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Surgical site infections (SSI) following congenital heart surgery (CHS) remain a significant source of morbidity. Delayed sternal closure (DSC) is often required to minimize the potential for hemodynamic instability. The purpose of this study was to determine the incidence of SSI among patients undergoing DSC versus primary chest closure (PCC) and to define a potential inflection point for increased risk of SSI as a function of open chest duration (OCD).A retrospective review of our institutional Society of Thoracic Surgeons dataset is to identify patients undergoing CHS at our institution between 2015 and 2020. Incidences of SSI were compared between DSC and PCC patients. DSC patients were evaluated to determine the association of OCD and the incidence of SSI.2582 operations were performed at our institution between 2015 and 2020, including 195 DSC and 2387 PCC cases. The incidence of SSI within the cohort was 1.8% (47/2,582). DSC patients had significantly higher incidences of SSI (17/195, 8.7%) than PCC patients (30/2387, 1.3%, p < 0.001). Further, patients with an OCD of four or more days had a significantly higher incidence of SSI (11/62, 17.7%, p = 0.006) than patients with an OCD less than 4 days (6/115, 5.3%).The incidence of SSI following CHS is higher in DSC patients compared to PCC patients. Prolonged OCD of 4 days or more significantly increases the risk of SSI and represents a potentially modifiable risk factor for SSI predisposition. These data support dedicated, daily post-operative assessment of candidacy for chest closure to minimize the risk of SSI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Small-molecule antivirals that prevent the replication of the SARS-CoV-2 virus by blocking the enzymatic activity of its main protease (Mpro) are and will be a tenet of pandemic preparedness. However, the peptidic nature of such compounds often precludes the design of compounds within favorable physical property ranges, limiting cellular activity. Here we describe the discovery of peptide aldehyde Mpro inhibitors with potent enzymatic and cellular antiviral activity. This structure-activity relationship (SAR) exploration was guided by the use of calculated hydration site thermodynamic maps (WaterMap) to drive potency via displacement of waters from high-energy sites. Thousands of diverse compounds were designed to target these high-energy hydration sites and then prioritized for synthesis by physics- and structure-based Free-Energy Perturbation (FEP+) simulations, which accurately predicted biochemical potencies. This approach ultimately led to the rapid discovery of lead compounds with unique SAR that exhibited potent enzymatic and cellular activity with excellent pan-coronavirus coverage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: all authors are current or former employees of Takeda Pharmaceuticals, Inc, Schrödinger, Inc, or Treeline Biosciences, Inc. (see affiliations) and may own shares of stock and/or stock options in these companies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Botryococcene is a branched triterpene produced by the algae Botryococcus braunii. Hydrocracking botryococcene yields a variety of combustible fuels such as gasoline and jet fuel. Engineering host systems and proteins involved in the biosynthesis of botryococcene to optimize production is of interest given these applications. The current study investigates the use of a diaryltetrazole based screen that undergoes a photoclick reaction with terminal alkenes, such as the branched terminal alkene present on botryococcene, to yield a fluorescent product. Host E. coli systems were established to produce botryococcene, squalene, and no triterpene to serve as a control. Cells were incubated with tetrazole and briefly irradiated with UV light to initiate the photoclick reaction. It was found that the botryococcene producing cells yielded observable fluorescence while the squalene and control cells had negligible fluorescence turn-on activity. Fluorescence-activated cell sorting (FACS) was subsequently used to identify and sort botryococcene producing E. coli from a mixture of control and squalene producing cells.

Objectives: To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting., Methods: Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session., Results: Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05)., Conclusions: Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD., Classification of Evidence: This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition., (© 2014 American Academy of Neurology.)

A Fourier-Bessel (FB) basis is used to solve two-dimensional (2D) cylindrical Maxwell's equations for localized states within dielectric structures that possess rotational symmetry. The technique is used to determine the wavelengths and profiles of the stationary states supported by the structure and identify the bandgaps. 12-fold quasi-crystals for the TE and TM polarizations are analyzed. Since the FB approach with 2D photonic crystals in this fashion is new, the accuracy of the results is confirmed using finite-difference time-domain simulations.

