Treatments for COVID-19.

The treatment for COVID-19 has evolved rapidly since the start of the pandemic and now consists mainly of antiviral and immunomodulatory agents. Antivirals, such as remdesivir and nirmatrelvir-ritonavir, have proved to be most useful earlier in illness (e.g., as outpatient therapy) and for less severe disease. Immunomodulatory therapies, such as dexamethasone and interleukin-6 or Janus kinase inhibitors, are most useful in severe disease or critical illness. The role of anti-SARS-CoV-2 monoclonal antibodies has diminished because of the emergence of viral variants that are not anticipated to be susceptible to these treatments, and there still is not a consensus on the use of convalescent plasma. COVID-19 has been associated with increased rates of venous thromboembolism, but the role of antithrombotic therapy is limited. Multiple investigational agents continue to be studied, which will alter current treatment paradigms as new data are released.

Analysis of the Infectious Diseases Fellowship Program Directors Postmatch 2023 Survey.

The 2023 United States infectious diseases (ID) fellowship match resulted in a large percentage of programs with unfilled positions. A survey was sent to ID program directors nationwide to better understand their perceptions on the match. Program directors perceived geography, a small applicant pool, and low specialty pay as contributing factors to the match results. Developing specialized fellowship tracks, increasing funding for the ID trainee pipeline, and national advocacy for higher compensation were identified as areas to focus on to increase the applicant pool. Areas of controversy, such as decreasing the number or size of fellowship programs, require further discussion.

Application of Tendon With Z-Lengthening Technique.

Tendon deficiency limits repair and reconstructive options after tendon and nerve injuries of the upper extremity. Current treatment options include intercalary tendon autograft, tendon transfers, and two-stage tenodesis, with sacrifice of the flexor digitorum superficialis. These reconstructive techniques are associated with donor site morbidity and limited in the setting of multiple tendon deficiencies. The tendon with z-lengthening (TWZL) technique is presented here as an alternative treatment method for tendon injuries and tendon transfer reconstruction after nerve injuries. The TWZL technique involves splitting a tendon longitudinally, reflecting the freed tendon limb distally, and suture augmentation at the bridge site located at the distal end of the native tendon. The TWZL technique has applications throughout the upper extremity-flexor and extensor tendons injuries, biceps and triceps tendon injuries, and tendon transfers for restoration of hand function after nerve injuries. An illustrative case example is also provided. The experienced hand surgeon should consider the TWZL technique as a potential treatment option when faced with difficult clinical conditions of the hand and upper extremities.

Weight-Bearing Computed Tomography of the Foot and Ankle in the Pediatric Population.

BACKGROUND: Newer cone-beam computed tomography (CT) technology has grown in popularity for evaluation of foot and ankle pathology in the weight-bearing (WB) position. Many studies have demonstrated its benefits within the adult population, but there is a paucity of its use within the pediatric literature. The purpose of this study was to describe the indications and clinical findings of WBCT within a pediatric population. METHODS: A retrospective cohort of 68 patients (86 extremities) who underwent WBCT for a variety of conditions were compared with 48 patients (59 extremities) who underwent traditional supine nonweight-bearing (NWB) CTs. Clinical indications, demographic data, radiation doses, and cost were obtained from the medical record. WBCTs were obtained in a private outpatient orthopaedic clinic, and the conventional NWBCTs were obtained within a hospital-based system. RESULTS: The most common indications for obtaining a WBCT and NWBCT in our study were fracture, tarsal coalition, and Lisfranc injury. The average WBCT radiation dose was 0.63 mGy for patients <100 lbs and 1.1 mGy for patients >100 lbs undergoing WBCT. For NWBCTs, the average radiation dose was 7.92 mGy for patients <100 lbs and 10.37 mGy for patients greater than 100 lbs. There was a significant reduction in radiation dose for all patients who underwent WBCT (P<0.0001 vs. 0.002). The average reimbursement for NWBCTs was $505 for unilateral studies and $1451 for bilateral studies. The average reimbursement for the WBCTs was $345 for unilateral studies and $635 for bilateral studies. CONCLUSIONS: WBCT offers a new modality for studying complex foot and ankle pathoanatomy in the pediatric population at a reduced radiation exposure and reduced cost. LEVEL OF EVIDENCE: Level III-a retrospective comparative study.

