Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.

Glioblastoma (GBM) is the most frequently diagnosed primary central nervous system tumor in adults. Despite the standard of care therapy, which includes surgical resection, temozolomide chemotherapy, radiation and the newly added tumor-treating fields, median survival remains only ∼20 months. Unfortunately, GBM has a ∼100% recurrence rate, but after recurrence there are no Food and Drug Administration-approved therapies to limit tumor growth and enhance patient survival, as these tumors are resistant to temozolomide (TMZ). Recently, our laboratory reported that lucanthone slows GBM by inhibiting autophagic flux through lysosome targeting and decreases the number of Olig2+ glioma stem-like cells (GSC) in vitro and in vivo. We now additionally report that lucanthone efficiently abates stemness in patient-derived GSC and reduces tumor microtube formation in GSC, an emerging hallmark of treatment resistance in GBM. In glioma tumors derived from cells with acquired resistance to TMZ, lucanthone retains the ability to perturb tumor growth, inhibits autophagy by targeting lysosomes, and reduces Olig2 positivity. We also find that lucanthone may act as an inhibitor of palmitoyl protein thioesterase 1. Our results suggest that lucanthone may function as a potential treatment option for GBM tumors that are not amenable to TMZ treatment. SIGNIFICANCE STATEMENT: We report that the antischistosome agent lucanthone impedes tumor growth in a preclinical model of temozolomide-resistant glioblastoma and reduces the numbers of stem-like glioma cells. In addition, it acts as an autophagy inhibitor, and its mechanism of action may be via inhibition of palmitoyl protein thioesterase 1. As there are no defined therapies approved for recurrent, TMZ-resistant tumor, lucanthone could emerge as a treatment for glioblastoma tumors that may not be amenable to TMZ both in the newly diagnosed and recurrent settings.

Evaluating the Outcome of Two Different Regimes in Adhesive Capsulitis: A Prospective Clinical Study.

OBJECTIVE: Adhesive capsulitis or frozen shoulder is a painful condition affecting up to 5% of the general population. We conducted this study with the aim of evaluating the results of physiotherapy plus intra-articular methylprednisolone injection versus physiotherapy alone in idiopathic frozen shoulder. METHODS: This prospective clinical study was conducted in a tertiary care center between August 2016 and August 2018. Patients who were diagnosed with idiopathic frozen shoulder were included in the study, and each patient was randomly allocated to one of two groups: physiotherapy alone (group A) and physiotherapy plus intra-articular steroid injection (group B). RESULTS: A total of 52 cases diagnosed with idiopathic frozen shoulder were included and treated with the two modalities. There was a significant improvement in group B compared to group A at 6 weeks and 3 months in the range of flexion, abduction, and external rotation. The Shoulder Pain and Disability Index showed improvement in both pain and disability score in group B -compared to group A, and improvement was significant at 6 weeks and 3 months. CONCLUSION: The results demonstrate the advantages of physiotherapy plus intra-articular steroid injection in idiopathic frozen shoulder. The predictability of results with physiotherapy plus intra-articular steroid injection in selected patients is excellent, and it is a better modality of treatment compared to physiotherapy alone.

Do we really need to repair the pronator quadratus after distal radius plating?

PURPOSE: Fractures of distal radius are one of the common orthopaedic injuries. Placing the plate on volar surface requires release of underlying pronator quadratus (PQ) muscle. No consensus is present in the literature about the repair or not of the PQ. The purpose of this study was to evaluate the influence of PQ repair on functional outcome and complications. METHODS: Retrospectively 83 patients of distal radius fractures managed with volar plating between 2014 and 2016 were evaluated. Demographic data, operative notes and physical therapy records were retrieved. Patients were divided into group A where PQ repair was done and group B where no repair was done. Functional data such as range of motion (ROM), grip strength, visual analogue scale (VAS) score and disabilities of arm, shoulder and hand (DASH) score at 4 weeks, 3 months, 6 months and finial follow-up were retrieved. RESULTS: Totally 63 patients (n = 29 in group A and n = 34 in group B) with the mean age of 51.64 years were examined. Patients were followed up for a mean of 35.2 months (range 27.2-47.1 months) in group A and 38.6 months (range 28.6-51.0 months) in group B. Though functional outcome of the affected limb was not significantly different between two groups after 3 months, PQ repair did affect the recovery at an early stage. Repair group had significantly better ROM (p = 0.0383) and VAS score at 4 weeks (p = 0.017) while grip strength (p = 0.014) was significantly better at 3 months. CONCLUSIONS: Repair of PQ may provide pain relief and increased ROM in early postoperative period and hence every attempt should be made to achieve the repair.

