On the Nature of the Rotational Energy Barrier of Atropisomeric Hydrazides.

N-N atropisomers represent a useful class of compounds that has recently received important attention from many research groups. This article presents an in-depth analysis of the energy barrier needed for the racemization process of atropoisomeric hydrazides, combining an experimental and computational approach. The focus is on examining how electronic and steric factors impact the racemization process. The results obtained indicate that the barrier observed during the racemization process mainly arises from an increase in the p-orbital character of the nitrogen atoms.

Synthesis of Atropisomeric Hydrazides by One-Pot Sequential Enantio- and Diastereoselective Catalysis.

The first catalytic enantioselective and diastereoselective synthesis of atropisomeric hydrazides was achieved using a sequential catalysis protocol. This strategy is based on a one-pot sequence of two organocatalytic cycles featuring the enamine amination of branched aldehydes followed by nitrogen alkylation under phase-transfer conditions. The resulting axially chiral hydrazides were obtained directly from commercially available reagents in high yields and with good stereocontrol. The permutation of organocatalysts allowed easy access to all stereoisomers, enabling a stereodivergent approach to enantioenriched atropisomeric hydrazides.

Isolated displaced type II partial articular radial head fracture: correlation of preoperative imaging with intraoperative findings of lateral ulnar collateral ligament tear.

BACKGROUND: The aim of this study was to determine the lateral ulnar collateral ligament (LUCL) injury associated with isolated radial head fracture (RHF) and the relationship of the ligament injury with the displacement of the fragment-loss of contact-in unstable displaced partial articular RHF in individuals without any history of ulnohumeral dislocation. METHODS: We retrospectively identified 131 consecutive patients who underwent open reduction and internal fixation of isolated closed Mason type II RHF performed at our institution. We identified 3 subsets by the pattern of RHF and the position of the unstable fragment (anterior or posterior) relative to the capitulum humeri: displaced stable (group I), displaced anterior unstable (group II), and displaced posterior unstable (group III). Standard radiographs were obtained preoperatively and postoperatively. The pattern of lateral collateral ligament avulsion and its distribution were inferred from intraoperative records. RESULTS: Preoperative radiographs of the 131 patients showed 101 nonseparated fractures (77%, group I) and 30 unstable fractures (23%). Anterior displacement of the fragment was found in 18 elbows (14%, group II) and posterior displacement in 12 (9%, group III). LUCL avulsion was found in 18 of 30 unstable RHFs (60%) and in 1 of 60 stable RHFs (1.6%). CONCLUSION: RHF is a complex fracture often associated with soft tissue lesions. It is important to determine which structures need to be repaired to avoid complications that could lead to elbow instability. The RHF pattern and classification as stable or unstable can help the surgeon in the identification and treatment of LUCL lesions.

Hallux valgus correction with a new percutaneous distal osteotomy: Surgical technique and medium term outcomes.

BACKGROUND: Many procedures and different osteotomies have been described for percutaneous hallux valgus correction. Percutaneous techniques may lead to reduced morbidity, surgery, and recovery time. The aim of this study is to evaluate the clinical and radiographic outcome of a new percutaneous procedure (PBS-Percutaneous Bianchi System). METHODS: Fifty-eight cases were treated with Percutaneous Bianchi System procedure for correction of mild, moderate or severe hallux valgus deformity. All patients were clinically assessed preoperatively and then followed up by weight-bearing x-rays, AOFAS (American Orthopedic Foot and Ankle Score), VAS (Visual Analog Scale) pain score, and patient satisfaction. RESULTS: AOFAS scores improved from 28.6 at the preoperative assessment to 91.7 at the latest follow-up. The VAS pain score improved from 6.7 before surgery to 0.6 at the latest follow-up. The mean Hallux valgus angle (HVA), Intermetatarsal angle (IMA) and Distal metatarsal articular angle (DMAA) significatively decreased from the preoperative assessment to the latest follow-up. CONCLUSIONS: The PBS technique is a safe, reliable, and effective procedure for the correction of symptomatic mild-to-severe hallux valgus.

Comparison of Scapular Mechanics After Activity With and Without a Targeted Compression Garment.