Starch storage capacity of sapwood is related to dehydration avoidance during drought.

PREMISE: The xylem tissue of plants performs three principal functions: transport of water, support of the plant body, and nutrient storage. Tradeoffs may arise because different structural requirements are associated with different functions or because suites of traits are under selection that relate to resource acquisition, use, and turnover. The structural and functional basis of xylem storage is not well established. We hypothesized that greater starch storage would be associated with greater sapwood parenchyma and reduced fibers, which would compromise resistance to xylem tensions during dehydration. METHODS: We measured cavitation resistance, minimum water potential, starch content, and sapwood parenchyma and fiber area in 30 species of southern California chaparral shrubs (evergreen and deciduous). RESULTS: We found that species storing greater starch within their xylem tended to avoid dehydration and were less cavitation resistant, and this was supported by phylogenetic independent contrasts. Greater sapwood starch was associated with greater parenchyma area and reduced fiber area. For species without living fibers, the associations with parenchyma were stronger, suggesting that living fibers may expand starch storage capacity while also contributing to the support function of the vascular tissue. Drought-deciduous species were associated with greater dehydration avoidance than evergreens. CONCLUSIONS: Evolutionary forces have led to an association between starch storage and dehydration resistance as part of an adaptive suite of traits. We found evidence for a tradeoff between tissue mechanical traits and starch storage; moreover, the evolution of novel strategies, such as starch-storing living fibers, may mitigate the strength of this tradeoff.

Reduction of the Spin Susceptibility in the Superconducting State of Sr_{2}RuO_{4} Observed by Polarized Neutron Scattering.

Recent observations [A. Pustogow et al., Nature (London) 574, 72 (2019).NATUAS0028-083610.1038/s41586-019-1596-2] of a drop of the ^{17}O nuclear magnetic resonance (NMR) Knight shift in the superconducting state of Sr_{2}RuO_{4} challenged the popular picture of a chiral odd-parity paired state in this compound. Here we use polarized neutron scattering (PNS) to show that there is a 34±6% drop in the magnetic susceptibility at the Ru site below the superconducting transition temperature. We measure at lower fields H∼1/3H_{c2} than a previous PNS study allowing the suppression to be observed. The PNS measurements show a smaller susceptibility suppression than NMR measurements performed at similar field and temperature. Our results rule out the chiral odd-parity d=z[over ^](k_{x}±ik_{y}) state and are consistent with several recent proposals for the order parameter including even-parity B_{1g} and odd-parity helical states.

Detection of Acoustic Plasmons in Hole-Doped Lanthanum and Bismuth Cuprate Superconductors Using Resonant Inelastic X-Ray Scattering.

High T_{c} superconductors show a rich variety of phases associated with their charge degrees of freedom. Valence charges can give rise to charge ordering or acoustic plasmons in these layered cuprate superconductors. While charge ordering has been observed for both hole- and electron-doped cuprates, acoustic plasmons have only been found in electron-doped materials. Here, we use resonant inelastic x-ray scattering to observe the presence of acoustic plasmons in two families of hole-doped cuprate superconductors (La_{1.84}Sr_{0.16}CuO_{4} and Bi_{2}Sr_{1.6}La_{0.4}CuO_{6+δ}), crucially completing the picture. Interestingly, in contrast to the quasistatic charge ordering which manifests at both Cu and O sites, the observed acoustic plasmons are predominantly associated with the O sites, revealing a unique dichotomy in the behavior of valence charges in hole-doped cuprates.

Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates.

We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k_{z} dispersion is observed along the nodal direction, whereas a significant antinodal k_{z} dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La_{2-x}Sr_{x}CuO_{4} cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.

Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT.

BACKGROUND: Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. METHODS: Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy-Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. RESULTS: Compared to CON, EX had a reduced time to complete a processing speed test (trail making test-A) (-14.2 seconds, P < .01; effect size 0.35). Compared to CON, there was no improvement in self-reported cognitive function and effect sizes were small. Interestingly, lack of between-group differences in Stroop behavioral performance was accompanied by functional changes in several brain regions of interest in EX compared to CON at 24 weeks. CONCLUSION: These findings provide preliminary proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment and will serve to inform the development of future trials.

Technique of Dynamic Flexor Digitorum Superficialis Transfer to Lateral Bands for Proximal Interphalangeal Joint Deformity Correction in Severe Dupuytren Disease.