Reducing shoulder dislocation without anaesthesia or assistant: Validation of a new reduction manoeuvre.

PURPOSE: Shoulder dislocation comprises 60% of all major joint dislocations worldwide and a number of reduction techniques are described in the literature with varying degrees of success. The description of a large number of techniques speaks for itself that no method is effective all the times and one should be acquainted with more than one technique. An ideal method of reduction should be simple, easily reproducible, relatively painless that can be performed unassisted without sedation or anaesthesia with minimal or no further complications. We report our results of using a novel method of anterior shoulder reduction described recently in the literature that claims to fulfil most of the characteristics of an ideal method if not all. METHODS: This prospective study was conducted in a tertiary care centre. All the cases of primary anterior shoulder dislocation presenting within three days of injury without any associated fracture or spine trauma with or without greater tuberosity fracture were included. The reduction was done using a novel method by orthopaedic residents in all cases. The need for a second reduction attempt or anaesthesia was considered a treatment failure. Time taken for reduction, pain felt during reduction and complications if any were noted. RESULTS: There were 47 (77.04%) males and 14 (22.95%) females with a mean age of (37.04 ± 12.63) years. The new technique was effective in locating a shoulder dislocation on the first attempt in 58 of the 61 dislocated shoulders (95.08%). The remaining three shoulders were reduced on second attempt by the same technique. Sedative, pre-medication or anaesthesia was not used in any case. The average time taken for the shoulder reduction was (130.5 ± 25.8) seconds and confidence interval (95%) 124-137 s. Iatrogenic complications were not seen in any of the patients. CONCLUSION: This relatively painless technique of shoulder reduction is easy to acquire and practice in emergency department. The advantages of this manoeuvre and its associated safety may justly lead surgeons to select it as their primary method for reduction of anterior shoulder dislocations.

A High-Resolution Digital Bathymetric Elevation Model Derived from ICESat-2 for Adam's Bridge.

This data descriptor elaborates the details of a high-resolution digital bathymetric elevation model generated for the region, namely, Adam's Bridge, which encompasses a chain of shoals between Rameswaram Island, off the southeastern coast of Tamil Nadu, India, and Mannar Island, off the northwestern coast of Sri Lanka. The proposed dataset has taken advantage of the photon penetrability in the shallow waters by the green laser of ICESat-2 LiDAR to derive the seabed topography. Seafloor depths from ~0.2 million geolocated photons of ICESat-2 for the study area were accrued and interpolated to generate a 10 m digital bathymetric elevation model. Adam's Bridge, an isthmus and submerged reefal assemblage in shallow and super-shallow waters, is a feature of scientific curiosity. Our dataset has the potential to enhance the understanding of Adam's Bridge structure by providing substantial information to reconstruct its evolution.

Physical features of Adam's Bridge interpreted from ICESat-2 based high-resolution digital bathymetric elevation model.

Adam's Bridge is a submerged ridge connecting India and Sri Lanka, generally regarded as a chain of shoals extending for ~ 29 km from Dhanushkodi on the Indian side to Talaimannar Island of Sri Lanka. A high-resolution digital bathymetric elevation model generated using the seafloor returned photons of ICESat-2 was used to understand the intricate details of Adam's Bridge structure. Photons emanating from ICESat-2's green laser have the potential to detect the seafloor up to a depth of ~ 40 m; taking a cue from this potentiality, in our research, we have accrued ~ 0.2 million photons representing the depth information and generated a 10 m resolution bathymetric data for the extent of Adam's Bridge. Visual interpretations made from this bathymetric data through 3D perspectives with multi-directional lighting effects, and also with the derived parameters like contours, slope, and volumetric analysis, enabled us to recognize the current form of Adam's Bridge's physical features. The results from our research confirm that, in its entirety, Adam's Bridge is a submarine continuation of Dhanushkodi and Talaimannar Island. Throughout the crest line of Adam's Bridge, approximately 1.5 km on either side is highly undulating within the super-shallow water with occurrences of sudden depths. There is an asymmetry of transverse slopes to the base on both sides of Adam's Bridge, indicating dominant transgression of material energy from the waters of the Gulf of Mannar compared to the Palk Strait. The volume of Adam's Bridge computed in our research yielded a value of ~ 1 km3; interestingly, only 0.02 percent of this volume is above the mean sea level, and in general, the same is visible in optical satellite imagery-in total ~ 99.98 percent of the Adam's Bridge is submerged in shallow and super-shallow waters.

