Quinacrine as a potential treatment for COVID-19 virus infection.

A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a current outbreak of infection termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 is currently a global pandemic that may cause close to half a billion deaths around the world. Until now, there is no effective treatment for COVID-19. Quinacrine (Qx) has been used since the 1930s as preventive antimalarial compound. It is a recognized small molecule inhibitor of RNA virus replication, with known anti-prion activity, and identified as a potent Ebola virus inhibitor both in vitro and in vivo. Recently, Qx has showed anti-SARS-CoV-2 activity. Herein, we review the potential mechanisms associated with quinacrine as an antiviral compound.

Primary Elbow Osteoarthritis: Evaluation and Management.

Most patients with primary osteoarthritis of the elbow report a history of heavy lifting with the affected upper extremity . Conservative treatment, including activity modifications, nonsteroidal anti-inflammatory drugs and the occasional intraarticular corticosteroid injection, may provide adequate pain relief in earlier stages . When surgery is required, and despite the presence of cartilage wear, many patients with primary elbow osteoarthritis experience substantial pain improvement with joint preserving procedures . The ulnar nerve needs to be carefully assessed and addressed at the time of surgery . Although open debridement procedures are effective, arthroscopic osteocapsular arthroplasty has emerged as the surgical procedure of choice . Total elbow arthroplasty is very successful in terms of pain relief and function, but it is reserved for patients with end-stage osteoarthritis who are relatively older and have failed joint preserving procedures.

Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab.

BACKGROUND: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. OBJECTIVE: To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index. METHODS: Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples. RESULTS: In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G â†’ C), leading to an amino acid change (Lys â†’ Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection. CONCLUSIONS: . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.

Adsorption of dyes on carbon nanomaterials from aqueous solutions.

The removal of methylene blue (MB), a cationic dye and orange II (OII), an anionic dye, from aqueous solution by using carbon nanomaterials as multiwalled carbon nanotubes (MWNTs) and carbon nanofibers (CNF) as adsorbents was studied in batch experiments. The effect of pH, temperature and surface modification of adsorbent on the removal of MB and OII was also investigated. The removals of OII and MB by adsorption on MWNT were maximum at pH 3.0 and pH 7.0, respectively. However, in the case CNF was employed as adsorbent, the optimum values of pH were 9.0 and 5.0 for OII and MB, respectively. Langmuir and Freundlich isotherms are applied to fit the adsorption data of both dyes. Equilibrium data were well described by the typical Langmuir adsorption isotherm. Overall, the study demonstrated that MWNTs and CNFs can effectively remove cationic and anionic dyes as MB and OII from aqueous solutions under these experimental conditions.

Gas exchange in Paulownia species growing under different soil moisture conditions in the field.

In order to evaluate their responses to drought, we determined the photosynthetic activity water potential, stomatal conductance, transpiration, water use efficiency photosynthetic photon flux density and leaf temperature of Paulownia imperialis, P. fortunei and P. elongata in three different soil moisture conditions in the field. Our results showed that P. imperialis had greater photosynthesis (8.86 micromol CO2 m(-2) s(-1)) and instantaneous water use efficiency (0.79 micromol CO2 mmol H2O(-1)) than either P. elongata (8.20 micromol CO2 m(-2) s(-1) and 0.71 micromol CO2 mmol H2O(-1)) or P. fortunei (3.26 micromol CO2 m(-2) s(-1) and 0.07 micromol CO2 mmol H2O(-1)). The rapid growth of Paulownia did not appear to be correlated with photosynthetic rates. Paulownia fortunei showed more transpiration (48.78 mmol H2O m(-2) s(-1)) and stomatal conductance (840 mmol m(-2) s(-1)) than P. imperialis (20 mmol H2O m(-2) s(-1) and 540 mmol m(-2) s(-1)) and P. elongata (20 mmol H2O m(-2) s(-1) and 410 mmol m(-2) s(-1)), which allowed these two Paulownia species to increase their tolerance to low soil moisture, and maintain higher water use efficiency under these conditions. According to our physiological gas exchange field tests, Paulownia imperialis does appear to be capable of successful growth in semiarid zones.

Autoantibodies against axonal neurofilaments in patients with Kuru and Creutzfeldt-Jakob disease.

The serums of some patients with subacute spongiform encephalopathies contain an autoantibody in higher titer against a normal fibrillar protein within the axon of mature central neurons in culture. The morphological features of this neurofilament, as demonstrated by immunofluorescence and immunoperoxidase staining, and the partial characterization of the antibody are described. The detection of this hetero-specific autoantibody is the first evidence of an immune reaction in the spongiform encephalopathies.

Shoulder and Elbow Fractures in Athletes.

