Of the wound complications, four were related to postoperative bleeding, one case of incisional bleeding, and three cases of incisional hematomas (three without AC/AP use and one with AC/AP use). None of these patients required additional intervention; their incisional bleeding or hematoma was resolved by their subsequent office visit. Sixty-five patients received postoperative antibiotics for infection concerns (59 without AC/AP use and six with AC/AP use). CONCLUSIONS: Prescription AC/AP medication use in the perioperative period for wide-awake hand surgery performed under local anesthesia was not associated with an increased risk for revision surgery or postoperative wound complications. This study demonstrates the safety of continuing patients' prescribed AC/AP medications during wide-awake hand surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Radiographic Edema Is a Predictor of de Quervain's Tenosynovitis.

Background de Quervain's tenosynovitis (DeQ) is a clinical diagnosis; however, due to the symptom overlap with other pathologies, it can occasionally be challenging to make an accurate diagnosis, especially for nonorthopaedic trained physicians. Questions/Purposes We hypothesized that the ratio of radial-sided to ulnar-sided soft tissue swelling could serve as a universally accessible diagnostic tool to assist in differentiating DeQ from other upper extremity conditions. Patients and Methods We retrospectively identified patients with isolated DeQ (M65.4), thumb carpometacarpal arthritis (M18.X), or carpal tunnel syndrome (G56.0x) between 2018 and 2019. Five blinded, independent reviewers evaluated anterior-posterior radiographs of the affected wrist. A digital caliper was used to measure the shortest distance from the lateral cortex of the distal radius and the medial cortex of the distal ulna to the outer edge of the radial and ulnar soft tissue shadows, respectively. Results The mean radial:ulnar ratio in the DeQ group was significantly larger than in the control groups. The interclass correlation coefficient showed strong agreement between all measurements. Patients with a radial:ulnar ratio of 1.7 or higher had a 61% chance of having DeQ with a 56.5% sensitivity, 66.3% specificity, 59.3% positive predictive value (PPV), and 63.8% negative predictive value. A ratio of more than 2.5 correlates to a 55% chance of having DeQ with a sensitivity of 12.9%, specificity of 96.9%, and PPV of 78.6%. Conclusion The ratio of radial- to ulnar-sided wrist edema can be used as a novel diagnostic aid in DeQ, especially for those not trained in orthopaedics or hand surgery. Level of Evidence Level IV, diagnostic study.

Cardiothoracic surgery training in Africa: History and developments.

Objective: Cardiovascular disease is the leading cause of death globally, responsible for 17.5 million deaths each year, 80% of which occur in low- and middle-income countries, including countries in Africa. Cardiothoracic surgery, with its heavy financial outlay, is unavailable in many African countries. Many African healthcare givers are under the erroneous impression that the cardiovascular surgical landscape of Africa is blank. This review aims at describing the cardiothoracic surgery practice in Africa, the different training programs in the region, and its future prospects. Method: Through a literature review, the authors elaborate on key points, such as healthcare and cardiothoracic surgery in Africa, African cardiothoracic practice and training, and the future of cardiothoracic surgery in Africa. Results: African countries with established cardiothoracic surgery capacity and training programs still face several challenges across multiple levels, including a persistent low enrollment rate in residency programs, insufficient local expertise, a lack of financial resources, an inadequate health infrastructure, and a skewed health insurance reimbursement system. Thus, there is still a growing burden of surgically correctable cardiovascular disease in these countries. Conclusions: Cardiothoracic surgery in Africa has faced great challenges due to resource constraints, but it has demonstrated resilience and growth through diverse models and initiatives. The burden of cardiovascular diseases in Africa remains high, yet the capacity to provide cardiothoracic surgery is limited. With investment, support, and the implementation of comprehensive healthcare policies, cardiothoracic surgery practice can improve in this region and this can make a significant impact on the health and well-being of its population.

Catheter-based pulmonary vein isolation fails to prevent transient atrial arrhythmogenic changes related to acute obstructive respiratory events in a porcine model.

