Computational Analysis of miR-140 and miR-135as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy

Background@#Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy. @*Methods@#The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed.Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach. @*Results@#Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming. @*Conclusions@#In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.

Trametes versicolor (L.) Lloyd as a source of thermostable serine protease: production and characterization

Proteases are ubiquitously present and are among the largest groups of commercially important enzymes. Here, we investigated a wood-rot basidiomycete Trametes versicolor (L.) Lloyd [Syn. Coriolus versicolor (L.) Quél.; Polyporus versicolor (L.) Fr.] as a source of the enzyme serine protease, its production, and optimized to obtain a higher yield of the enzyme.. The significant variables with optimized values for maximum production of the enzyme were temperature (30?C), incubation time (120 h) and wheat bran (10 g). The yield increased by 30.76% by statistically optimizing the media. The optimized temperature and pH for the maximum protease activity was 50?C and pH 7.0, respectively. The enzyme was purified through ion exchange (using DEAE cellulose 52 resin) and gel filtration chromatography (using Superdex 200 column). The purified enzyme had a retention time of 7 min in RP-HPLC. The enzyme was stable at a broad range of temperature (30-60?C) and pH (5.0-8.0) with a half-life of 58.72 min, Vmax of 37.17 ?M min/mL and Km of 0.657 mg/mL. Its activity was enhanced by Na+, Ca2+, Mg2+ ions and SDS surfactant. These properties make this enzyme a valuable candidate for industrial applications

Effect of Anti?Platelet Therapy on Peri?Operative Blood Loss in Patients Undergoing Off?Pump Coronary Artery Bypass Grafting

Purpose:The purpose of this study was to review the effect of the pre?operative use of clopidogrel and aspirin on peri?operative bleeding, blood product transfusion, and resource utilization after coronary artery bypass grafting (CABG). Materials and Methods: A total of 1200 patients who underwent off?pump CABG (OPCABG) between 2010 and 2012 were retrospectively studied. Patients were divided into three groups: group 1: discontinued aspirin and clopidogrel 6 days prior to surgery (n = 468), group 2: discontinued both drugs 3 to 5 days prior to surgery (n = 621), and group 3: discontinued both drugs 2 days prior to surgery (n = 111). The bleeding pattern and blood product transfusion were studied and compared between the groups. Patients having history of other drugs affecting the coagulation profile, other organ dysfunction, on?pump CABG, and the combined procedure were excluded from the study. Results: Group 2 patients had a higher rate of bleeding and a reduced mean value of hemoglobin (Hb) as compared to other groups. The same results were seen in blood and blood product transfusion. Patients of group 2 and group 3 were associated with higher blood loss in terms of drainage at 12 and 24 hours. Post?operatively, this was statistically significant. Re?exploration was statisitically significant in group 3 patients (9.01%) than in group 2 (2.58%) and group 1 (1.07%) patients. Conclusion: The pre?operative use of clopidogrel and aspirin in patients undergoing OPCABG showed limited clinical benefits; however, its use significantly increased the risk of bleeding and blood transfusion, thus increasing morbidity and resource utilization. Hence, clopidogrel and aspirin should be stopped at least 6 days prior to surgery.

Comparative analysis of P-POSSUM score at admission and pre-operatively in predicting postoperative mortality in patients undergoing emergency laparotomy

Introduction: Laprotomy remains one of the commonest emergency surgical procedure performed worldwide. But over the last few years, various perioperative quality improvement initiatives involving early interventions, intensive postoperative care, and indivisualised care approaches have ensured a decrease in the average mortality rate by 3.8%-8.3. An ideal scoring system should accurately predict outcomes, help determine who deserves more aggressive care, guide in deciding the extensiveness of surgery, and can be used broadly access emergency laprotomies for various disease pathologies. The scoring system should also be capable of analyzing risk adjusted morbidity and mortality amongst various healthcare providers. Aim: To access the accuracy of P-POSSUM score on predicting the mortality and morbidity in emergency laparotomy patients and to establish that the preoperative score is more accurate that admission score. Materials and Methods: 150 Cases of emergency laparotomy in General Surgery Department in IGIMS, Patna from September, 2020 to February, 2022 were taken up in this study. Patients below 18 years, routine surgery and 6 patients who could not be followed up for complete 30 days were excluded. Physiological P-POSSUM was calculated at the time of admission and just before operation, post resuscitation. Operative score was same for both Physiological P-POSSUM scores. Results: Mortality predicted at admission had statistically significant difference and p value was<0 xss=removed>.05. Most common complication was wound infection followed by septicaemia. Conclusion: P-POSSUM is a better predictor of mortality and morbidity in emergency laparotomies when scoring is done preoperatively.