The effect of adding a thin high index dielectric overlay layer onto a 3-layer slab waveguide demonstrates several interesting features that can be exploited in integrated optical device configurations. A simple modal analysis is employed to examine the behavior of guided light launched from a 3-layer waveguide structure then coupled and propagated in the 4-layer overlay region. Modal properties typically overlooked in conventional slab waveguides are made use of in the design and theoretical analysis of an MMI device and optical index of refraction sensor. The optical structure presented here can form the backdrop waveguide design for more complex and active devices., (© 2012 Optical Society of America)

Background: Atypical fibroxanthoma (AFX) is an unusual malignant fibrohistiocytic tumor of sun-damaged skin. When first described, it was felt to be a reactive tumor of low malignant potential. More recently, it has been shown to be a tumor of intermediate malignant potential., Objective: To describe five cases of metastatic AFX., Results: Five patients ranging in age from 65 to 85 years old presented with metastatic AFX. Three of the five cases presented with regional lymph node disease. Also, three of the five cases had other aggressive cutaneous malignancies. LN-2 (CD74) staining was positive in three of five primary tumors and two of five metastatic tumors., Conclusion: The metastatic potential of AFX may be underestimated. LN-2 staining may be a useful marker in identifying more aggressive tumor behavior.

The deposition of budesonide at fast (60 l min(-1)) and slow (301 min(-1)) inspiratory flow rates from Airmax, a new multi-dose dry powder inhaler, was compared with that from Turbuhaler and a standard pressurized metered dose inhaler (pMDI). Twelve patients with mild to moderate asthma took part in a five-way randomized crossover study, and inhaled a single nominal dose of 200 microg budesonide, labelled with 99mTc, on each study day. Deposition was determined by gamma scintigraphy. At the fast flow rate, Airmax and Turbuhaler deposited 25.8+/-6.5% (mean +/- sD) and 29.8+/-6.9%, respectively of the delivered dose in the whole lung (P = 0.080). At the slow flow rate, Airmax deposited 28.3+/-5.6%, Turbuhaler 22.7+/-5.6% and pMDI 12.1+/-3.4%. Using data on emitted doses determined in vitro, it was estimated that Airmax deposited 53.1+/-13.3 microg and 43.6+/-8-6 microg budesonide in the lungs at 60 l min(-1) and 30 l min(-1) respectively whilst Turbuhaler deposited 48.3+/-11.2 microg at 60 l min -and 24.2+/-6.0 microg at 30 l min(-1). In conclusion, lung deposition of budesonide from Airmax was comparable to that of Turbuhaler at a high flow rate but was markedly superior to Turbuhaler and pMDI at a lower flow rate. Unlike Turbuhaler, Airmax performs with relative flow-rate independence.

Background: The percentage of family physicians delivering babies decreased from 46% in 1978 to 32% in 1992. Some family practice leaders predicted that, by the turn of the century, training for family practice obstetrics would focus primarily on those planning to work in remote or rural settings. A 1993 study found three primary factors associated with an increased incidence of future maternity care. In 1997 the Residency Review Commission (RRC) stipulated that all family practice residencies have at least 1 family physician serve as an intrapartum attending physician for family practice resident deliveries., Methods: Using an instrument similar to that used in 1993, we surveyed the directors of 462 family practice residencies in the United States. Sixty-four percent (295) of the program directors responded to one of two mailings., Results: Compared with the survey published in 1993, program directors estimated a 16% increase in the number of residents who included obstetrics in their first practice after residency. Factors associated with increased obstetric participation included having only family physician faculty supervise uncomplicated deliveries and having family physician faculty who could perform other perinatal procedures. Programs that had 4 or more family physician faculty doing obstetrics and those that had more than 10 deliveries per month also produced more physicians who provided maternity care. Fifty-three percent of residencies that did not have family physician faculty attending deliveries before 1997 now meet this RRC requirement., Conclusions: This study shows that, according to their program directors' estimates, more family practice residents are including obstetrics in their first practice after residency compared with 5 years ago. The new RRC regulation was associated with more than 50% of previously noncompliant programs adding or retraining faculty who could attend resident deliveries within 12 months of the inception of the new policy.

Six classes of nonpeptide bradykinin antagonists were designed using a template derived from structural studies of peptide antagonists. Several compounds from each class were synthesized and assayed for binding to the human bradykinin B2 receptor. Each family showed compounds active at the level of the smallest template peptide; three classes contained compounds with Kd < 8 microM. These results provide diverse leads for a medicinal chemistry-based optimization program.