AIMS: Pulmonary vein isolation (PVI) is the corner stone of modern rhythm control strategies in patients with atrial fibrillation (AF). Sleep-disordered breathing (SDB) is prevalent in more than 50% of patients undergoing AF ablation, and studies have indicated a greater recurrence rate after PVI in patients with SDB. Herein, we study the effect of catheter-based PVI on AF in a pig model for SDB. METHODS AND RESULTS: In 11 sedated spontaneously breathing pigs, obstructive apnoeas were simulated by 75 s of intermittent negative upper airway pressure (INAP) applied by a negative pressure device connected to the endotracheal tube. Intermittent negative upper airway pressures were performed before and after PVI. AF-inducibility and atrial effective refractory periods (aERPs) were determined before and during INAP by programmed atrial stimulation. Pulmonary vein isolation prolonged the aERP by 48 ± 27 ms in the right atrium (RA) (P < 0.0001) and by 40 ± 34 ms in the left atrium (LA) (P = 0.0004). Following PVI, AF-inducibility dropped from 28 ± 26% to 0% (P = 0.0009). Intermittent negative upper airway pressure was associated with a transient aERP-shortening (ΔaERP) in both atria, which was not prevented by PVI (INAP indued ΔaERP after PVI in the RA: -57 ± 34 ms, P = 0.0002; in the LA: -42 ± 24 ms, P < 0.0001). Intermittent negative upper airway pressure was associated with a transient increase in AF-inducibility (from 28 ± 26% to 69 ± 21%; P = 0.0008), which was not attenuated by PVI [INAP-associated AF-inducibility after PVI: 58 ± 33% (P = 0.5)]. CONCLUSION: Transient atrial arrhythmogenic changes related to acute obstructive respiratory events are not prevented by electrical isolation of the pulmonary veins, which partially explains the increased AF recurrence in patients with SDB after PVI procedures.

Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study.

PURPOSE: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown. METHODS: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. RESULTS: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. CONCLUSION: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association.

Electrocardiographic markers in patients with type 2 diabetes and the role of diabetes duration.

BACKGROUND: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. METHODS: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. RESULTS: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. CONCLUSIONS: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.

Strategies for knee stabilising and pivot-shift avoidance in a step-down and cross-over task observed sub-acutely after anterior cruciate ligament reconstruction.

BACKGROUND: Individuals with a recent anterior cruciate ligament reconstruction may demonstrate an altered movement strategy for protecting the knee and maintaining stability. Altered knee movement might lead to abnormal intra-articular load, potentially contributing to early knee osteoarthritis onset. A protective strategy may be particularly evident during active tasks that induce a pivot-shift manoeuvre, such as a step-down and cross-over task. In this study, we investigated whether knee joint mechanics and muscle activity differed between participants early (∼3 months) following reconstruction (n = 35) to uninjured controls (n = 35) during a step-down and cross-over task with a 45° change-of-direction. METHODS: We used motion capture, force plates and surface electromyography to compare time-normalised curves of sagittal and transverse-plane knee mechanics and muscle activity during the cross-over phase between groups using functional t-tests. We also compared knee mechanics between sides within the injured group and compared discrete outcomes describing the cross-over phase between groups. FINDINGS: Compared to controls, the injured participants had greater knee flexion angle and moment, lower internal rotation moment, more preparatory foot rotation of the pivoting leg, a smaller cross-over angle, and a longer cross-over phase for both the injured and uninjured sides. The injured leg also had greater biceps femoris and vastus medialis muscle activity compared to controls and different knee mechanics than the uninjured leg. INTERPRETATION: Individuals with anterior cruciate ligament reconstruction showed a knee-stabilising and pivot-shift avoidance strategy for both legs early in rehabilitation. These results may reflect an altered motor representation and motivate considerations early in rehabilitation.

Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.

Screw Position Following Percutaneous Versus Mini-Open Intramedullary Retrograde Screw Fixation of Metacarpal Fractures.