Protein-polymer bioconjugation, immobilization, and encapsulation: a comparative review towards applicability, functionality, activity, and stability.

Polymer-based biomaterials have received a lot of attention due to their biomedical, agricultural, and industrial potential. Soluble protein-polymer bioconjugates, immobilized proteins, and encapsulated proteins have been shown to tune enzymatic activity, improved pharmacokinetic ability, increased chemical and thermal stability, stimuli responsiveness, and introduced protein recovery. Controlled polymerization techniques, increased protein-polymer attachment techniques, improved polymer surface grafting techniques, controlled polymersome self-assembly, and sophisticated characterization methods have been utilized for the development of well-defined polymer-based biomaterials. In this review we aim to provide a brief account of the field, compare these methods for engineering biomaterials, provide future directions for the field, and highlight impacts of these forms of bioconjugation.

Role of creatine phosphokinase as a diagnostic marker in tubal ectopic pregnancy.

Background and Aim: Ectopic pregnancy (EP) is still one of the leading preventable causes of maternal morbidity and mortality in the first trimester. Amidst the use of sensitive assays for ß-HCG and high-definition ultrasonography for the identification of EP, the search for a more reliable and sensitive marker remains a challenge till date. Our aim was to determine the validity of creatine phosphokinase (CPK) and its isoenzyme (CPK-MB) in the prediction of tubal EP. Materials and Methods: A prospective and comparative diagnostic accuracy study was conducted among 105 pregnant women in the first trimester who met the eligibility criteria in the Department of Obstetrics and Gynecology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS). The study included 35 patients each with tubal EP (EP), abortive intrauterine pregnancy (AP), and normal intrauterine pregnancy (NP). CPK, CPK-MB, and ß-HCG were measured among all the participants, and the participants were followed up longitudinally. Results: A total of 105 pregnant women were included. The mean CPK and CPK-MB levels were significantly higher among the women with EP when compared to NP (P < 0.05) and AP (P < 0.05) women; however, there was no significant difference between the NP and AP groups (P > 0.05). Moreover, the receiver operating characteristic (ROC) curve showed that both CPK and CPK-MB were good predictors of EP, with CPK (area under the curve [AUC] = 0.764) being a better predictor than CPK-MB (AUC: 0.650) in the diagnosis of EP. Conclusion: Early diagnosis of EP allows appropriate and timely management, which would not only reduce mortality and morbidity associated with the condition but also enable preservation of fertility and improve future pregnancy outcome. Hence, the need of the hour is a reliable biochemical diagnostic marker for EP, such as CPK.

Equilibrium states of Burgers and Korteweg-de Vries equations.

We simulate Korteweg-de Vries (KdV) and dissipationless Burgers equations using δ-correlated random noise as an initial condition. We observe that the energy fluxes of the two equations remain zero throughout, thus, indicating their equilibrium nature. We characterize the equilibrium states using Gaussian probability distribution for the real space field, and using Boltzmann distribution for the modal energy. We show that the single soliton of the KdV equation too exhibits zero energy flux, hence, it is in equilibrium. We argue that the energy flux is a good measure for ascertaining whether a system is in equilibrium or not.

Correction to: Bilateral Radial Head Fracture Secondary to Weighted Push-Up Exercise: Case Report and Review of Literature of a Rare Injury.

[This corrects the article DOI: 10.1007/s43465-021-00427-0.].

Bilateral Radial Head Fracture Secondary to Weighted Push-Up Exercise: Case Report and Review of Literature of a Rare Injury.

A 33-year-old male presented with bilateral radial head fractures after weighted prone push-up exercise. The patient had Mason type I and II on right and left sides, respectively. He was managed conservatively with limited immobilisation and early range of motion exercises. The fracture healed and patient had no complaints at the last follow-up of 13 months. Bilateral radial head fracture is rare with push-up exercise, and can be successfully treated conservatively with immobilisation and early rehabilitation. Although push-up exercises are an excellent workout with known benefits, unusual modifications of standard techniques should be avoided.

Universal Epidemic Curve for COVID-19 and Its Usage for Forecasting.