Comparative study of wound healing following purse-string closure versus conventional linear closure for stoma reversal

Background: Stoma closure is associated with several complications, wound infection being the most common. This study is done to establish that purse string suture closure method for stoma closure is superior to the conventional linear mattress closure and is associated with better wound healing cosmesis. Materials and Methods: This Prospective randomized controlled study enrolled 80 patients who underwent stoma closure from April 2021 to March 2022 in department of General Surgery in IGIMS, Patna. Patients were divided in two groups inclusive of ileostomy and colostomy based on type of closure technique. Conventional linear closure method was applied to Group A and purse-string technique applied to Group B patients. All Patients were followed regularly upto three months after operation. Rate of infection, pain as assessed by VAS score and satisfaction as assessed by POSAS Score were done. Results: Purse string Closure had better outcome in terms of wound infection rate and Cosmetic results over a 3 months follow up. Ten patients in Group A and 2 from Group B out of 40 patients had wound infection. Patients with purse-string suture had statistically significant greater satisfaction over 3 months. Medium operative time of Group A was 100 minutes and that of Group B was 98 minutes. There were no significant difference in regards duration of hospital stay was more in Linear Group than Purse String (Group B). Conclusion: Purse-string closure was associated with better cosmesis and lower infection rate in comparison to Linear conventional closure.

Diagnostic performance of microRNA-34a, let-7f and microRNA-31 in epithelial ovarian cancer prediction / 부인종양

Objective@#To correlate the genome-wide methylation signature of microRNA genes with dysregulated expression of selected candidate microRNA in tissue and serum samples of epithelial ovarian cancer (EOC) and control using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and evaluation of EOC predictive value of candidate microRNA at an early stage. @*Methods@#We performed Methylated DNA Immunoprecipitation coupled with NGS (MeDIP-NGS) sequencing of 6 EOC and 2 normal tissue samples of the ovary. Expression of selected microRNA from tissue (EOC=85, normal=30) and serum (EOC=50, normal=15) samples was evaluated using qRT-PCR. We conducted bioinformatics analysis to identify the candidate miRNA’s potential target and functional role. @*Results@#MeDIP-NGS sequencing revealed hypermethylation of several microRNAs gene promoters. Three candidate microRNAs were selected (microRNA-34a, let-7f, and microRNA-31) from MeDIP-NGS data analysis based on log2FC and P-value. The relative expression level of microRNA-34a, let-7f, and microRNA-31 was found to be significantly reduced in early-stage EOC tissues and serum samples (p<0.0001). The receiver operating characteristic analysis of microRNA-34a, let-7f and miR-31 showed improved diagnostic value with area under curve(AUC) of 92.0 (p<0.0001), 87.9 (p<0.0001), and 85.6 (p<0.0001) and AUC of 82.7 (p<0.0001), 82.0 (p<0.0001), and 81.0 (p<0.0001) in stage III-IV and stage I-II EOC serum samples respectively. The integrated diagnostic performance of microRNA panel (microRNA-34a+let-7f+microRNA-31) in late-stage and early-stage serum samples was 95.5 and 96.9 respectively. @*Conclusion@#Our data correlated hypermethylation-associated downregulation of microRNA in EOC. In addition, a combined microRNA panel from serum could predict the risk of EOC with greater AUC, sensitivity, and specificity.

Carotid cavernous fistula: Redefining the angioarchitecture

Objective@#Numerous classification schemes have been used for carotid cavernous fistula (CCF), each describing some aspect of the disease process but none of them provides a complete description of the fistula including its clinical features, natural history, arterial and venous architecture. @*Methods@#Retrospective clinical and radiological review was done for all the patients diagnosed with CCF and treated at our institute. The CCF were classified according to the proposed API-ACE classification along with Barrow and Thomas classification. @*Results@#Overall 28 patients (M=21, F=7) were diagnosed and treated during the 6-year period. 89.2% of CCF developed following an episode of head injury. Orbital symptoms were the most common presenting complaints. Barrows type A was the most predominant subtype (n=24) and most of the patients (n=23) demonstrated decreased ipsilateral carotid filling. Combined anterior and posterior drainage pattern was the most common drainage pattern and anterior drainage was more commonly observed than posterior drainage. @*Conclusions@#API-ACE classification helps to better understand and classify the angioarchitecture of CCF which could help better understand the clinical manifestations and guide in appropriate endovascular approach selection for treatment.