BACKGROUND: Metacarpal fracture fixation using the retrograde intramedullary screw technique can be performed through two different approaches. The mini-open approach requires greater soft tissue dissection but allows for direct visualization of the metacarpal head compared with the percutaneous approach. Our aim was to determine which approach resulted in optimal screw position. METHODS: Eighty-one consecutive patients that underwent intramedullary screw fixation for metacarpal fractures from 2016 to 2021 were identified. Patients were treated by 4 fellowship-trained orthopedic hand surgeons who employed the mini-open or percutaneous approach. Postoperative radiographs were reviewed for screw position. RESULTS: A total of 81 patients (41 mini-open, 40 percutaneous) were included in this study. There were no significant differences between the two groups in age, sex, hand dominance, or affected digit. Postoperative screw position at first postoperative visit was not significantly different between the two groups on anteroposterior or lateral radiographs. CONCLUSION: Postoperative screw position is not significantly different between the mini-open and percutaneous approaches for intramedullary screw fixation of metacarpal fractures. LEVEL OF EVIDENCE: Level III, therapeutic.

Engineering Saccharomyces cerevisiae for targeted hydrolysis and fermentation of glucuronoxylan through CRISPR/Cas9 genome editing.

BACKGROUND: The abundance of glucuronoxylan (GX) in agricultural and forestry residual side streams positions it as a promising feedstock for microbial conversion into valuable compounds. By engineering strains of the widely employed cell factory Saccharomyces cerevisiae with the ability to directly hydrolyze and ferment GX polymers, we can avoid the need for harsh chemical pretreatments and costly enzymatic hydrolysis steps prior to fermentation. However, for an economically viable bioproduction process, the engineered strains must efficiently express and secrete enzymes that act in synergy to hydrolyze the targeted polymers. RESULTS: The aim of this study was to equip the xylose-fermenting S. cerevisiae strain CEN.PK XXX with xylanolytic enzymes targeting beechwood GX. Using a targeted enzyme approach, we matched hydrolytic enzyme activities to the chemical features of the GX substrate and determined that besides endo-1,4-ß-xylanase and ß-xylosidase activities, α-methyl-glucuronidase activity was of great importance for GX hydrolysis and yeast growth. We also created a library of strains expressing different combinations of enzymes, and screened for yeast strains that could express and secrete the enzymes and metabolize the GX hydrolysis products efficiently. While strains engineered with BmXyn11A xylanase and XylA ß-xylosidase could grow relatively well in beechwood GX, strains further engineered with Agu115 α-methyl-glucuronidase did not display an additional growth benefit, likely due to inefficient expression and secretion of this enzyme. Co-cultures of strains expressing complementary enzymes as well as external enzyme supplementation boosted yeast growth and ethanol fermentation of GX, and ethanol titers reached a maximum of 1.33 g L- 1 after 48 h under oxygen limited condition in bioreactor fermentations. CONCLUSION: This work underscored the importance of identifying an optimal enzyme combination for successful engineering of S. cerevisiae strains that can hydrolyze and assimilate GX. The enzymes must exhibit high and balanced activities, be compatible with the yeast's expression and secretion system, and the nature of the hydrolysis products must be such that they can be taken up and metabolized by the yeast. The engineered strains, particularly when co-cultivated, display robust growth and fermentation of GX, and represent a significant step forward towards a sustainable and cost-effective bioprocessing of GX-rich biomass. They also provide valuable insights for future strain and process development targets.

Spatiotemporal lower-limb asymmetries during stair descent in athletes following anterior cruciate ligament reconstruction.

