Synthesis of Pyrrole-2-Carboxylic Acid from Cellulose- and Chitin-Based Feedstocks Discovered by the Automated Route Search.

The shift towards sustainable feedstocks for platform chemicals requires new routes to access functional molecules that contain heteroatoms, but there are limited bio-derived feedstocks that lead to heteroatoms in platform chemicals. Combining renewable molecules of different origins could be a solution to optimize the use of atoms from renewable sources. However, the lack of retrosynthetic tools makes it challenging to examine the extensive reaction networks of various platform molecules focusing on multiple bio-based feedstocks. In this study, a protocol was developed to identify potential transformation pathways that allow for the use of feedstocks from different origins. By analyzing existing knowledge on chemical reactions in large databases, several promising synthetic routes were shortlisted, with the reaction of D-glucosamine and pyruvic acid being the most interesting to make pyrrole-2-carboxylic acid (PCA). The optimized synthetic conditions resulted in 50 % yield of PCA, with insights gained from temperature variant NMR studies. The use of substrates obtained from two different bio-feedstock bases, namely cellulose and chitin, allowed for the establishment of a PCA-based chemical space.

Highly Stereoselective Asymmetric Total Synthesis of (-)-Jimenezin via Sequential Intramolecular Amide Enolate Alkylation.

A highly stereoselective asymmetric total synthesis of (-)-jimenezin (1), a potent anticancer acetogenin, was efficiently completed with the key feature being a sequential intramolecular amide enolate alkylation (IAEA). Our investigation to probe the origin of the complete stereoselectivity in the second IAEA step to form the conformationally flexible tetrahydrofuran with perfect stereocontrol identified the presence of the oxygen atom in the adjacent tetrahydropyran ring to be crucial.

Implantation of an Actifit® Polyurethane Meniscal Scaffold 18 Months After Subtotal Lateral Meniscectomy in a 13-Year-Old Male Adolescent.

BACKGROUND Implantation of the Actifit® polyurethane meniscal scaffold is indicated for knee pain after partial meniscectomy in adults who are skeletally mature. This report is of a case of implantation of an Actifit® polyurethane meniscal scaffold 18 months after subtotal lateral meniscectomy in a 13-year-old male adolescent. CASE REPORT A 13-year-old male presented with right knee pain, localized to the lateral joint, 18 months after undergoing subtotal lateral meniscectomy. Magnetic resonance imaging (MRI) of the knee showed a complete amputation of the lateral meniscal middle segment with subchondral bone damage. Arthroscopic exploration of the knee joint showed a subtotal posterior and middle lateral meniscectomy and a 4 cm² area of International Cartilage Repair Society (ICRS) grade 3 cartilage damage on the posterior aspect of the lateral tibial plateau. The anterolateral portal was enlarged to introduce the Actifit® scaffold. The implant was secured using three all-inside Fast-Fix® sutures and three outside-in vertical sutures, which rapidly reduced the pain symptoms. At five-year follow-up, the patient reported no pain, and he had resumed sporting activities and recovered a full knee range of motion at 0/0/145°. MRI showed a type 2 meniscal implant shape and size, according to the Genovese MRI score. The ICRS MRI score was stable at grade 3b. CONCLUSIONS This case showed that the use of the Actifit® polyurethane meniscal scaffold is an option for the treatment of knee pain after partial or subtotal meniscectomy in skeletally immature patients, resulting in a stable functional outcome at five-year follow-up.

Radial head arthroplasty: a historical perspective.

There has been lively debate regarding the rationale behind the use of radial head arthroplasty (RHA) for more than 80 years. Currently, its primary indication is for treatment of non-reconstructible RH fractures. The first RH implant, released in 1941, was a ferrul cap used to prevent heterotopic ossification. Biomechanical studies in the 1980s stimulated a revolution in RHA design by promoting modular implants that replicated the native bony anatomy of the elbow. Subsequent data-driven evolution in design led to the creation of a variety of devices that also accommodated for common ligamentous injuries occurring at the time of RH fracture. Despite significant advances in our understanding of complex elbow instability, improvements in implant design have to make RHA the gold standard for treatment of non-reconstructible RH fractures. The challenge in the coming years will be to perform high-level clinical studies in order to obtain consensus regarding the most appropriate treatment for comminuted RH fractures.

Combined median and ulnar nerve palsy complicating distal radius fractures.