PURPOSE OF REVIEW: The purposes of this review are to discuss the management of shoulder and elbow fractures in athletes to optimize the return to sport and to highlight treatment impact on the return to play. RECENT FINDINGS: Fractures of the shoulder and elbow can have profound implications in an athlete career. Recent technique of fractures management trended toward to preserve soft tissue which is critical for an early recovery in athletic population. Arthroscopy presents a strong interest for the treatment of intra-articular fracture, and minimally invasive approach as developed in humeral shaft fracture can be considered to avoid soft tissue damage. Non-articular, stable, and minimally displaced fractures are mainly treated conservatively. However, we encourage a more aggressive approach in shoulder and elbow injuries in the athletes including minimally invasive and stable fixation to preserve vascularity and muscle environment.

Mid-term radiological results of a cementless short humeral component in anatomical and reverse shoulder arthroplasty.

AIMS: Shoulder arthroplasty using short humeral components is becoming increasingly popular. Some such components have been associated with relatively high rates of adverse radiological findings. The aim of this retrospective review was to evaluate the radiological humeral bone changes and mechanical failure rates with implantation of a short cementless humeral component in anatomical (TSA) and reverse shoulder arthroplasty (RSA). PATIENTS AND METHODS: A total of 100 shoulder arthroplasties (35 TSA and 65 RSA) were evaluated at a mean of 3.8 years (3 to 8.3). The mean age at the time of surgery was 68 years (31 to 90). The mean body mass index was 32.7 kg/m2 (17.3 to 66.4). RESULTS: Greater tuberosity stress shielding was noted in 14 shoulders (two TSA and 12 RSA) and was graded as mild in nine, moderate in two, and severe in three. Medial calcar resorption was noted in 23 shoulders (seven TSA and 16 RSA), and was graded as mild in 21 and moderate in two. No humeral components were revised for loosening or considered to be loose radiologically. Nine shoulders underwent reoperation for infection (n = 3), fracture of the humeral tray (n = 2), aseptic glenoid loosening (n = 1), and instability (n = 3). No periprosthetic fractures occurred. CONCLUSION: Implantation of this particular short cementless humeral component at the time of TSA or RSA was associated with a low rate of adverse radiological findings on the humeral side at mid-term follow-up. Our data do not raise any concerns regarding the use of a short stem in TSA or RSA. Cite this article: Bone Joint J 2019;101-B:610-614.

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis.

Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the expression of ANGII receptors - AT1 and AT2 - and their relationship with prognosis. We studied 133 tumours from patients with diagnosis of astrocytoma who underwent surgery from 1997 to 2002. AT1 and AT2 were expressed in 52 and 44% of the tumours, respectively, when determined by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Ten per cent of low-grade astrocytomas were positive for AT1, whereas grade III and IV astrocytomas were positive in 67% (P<0.001). AT2 receptors were positive in 17% of low-grade astrocytomas and in 53% of high-grade astrocytomas (P=0.01). AT1-positive tumours showed higher cellular proliferation and vascular density. Patients with AT1-positive tumours had a lower survival rate than those with AT1-negative (P<0.001). No association to survival was found for AT2 in the multivariate analysis. Expression of AT1 and AT2 is associated with high grade of malignancy, increased cellular proliferation, and angiogenesis, and is thus related to poor prognosis. These findings suggest that ANGII receptors might be potential therapeutic targets for high-grade astrocytomas.

Can a reverse shoulder arthroplasty be used to revise a failed primary reverse shoulder arthroplasty?: Revision reverse shoulder arthroplasty for failed reverse prosthesis.

AIMS: Patients with a failed reverse shoulder arthroplasty (RSA) have limited salvage options. The aim of this study was to determine the outcome of revision RSA when used as a salvage procedure for a failed primary RSA. PATIENTS AND METHODS: We reviewed all revision RSAs performed for a failed primary RSA between 2006 and 2012, excluding patients with a follow-up of less than two years. A total of 27 revision RSAs were included in the study. The mean age of the patients at the time of revision was 70 years (58 to 82). Of the 27 patients, 14 (52% were female). The mean follow-up was 4.4 years (2 to 10). RESULTS: Six patients (22%) developed complications requiring further revision surgery, at a mean of 1.7 years (0.1 to 5.3) postoperatively. The indication for further revision was dislocation in two, glenoid loosening in one, fracture of the humeral component in one, disassociation of the glenosphere in one, and infection in one. The five-year survival free of further revision was 85%. Five additional RSAs developed complications that did not need surgery, including dislocation in three and periprosthetic fracture in two. Overall, patients who did not require further revision had excellent pain relief, and significant improvements in elevation and external rotation of the shoulder (p < 0.01). The mean postoperative American Shoulder and Elbow Surgeons (ASES), and simple shoulder test (SST) scores were 66 and 7, respectively. Radiological results were available in 26 patients (96.3%) at a mean of 4.3 years (1.5 to 9.5). At the most recent follow-up, six patients (23%) had glenoid lucency, which were classified as grade III or higher in three (12%). Smokers had a significantly increased risk of glenoid lucency (p < 0.01). CONCLUSION: Revision RSA, when used to salvage a failed primary RSA, can be a successful procedure. At intermediate follow-up, survival rates are reasonable, but dislocation and glenoid lucency remain a concern, particularly in smokers. Cite this article: Bone Joint J 2018;100-B:1493-98.