Pseudo-boutonniere deformity is an uncommon complication from long-standing proximal interphalangeal (PIP) joint contracture in Dupuytren disease. Prolonged flexion contracture of the PIP joint can lead to central slip attenuation and resultant imbalances in the extensor mechanism. We present a technique of flexor digitorum superficialis (FDS) tendon transfer to the lateral bands to correct pseudo-boutonniere deformity at the time of palmar fasciectomy for the treatment of Dupuytren disease. The FDS tendon is transferred from volar to dorsal through the lumbrical canal and sutured into the dorsally mobilized lateral bands. This technique presents an approach to the repair of pseudo-boutonniere deformity in Dupuytren disease.

Cost Analysis of Sending Routine Pathology Specimens following Total Joint Arthroplasty in the Age of Bundled Payments.

Bundled payment plans are being developed as a means to curb healthcare spending. Routine histology following total hip arthroplasties (THA) and total knee arthroplasties (TKA) is standard practice at many institutions. Recently, the value of this practice has been questioned as histologic diagnoses in THA and TKA rarely differ from the clinical diagnoses. The goal of this study is to identify discrepant and discordant diagnoses following THA and TKA at an academic medical center and to calculate the cost-saving potential in the setting of a bundled payment plan. A retrospective chart review was conducted on 1,213 primary THA and TKA performed by two orthopaedic surgeons from 2012 to 2014. The clinical and histologic diagnoses were compared and classified as concordant, discrepant, or discordant. Cost information was obtained from the institutional billing office. One thousand one hundred and sixty-six THA and TKA were analyzed in the final cohort. Nineteen (1.6%) diagnoses were classified as discrepant while none were discordant. The cost of histologic examination per specimen was estimated to be $48.56. The total cost of all arthroplasties was $14,999,512.46, of which histologic examination made up 0.31% of the total cost. The results of this study corroborate the results of previous studies and support the proposition that routine histologic examination is not cost-effective. The cost incurred to perform histologic examination will become a cost deduction from future bundled payments. The practice of sending routine histologic specimens following TJA should be decided upon by the operating orthopaedic surgeon.

Field-tunable spin-density-wave phases in Sr3Ru2O7.

The conduction electrons in a metal experience competing interactions with each other and the atomic nuclei. This competition can lead to many types of magnetic order in metals. For example, in chromium the electrons order to form a spin-density-wave (SDW) antiferromagnetic state. A magnetic field may be used to perturb or tune materials with delicately balanced electronic interactions. Here, we show that the application of a magnetic field can induce SDW magnetic order in a quasi-2D metamagnetic metal, where none exists in the absence of the field. We use magnetic neutron scattering to show that the application of a large (B ≈ 8 T) magnetic field to the perovskite metal Sr3Ru2O7 (refs 3-7) can be used to tune the material through two magnetically ordered SDW states. The ordered states exist over relatively small ranges in field (≲0.4 T), suggesting that their origin is due to a new mechanism related to the electronic fine structure near the Fermi energy, possibly combined with the stabilizing effect of magnetic fluctuations. The magnetic field direction is shown to control the SDW domain populations, which naturally explains the strong resistivity anisotropy or 'electronic nematic' behaviour observed in this material.

Structural determinants of increased susceptibility to dehydration-induced cavitation in post-fire resprouting chaparral shrubs.

It is well established that transpiration and photosynthetic rates generally increase in resprouting shoots after fire in chaparral shrublands. By contrast, little is known about how plant hydraulic function varies during this same recovery period. We hypothesized that vascular traits, both functional and structural, would also shift in order to support this heightened level of gas exchange and growth. We examined stem xylem-specific hydraulic conductivity (Ks ) and resistance to cavitation (P50 ) for eight chaparral shrub species as well as several potential xylem structural determinants of hydraulic function and compared established unburned plants and co-occurring post-fire resprouting plants. Unburned plants were generally more resistant to cavitation than resprouting plants, but the two groups did not differ in Ks . Resprouting plants had altered vessel structure compared with unburned plants, with resprouting plants having both wider diameter vessels and higher inter-vessel pit density. For biomechanics, unburned plants had both stronger and denser stem xylem tissue than resprouting plants. Shifts in hydraulic structure and function resulted in resprouting plants being more vulnerable to dehydration. The interaction between time since disturbance (i.e. resprouting versus established stands) and drought may complicate attempts to predict mortality risk of resprouting plants.