Muscle fatigue can result in scapular dyskinesis, which has been implicated in impingement, labral injury, and rotator cuff injury. This study evaluated the ability of a compression shirt to maintain scapular alignment after fatiguing of periscapular musculature. Subjects' scapular movements were monitored before and after a periscapular muscle- fatiguing exercise program. In the anterior and posterior tilt and medial and lateral rotation dimensions, control and shirt subjects both exhibited differences between the prefatigue and postfatigue measurements throughout humeral elevation. In the retraction and protraction dimension, control subjects exhibited differences between prefatigue and postfatigue measurements for a large portion of elevation, while shirt subjects only had different measurements toward the extreme of shoulder flexion. Thus the shirt does not stabilize the scapula in the anterior and posterior tilt and medial and lateral rotation dimensions. In the retraction and protraction dimension, the shirt provides stability to the scapula and maintains prefatigue position. It is currently unclear if preserving one plane of scapular motion has clinical significance. (Journal of Surgical Orthopaedic Advances 28(1):18-23, 2019).

Behavioural But Not Cognitive Impairment Is a Determinant of Caregiver Burden in Amyotrophic Lateral Sclerosis.

BACKGROUND: Caregivers of patients affected by amyotrophic lateral sclerosis (ALS) are involved with great determination in the treatment process since the earliest stages of the disease with an increasing burden to be of help to the ailing persons. AIM: To test separately the impact of ALS patients' cognitive and behavioural impairments on caregiver burden and mood status in 84 outpatient/main caregiver couples. DESIGN: Patients were tested with the ALS-Cognitive Behavioural Screen (ALSCBS-ci and -bi), Frontal Assessment Battery, Weigl's Sorting Test, Mini-Mental State Examination, Beck's Depression Inventory (BDI). Analogously, caregivers completed the BDI and Caregiver Burden Inventory (CBI). RESULTS: CBI correlated with ALSCBS-bi, besides ALSFRS-R, disease progression index and caregiver BDI. Caregiver BDI also correlated with ALSCBS-bi scores. No correlations were found with cognitive tests. The correlation between CBI and the ALSCBS-bi score was specifically sustained by the social burden sub-domain of CBI. CONCLUSIONS: As previously reported using other tools, behavioural impairment is a determinant of burden and mood in ALS caregivers. Conversely, cognitive impairment fails to emerge as a major target when aiming at easing the increasing burden or improving mood in ALS caregivers.

BDNF Serum Levels with Respect to Multidimensional Assessment in Amyotrophic Lateral Sclerosis.

BACKGROUND: The clinical presentation of amyotrophic lateral sclerosis (ALS) is characterized by high heterogeneity, the greatest part of which still remains unexplained. OBJECTIVE: To assess serum levels of brain-derived neurotrophic factor (BDNF) in ALS patients, implementing a multidimensional characterization focused on four a priori chosen elements of phenotypic variability: ALS bulbar/spinal subtype, cognitive impairment, mood dysfunction and disease progression speed. METHODS: Serum samples were obtained from 45 ALS outpatients (16% bulbar onset) and 22 healthy controls. Each patient underwent the Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory (BDI), and disease progression speed was estimated by calculating the decay of the ALSFRS-R score over time. RESULTS: BDNF serum levels did not differ between patients and controls, although ∼25% lower levels characterized those patients carrying a depressive trait. Finally, BDNF serum levels were significantly lower in ALS patients expressing lower ALSFRS-R scores (r = 0.39, p < 0.01). No differences were found when considering cognitive impairment, disease progression speed and site of onset. CONCLUSION: BDNF serum levels might mark and possibly contribute in part to ALS phenotypic variability.

A 3D finite element model for geometrical and mechanical comparison of different supraspinatus repair techniques.