Inhibitory effect of Thymus vulgaris and Origanum vulgare essential oils on virulence factors of phytopathogenic Pseudomonas syringae strains.

Pseudomonas syringae is a phytopathogenic bacterium that causes lesions in leaves during the colonisation process. The damage is associated with production of many virulence factors, such as biofilm and phytotoxins. The essential oils of Thymus vulgaris (thyme) and Origanum vulgare (oregano) have been demonstrated to inhibit P. syringae. The aim of this study was to investigate the effects of T. vulgaris and O. vulgare essential oils on production of virulence factors of phytopathogenic P. syringae strains, including anti-biofilm and anti-toxins activities. The broth microdilution method was used for determination of MIC and biofilm inhibition assays. Coronatine, syringomycin and tabtoxin were pheno- and genotypically evaluated. Both oils showed good inhibitory activity against P. syringae, with MIC values from 1.43 to 11.5 mg·ml-1 for thyme and 5.8 to 11.6 mg·ml-1 for oregano. Biofilm formation, production of coronatine, syringomycin and tabtoxin were inhibited by thyme and oregano essential oil in most strains. The results presented here are promising, demonstrating the bactericidal activity and reduction of virulence factor production after treatment with thyme and oregano oil, providing insight into how they exert their antibacterial activity. These natural products could be considered in the future for the control of diseases caused by P. syringae.

Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints.

OBJECTIVES: Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. MATERIALS AND METHODS: A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. RESULTS: Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals CONCLUSION: Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture.Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162-171. DOI: 10.1302/2046-3758.63.BJR-2016-0193.

Infection in total elbow arthroplasty with stable components: outcomes of a staged surgical protocol with retention of the components.

AIMS: We describe the use of a protocol of irrigation and debridement (I&D) with retention of the implant for the treatment of periprosthetic infection of a total elbow arthroplasty (TEA). This may be an attractive alternative to staged re-implantation. PATIENTS AND METHODS: Between 1990 and 2010, 23 consecutive patients were treated in this way. Three were lost to follow-up leaving 20 patients (21 TEAs) in the study. There were six men and 14 women. Their mean age was 58 years (23 to 76). The protocol involved: component unlinking, irrigation and debridement (I&D), and the introduction of antibiotic laden cement beads; organism-specific intravenous antibiotics; repeat I&D and re-linkage of the implant if appropriate; long-term oral antibiotic therapy. RESULTS: The mean follow-up was 7.1 years (2 to 16). The infecting micro-organisms were Staphylococcus aureus in nine, coagulase-negative Staphylococcus in 13, Corynebacterium in three and other in six cases. Re-operations included three repeat staged I&Ds, two repeat superficial I&Ds and one fasciocutaneous forearm flap. One patient required removal of the implant due to persistent infection. All except three patients rated their pain as absent or mild. Outcome was rated as good or excellent in 15 patients (mean Mayo Elbow Performance Score 78 points, (5 to 100) with a mean flexion-extension arc of 103° (40° to 150°)). CONCLUSION: A staged protocol can be successful in retaining stable components of an infected TEA. Function of the elbow may compare unfavourably to that after an uncomplicated TEA. Cite this article: Bone Joint J 2016;98-B:976-83.

Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis.

AIMS: Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. METHODS: A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. RESULTS: There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. DISCUSSION: Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties.Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11-17. doi: 10.1302/2046-3758.51.2000593.

Cloning of new members of heat shock protein HSP101 gene family in wheat (Triticum aestivum (L.) Moench) inducible by heat, dehydration, and ABA(1).

We have cloned two cDNAs, TaHSP101B and TaHSP101C, encoding two heat stress-inducible members of HSP101/ClpB family in bread wheat (Triticum aestivum (L.) Moench.). Proteins encoded by these cDNAs are highly similar at the primary sequence level and diverged from the previously reported TaHSP101 (designated TaHSP101A) both in the consensus ATP/GTP-binding region II and in the carboxy terminal region. The HSP101 gene was determined to be a single copy gene or a member of a small gene family in hexaploid wheat. Messages encoding HSP101 proteins were inducible by heat stress treatments in both wheat leaves and roots. Accumulation of the TaHSP101C mRNA was less abundant than that of TaHSP101B mRNA. We are showing for the first time that in addition to heat stress, expression of HSP101 mRNAs in wheat leaves was induced by a 2-h dehydration and a treatment with 5x10(-5)M ABA, but not affected by chilling or wounding, indicating that HSP101 proteins may be involved in both heat and drought responses in wheat.