Educational effectiveness of gynaecological teaching associates: a multi-centre randomised controlled trial.

OBJECTIVE: To evaluate, among medical students learning the female pelvic examination, the added benefits of training by gynaecological teaching associates compared with training involving a manikin only. DESIGN: Randomised controlled trial. SETTING: Nine university teaching hospitals. POPULATION: Ninety-four medical students recruited prior to commencing a 4-week obstetrics and gynaecology rotation. METHODS: The control training consisted of lectures, demonstration of the pelvic examination on a manikin, and opportunities to practise on this low-fidelity simulation (n = 40). The experimental group received additional gynaecological teaching associate training, delivered by pairs of experienced associates to groups of four medical students (n = 54). MAIN OUTCOME MEASURES: Outcomes measured at the end of the rotation included knowledge of the correct order of examination components (Yes/No), and student comfort [Likert scales anchored between 1 (very uncomfortable) and 4 (very comfortable) on four items] and confidence [Likert scales anchored between 1 (No) and 3 (Yes) on six items]. The primary outcome, measured at the end of the academic year, was the objective structured clinical examination of a female pelvis (score range 0-54). RESULTS: At baseline, the groups were similar in age, gender, and ethnicity. At the end of the clinical rotation, when compared with the control intervention, the experimental intervention had a moderate effect on student knowledge [difference 29.9% (95% CI 11.2-48.6%); P = 0.002] and confidence [difference 1 (95% CI 0-2); P < 0.001], and a large effect on student comfort [difference 1.8 (95% CI 0.6-3.0); P = 0.004]. At the end of the academic year, the experimental intervention had no impact on skills compared with the control [difference 2 (95% CI-1 to 4); P = 0.26]. CONCLUSIONS: Among medical students taught the female pelvic examination by low-fidelity simulation, additional training by gynaecology teaching associates improved knowledge, comfort, and confidence at the end of the clinical rotation but did not improve examination skills at end of the academic year.

Critical role of a buried interface in the Stranski-Krastanov growth of metallic nanocrystals: quantum size effects in Ag/Si(111)-(7×7).

We show that the buried interface between a metallic nanocrystal and its supporting substrate is essential for understanding the stability of the ubiquitous class of nanomaterials that grow on a wetting layer in the Stranski-Krastanov growth mode. Importantly, these new results reveal the broad role played by quantum confinement effects in the growth of thin nanoscale metals. In situ x-ray scattering experiments on Ag/Si(111)-(7×7), where the apparent minimum stable thickness of the first two atomic layers on top of the wetting layer has posed a long-standing puzzle, show that the commensurate wetting layer is locally removed by the formation of incommensurate nanoislands, which is unanticipated for the conventional Stranski-Krastanov growth mode. The anomalous lattice expansion that had been previously proposed is not observed, and these new results for Ag are explained by electron confinement effects whose manifestation differs from other metals.

The utility of blow fly (Diptera: Calliphoridae) evidence from burned human remains.

Burning of human remains is a common method to conceal or destroy evidence associated with homicides and illegal activities. However, data regarding blow fly colonization of burned remains are scarce, with all previously published empirical studies focusing only on non-human animals. It is critically important to obtain basic data on blow fly colonization patterns of burned human remains as such evidence may represent the only feasible method for PMI estimation in cases of burning. In this study, we thermally altered six human donors to a Crow-Glassman Scale Level 3 (CGS-3) and placed them at the Anthropology Research Facility at the University of Tennessee in Summer 2021, Spring 2022, and Summer 2022. Six unburned human donors were used as controls. Observations for insect activity began within 24 h of placement and continued twice weekly through decomposition. Age estimations were performed with immature blow flies to estimate the time of colonization (TOC), and accuracy was assessed against the time of placement for each donor. All burned donors examined in this study were colonized by blow flies. No significant difference in species composition was determined between treatments, though TOC estimations from burned donors were slightly (but significantly) less accurate than TOC estimations from unburned donors (80% vs. 83% accuracy; χ2 = 0.041, df = 1, P = 0.840). These results indicate that blow flies can successfully colonize human remains burned to CGS-3 and that accurate TOC estimations can still be generated from larval specimens. Though several limitations to this study exist (e.g., inconsistent donor BMI, lack of donor temperature data), our results underscore the utility of entomological evidence in cases of burned human remains.

