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Background Oral anticoagulant which don’t interfere with haemostasis physiology have potential application in management of acute cardiovascular events. Asundexian is once such oral anticoagulant, which is reported to be beneficial by minimising the rate of ischemic events. This study examined the pharmacological basis for cardiovascular benefits of asundexian. Materials and Methods All potential targets of asundexian in humans were identified by Insilco screening in the SwissTargetPrediction server and analysed. Results Unexpectedly factor XI or Xia was not observed to be targeted by asundexian in this study. However factor XII and thrombin were observed to be targeted by asundexian. In addition several GPCR’s, ion channels, enzymes and kinases relevant to positive modulation of cardiovascular physiology were observed to be targeted by asundexian. Conclusion The anticoagulant effects of asundexian is likely to be by indirect inhibition of factor XI or Xia by interfering with factor XII and/or thrombin. The cardiovascular benefits of asundexian is likely mediated by broader relevant off target effects.

The pharmacodynamics effects of therapeutically administered calcitonin is observed for extended duration much beyond its reported short half-life. The rationale for this pharmacodynamic-pharmacokinetics mismatch of calcitonin is not known. Hence in this study the hypothesis on sub-compartmentalization of calcitonin in blood to explain the extended pharmacodynamics effects of calcitonin was evaluated in vitro using the sheep blood model. A relatively higher proportion of calcitonin concentration was observed in the WBC compartment. The partition coefficient analysis showed levels of calcitonin to be higher on WBC membrane compared to intracellular. Molecular modelling to assess the binding of calcitonin with protein in plasma and WBC membranes indicated physiologically relevant higher affinity with beta-2-microglobulin’s in plasma and glycoproteins (CD44), sushi domains (CD25), fibronectins (CD206) and siglecs (CD22) on WBC membrane. The physiologically relevant higher affinity with several proteins on WBC membrane and plasma can be responsible for extended pharmacodynamics effects observed for therapeutically administered calcitonin.

BackgroundGlioblastoma multiforme (GBM) is one of the most aggressive and difficult to treat brain tumour in humans with a 5 year survival rate of less than 6%. SERPINE1 is a novel tumour receptor found on GBM that modulates the progression of this cancer through growth signals and remodelling of the extracellular matrix. Hence, we investigated the role of SERPINE1 and its network proteins in pathogenesis of GBM and assessed its targetability.Material and methodsNetwork proteins of SERPINE1 in homo sapiens was identified using the String database, and the affinity of the protein-protein interaction of this network was analysed using Chimera software. The expression profile of SERPINE1 in the different brain regions was evaluated to correlate its relevance to GBM pathology. Selected small molecules fromCalotropis giganteawere screened using AutoDock vina to assess targetability of human SERPINE1.ResultsVTN, PLG, TGFB1, VWF, FGF2 and CXCR1 were identified as the major network proteins of SERPINE1. The strongest interaction was observed between SERPINE1 and FGF2 (42884 H-bonds) followed by CXCR1 (20279 H-bonds). Our results suggest that SERPINE1 and its network proteins identified here play a vital role in GBM development and progression through brain parenchyma by creating the prime microenvironment for carcinogenesis, tumour invasion and migration. The highest expression of SERPINE1 was observed in the pons, medulla, midbrain, corpus callosum and spinal cord. Expression of SERPINE1 was consistent with high grade lesions of GBM, suggesting association of SERPINE1 with advanced stages of GBM. The selected small molecules fromCalotropis giganteawere observed to have therapeutically feasible binding affinity (140 - 550 μM) and predicted efficacy (290 - 1115 μM) against human SERPINE1.ConclusionSERPINE1 plays a vital role in the progression of GBM through its critical network proteins identified in this study. The expression of SERPINE1 aligns with the advanced stages of GBM. Small molecules fromCalotropis giganteatested in this study can serve as lead compounds for developing novel anti-SERPINE1 therapeutics for advanced stages of GBM.