BACKGROUND: Fractures of the distal radius only rarely give rise to complications in the immediate postoperative period. Combined median and ulnar nerve palsy is a complication that can be missed by the surgeon. MATERIALS AND METHODS: Three cases diagnosed early after surgery are reported here. The patients were 15, 16, and 30 years of age, respectively. None had preoperative neurological deficits. The youngest patient was injured during sports and the other 2 patients during traffic accidents. All 3 patients had a displaced fracture of the distal radius combined with a fracture of the distal fourth of the ulna or ulnar styloid process and were treated by anterior plate fixation. Operative times were 47, 62, and 120minutes, respectively. Compartment syndrome was ruled out based on low pain intensity and absence of forearm tightness to palpation. RESULTS: The electrophysiological study performed 1 month post-injury in all 3 patients showed severe impairments of both median and ulnar nerve function. Median and ulnar nerve release surgery was performed in the 15-year-old 6 weeks post-injury. No nerve damage or fibrosis was seen during the procedure. All patients recovered fully within 3 months and had normal findings from follow-up electrophysiology testing after 6 months. DISCUSSION: Combined median and ulnar nerve palsy has rarely been reported and is among the rare complications of distal radial fractures that can develop in the event of a high-energy trauma and/or major displacement. Both previously published data and our experience indicate that surgical nerve release is unnecessary. Clinical recovery within 3 months is the rule. LEVEL OF EVIDENCE: IV, case-reports.

Antiviral and Anti-Inflammatory Activities of Pochonin D, a Heat Shock Protein 90 Inhibitor, against Rhinovirus Infection.

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

Coonrad-Morrey total elbow arthroplasty for patients with rheumatoid arthritis: 54 prostheses reviewed at 7 years' average follow-up (maximum, 16 years).

BACKGROUND: Total elbow arthroplasty is a therapeutic option for severe rheumatoid arthritis. We hypothesized that the semiconstrained characteristics of the Coonrad-Morrey prosthesis do not compromise the survival rate of the implant in a rheumatoid elbow. METHODS: Between 1997 and 2012, there were 54 Coonrad-Morrey total elbow prostheses performed for rheumatoid arthritis in 46 patients. Minimum follow-up was 2 years. There were 35 women and 11 men with a mean age of 60 years (29-83 years). According to the Mayo classification for rheumatoid elbow, there were 30 type IIIA, 21 type IIIB, and 3 type IV. The surgical procedure was the same for all patients. Survivorship was assessed with use of the Kaplan-Meier method, with revision surgery as the end point. RESULTS: The survival rate was 97% (95% confidence interval, 83.6-99.6) at 5 years and 85% (95% confidence interval, 68.3-93.7) at 10 years. At an average of 7 years of follow-up (2-16 years), the mean Mayo Elbow Performance Score was 91 points (55-100 points), and the shortened version of the Disabilities of the Arm, Shoulder, and Hand score was 34 points (0-75 points). There was a significant improvement in Mayo Elbow Performance Score and in all range of motion at latest follow-up in comparison to preoperative values (P < .0001). Radiolucencies were observed in 6 cases around the humeral component and in 6 cases around the ulnar component. Bushing wear was observed in 16 cases (29%). There were 14 complications (26%). Revisions were performed in 6 of them (11%). CONCLUSION: The Coonrad-Morrey prosthesis provides satisfactory results with follow-up. The rate of complications remains high even if the rate of implant revision stayed low.

Arthroscopic Osteochondral Autograft Transfer for Juvenile Osteochondritis Dissecans of the Humeral Head: A Case Report.

CASE: Osteochondritis dissecans (OCD) rarely affects the humeral head. We describe a 14-year-old adolescent who, despite conservative treatment, had persistent pain in the left shoulder as well as limited function. Radiographs and a computed tomography (CT) arthrogram revealed an osteochondral defect of the humeral head. He was managed with an arthroscopic osteochondral autograft transfer from the knee, which provided a satisfactory outcome. CONCLUSION: Arthroscopic osteochondral autograft transfer is an effective option for the treatment of OCD of the humeral head.

No difference in outcome for open versus arthroscopic rotator cuff repair: a prospective comparative trial.