HMGB1 restores a dynamic chromatin environment in the presence of linker histone by deforming nucleosomal DNA.

The essential architectural protein HMGB1 increases accessibility of nucleosomal DNA and counteracts the effects of linker histone H1. However, HMGB1 is less abundant than H1 and binds nucleosomes more weakly raising the question of how HMGB1 effectively competes with H1. Here, we show that HMGB1 rescues H1's inhibition of nucleosomal DNA accessibility without displacing H1. HMGB1 also increases the dynamics of condensed, H1-bound chromatin. Cryo-EM shows that HMGB1 binds at internal locations on a nucleosome and locally distorts the DNA. These sites, which are away from the binding site of H1, explain how HMGB1 and H1 co-occupy a nucleosome. Our findings lead to a model where HMGB1 counteracts the activity of H1 by distorting nucleosomal DNA and by contacting the H1 C-terminal tail. Compared to direct competition, nucleosome co-occupancy by HMGB1 and H1 allows a greater diversity of dynamic chromatin states and may be generalizable to other chromatin regulators.

X-ray diffraction observations of a charge-density-wave order in superconducting ortho-II YBa2Cu3O6.54 single crystals in zero magnetic field.

X-ray diffraction measurements show that the high-temperature superconductor YBa2Cu3O6.54, with ortho-II oxygen order, has charge-density-wave order in the absence of an applied magnetic field. The dominant wave vector of the charge density wave is q(CDW)=(0,0.328(2),0.5), with the in-plane component parallel to the b axis (chain direction). It has a similar incommensurability to that observed in ortho-VIII and ortho-III samples, which have different dopings and oxygen orderings. Our results for ortho-II contrast with recent high-field NMR measurements, which suggest a commensurate wave vector along the a axis. We discuss the relationship between spin and charge correlations in YBa2Cu3O(y) and recent high-field quantum oscillation, NMR, and ultrasound experiments.

Management of Gout in the Hand and Wrist.

Gout, or monosodium urate deposition disease, is the most common form of inflammatory arthritis that affects almost 4% of adults in the United States.Medical management involves lifestyle modifications and urate-lowering therapy to reduce the frequency of gout flares, decrease the tophi size, and improve upper extremity function. Goals for surgical management of gout include functional optimization, symptomatic treatment, and cosmetic restoration.This article focuses on the medical and surgical treatment of the common manifestations of gout in the upper extremity including tophi, tenosynovitis, joint contractures, neural compression, and arthropathy.

C3a-C3aR signaling is a novel modulator of skeletal homeostasis.

Osteoimmune studies have identified complement signaling as an important regulator of the skeleton. Specifically, complement anaphylatoxin receptors (i.e., C3aR, C5aR) are expressed on osteoblasts and osteoclasts, implying that C3a and/or C5a may be candidate mediators of skeletal homeostasis. The study aimed to determine how complement signaling influences bone modeling/remodeling in the young skeleton. Female C57BL/6J C3aR-/-C5aR-/- vs. wildtype and C3aR-/- vs. wildtype mice were examined at age 10 weeks. Trabecular and cortical bone parameters were analyzed by micro-CT. In situ osteoblast and osteoclast outcomes were determined by histomorphometry. Osteoblast and osteoclast precursors were assessed in vitro. C3aR-/-C5aR-/- mice displayed an increased trabecular bone phenotype at age 10 weeks. In vitro studies revealed C3aR-/-C5aR-/- vs. wildtype cultures had less bone-resorbing osteoclasts and increased bone-forming osteoblasts, which were validated in vivo. To determine whether C3aR alone was critical for the enhanced skeletal outcomes, wildtype vs. C3aR-/- mice were evaluated for osseous tissue outcomes. Paralleling skeletal findings in C3aR-/-C5aR-/- mice, C3aR-/- vs. wildtype mice had an enhanced trabecular bone volume fraction, which was attributed to increased trabecular number. There was elevated osteoblast activity and suppressed osteoclastic cells in C3aR-/- vs. wildtype mice. Furthermore, primary osteoblasts derived from wildtype mice were stimulated with exogenous C3a, which more profoundly upregulated C3ar1 and the pro-osteoclastic chemokine Cxcl1. This study introduces the C3a/C3aR signaling axis as a novel regulator of the young skeleton.