PURPOSE: This study evaluated motor control recovery at different times following anterior cruciate ligament reconstruction (ACLR) by investigating lower-limb spatiotemporal symmetry during stair descent performances. METHODS: We used a cross-sectional design to compare asymptomatic athletes (Controls, n = 18) with a group of people with ACLR (n = 49) divided into three time-from-ACLR subgroups (Early: <6 months, n = 17; Mid: 6-18 months, n = 16; Late: ≥18 months, n = 16). We evaluated: "temporal symmetry" during the stance subphases (single-support, first and second double-support) and "spatial symmetry" for hip-knee-ankle intra-joint angular displacements during the stance phase using a dissimilarity index applied on superimposed 3D phase plots. RESULTS: We found significant between-group differences in temporal variables (p ≤ 0.001). Compared to Controls, both Early and Mid (p ≤ 0.05) showed asymmetry in the first double-support time (longer for their injured vs. non-injured leg), while Early generally also showed longer durations in all other phases, regardless of stepping leg. No statistically significant differences were found for spatial intra-joint symmetry between groups. CONCLUSION: Temporal but not spatial asymmetry in stair descent is often present early after ACLR; it may remain for up to 18 months and may underlie subtle intra- and inter-joint compensations. Spatial asymmetry may need further exploration.

Asymmetric loading strategies during squats following anterior cruciate ligament reconstruction: A longitudinal investigation with curve analyses throughout and after rehabilitation.

Investigations of kinetic asymmetries during bilateral squats following anterior cruciate ligament reconstruction (ACLR) are limited to mainly cross-sectional studies and discrete value data extracted at specific knee angles. We assessed loading asymmetries during squats longitudinally throughout rehabilitation using curve analysis and compared patient-reported outcome measures (PROMs) between those with and without asymmetry. Bodyweight squats were performed by 24 individuals (13 females) post-ACLR on three occasions: (1) Early 2.9 (1.1) months; (2) Mid 8.8 (3.1) months; (3) at Return to Sport (RTS) 13.1 (3.6) months; and 29 asymptomatic controls (22 females) once. Time-normalized between-leg asymmetry curves of sagittal plane hip, knee, and ankle moments and vertical ground reaction forces were compared using functional data analysis methods. Individual asymmetrical loading for ACLR was classified when exceeding the 95% confidence interval of controls during ≥50% of the squat. At Early, ACLR had greater asymmetry than controls for knee (15%-100% eccentric phase; 0%-100% concentric) and ankle flexion moments (56%-65% concentric). At Mid, ACLR had greater asymmetry for knee (41%-72% eccentric) and ankle flexion moments (56%-69% concentric). No between-group differences were found at RTS. From Early to RTS, ACLR reduced asymmetry for hip (21%-46% eccentric), knee (27%-58% concentric), and ankle flexion moments (21%-57% eccentric). At Early, 11/24 underloaded their ACLR knee and 1 overloaded compared with controls. At RTS, 4 underloaded and 6 overloaded. No differences in PROMs were found based on loading asymmetry. Beyond the early phase of rehabilitation from ACLR, individual-level analyses are required to reveal differing loading strategies during bilateral squats.

Trigger Finger Release: Are Sutures Requiring Removal Necessary?

Purpose: There is no consensus regarding optimal closure for trigger finger release (TFR) surgery. The purpose of this study was to compare the number of postoperative visits and complications following TFR closure with nonabsorbable sutures versus those following TFR closure with absorbable sutures and skin glue. The hypothesis was that wound closure with absorbable sutures and glue will result in fewer postoperative visits, while having similar complication rates as that with nonabsorbable sutures. Methods: A retrospective review identified all patients undergoing open TFR over a 3-year period performed by two hand surgery fellowship-trained hand surgeons who adhered to an identical surgical protocol except for incisional closure. Patients were divided into two groups: a control group with nonabsorbable 4-0 monofilament sutures requiring removal ("suture" group) and a study group with buried absorbable 4-0 monofilament sutures not requiring removal as well as skin glue ("glue" group). The data collected included age, sex, number of postoperative visits, wound complications, infections, antibiotic use, prescribed hand therapy, hospital admission, and reoperation. Results: A total of 305 open TFR surgeries in 278 patients were included in the study, with 155 digits in the "suture" group and 150 in the "glue" group. Both groups were similar in age and sex. The "suture" group had significantly more total postoperative visits (185 vs 42, respectively, P < .001) and postoperative visits within the first 2 weeks (155 vs 10, respectively, P < .001) than the "glue" group. Additional postoperative visits beyond 2 weeks of surgery were similar between the two groups. Three (1.9%) patients in the "suture" group and two (1.3%) patients in the "glue" group developed a superficial surgical site infection within 30 days after surgery. Neither had deep infections requiring hospitalization or reoperation. Both groups required similar rates of postoperative hand therapy. Conclusions: Absorbable sutures afford fewer postoperative visits while having a similar complication rate as nonabsorbable sutures requiring removal. Type of study/level of evidence: Therapeutic IV.