Objective: This study was undertaken to determine the efficiency of the shoulder girdle muscles during axial humeral rotation based on measurements of the moment arms., Design: The instantaneous muscle moment arms of 10 shoulder muscles, including the three portions of the deltoid, the rotator cuff muscles, teres major, and the thoracohumeral muscle group, were measured during four specified glenohumeral rotations., Background: Axial humeral rotation is a commonly performed movement during activities of daily living and is a targeted motion of shoulder rehabilitation, particularly in those protocols emphasizing rotator cuff strengthening. An understanding of the function of the movers and stabilizers of the shoulder requires such basic information of muscle moment arms., Methods: The instantaneous moment arm values of the muscles were derived from the slope of the plot of tendon excursion versus glenohumeral joint rotation angle. Motion studied included axial rotation with the humerus elevated 90 degrees in the coronal, scapular, and sagittal planes, as well as in the neutral position with the arm at the side., Results: Based on the findings, with the humerus in both neutral and elevated positions, the infraspinatus is potentially the most powerful external rotator, followed by teres minor and posterior deltoid. Subscapularis and possibly pectoralis major are the most effective internal rotators in this position., Conclusions: The moment arm in providing axial humeral rotation of 10 shoulder muscles in four planes were obtained. In general, the teres minor and infraspinatus had the largest moment arms in external rotation, and the subscapularis had the largest moment arm in internal rotation. The muscle function for axial humeral rotation was found to be modified by the plane of arm elevation., Relevance: The data could be used for developing exercise programs in physical therapy.

Unlabelled: There has been an ongoing effort to describe the physiologic factors associated with perceived and/or measured human voice changes that occur with age. In our study we focused on possible endocrine involvement on voice by using immunohistochemical staining to observe hormone receptor presence in vocal folds from 42 deceased subjects (fresh cadavers), male and female, ranging in age from 2 months to 82 years (average 37.7 years). On statistical analysis, age and gender were found to be associated with progesterone receptor staining of the glandular nuclei (young>old P = 0.013; male>female, P = 0.060). Gender was associated with androgen receptor staining in glandular cytoplasm (male>female, P = 0.014) and progesterone receptor staining in the epithelial cytoplasm (male>female, P = 0.039). No statistical significance was noted in other categories., Conclusion: Hormone receptors are found in the nucleus and cytoplasm of cells in the vocal fold with statistically significant differences in age and gender distribution.

The instantaneous muscle moment arms of 10 shoulder muscles including the three portions of the deltoid and the rotator cuff and scapulohumeral muscle groups during four specified glenohumeral motions were calculated. Moment arm values were derived from a plot of tendon excursion versus glenohumeral joint rotation angle during horizontal flexion along the 90 degrees elevation plane and elevation in the sagittal, scapular, and coronal planes. The deltoid had the largest moment arm in elevation. The anterior deltoid has a larger moment arm in the anterior planes, whereas the midportion is greater in the scapular and coronal planes. The muscles with the largest depressor (adductor) moment arms are the pectoralis major, latissimus dorsi, and teres major. Contrary to the findings of other investigators, the supraspinatus and infraspinatus have a smaller potential elevation torque in the scapular plane than has been previously reported. Furthermore the subscapularis may potentially be a more important elevator in the scapular plane than either the supraspinatus or infraspinatus, especially in the latter phases of motion. The pectoralis major has the largest horizontal flexion moment arm with the humerus elevated 90 degrees, whereas the posterior deltoid and infraspinatus have the largest horizontal extension moment arms in this plane.

The stabilising effects on the glenohumeral joint of each of the rotator-cuff muscles and of the biceps were studied with the arm in abduction and external rotation in 13 cadaver shoulders. The muscles were loaded one at a time with forces proportional to their cross-sectional areas. We recorded the positions of the humeral head before and after the application to the humerus of an anterior force of 1.5 kg. When the capsule was intact, the anterior displacement with the subscapularis loaded was significantly larger than with the other muscles loaded (p = 0.0009). With the capsule vented, the displacement with the biceps loaded was significantly smaller than that with the subscapularis loaded (p = 0.0052). After creating an imitation Bankart lesion, the displacement with the biceps loaded was significantly less than with any of the rotator-cuff muscles loaded (p = 0.0132). We conclude that in the intact shoulder, the subscapularis is the least important anterior stabiliser, and that the biceps becomes more important than the rotator-cuff muscles as stability from the capsuloligamentous structure decreases. Strengthening of the biceps as well as the rotator-cuff muscles should be part of the rehabilitation programme for anterior shoulder instability.