IntroductionIris-pupillary area ratio (IPR) is an objective and non-invasive index of autonomic nervous system activity and stress, which can be confounded by light intensity or age of an individual. Evaluating the influence of ambient light intensity variations or age on IPR is necessary to improve the validity of IPR for its clinical application in objective assessment of welfare and stress.Materials and MethodsIn this study we evaluated the influence of ambient light intensity variations and age on IPR in beef cattle breeds (Limousin, Belgian Blue and Charolais) and analysed the data using correlation statistics.ResultsThe correlation between the light intensity (20 to 500 lux; r = 0.22, p = 0.08) or age (10 to 145 months, r = 0.20, p = 0.12) and IPR was weak and statistically not significant. A sub-group analysis assessing the influence of gender on correlation between the light intensity and IPR also was not statistically significant.ConclusionOur results suggest that within the ambient light intensity (20 to 500 lux) and age (10 to 145 months) the variation in IPR is minimal. Hence our results validate the merit of IPR in objectively measuring autonomic activity/stress and demonstrate the practicality of using IPR for welfare assessment under ambient light conditions in wider age cohorts of beef cattle.

Back ground and objectives: Clavicle fracture accounts for approximately 2.6% of all the skeletal fractures. These fractures are often associated with shoulder girdle injuries in approximately 44% of cases. Non operative treatment has been a mainstay of a modality of treatment, and irrespective of the type of fracture and amount of comminution, all these fractures were treated non-operatively. Different surgical methods for clavicle midshaft fractures have been described and these are locking compression plate fixation, intramedullary K-wires, Steinmann pin fixation, and intramedullary nailing with TENS. Therefore in this study we have compared the functional outcome of displaced clavicle fractures treated by non-surgical management with that of surgical management by TENS and by open reduction and internal fixation with clavicular locking compression plate. Methods: 60 patients with clavicle fractures presenting to the Orthopaedic Department of R L Jalappa hospital from Nov. 2017 to April 2019 are included in the study after obtaining informed consent. Result: Among 60 patients with clavicle fractures, majority of the injury occurred in male patients- 45 cases (75%), whereas a total of 15 cases (25%) were seen in females. The functional outcome at the end of 6 months in 30 conservatively managed cases showed, 4 cases (13.3%) with excellent outcome; 6 cases (20%) had good outcome. 16 cases (53.3%) had fair and 4 cases (13.3%) had poor outcome. While in surgically managed 30 cases, the functional outcome at the end of 6months showed a total of 23(76.6%) cases with excellent outcome, 4 cases (13.3%) had good outcome 2 cases (6.6%) had a fair, and 1 case (3.33%) had poor outcome. At the end of 6 months, functional outcome of both the groups were compared by applying chi square test, the p value was

Introduction: Frozen shoulder” is a chronic condition characterized by gradually progressive, painful restriction of all shoulder joint movement, with slow spontaneous recovery of either partial or complete movement over a period of time. Although many treatment options have been proposed for the frozen shoulder syndrome, each has limitations. Hydro dilation technique was developed in order to loosen the reported contraction and adhesion. we evaluated the Range of movement and pain relief of shoulder following “Hydraulic distension under local anaesthesia along with a steroid” pre and post distension. Material and methods: A prospective observational study was conducted in the department of orthopaedics at RLJ hospital attached to Sri Devaraj Urs Medical College between June 2018 to November 2019 for a period of 1.5 year. All the Patients with Peri arthritis shoulder and age above 30 years were included in the study. After obtaining the informed consent from the patients, Demographic data, History, Clinical Examination and details of investigations were recorded in study proforma. The pain and functional scoring used as per “The society of American Shoulder and elbow surgeons” and follow-up was done at 3 weeks, 6 weeks and 12 weeks after procedure. IBM SPSS version 22 was used for statistical analysis. Results: Total 50 patients were included in the study. The average age of the study population was 52.68 ± 9.79. There were no patients with complete disability. Marked pain (grade 1) was observed on presentation in 46(92%) of the subjects. Post distension only 9(18%) had pain. Flexion, abduction, internal rotation, external rotation movements of the shoulder have improved post distention and were statistically significant at 3rd, 6th, 12 th week. The mean ASES was 36.04 ± 5.84 at base line, it was 67.6 ± 7.64 at 6th week and 91.04 ± 8.68 at 12th week. The differences in the ASES score at 6th week and 12th week follow up period with baseline value were statistically significant (P value