BACKGROUND: Contact pressure and contact area are among the most important mechanical factors studied to predict the effectiveness of a rotator cuff repair. The suture configurations can strongly affect these factors but are rarely correlated with each other. For example, there is a significant difference between the single-row technique and the transosseous or transosseous-like approaches in terms of footprint contact area coverage. A finite element model-based approach is presented and applied to account for various parameters (eg, suture pretension, geometry of the repair, effect of the sutures, geometry of the lesion) and to compare the efficacy of different repair techniques in covering the original footprint. METHODS: The model allows us to evaluate the effect of parameters such as suture configuration and position and suture pretension. The validity of such an approach was assessed in comparing 3 different repair techniques: single row, transosseous equivalent, and double row. RESULTS: Results from the application of the models show that the double-row and transosseous-equivalent techniques lead to progressive increase of the contact area compared with the single-row approach, supporting the conclusion that transosseous-equivalent fixation leads to an increase of the contact area and a better distribution of the pressure coverage. CONCLUSION: The 3-dimensional finite element model approach allows multiple variables to be assessed singularly, weighing the specific influence. Moreover, the approach presented in this study could be a valid tool to predict and to reproduce different configurations, identifying how to reduce the stress over the tendon and when a repair could be effective or not.

Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection.

Myeloid-derived suppressor cells (MDSCs) are key players in the immune suppressive network. During acute infection with the causative agent of Chagas disease, Trypanosoma cruzi, BALB/c mice show less inflammation and better survival than C57BL/6 (B6) mice. In this comparative study, we found a higher number of MDSCs in the spleens and livers of infected BALB/c mice compared with infected B6 mice. An analysis of the two major MDSCs subsets revealed a greater number of granulocytic cells in the spleens and livers of BALB/c mice when compared with that in B6 mice. Moreover, splenic MDSCs purified from infected BALB/c mice inhibited ConA-induced splenocyte proliferation. Mechanistic studies demonstrated that ROS and nitric oxide were involved in the suppressive activity of MDSCs, with a higher number of infected CD8(+) T cells suffering surface-nitration compared to uninfected controls. An upregulation of NADPH oxidase p47 phox subunit and p-STAT3 occurred in MDSCs and infected IL-6 KO mice showed less recruitment of MDSCs and impaired survival. Remarkably, in vivo depletion of MDSCs led to increased production of IL-6, IFN-γ, and a Th17 response with very high parasitemia and mortality. These findings demonstrate a new facet of MDSCs as crucial regulators of inflammation during T. cruzi infection.

Trypanosoma cruzi, the causative agent of Chagas disease, modulates interleukin-6-induced STAT3 phosphorylation via gp130 cleavage in different host cells.

Interleukin-6 mediates host defense and cell survival mainly through the activation of the transcription factor STAT3 via the glycoprotein gp130, a shared signal-transducing receptor for several IL-6-type cytokines. We have reported that the cardiotrophic parasite Trypanosoma cruzi protects murine cardiomyocytes from apoptosis. In agreement, an intense induction of the anti-apoptotic factor Bcl-2 is found in cardiac fibers during the acute phase of infection, establishing a higher threshold against apoptosis. We report here that inactive cruzipain, the main cysteine protease secreted by the parasite, specifically triggered TLR2 and the subsequent release of IL-6, which acted as an essential anti-apoptotic factor for cardiomyocyte cultures. Although comparable IL-6 levels were found under active cruzipain stimulation, starved cardiac cell monolayers could not be rescued from apoptosis. Moreover, cardiomyocytes treated with active cruzipain completely abrogated the STAT3 phosphorylation and nuclear translocation induced by recombinant IL-6. This inhibition was also observed on splenocytes, but it was reverted when the enzyme was complexed with chagasin, a parasite cysteine protease inhibitor. Furthermore, the inhibition of IL-6-induced p-STAT3 was evidenced in spleen cells stimulated with pre-activated supernatants derived from trypomastigotes. To account for these observations, we found that cruzipain enzymatically cleaved recombinant gp130 ectodomain, and induced the release of membrane-distal N-terminal domain of this receptor on human peripheral blood mononuclear cells. These results demonstrate, for the first time, that the parasite may modify the IL-6-induced response through the modulation of its cysteine protease activity, suggesting that specific inhibitors may help to improve the immune cell activation and cardioprotective effects.

Isokinetic strength test and functional outcomes in proximal humeral fractures treated with a locking plate.