We studied the contributions of the long and short heads of the biceps (LHB, SHB) to anterior stability in 13 cadaver shoulders. The LHB and SHB were replaced by spring devices and translation tests at 90 degrees abduction of the arm were performed by applying a 1.5 kg anterior force. The position of the humeral head was monitored by an electromagnetic tracking device with or without an anterior translational force; with 0 kg, 1.5 kg or 3 kg loads applied on either LHB or SHB tendons in 60 degrees, 90 degrees or 120 degrees of external rotation; and with the capsule intact, vented, or damaged by a Bankart lesion. The anterior displacement of the humeral head under 1.5 kg force was significantly decreased by both the LHB and SHB loading in all capsular conditions when the arm was in 60 degrees or 90 degrees of external rotation. At 120 degrees of external rotation, anterior displacement was significantly decreased by LHB and SHB loading only when there was a Bankart lesion. We conclude that LHB and SHB have similar functions as anterior stabilizers of the glenohumeral joint with the arm in abduction and external rotation, and that their role increases as shoulder stability decreases. Both heads of the biceps have been shown to have a stabilising function in resisting anterior head displacement, and consideration should therefore be given to strengthening the biceps during rehabilitation programmes for chronic anterior instability of the shoulder.

Surgical correction of bunion deformity in adolescents is performed infrequently. Double osteotomy and longitudinal pin fixation of the first ray was performed on 15 feet. This procedure is technically easy, provides excellent correction and stability, and has a low rate of recurrence of deformity. Five numerical determinations were obtained from preoperative, intraoperative, and final follow-up radiographs. They included intermetatarsal angle, first-fifth metatarsal angle, and metatarsophalangeal angle, first-second metatarsal distance, and length of the first and second metatarsals. The mean length of follow-up was 32.5 months. The operation is indicated for severe deformities and should be applicable to adults.

Vaccinia virus encodes VGF, an early protein of relative molecular mass 19,000 (19K) which, from amino-acid residues 45 to 85, is homologous in 19 residues to epidermal growth factor (EGF), and transforming growth factor-alpha (TGF-alpha). The conserved sequence includes a region of high homology (6 out of 10 amino acids) from residues 71 to 80, corresponding to the third disulphide loop of both EGF and TGF-alpha. This region has recently been shown to contain a binding region of TGF-alpha for the EGF receptor, and this raises the question of whether vaccinia virus utilizes the EGF receptor in order to bind to and infect cells. We now show that occupancy of the EGF receptor inhibits vaccinia virus infection. Inhibition is observed in a dose-dependent fashion by pre-treatment with either EGF or synthetic decapeptide antagonists of EGF's mitogenic activity which correspond to the sequence of the third disulphide loop of VGF or TGF-alpha. The relative ability of the peptides to inhibit vaccinia virus infection parallels their binding affinity to the EGF receptor.

We describe a synthetic ligand, "DAKLI" (Dynorphin A-analogue Kappa LIgand), related to the opioid peptide dynorphin A. A single reactive amino group at the extended carboxyl terminus permits various reporter groups to be attached, such as 125I-labeled Bolton-Hunter reagent, fluorescein isothiocyanate, or biotin. These derivatives have high affinity and selectivity for the dynorphin (kappa opioid) receptor. An incidental finding is that untreated guinea pig brain membranes have saturable avidin binding sites.

A fragment of rat transforming growth factor alpha (TGF alpha) comprising the third disulfide loop (residues 34-43) was selected as a potential antigenic and receptor binding region. Immunization of rabbits with a peptide conjugate resulted in antibodies which were specific for both the peptide and rat TGF alpha, but not for the homologous epidermal growth factor (EGF). The synthetic decapeptide exhibited low affinity for EGF receptors on human cells. Affinity was increased 100x to 0.2% of EGF or TGF alpha binding by blocking the peptide ends. The blocked decapeptide had no mitogenic activity but prevented the mitogenic effect of EGF and TGF alpha on fibroblasts. This decapeptide is an antagonist and contains an important receptor binding region of TGF alpha.

A decapeptide isolated from highly purified preparations of human prealbumin was able to restore azathioprine (Az) sensitivity, a property of a sub-class of T-lymphocytes, to the spleen rosette-forming cells (RFC) of adult thymectomized (ATx) mice in vitro. The peptide was sequenced by the Edman method and shown to correspond to the ten amino-terminal residues of prealbumin, Gly-Pro-Thr-Gly-Thr-Gly-Glu-Ser-Lys-Cys. Synthesis of this peptide by solid phase methodology confirmed its activity both in vitro and in vivo. Synthesis of a number of structural analogues indicated that the amino-terminal deca, undeca and dodecapeptides of prealbumin as well as some of their derivatives were also able to restore Az sensitivity to RFC in vitro and in vivo. The Cys10 residue and the Glu7 residues both contributed significantly to potency in vitro. Removal of up to three amino acids from the N-terminus of the decapeptide led to a progressive loss of activity. The data indicates that the ability of human prealbumin to restore the Az sensitivity to the RFC of adult Tx mice is intrinsic to the protein and resides in the amino-terminal domain of the molecule.