Introduction: Osteoarthritis (OA) is a painful chronic degenerative joint. As of now, there are less options available for patients with mild to moderate arthritis. Most of the approaches are palliative and address the symptoms rather than influencing the biochemical environment of the joint or the disease process.PRP is a newer treatment option emerging in the recent times and its efficacy needs to be examined in our population and hence the study.Materials and Methods: It is a prospective, observational, time bound, hospital-based study conducted from November 2017 to May 2019, after obtaining institutional Ethical committee approval. 60 primary OA knee joints, included in this study, selected from R L Jalappa Hospital and Research centre, Department of Orthopaedics, Kolar. Autologous PRP prepared and infiltration was done under strict aseptic conditions. Patients assessed with WOMAC scoring &VAS for pain, before giving the PRP injection & after giving the injection at periods of 1 month, 3 & 6 months. The decrease in WOMAC & VAS scores was suggestive of improvement in patient’s condition.Results: Significant difference was observed in mean VAS and WOMAC total scores. No local or systemic complications noted during the study period. The mean VAS score at baseline was 7.08 ± 0.79 and the decrease in mean VAS score continued up to six months follow-up that is 2.78 ±1.22 (P value

Background: An injury to the anterior cruciate ligament (ACL) is a multifactorial injury and is influenced by intrinsic and extrinsic risk factors. Recently, study of variable anatomy of the proximal tibia has come up as a possible risk factor for an ACL injury. Increased posterior tibial slope (PTS) has been identified as a potential risk factor for anterior cruciate ligament (ACL) injury, but studies which have examined this relationship are inconclusive and sometimes results are contradictory. Methodology: In this study sample size of total 72 patients was included, in which 38 patients had non-contact ACL injury and rest 34 constituted as a control group, who has same demographic characteristics as patients in ACL injury group. This study was conducted in period of April 2017 – Feb 2019 at tertiary care hospital, R.L. Jalappa Hospital, Sduaher, Tamaka, Kolar. All patients included in the study were above 18 years of age and also were willing to participate in the study. Patients with open injury of ipsilateral knee and with previous history of surgery over knee were excluded from the study. The posterior tibial slope was measured from a lateral knee radiograph in all the 72 cases. The data was analyzed for the association between an increased posterior tibial slope and the incidence of ACL injury. Results: In injured group of 38 patients, 15 patients were female and 23 were male. The average age of the patients in this group was 26.7 years (±6.3 years). The control group consisted of 34 patients, in which 24 were men and10 were women. The average age of the control group was 26.2 years (±6.5 years). An ANOVA revealed significant differences in tibial slope angle between the 2 groups. Subjects in the noncontact ACL group had significantly greater tibial slope angles (8.81° ± 2.58°) when compared with control subjects (6.9° ± 2.67°). The trend toward greater tibial slope angles in the noncontact ACL group was also observed when each gender was examined independently; however, the difference was only statistically significant for women between the injury and control groups (8.9° ± 2.6° vs 7.2° ± 2.4°). Conclusion: Our results concluded that, in patients who had non contact ACL injury, had increased posterior tibial slope. But despite of these findings, the clinical significance of an increased tibial slope as an isolated risk factor for ACL injury still remains unanswered. The question also remains as to what degree of increased tibial slope should raise concerns about the increased risk for subsequent injury. Limitations of this study were less number of cases and the study included only non contact ACL injuries. Thus, a study with more number of subjects and also comprising of contact ACL injuries, probably give a better conclusion. Level of evidence: Case-control retrospective study; Level III.