BACKGROUND: Despite the use of many shoulder outcome scales in subjects with rotator cuff pathology or instability symptoms, it can be problematic to select an instrumental evaluation in the shoulder trauma population. In this study we evaluated patients with proximal humeral fractures treated with internal fixation with a locking plate, analyzing the recovery of strength with an isokinetic test and its correlation with clinical and functional outcomes. METHODS: We enrolled 46 individuals (17 men, 29 women). The evaluation included a structured interview, measurement of ROM, isokinetic strength test and Constant-Murley and QuickDASH scores. The isokinetic test was performed in flexion/extension and external/internal rotation of the operated shoulder in comparison with the contralateral side and concentric contractions in all movements. The parameter tested was peak torque. RESULTS: In the operated shoulder values we noticed a statistically significant correlation between the QuickDASH and Constant-Murley score. QuickDASH showed a significant correlation with flexion isokinetic strength, partial correlation with extension isokinetic values and no correlation with external/internal rotation values. In addition, we found a correlation between the Constant-Murley score and all the isokinetic strength parameters. Comparing the operated shoulder and the contralateral, in Neer type 2 fractures there was no significant difference in all the isokinetic peak torque values; in Neer type 3 and type 4, there was a significant statistical difference in both flexion peak torque values and no significant difference in the other movements. CONCLUSIONS: The isokinetic test can give objective data on strength recovery and could help the surgeon's clinical evaluation to assess the functional recovery of the operated shoulder over time. We believe that the isokinetic test and Constant-Murley score could act as a reference in the evaluation of post-surgical outcome of proximal humeral fractures. Furthermore, the type of fracture could be a post-surgical limb recovery predictor and the shoulder flexion force could be the best functionality recovery indicator.

Pectoralis minor tendon transfer for irreparable anterosuperior cuff tears.

BACKGROUND: Tears of the subscapularis tendon are a frequent cause of shoulder dysfunction. Tendon transfer techniques have been devised to treat irreparable tears. The objectives of this study were to explore the anatomic feasibility of using the pectoralis minor tendon as a graft for subscapularis tendon tears, the safety of the procedure, and the scope of this approach in improving shoulder function. MATERIALS AND METHODS: We performed open pectoralis minor transfer in 27 patients (22 men; mean age, 60 years) with irreparable tears of the upper two-thirds of the subscapularis tendon, grade III fatty degeneration, and irreparable supraspinatus tears. Constant and Simple Shoulder Test scores and functional outcomes were evaluated at 3, 12, and 24 months. All patients were available for follow-up. RESULTS: The pectoralis minor tendon easily reached the subscapularis footprint. There were no cases of musculocutaneous nerve or brachial plexus injury or graft failure. Active forward flexion improved from 127° to 177°; external rotation with the arm at the side declined by 11°. The Simple Shoulder Test score improved by 5 points and the Constant score by 41 points, although the strength subscore did not rise significantly. CONCLUSIONS: This study showed that it is anatomically feasible to use the pectoralis minor tendon as a graft to treat upper subscapularis lesions; the procedure is safe in terms of brachial plexus and musculocutaneous nerve injury; and pectoralis minor transfer can improve shoulder function and provide pain relief in patients with Lafosse grade III subscapularis tears, likely through a tenodesis effect, even in the presence of irreparable supraspinatus tears.

Humeral shaft fractures treated with antegrade intramedullary nailing: what are the consequences for the rotator cuff?

PURPOSE: The purpose of this study was to investigate the clinical and sonographic impact on the rotator cuff (RC) of the use of the anterolateral approach for nailing. METHODS: A retrospective cohort of 48 patients treated for humeral diaphyseal fractures at the University Hospital of Parma between 2007 and 2011 was analysed. Inclusion criteria were (1) acute humeral shaft fractures treated with T2-proximal humeral nail (PHN) and (2) a minimum follow-up of one year. Exclusion criteria were (1) history of proximal and metaphyseal humeral fractures, (2) pathological fractures or open fractures of the humerus, and (3) RC lesions. Clinical assessment using the Constant score, simple shoulder test and through shoulder examination tests was carried out. The sonographic study investigated the integrity of the RC. RESULTS: Mean score on Constant's scale was 78.21 points, with most patients achieving a good result (79% obtained more than 65 points). One patient had a limited functional outcome (Constant's score of 49 points). The sonographic findings described for supraspinatus tendon were a partial ruptures of less than 30 mm in three patients and a complete tendon rupture in one case. CONCLUSIONS: The results of this study suggest that the use of the anterolateral approach for antegrade humeral nailing ensures a good functional result with no significant clinical-sonographic impact on the rotator cuff and a satisfactory long term clinical outcome.