PURPOSE: Arthroscopic techniques tend to become the gold standard in rotator cuff repair. However, little data are reported in the literature regarding the improvement of postoperative outcomes and re-tear rate relative to conventional open surgery. The aim of this study was to compare clinical outcomes and cuff integrity after arthroscopic versus open cuff repair. METHODS: We prospectively assessed clinical outcomes and cuff integrity after an arthroscopic or open rotator cuff repair with a minimum follow-up of 12 months. Clinical evaluation was based on Constant score, Simple Shoulder Value (SSV) and American Shoulder and Elbow Score (ASES). Rotator cuff healing was explored with ultrasound. RESULTS: 44 patients in arthroscopic group A (mean age 56-year-old) and 43 in open group O (mean age 61-year-old) fulfilled the inclusion criteria. Tendons were repaired with a single row technique associated with biceps tenodesis and subacromial decompression. All objective clinical scores significantly improved postoperatively in both groups. No statistical difference was identified between group A and O regarding, respectively, Constant score (72 vs 75 points; p = 0.3), ASES score (88 vs 91 points; p = 0.3), and SSV (81 vs 85%). The overall rate of re-tear (Sugaya type IV or V) reached 7 and 9%, respectively, in group A and O (p = 0.8). CONCLUSION: This study did not prove any difference of arthroscopic over open surgery in case of rotator cuff repair regarding clinical outcome and cuff integrity at 1-year follow-up. LEVEL II: Prospective comparative study.

Gartland types IIB and III supracondylar fractures of the humerus in children: is Blount's method effective and safe?

BACKGROUND: Blount's method is controversial for the treatment of Gartland types IIB and III supracondylar fracture of the humerus (SCFH) in children. The purpose of this study was to evaluate the clinical and radiologic outcomes and the failure and complication rates. METHODS: All types IIB and III SCFH treated with Blount's method from 2003-2013 were included in this retrospective single-center study. Clinical assessment was performed according to Flynn criteria. Baumann angle, anteversion angle, anterior humeral line, and humeroulnar angle were measured for radiographic assessment. RESULTS: Among 447 children with types IIB and III SCHF, 339 were treated according to Blount's method. There were 173 boys (51%), and the mean age was 6.3 years (1-14 years); 71% were type III. Mean time to surgery was 5.7 hours. According to Flynn criteria, results were satisfactory in 91% of cases. No compartment syndrome was encountered. There were 16 (4.7%) secondary displacements requiring surgical revision. Five (1.9%) children developed a cubitus varus deformity. At latest follow-up, the mean Baumann angle was 74.7° (95% confidence interval, 74.1-75.3), the mean anteversion angle was 39.9° (95% confidence interval, 39.5-40.3), the anterior humeral line was normal in 87.6% of cases, and the mean humeroulnar angle was 8.7°. CONCLUSION: Blount's method is appropriate to manage types IIB and III SCFH, provided anatomic and stable reduction is obtained.

Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells.

Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC50 of 0.98 ± 0.15 µM, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti-metastatic effects in cancer therapy.

Nerve stress during reverse total shoulder arthroplasty: a cadaveric study.

BACKGROUND: Neurologic lesions are relatively common after total shoulder arthroplasty. These injuries are mostly due to traction. We aimed to identify the arm manipulations and steps during reverse total shoulder arthroplasty (RTSA) that affect nerve stress. METHODS: Stress was measured in 10 shoulders of 5 cadavers by use of a tensiometer on each nerve from the brachial plexus, with shoulders in different arm positions and during different surgical steps of RTSA. RESULTS: When we studied shoulder position without prostheses, relative to the neutral position, internal rotation increased stress on the radial and axillary nerves and external rotation increased stress on the musculocutaneous, median, and ulnar nerves. Extension was correlated with increase in stress on all nerves. Abduction was correlated with increase in stress for the radial nerve. We identified 2 high-risk steps during RTSA: humeral exposition, particularly when the shoulder was in a position of more extension, and glenoid exposition. The thickness of polyethylene humeral cups used was associated with increased nerve stress in all but the ulnar nerve. CONCLUSION: During humeral preparation, the surgeon must be careful to limit shoulder extension. Care must be taken during exposure of the glenoid. Extreme rotation and oversized implants should be avoided to minimize stretch-induced neuropathies.

Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11ß-Hydroxycurvularin.

The first total synthesis and structure revision of (-)-11ß-hydroxycurvularin (1b), a macrolide possessing a ß-hydroxyketone moiety, were accomplished. The ß-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.