Designing 2D stripe winding network through crown-ether intermediate Ullmann coupling on Cu(111) surface.

Chemical synthesis typically yields the most thermodynamically stable ordered arrangement, a principle also governing surface synthesis on an atomically level two-dimensional (2D) surface, fostering the creation of structured 2D formations. The linear connection arising from energetically stable chemical bonding precludes the generation of a 2D random network comprised of one-dimensional (1D) convoluted stripes through on-surface synthesis. Nonetheless, we underscored that on-surface synthesis possesses the capability not solely to fashion a 2D ordered linear network but also to fabricate a winding 2D network employing a precursor with a soft ring and intermediate state bonding within the Ullmann reaction. Here, on-surface synthesis was exhibited on Cu(111) employing a 2D self-assembled monolayer array of 4,4',5,5'-tetrabromodibenzo[18]crown-6 ether (BrCR) precursors. These precursors were purposefully structured, with a crown ether ring at the core and Br atoms positioned at the head and tail ends, facilitating preferential connections along the elongated axis to foster a 1D stripe configuration. We illustrate how adjustments in the quantities of the intermediate state, serving as a primary linkage, can yield a labyrinthine, convoluted winding 2D network of stripes. The progression of growth, underlying mechanisms, and electronic structures were scrutinized using an ultrahigh vacuum low-temperature scanning tunneling microscopy and spectroscopy (STM/STS) setup combined with density functional theory (DFT) calculations. This experimental evidence opens a novel functionality in leveraging on-surface synthesis for the formation of a 2D random network. This discovery holds promise as a pioneering constituent in the construction of a ring host supramolecule, augmenting its capability to ensnare guest atoms, molecules, or ions.

S.P.O.R.R.T.-A Comprehensive Approach to the Assessment and Non-Operative Management of Overuse Knee Conditions in Youth Athletes.

PURPOSE OF REVIEW: The evaluation of a young athlete with an overuse injury to the knee involves a comprehensive approach. There are a number of elements to consider including assessments of skeletal maturity (biologic maturation), workload (training load + competition load), sport specialization status, and biomechanics. The type of injury and treatment, as well as future prognosis, may be influenced by these and other factors. RECENT FINDINGS: Calculating the percentage of predicted adult height (PPAH) is a valuable tool in assessing overuse injury patterns and diagnoses in youth athletes. Modifiable and non-modifiable overuse injury risk factors require monitoring from clinicians as young athletes mature and develop over time. Training and rehabilitation programs should be adapted to account for these. In this manuscript, we seek to introduce a novel, comprehensive approach: S.P.O.R.R.T. (Skeletal Maturity, Prior Injury Risk, One Sport Specialization, Rehabilitation, Return to Play, Training Recommendations) (Fig. 1). Overuse, non-traumatic injuries to the knee in youth athletes will be presented in a case-based and evidence-based model to provide a framework for a comprehensive approach to the assessment and treatment of youth athletes with overuse injuries.

Application of the International Classification of Functioning principles to guide rehabilitation following hemipelvectomy in an adolescent with Li-Fraumeni syndrome: A case report.

This case report details the complex case of an adolescent patient with chondroblastic osteosarcoma in the setting of Li-Fraumeni syndrome, leading to hemipelvectomy and post-operative complications. International Classification of Functioning principles were used as a roadmap for optimization of functional restoration and transition of care coordination.

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.

BACKGROUND: Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle.

PURPOSE: Exercise intolerance, evaluated by O2 consumption, predicts mortality in cystic fibrosis (CF). People with CF exhibit skeletal muscle dysfunctions that may contribute to an imbalance between O2 delivery and utilization. Sildenafil, a phosphodiesterase type 5 inhibitor, increases blood flow and improves O2 consumption, although the exact mechanisms in CF have yet to be elucidated. Thus, we hypothesized that exercise intolerance in CF is limited primarily by an impaired skeletal muscle O2 utilization, and sildenafil improves exercise tolerance in CF by addressing this mismatch between O2 demand and extraction. METHODS: Fifteen individuals with mild to moderate CF and 18 healthy controls completed an incremental exercise test and measurements of gaseous exchange, chronotropic response, hemodynamics, and O2 extraction and utilization. People with CF also completed a 4-wk treatment with sildenafil with a subsequent follow-up evaluation after treatment. RESULTS: Skeletal muscle O2 extraction and utilization during exercise were reduced in people with CF when compared with controls. Exercise capacity in our CF population was minimally limited by hemodynamic or chronotopic responses, whereas peripheral O2 extraction was more closely associated with exercise capacity. The study also demonstrated that 4 wk of sildenafil improved skeletal muscle O2 utilization during exercise to similar values observed in healthy individuals. CONCLUSIONS: Individuals with mild to moderate CF exhibit exercise intolerance secondary to a reduction in O2 utilization by the exercising skeletal muscle. The present study demonstrated that 4 wk of sildenafil treatment improves the capacity of the skeletal muscle to use O2 more efficiently during exercise. Findings from the present study highlight the importance of targeting skeletal muscle O2 utilization to improve exercise tolerance in CF.

Antibody Clicking as a Strategy to Modify Antibody Functionalities on the Surface of Targeted Cells.

We established a methodology for initiating cross-linking of antibodies selectively on the cell surface through intermolecular copper-free click reactions facilitated by increased effective concentrations of antibodies binding to target antigens. Upon cross-linking of tetrazine- and bicyclononyne-modified trastuzumab on the surface of HER2-overexpressing cells, increased antibody uptake and activation of intracellular signaling were observed. Our findings demonstrate that the cross-linking reaction can significantly alter the biophysical properties of proteins, activating their unique functionalities on targeted cells to realize an increased cargo delivery and synthetic manipulation of cellular signaling.

Sildenafil improves exercise capacity in patients with cystic fibrosis: a proof-of-concept clinical trial.

BACKGROUND: Exercise intolerance is a common phenotype observed in patients with cystic fibrosis (CF). Treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has previously been shown to improve exercise capacity (VO2 peak) in other patient populations. Thus, the present study sought to determine the acute and subacute effects of sildenafil on exercise capacity in patients with CF. METHODS: The present investigation utilized a randomized, double-blind, placebo-controlled, crossover study with an acute dose of either sildenafil (50 mg) or placebo (n = 13, age 25 ± 10), followed by a 4 week open-label extension with sildenafil (20 mg, TID; n = 15, age 23 ± 11). A comprehensive evaluation of pulmonary function and a maximal exercise test were each performed at every visit. RESULTS: A significant increase in VO2 peak was observed after the acute sildenafil dose with no changes following placebo (77 ± 13 versus 72 ± 13% predicted; p = 0.033). In addition, after 4 weeks of treatment, patients showed a significant increase in exercise capacity (72 ± 12 versus 75 ± 12% predicted; p = 0.028) and exercise duration (409 ± 98 versus 427 ± 101 s; p = 0.014). A robust correlation (r = 0.656; p = 0.008) between baseline FEV1 (% predicted) and the change in exercise capacity following 4 weeks of treatment was identified. CONCLUSIONS: This proof-of-concept clinical trial demonstrates that sildenafil treatment can improve exercise capacity in patients with CF and that pulmonary function may play an important role in the effectiveness of treatment. Future investigations of sildenafil treatment in patients with CF are certainly warranted.