We construct a universal epidemic curve for COVID-19 using the epidemic curves of eight nations that have reached saturation for the first phase and then fit an eight-degree polynomial that passes through the universal curve. We take India's epidemic curve up to January 1, 2021 and match it with the universal curve by minimizing square-root error between the model prediction and actual value. The constructed curve has been used to forecast epidemic evolution up to February 25, 2021. The predictions of our model and those of supermodel for India (Agrawal et al. in Indian J Med Res, 2020; Vidyasagar et al. in https://www.iith.ac.in/~m_vidyasagar/arXiv/Super-Model.pdf, 2020) are reasonably close to each other considering the uncertainties in data fitting.

Is Flexion Gap Rectangular in Native Indian Knees? Results of an MRI Study.

BACKGROUND: The purpose of this study was to evaluate the flexion-gap of the native knees in the normal population and to assess any gender-specific variations in the flexion gap of the knees. METHODS: A total of 50 normal asymptomatic volunteers with normal knee radiographs were selected for MRI of the knee. The left knee was scanned in an open MRI using a T1-weighted sequence. Imaging was performed in neutral, passive varus and valgus stress at 90° of knee flexion by placing custom-made blocks on a special board consecutively below the distal part of the leg. RESULTS: The study population consisted of 26 males and 24 females with a mean age of 25.77 years. Under varus stress, the mean lateral flexion gap increased to 9.28 ± 1.53 mm and under valgus stress, the mean medial flexion gap increased to 2.75 ± 1.22 mm from neutral. The increase in the flexion gap on the lateral side was 5.28 ± 1.79 mm, which was significantly higher compared to that on the medial side. In gender-specific analysis, the mean lateral flexion gap was 10.21 mm in females and 8.46 mm in males under varus stress. CONCLUSION: The findings of the study indicate that the lateral soft tissues are more lax compared to the medial soft tissue structures and this laxity is higher in females as compared to males. The study provides evidence of the existing physiological variations of these soft tissue structures resulting in a trapezoidal flexion gap in the native knees rather than the recommended rectangular gap.

A Shepherd's Crook Deformity of Proximal Femur Treated by Valgus Osteotomy and Bone Grafting.

The Shepherd's crook deformity of the proximal femur is a characteristic radiologic feature of fibrous dysplasia. It may be limited to a single bone, which is called monostotic, or may be polyostotic involving multiple bones as seen in McCune-Albright Syndrome. We report a case of a 19-year-old male patient who presented to us with pain in the right hip for one year. He had dysmorphic facies and multiple café-au-lait spots over the back, which were suggestive of McCune-Albright Syndrome. The radiographs of the hip showed varus deformity of the proximal femur. A lateral closing wedge osteotomy was done and the defect was filled with morselised femoral head allografts and fibular strut allografts. At the 14-month follow-up, the patient remained functionally active without any symptoms. The use of morselised femoral head allograft combined with strut fibular allograft ensures both stability and improved biology at the site of the lesion without any donor site morbidity.

Plate Osteosynthesis or Figure-of-Eight Brace: Which One Is Better in Midshaft Clavicle Fractures?

Introduction Fracture of the clavicle bone is a very common injury owing to its subcutaneous location. Controversy exists about the optimal treatment of midshaft clavicle fractures in the presence of significant displacement and comminution of the fracture. Traditionally, non-surgical management was considered the first treatment option for most clavicle fractures. However, recent evidence shows that the non-surgical option causes more complications than previously reported. The purpose of this study was to compare the clinical and radiological outcomes of conservative treatment and surgical treatment for midshaft clavicle fractures. Materials and methods A total of 45 patients meeting the inclusion criteria were included in this randomized study. The patients were allocated to two groups: conservative and operative on an alternate basis. Patients in the conservative group were managed with figure-of-eight bandage, whereas patients in the operative group were treated surgically by plate fixation. Primary outcome was recorded at six weeks, three months, six months, and 12 months follow-up using the Disabilities of the Arm, Shoulder, and Hand (DASH) and American Shoulder and Elbow Surgeons (ASES) scores. We also assessed patient's satisfaction after the treatment, fracture union, and complication rates among the study cohort. Results The ASES scores were significantly better in the operative group at three months and six months follow-up; however, at 12 months follow-up, there was no significant difference in the score between the groups. Although not statistically significant, the DASH score was better in the operative group than in the conservative group at all the follow-ups. This study showed that the time to union was lesser, rate of non-union was lower, and return to work was faster on the operative group. The mean satisfaction score in the operative and conservative groups was 4.16±0.76 and 4.05±1.24, respectively (p = 0.76). Conclusion This study suggests that open reduction and internal fixation with plate reduced the incidence of mal-union and non-union; however, surgical treatment showed no significant difference in the functional outcome as compared to conservative treatment.