Ventricular tachycardia and in-hospital mortality in the intensive care unit.

Background: Continuous electrocardiographic (ECG) monitoring is used to identify ventricular tachycardia (VT), but false alarms occur frequently. Objective: The purpose of this study was to assess the rate of 30-day in-hospital mortality associated with VT alerts generated from bedside ECG monitors to those from a new algorithm among intensive care unit (ICU) patients. Methods: We conducted a retrospective cohort study in consecutive adult ICU patients at an urban academic medical center and compared current bedside monitor VT alerts, VT alerts from a new-unannotated algorithm, and true-annotated VT. We used survival analysis to explore the association between VT alerts and mortality. Results: We included 5679 ICU admissions (mean age 58 ± 17 years; 48% women), 503 (8.9%) experienced 30-day in-hospital mortality. A total of 30.1% had at least 1 current bedside monitor VT alert, 14.3% had a new-unannotated algorithm VT alert, and 11.6% had true-annotated VT. Bedside monitor VT alert was not associated with increased rate of 30-day mortality (adjusted hazard ratio [aHR] 1.06; 95% confidence interval [CI] 0.88-1.27), but there was an association for VT alerts from our new-unannotated algorithm (aHR 1.38; 95% CI 1.12-1.69) and true-annotated VT(aHR 1.39; 95% CI 1.12-1.73). Conclusion: Unannotated and annotated-true VT were associated with increased rate of 30-day in-hospital mortality, whereas current bedside monitor VT was not. Our new algorithm may accurately identify high-risk VT; however, prospective validation is needed.

Comparing the efficiency of forward and backward contact tracing.

Tracing potentially infected contacts of confirmed cases is important when fighting outbreaks of many infectious diseases. The COVID-19 pandemic has motivated researchers to examine how different contact tracing strategies compare in terms of effectiveness (ability to mitigate infections) and cost efficiency (number of prevented infections per isolation). Two important strategies are so-called forward contact tracing (tracing to whom disease spreads) and backward contact tracing (tracing from whom disease spreads). Recently, Kojaku and colleagues reported that backward contact tracing was "profoundly more effective" than forward contact tracing, that contact tracing effectiveness "hinges on reaching the 'source' of infection," and that contact tracing outperformed case isolation in terms of cost efficiency. Here we show that these conclusions are not true in general. They were based in part on simulations that vastly overestimated the effectiveness and efficiency of contact tracing. Our results show that the efficiency of contact tracing strategies is highly contextual; faced with a disease outbreak, the disease dynamics determine whether tracing infection sources or new cases is more impactful. Our results also demonstrate the importance of simulating disease spread and mitigation measures in parallel rather than sequentially.

Dynamic Amygdala Nuclei Alterations in Relation to Weight Status in Anorexia Nervosa Are Mediated by Leptin.

OBJECTIVE: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels. METHOD: T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n = 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n = 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n = 271) using linear mixed effects models. RESULTS: Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d = 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei. CONCLUSION: Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN. PLAIN LANGUAGE SUMMARY: The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weight-restoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Recognition and reconstruction of cell differentiation patterns with deep learning.