Are percutaneous pinning the best treatment for gartland type iii supracondylar humeral fractures in children?

Background. Supracondylar humeral fractures are the most frequent fractures of the elbow in children. Gartland type III fractures require a surgical treatment. The preferred management is closed reduction and percutaneous pinning with K-wires. Methods. We have treated 15 patients (mean age 6,5 years) with Gartland type III fractures. In 14 patients the percutaneous reduction with K-wires was possible but in 1 case the open reduction was necessary due to the irreducibility of the fracture. In all cases a cycle of rehabilitation was performed. Results. All patients have been evaluated using Flynn's criteria with a mean follow-up of 24 months. All cases resulted excellent except the one that required open reduction, that resulted good. Conclusions. Percutaneous pinning is at our days the gold standard of treatment but open reduction must always be considered mandatory when an anatomical closed reduction is not possible. Rehabilitation is also fundamental though the young age of the patients.

Arthroscopic treatment of early glenohumeral arthritis.

BACKGROUND: The articular cartilage of the shoulder is not endowed with intrinsic repair abilities, so the detection of chondral lesions during arthroscopy may indicate that additional articular procedures are needed. The aim of the current study was to evaluate the benefits of arthroscopy in patients with early shoulder arthritis, and to assess which clinical and radiological features are correlated with better arthroscopic outcomes. MATERIALS AND METHODS: Out of a total of 2,707 shoulders, 61 arthroscopies were performed on patients aged 30-55 years suffering from a painful early arthritic shoulder. We performed a retrospective study of 47 of those 61 patients with osteoarthritis at Samilson-Prieto stage I or II. SST and Constant score were used as outcome measures. Arthroscopic circumferential capsulotomy was performed to release the soft tissues and increase the joint space. Glenoid chondral lesions were caregorized according to location (anterior, posterior, centered) and size (small, large, total) and treated with microfractures; in the last 11 patients, we placed a engineered hyaluronic acid membrane, Hyalograft(®) C, on the surface of the glenoid. Postoperative care included mobilization the day after surgery, with the arm protected in a sling for two weeks. Follow-up examinations were performed at 3, 6, 12, and 24 months after surgery. The clinical and radiographic data collected were compared with those obtained at the last examination. RESULTS: The mean Constant score increased from 43.8 points to 79.1, and the mean SST score increased from 4.9 points to 9.4 points. Clinical outcomes improved significantly in 44 patients (93.6 %). The three patients (6.4 %) with the lowest scores showed progression of arthritis. Age, gender, glenohumeral distance, and presence of engineered hyaluronic acid membrane were not related to clinical scores. Recovery of range of motion as well as small and centered cartilage lesions were statistically associated with improved outcome. CONCLUSION: The main finding was that soft tissue procedures (including capsulotomy and synovectomy) associated with glenoid microfractures are only suitable for patients with early arthritis and preserved humeral head shape, particularly in cases with small and centered glenoid cartilage lesions.

Single-Flask Enantioselective Synthesis of α-Amino Acid Esters by Organocatalysis.

An operationally simple Knoevenagel condensation/asymmetric epoxidation/domino ring-opening esterification (DROE) approach has been disclosed to successfully access a good variety of (R)- and (S)-α-arylglycine esters from commercially available aldehydes, phenylsulfonyl acetonitrile, cumyl hydroperoxide, anilines, and readily available Cinchona alkaloid-based catalysts using a single solvent and reaction vessel. DFT calculations performed on the key asymmetric epoxidation showed the importance of cooperative H-bonding interactions in affecting the stereocontrol.

Correction: Importance of TLR2 on Hepatic Immune and Non-Immune Cells to Attenuate the Strong Inflammatory Liver Response During Trypanosoma cruzi Acute Infection.

[This corrects the article DOI: 10.1371/journal.pntd.0000863.].

Over the top or endobutton for ACL reconstruction?