Bent Tibial Nail with Refracture: A Cost-Effective Removal Method: A Case Report.

CASE: A 45-year old man presented with a right open tibial fracture with a prominent, fixed deformity because of a retained right tibial intramedullary nail from a previous tibial fracture. After multiple futile intraoperative attempts to extract the bent nail, it was finally sectioned using an industrial drill bit that permitted its removal and revision tibial nailing. CONCLUSIONS: A tibial fracture resulting in a retained, bent nail presents unique challenges for nail extraction and subsequent exchange nailing. Failed implant removal can be limited by the equipment available in the operating theater. In this setting, the judicious use of inexpensive industrial materials and instruments may be effective in select cases.

A Large Posteromedial Parameniscal Cyst Masquerading a Baker's Cyst: An Unusual Presentation.

INTRODUCTION: Meniscal cysts are rare and strongly associated with a horizontal meniscal lesion. Arthroscopic partial meniscectomy of the meniscus with intra-articular cyst drainage has become the standard of care for small cyst; however, sometimes large cyst requires open excision. CASE PRESENTATION: We report a case of a large symptomatic medial parameniscal cyst in 52-year-old female which was clinically misdiagnosed as Baker's cyst. The patient had swelling over the posteromedial aspect of the right knee with difficulty and pain on squatting. Magnetic resonance imaging (MRI) reported horizontal tear in the posterior horn of medial meniscus and parameniscal cyst adjacent to medial meniscus with features of early osteoarthritis of the knee. She was successfully treated with open excision and repair of the defect of the cyst along with arthroscopic partial medial meniscectomy. CONCLUSION: This case highlights the importance of MRI in diagnosis and planning and the use of a combined approach for successful management of large parameniscal cyst.

Prospective Randomized Study Comparing the External Fixator and Volar Locking Plate in Intraarticular Distal Radius Fractures: Which Is Better?

Introduction Various treatment options for patients with an intraarticular distal radius fracture are available, but in cases of comminuted fractures, these narrow down to either a volar locking plate, an external fixator, or a combination of these two. We conducted this prospective study to compare the external fixation and internal fixation of intraarticular fractures of the distal radius in terms of clinical/functional outcome and complications and with the available literature. Material and method This prospective randomized study consisted of a total number of 30 patients with intraarticular fractures of the distal end of the radius divided randomly into two groups (A and B), treated by external fixation (Group A) and volar plating (Group B), in a tertiary care institute during the study period. Result The most patients were males >50 years of age, with injury to the right dominant hand most commonly caused by a fall on an outstretched hand. As per the modified Green & O'Brien scoring system, the volar plating group showed the final result as excellent in two (13.33%), good in seven (46.6%), fair in four (26.6%), and poor in two (13.3%) whereas an excellent outcome was seen in one (6.66%), good and fair in five patients each (33.3%), and poor in four (26.66%) patients at the six months follow-up. Conclusion Overall, both fixation techniques seem to apply sufficient stabilization to restore function and retain anatomy; however, volar locking plates have certain advantages over external fixator in the early postop period in terms of earlier recovery and mobilization.

A Rare Case Report on Xanthogranulomatous Osteomyelitis of Hip Mimicking Tuberculosis and Review of Literature.

Xanthogranulomatous osteomyelitis (XO) is a rare chronic inflammatory process characterized by the presence of a large number of lipid-containing macrophages with lymphocytes and plasma cells. We present a case of XO of the hip in a 50-year-old woman with pain in the left hip for 28 months. The patient had a history of taking anti-tuberculosis chemotherapy for five months. Laboratory data revealed an increased erythrocyte sedimentation rate and C-reactive protein (CRP) level. Plain radiographs showed the destruction of the femoral head with arthritis and subluxation. Magnetic resonance imaging (MRI) was suggestive of tubercular infection of the left hip and a benign lesion in the left ilium. The histopathologic examination of the specimen demonstrated the presence of dead bone surrounded by lymph-plasma cells, foamy cells, and histocytes, which was consistent with XO, and culture was positive for Staphylococcus aureus infection. The patient was successfully treated with resection arthroplasty and antibiotics. It is important for the surgeons to keep XO in the list of differentials in cases with lytic lesions of bone and assessment should include microbiological culture along with the biopsy.