Blunt Hohman-Lever Technique for Reduction of Intertrochanteric Fracture – A Surgical Technique

We present a 60 years old patient who presented to us with history of domestic fall and sustained injury to the right hip and was diagnosed with trochanteric fracture right side. As closed reduction was not acceptable and bone spike was not available in the set, we designed our own technique of using a bone lever introduced from the same incision from where reaming/nail insertion was done. To the best of our knowledge this technique has never been described before in english literature.Since our first case we have tried it in 6 other patients and without any issues

Bilateral Transolecranon Fracture-Dislocation Elbow with Bilateral Coronoid and Radial Head Fractures – A Rare Complex Elbow Injury: A Case Report and Review of Literature

Bilateral olecranon fractures are a rare occurrence. Direct trauma usually results in comminuted fractures and indirect trauma in transverse fractures. We describe a case of bilateral olecranon fracture with a radial head comminuted fracture with coronoid fracture without the involvement of collaterals. Olecranon fractures are usually a result of direct trauma (fall from height/motor vehicle accidents) or indirect trauma. A 22year old male patient presented to the emergency department with complaints of pain and swelling around both elbows following a motor vehicle accident. The patient also sustained trauma to the head and had a history of transient loss of consciousness. CT brain at the time of presentation was normal and the patient was conscious. The Olecranon Fracture was fixed with a pre-contoured olecranon locking compression plate (Synthes, USA). In our case, the collaterals were intact and as the radial head was comminuted, we excised the radial head. The radial head being secondary stabilizer of the elbow in injuries to the medial collateral ligament complex. The excision of the radial head would not cause any instability. Bilateral olecranon fractures need to be fixed anatomically, the comminuted radial head was excised and the anterior capsule was repaired

Bilateral Elbow Dislocation with Radial Head Fractures in a 33 Year Male – A Rare Case Report

The authors report a rare case of bilateral elbow dislocation with associated radial head fractures in a 33 year male who presented to our hospital following a road traffic accident. The elbow dislocations were reduced in the emergency room, the left radial head fracture was treated conservatively in an above elbow slab for four weeks and the right radial head and neck fracture was treated operatively with Herbert screw fixation for the radial head fracture andbuttress plating for the radial neck fracture. At six months follow-up, the patient was pain free and had functional range of flexion and extension of both elbows with pronation and supination of the right elbow up to 50°and 40° and that of the left elbow up to 60° and 45° respectively.

Os Acromiale-unusual Manifestation as Superior Spur and Bursitis-A Case Report

An Os acromiale is a condition that results from the failure of fusion of the anterior acromial apophysis. It can be asymptomatic. It can also result in subacromial impingement and rotator cuff tear. In this case report of a 39year-old lady we would like to present the management of the painful bursitis and spur formation on the superior surface of a meso-type of os acromiale. Conservative management in the form of rest, anti-inflammatory drugs and physiotherapy did not provide symptomatic relief. Patient then underwent surgical excision of the superior spur. Open reduction and internal fixation was not carried out. Patient had resolution of pain and no recurrence of symptoms or features of impingement at 6 months follow up. To the best of our knowledge there are limited reportsin English literature about this rare subset of patients with symptomatic os acromiale with superior spur formation and with no features of impingement or cuff pathology.

Distal Humeral Shear Fracture - A Modified Technique for Exposure

Coronal shear fractures of the distal humerusare rare, complex fractures that can be technically challenging even in the best of hands. Their peak incidence is seen in elderly females and is usually the result of low energy fall. The injury is usually part of complex elbow injury and in rare instances can be isolated entity. Complex injury pattern is characterized by shear fracture combined with fracture of radial head and collateral ligament injury. The preferred treatment for this complex fracture is Open reduction and internal fixation. The usual recommendation is a two-incision approach. We report a rare case in which fracture could not be classified using the traditional classification systems and in which entire fracture was managed via a single approach

A novel microwave mediated disinfection method for hospital linen

Linen fabrics used in healthcare facilities need proper disinfection and sterilization to ensure hygiene. Due to several side effects from the recommended chemical disinfectants, there is always a need for appropriate and affordable technology to disinfect and sterilize the linen. Here, we propose a device for dry sterilization of linen using microwave associated thermal heating system. The principle behind this device is dielectric heating, several optimizations, such as microwave strength, exposure, hold time; system heating, etc. was done to achieve an optimum cycle to disinfect the hospital linen. The optimized cycle was sufficient to reduce the surviving rate of microbes up to log 10 value at 70°C system temperature. This low temperature direct killing is suitable for both the life of linen and energy consumption