IntroductionHepatocellular carcinoma (HCC) is the most prevalent malignancy of the liver with limited clinical efficacy of currently used drugs such as sorafenib. Hence in this study we assessed the network proteins of HCC targets to identify the target/s which can achieve optimal clinical efficacy.Materials and MethodsThe reported HCC targets and their network proteins were identified in the string database. The interactions of the network proteins based on the number of hydrogen bonds formed were evaluated using the chimera software and used to merit the network protein interactions. The merit of network protein interactions in clinical efficacy was assessed based on the expression pattern of the network proteins and corelating their targeting by sorafenib.Results22 potential HCC targets were identified along with their 152 unique network proteins. The following HCC targets; PDGFRB, IFNA2, VEGFR2, PD1, C-MET, RAR and IGF1R were observed to be among the top networks with the most number of hydrogen bond interactions between them. Among these, C-MET, RAR and IGF1R were significantly expressed in hepatocytes, making them relevant HCC targets. PD-1 and PD-L1, which are immune checkpoint regulators and hence used as part of immune therapy, were observed to form higher numbers of hydrogen bonds with HCC network proteins.ConclusionOur analysis suggest that selectively targeting IGF1R, C-MET and RAR in hepatocytes together with immunotherapy will result in optimal clinical efficacy in the management of HCC.

Background: Distal femoral fractures reportedly account for less than 1% of all fractures and comprise between 4%–6% of all femoral fractures. The current method of open reduction and internal fixation has become evident in the recent years with good results being obtained with the AO blade plate, dynamic condylar screw and other implant systems like intramedullary retrograde nails and recently locking compression plate. Controversy still remains regarding the optimum device for distal femur fixation. Objectives: To compare functional outcomes of fractures of distal femur operated with distal femur locking compression plate and distal femur nail using range of motion at knee and Neers knee scoring system and to compare rate of complications associated with both treatment modalities. Materials and methods: In this retrospective study, 60 patients with displaced distal femur fractures presented to our hospital were studied from January 2012-june 2017. 30 patients underwent fixation with locking compression plate and rest 30 underwent distal femur nailing. Outcomes were measured and assessed at 1 months, 3 months and 6 months using Neers knee scoring system.Results: Union was achieved in all patients with mean time to radiological union being 20 weeks in retrograde nailing patients and 24 weeks in locking compression plating. Neer scores were graded as excellent in 51.7 % in retrograde nailing patients and 56.6 % in plating patients. Mean range of motion was more (115 degree) in retrograde nailing patients compared to locking compression plating patients (114 degree) at the end of follow up.Conclusion: There were no statistically significant differences found in functional outcome of the patients between the two surgical methods. Locking compression plate is better implant in comminuted intra-articular fractures of distal end of femur, particularly in elderly patients with osteoporotic bone. Retrograde intramedullary nailing is a good operative technique for extra-articular distal third femoral fractures. However, both techniques require sufficient surgical experience and appropriate preoperative planning.

Peritrochanteric fractures are devastating injuries that most commonly affect the elderly population and also the young. Peritrochanteric fracture is a leading cause of hospital admissions in elderly people. The number of such admissions is on a raise because of increasing life span and sedentary habits. Conservative methods of treatment results in malunion with shortening and limitation of hip movement as well as complications of prolonged immobilization. This study was done to analyze the surgical management of Peritrochanteric fractures using Proximal Femoral Nail. This is a retrospective study of 20 cases of trochanteric and subtrochanteric fractures admitted to R.L. Jalappa Hospital and Research Centre, S.D.U, M.C, Kolar, between July 2009 to October 2011. Patients with Peritrochanteric fracture above the age of 18yrs were included while pathological fractures and patients with associated co-morbidities posing a risk for surgery were excluded from the study. In our series of 20 cases, excellent results were seen in 50% cases, good in 33.3% cases, fair in 16.7% in trochanteric fractures. In subtrochanteric fractures, excellent results were seen in 64.3%, good in 21.4% cases and fair in 14.3%. From this sample study, we consider that PFN is an excellent implant for the treatment of Peritrochanteric fractures. The terms of successful outcome include a good understanding of fracture biomechanics, proper patient selection, good preoperative planning, accurate instrumentation, good image intensifier.