Cell lineage decisions occur in three-dimensional spatial patterns that are difficult to identify by eye. There is an ongoing effort to replicate such patterns using mathematical modeling. One approach uses long ranging cell-cell communication to replicate common spatial arrangements like checkerboard and engulfing patterns. In this model, the cell-cell communication has been implemented as a signal that disperses throughout the tissue. On the other hand, machine learning models have been developed for pattern recognition and pattern reconstruction tasks. We combined synthetic data generated by the mathematical model with spatial summary statistics and deep learning algorithms to recognize and reconstruct cell fate patterns in organoids of mouse embryonic stem cells. Application of Moran's index and pair correlation functions for in vitro and synthetic data from the model showed local clustering and radial segregation. To assess the patterns as a whole, a graph neural network was developed and trained on synthetic data from the model. Application to in vitro data predicted a low signal dispersion value. To test this result, we implemented a multilayer perceptron for the prediction of a given cell fate based on the fates of the neighboring cells. The results show a 70% accuracy of cell fate imputation based on the nine nearest neighbors of a cell. Overall, our approach combines deep learning with mathematical modeling to link cell fate patterns with potential underlying mechanisms.

Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification.

Generating primordial germ cell-like cells (PGCLCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but often entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days. We use our simplified differentiation platform and single-cell RNA-sequencing to achieve further insights into PGCLC specification. Transient WNT activation for 12 h followed by WNT inhibition specified PGCLCs; by contrast, sustained WNT induced primitive streak. Thus, somatic cells (primitive streak) and PGCLCs are related-yet distinct-lineages segregated by temporally-dynamic signaling. Pluripotency factors including NANOG are continuously expressed during the transition from pluripotency to posterior epiblast to PGCs, thus bridging pluripotent and germline states. Finally, hPSC-derived PGCLCs can be easily purified by virtue of their CXCR4+PDGFRA-GARP- surface-marker profile and single-cell RNA-sequencing reveals that they harbor transcriptional similarities with fetal PGCs.

The Effect of Percutaneous Retrograde Metacarpal Intramedullary Screw Insertion on the Extensor Tendon.

PURPOSE: Both limited-open and percutaneous techniques have been described for retrograde insertion of intramedullary metacarpal screws. The percutaneous approach does not allow direct visualization of the starting point at the metacarpal head. However, it limits soft tissue dissection and expedites the procedure. The purpose of our study was to determine whether percutaneous, retrograde intramedullary screw fixation causes substantial iatrogenic damage to the extensor tendon. We also investigated whether larger sized screws would cause greater tendon injury compared to smaller screws. METHODS: Eight fresh frozen cadaver hands were used for percutaneous, retrograde intramedullary screw insertion of the index, long, ring, and small finger metacarpals of each specimen. Three different types of headless compression screws were used: a small fully threaded screw, a large fully threaded screw, and a Herbert-style partially threaded screw. After insertion, dissection was carried down to the screw entry site. Extensor tendon damage was evaluated, including tendon defect size and any irregularities noted in the tendon. RESULTS: There was no statistical difference with respect to how frequently a screw perforated the extensor tendons between all four finger metacarpals. Overall, the defect width caused by the screw was minimal, ranging from 0.66 mm to 1.89 mm for all finger and screw types. The large style screw did cause the greatest mean defect width, however, this was not statistically significant. When normalized to total tendon width, the defect was less than 28% of the total tendon width, with an average of 20% for all finger and screw types. Upon gross inspection, there was no fraying or irregularity noted at the screw-tendon insertion site, and it was often difficult to identify the screw entry site through the tendon by direct visualization alone. No tendon ruptures were noted. CONCLUSIONS: This study found that percutaneous insertion of a retrograde, intramedullary metacarpal screw causes minimal extensor tendon injury. In contrast to the limited-open approach, the percutaneous technique requires less soft tissue dissection and the possibility of reduced swelling, scarring, and risk of adhesions. Moreover, it has the potential to allow for early functional rehabilitation and reduced operative time. Interestingly, none of the tendons demonstrated fraying or rupture, as one might expect to occur with blind passage of a drill and screw through a tendon. Overall, the percutaneous, retrograde intramedullary screw technique appears to cause minimal iatrogenic injury to the extensor tendon.