Ligamentous repair and reconstruction for posterolateral rotatory instability of the elbow.

We describe the intermediate results of lateral ligamentous repair or reconstruction for posterolateral rotatory instability of the elbow. Between 1986 and 1999, we performed 12 direct repairs and 33 ligament reconstructions with a tendon autograft. One patient was lost to follow-up and 44 were retrospectively studied at a mean of six years (2 to 15). Surgery restored stability in all except five patients. In two the elbow became stable after a second procedure. The mean post-operative Mayo elbow performance score was 85 points (60 to 100). The result was classified as excellent in 19, good in 13, fair in seven and poor in five patients. Thirty-eight patients (86%) were subjectively satisfied with the outcome of the operation. Better results were obtained in patients with a post-traumatic aetiology (p = 0.03), those with subjective symptoms of instability at presentation (p = 0.006) and those who had an augmented reconstruction using a tendon graft (p = 0.04). Reconstruction using a tendon graft seems to provide better results than ligament repair and the results do not seem to deteriorate with time. The outcome of this procedure is less predictable in patients with no subjective instability.

Neurocysticercosis: a new classification based on active and inactive forms. A study of 753 cases.

Cysticercosis of the central nervous system, because of the combination of inflammatory response, topography of lesions, degree of parasitic infestation, and sequelae of previous infestations produces a most variable clinical picture. The symptomatology may range from a discrete neurological disturbance to the most dramatic brain disorder. Severity of the disease, prognosis, and medical or surgical decision for treatment largely depend on the individual amalgam of the above-referred factors. An improved classification of neurocysticercosis (NCC) that delineates active from inactive forms of the disease will eventually be important in the research of immunodiagnosis and in therapeutic trials. In this report, a classification is presented that separates active from nonactive forms of NCC and is based on our experience with 735 patients studied. Characteristics of each form of NCC, frequency of principal signs and symptoms, and findings in cerebrospinal fluid analysis are discussed.

Cysticercosis. Clinical classification based on imaging studies.

Cysticercosis is a pleomorphic disease in which the diagnosis, treatment, and prognosis greatly vary in relation to the location, number, and stage of the lesions. A new classification is proposed that includes the information gathered by magnetic resonance imaging and computed tomography, supplemented by immunodiagnostic studies and clinical data. The different clinical entities produced by cysticercosis are grouped by the frequency and location of the parasites, including valuable data as the number and stage of the lesions as well as the degree of the inflammatory response from the host to the parasite. In this way, the disease can be individualized to define the reliability of diagnostic studies and to design specific therapeutic approaches that depend on the characteristics that the disease acquires in every location.

Albendazole therapy for neurocysticercosis.

Seven patients with chronic parenchymal brain cysticercosis were treated with albendazole for one month at daily doses of 15 mg/kg of body weight. Computed tomographic follow-up studies were made at the following times: a mean of 16 months before the trial; the beginning of treatment; the end of treatment; and three months afterward. Computed tomographic studies at the beginning of treatment showed a total of 157 cysts, the last day of treatment the number had decreased to 39 cysts, and three months later, the total number of lesions was 22; this represents 86% improvement in the number of cystic lesions. Control studies in the same group of patients had shown chronic persistence of lesions without spontaneous improvement in most cases. Two patients had been treated with praziquantel previously with partial response; in both cases albendazole therapy was effective with 100% and 77% improvement. We conclude that albendazole is highly effective for the treatment of parenchymal brain cysticercosis. It is also effective in patients who had shown poor therapeutic response to praziquantel.

Sex-related severity of inflammation in parenchymal brain cysticercosis.

To determine sex-related differences in the severity of host inflammatory reaction to cysticercosis, we studied computed tomographic findings in 100 patients with parenchymal neurocysticercosis and cerebrospinal fluid results in 239 patients with subarachnoid neurocysticercosis. Computed tomographic and cerebrospinal fluid data in male subjects were compared with those obtained in female subjects. We found that when cysticerci are found in brain parenchyma, women develop a greater degree of inflammation; such differences disappear when cysticerci are found in the subarachnoid space. Our results point out the possibility of a factor located within brain parenchyma that accounts for the observed sex-related differences in the severity of immune response to the parasite; this factor could also play a role in the pathogenesis of other immunologically mediated diseases of the brain that may occur more frequently in women. To our knowledge, this study is the first in demonstrating that sex is a risk factor for the severity of inflammatory response within brain parenchyma to a parasitic disease.