Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis.

A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC.

Further studies on the application of vinylogous amides and ß-halovinylaldehydes to the regiospecific synthesis of unsymmetrical, polyfunctionalized 2,3,4- and 1,2,3,4- substituted pyrroles.

Highly functionalized pyrroles with appropriate regiochemical functionality represent an important class of marine natural products and potential drug candidates. We describe herein a detailed study of the reaction of α-aminoacid esters with vinylogous amides and also ß-halovinylaldehydes for the regiospecific synthesis of 2,3,4-trisubstituted and 1,2,3,4-tetrasubstituted pyrroles. Since the vinylogous amides and ß-halovinylaldehydes are readily available precursors, rapid access to a wide variety of unsymmetrically substituted pyrroles is accomplished via this methodology.

Traumatic Supraspinatus Tears in Patients Younger Than 25 Years.

Traumatic rotator cuff tears in patients younger than 25 years are rare events, with few reports in the literature. When compared with the more mature shoulder, the young, healthy supraspinatus tendon is a robust tendon that is able to absorb a significant amount of energy before tendon failure. Therefore, the diagnosis of a rotator cuff tear can be often overlooked in this population due to the patient's age. This is a report of traumatic supraspinatus repairs in patients younger than 25 years. Nine patients younger than 25 years were identified with a posttraumatic supraspinatus tear as visualized during routine diagnostic shoulder arthroscopy. These 9 patients represented 0.33% of all rotator cuff repairs during a 9-year period. Average patient age was 19.1 years (±3.7 years; range, 13 to 25 years). Magnetic resonance imaging failed to diagnose a rotator cuff tear in 50% of the patients. Mean delay from injury to surgery was 6.6 months. All tears were arthroscopically repaired. Concomitant anterior instability pathology was demonstrated among 66.7% of the patients. No complications were reported. At latest follow-up, all patients reported minimal to no shoulder pain and were tolerating strenuous work, activities, and sports without significant complaints. Even with advanced imaging, the diagnosis of a rotator cuff tear can often be missed in this patient population. Although clinical outcomes can be good, care must be taken to broaden the diagnostic differential in young patients with posttraumatic shoulder pain.

Postarthroscopic humeral head osteonecrosis treated with reverse total shoulder arthroplasty.

Although postarthroscopic glenohumeral chondrolysis has become a well-known disastrous complication of arthroscopic shoulder surgery, little is known about postarthroscopic humeral head osteonecrosis. This article describes 3 patients who were referred to the authors' practice with end-stage osteonecrosis after an arthroscopic rotator cuff repair or debridement.Three patients (average age, 63.3 years) presented to the authors' practice reporting severe shoulder pain after a rotator cuff debridement or repair was performed at an outside facility. After an interval period of mild improvement, all patients experienced progressive pain and loss of shoulder range of motion at a mean of 4.8 months postoperatively. Plain radiographs and magnetic resonance imaging obtained prior to the index operation showed no evidence of osteonecrosis. Postoperatively, progressive clinical and radiographic evidence showed humeral head osteonecrosis and subsequent glenohumeral destruction with cuff tear arthropathy. The authors managed all patients with a reverse total shoulder arthroplasty due to severe glenohumeral arthrosis and massive rotator cuff tears not amendable to repair. Satisfactory results were achieved in all cases.Although many complications of arthroscopic shoulder surgery are documented, little is known about postarthroscopic humeral head osteonecrosis. Shoulder surgeons should be aware of this potential complication when performing arthroscopic rotator cuff surgery and when evaluating painful and stiff postarthroscopic shoulders.

Googling suicide: surfing for suicide information on the Internet.

OBJECTIVE: This study examined the types of resources a suicidal person might find through search engines on the Internet. We were especially interested in determining the accessibility of potentially harmful resources, such as prosuicide forums, as such resources have been implicated in completed suicides and are known to exist on the Web. METHOD: Using 5 popular search engines (Google, Yahoo!, Ask.com, Lycos, and Dogpile) and 4 suicide-related search terms (suicide, how to commit suicide, suicide methods, and how to kill yourself), we collected quantitative and qualitative data about the search results. The searches were conducted in August and September 2006. Several coraters assigned codes and characterizations to the first 30 Web sites per search term combination (and "sponsored links" on those pages), which were then confirmed by consensus ratings. Search results were classified as being prosuicide, antisuicide, suicide-neutral, not a suicide site, or error (i.e., page would not load). Additional information was collected to further characterize the nature of the information on these Web sites. RESULTS: Suicide-neutral and anti-suicide pages occurred most frequently (of 373 unique Web pages, 115 were coded as suicide-neutral, and 109 were anti-suicide). While pro-suicide resources were less frequent (41 Web pages), they were nonetheless easily accessible. Detailed how-to instructions for unusual and lethal suicide methods were likewise easily located through the searches. CONCLUSIONS: Mental health professionals should ask patients about their Internet use. Depressed, suicidal, or potentially suicidal patients who use the Internet may be especially at risk. Clinicians may wish to assist patients in locating helpful, supportive resources online so that patients' Internet use may be more therapeutic than harmful.

Late reconstruction of chronic distal biceps tendon ruptures with a semitendinosus autograft technique.

We compared 2 groups of patients with chronic distal biceps tendon ruptures, 7 patients treated nonoperatively and 7 undergoing semitendinosus autograft tendon reconstruction. The mean time to surgery after the initial injury was 17 weeks. The mean clinical follow-up in the operative group was 63 months. Functional strength and endurance testing was measured at a mean of 30 months after injury in the nonoperative group and 26 months in the operative group. A 2-incision technique was used. In the allograft reconstruction group, flexion and supination strength was restored to the normal range. The nonoperative group lacked 20% of normal strength. Endurance in both groups was within the normal range. Autograft semitendinosus reconstruction in chronic distal biceps tendon ruptures improves flexion and supination strength when compared with nonoperative treatment. No radial nerve injuries or heterotopic ossification occurred, and all reconstructions remain intact.

Degenerative sternoclavicular arthritis and hyperostosis.

Symptomatic arthritic involvement of the sternoclavicular joint is relatively uncommon and can be a result of distant trauma, infection, and sternocostoclavicular hyperostosis, post-menopausal arthritis, condensing osteitis of the proximal clavicle, or secondary to an underlying arthropathy. Patients with degenerative osteoarthritis due to trauma most commonly have had either an anterior or posterior dislocation, subluxation, or periarticular fracture. Medical claviculectomy with or without ligamentous stabilization is indicated only in situations of painful primary and secondary rheumatoid arthritis, or in patients with neoplastic lesions. Numerous authors have recommended surgical reconstruction but few have reported series larger than two or three cases. This article reviews a few specific arthropathy conditions about the sternoclavicular joint and discusses their nonoperative and operative management.