There are an estimated 80-100,000 ACL repairs in the US each year: most ACL tears occurs from noncontact injuries. The 3.9% of the knee ligament injuries undergoes surgery: in the 80% of these patients, this means ACL reconstruction. The purpose of this study is to compare two surgical techniques normally used for acl recustruction; the first one is the intra- extra articular technique with single bundle fixed with staples and the second one is the intra-articular technique with double bundle and endobutton post-fixation. We evaluate the clinical outcome of our patients at the time of 4 years follow up. From January 2006 to April 2009 40 patients underwent to ACL reconstruction, all operated by using hamstring tendons: 20 patients with an average age of 28,75 years (12 men and 8 women) underwent surgery using the intra-extra articular technique, whereas the remaining 20 patients with an average age of 34,5 years (11 men and 9 women) benefited the intra-articular technique with double bundle ligament and endobutton post-fixation. Our study shows no substancial difference between these'two technique, but clinical outcome measures (I.K.D.C., Lysholm and Tegner) estimated better results for the double bundle technique with Endobutton post-fixation. (www.actabiomedica.it).

Prevalence of shoulder discomfort in paraplegic subjects.

INTRODUCTION: The annual incidence of acute spinal cord injury, as reported in the National Spinal Cord Injury Statistical Center, was estimated to be approximately 40 cases per million, or approximately 11.000 new cases in the United States each year (1). In subjects with spinal cord injury, overstress of the upper extremities occurs not only during daily life activities, but also utilizing wheelchair. The aim of this study is to determine the prevalence of shoulder discomfort in subjects affected by paraplegia living in our country area and evaluate the associated risk factors negatively affecting the shoulder function. MATERIAL AND METHOD: A computerized database search for paraplegic patients was performed at the Department of Orthopedic Surgery, Trauma Surgery and Rehabilitation Medicine. Among the 54 selected paraplegic patients, 47 accepted to participate at the study. Once the patients were contacted, the medical records were reviewed to obtain information regarding shoulder, elbow and spine region pain and discomfort. RESULTS: The 60% of all the patients who answered to the questionnaire complain shoulder pain, 90% bilaterally, and the 30% referred elbow pain, 20% bilaterally. 77% complains back pain, involving particularly lumbar region. Only 2% of this population undergoes a shoulder surgery treatment for cuff tear and shoulder disability. DISCUSSION AND CONCLUSION: The present study is the first in our country that gives an overview of prevalence of upper limb discomfort in paraplegic patients. We have shown the interplay between shoulder elbow and spine with pain, age of patients and type of wheel chair utilized. The previous factors can be corrected and upper limb discomfort relieved.

Early caloric deficit is associated with a higher risk of death in invasive ventilated COVID-19 patients.

BACKGROUND & AIMS: The aim of this study was to evaluate the nutritional support management in mechanically ventilated coronavirus disease 2019 (COVID-19) patients and explore the association between early caloric deficit and mortality, taking possible confounders (i.e. obesity) into consideration. METHODS: This was a prospective study carried out during the first pandemic wave in the intensive care units (ICUs) of two referral University Hospitals in Lombardy, Italy. Two hundred twenty-two consecutive mechanically ventilated COVID-19 patients were evaluated during the ICU stay. In addition to major demographic and clinical data, we recorded information on the route and amount of nutritional support provided on a daily basis. RESULTS: Among patients still in the ICUs and alive on day 4 (N = 198), 129 (65.2%) and 72 (36.4%) reached a satisfactory caloric and protein intake, respectively, mainly by enteral route. In multivariable analysis, a satisfactory caloric intake on day 4 was associated with lower mortality (HR = 0.46 [95%CI, 0.42-0.50], P < 0.001). Mild obesity (body mass index [BMI] ≥30 and < 35 kg/m2) was associated with higher mortality (HR = 1.99 [95%CI, 1.07-3.68], P = 0.029), while patients with moderate-severe obesity (BMI≥35 kg/m2) were less likely to be weaned from invasive mechanical ventilation (HR = 0.71 [95%CI, 0.62-0.82], P < 0.001). CONCLUSIONS: This study confirmed the negative prognostic and clinical role of obesity in mechanically ventilated COVID-19 patients and suggested that early caloric deficit may independently contribute to worsen survival in this patients' population. Therefore, any effort should be made to implement an adequate timely nutritional support in all COVID-19 patients during the ICU stay.