Primary Non-Hodgkin’s Lymphoma Of Epidural Space- A Case Report Of Great Mimicker And Review Of Literature

Primary Non-Hodgkin’s lymphoma of epidural space is a rare entity. Clinical presentation and imaging studies were bizarre and posed the difficulty in diagnosis. Since the management protocol of spinal lymphoma is yet to be standardized, so the prognosis is still looming. Here we are reporting a case of epidural primary Non-Hodgkin’s lymphoma in young adult female, who presented with backache and weaknes

A case report on hyperpigmentation in vitamin B12 deficiency

Cobalamin (Vitamin B12) is a water-soluble vitamin. Cobalamin is synthesized only by microorganisms. The only source of vitamin B12 for humans is food of animal origin. Hyperpigmentation of skin has been reported only rarely as the presenting manifestation of vitamin B12 deficiency. We report a patient who had hyperpigmentation as her presenting medical complaint and in whom Vitamin B12 deficiency was the cause.  A 36-year-old female presented with generalised weakness and progressive and asymptomatic hyperpigmentation of hand and feet for 5 months. She is vegetarian by diet. On examination, hyperpigmentation was present over dorsal aspect of metacarpophalangeal, proximal and distal interphalangeal joints. Hyperpigmentation were present over dorsum of the foot and over the joints. The tongue was depaillated, and hyperpigmentation was present. Her serum level of vitamin B12 was diminished (83pg/ml). Megaloblastic anemia presents with protean manifestations. The association between vitamin B12 deficiency and hyperpigmentation, although unusual, has been described. Cutaneous manifestations associated with B12 deficiency include characteristic mucocutaneous hyperpigmentation (most common), vitiligo, angular cheilitis, and hair-nail changes. It mainly affects knuckle pads and oral mucosa. It is an under-recognized sign of megaloblastic anemia and should always be looked for in the setting of pallor. Hyperpigmentation could be the earliest manifestation of vitamin B12 deficiency before anemia sets in. It is worthwhile to consider the possibility of vitamin B12 or folate deficiency in a patient with unexplained pigmentary changes. Early detection and adequate treatment will prevent anemia and various neurological manifestations.

Study of association between the serum lipid profile and age-related macular degeneration in a tertiary care centre of Central UP

Background: Age-related macular degeneration (ARMD) is the major challenge in the new millennium in the developing countries as the size of elderly population continues to rise due to betterment of medical facilities and increased life expectancy. Lipids are implicated in the pathogenesis of ARMD. The relationship between systemic lipids and ARMD has not been well characterized, especially in rural population. The objective was to investigate the relationship between serum lipids and ARMD in older adults.Methods: In this case-control study, 300 adults, aged ≥50 years, 150 each among cases and controls were included in the study. Mean lipids values between cases and controls were compared.Results: Mean age of cases was 62.45±8.472 years and mean age of controls was 61.89±8.51 years. Among 150 cases, 124 (82.66%) cases were of dry ARMD while 26 (17.33%) cases were Wet ARMD. Author found that 38 cases among total cases (25.33%) and 15 individuals (10%) among controls had altered lipid profile. All mean lipid values were higher among cases compare to controls (p>0.05), while the mean of VLDL, TG and TG/HDL were significantly raised showing positive association (p<0.05).Conclusions: Present study showed that high levels of serum lipid values especially VLDL, TG and TG/HDL positive association with an increased risk for development of ARMD, implying that strategies reducing serum lipid levels may be useful to prevent the development of the disease.

Bubaline Diaphragm Matrix: Development and Clinical Assessment into Cattle Abdominal Hernia Repair

Abstract The purpose of the study was to develop a xenogenic bubaline diaphragm matrix (BDM) for abdominal hernia repair. A fresh diaphragm was decellularized using aqueous sodium dodecyl sulfate (SDS) solutions (0.5-4% w/v) over a period. Acellularity was confirmed histologically and characterized by Masson's trichrome staining, scanning electron microscopy (SEM), DNA quantification, agarose gel electrophoresis, and Fourier-transform infrared spectroscopy. The BDM was used for clinical abdominal hernia repair in six cattle. Clinical, hemato-biochemical and antioxidant parameters were evaluated to assess biocompatibility of xenogenic BDM. Histologically, the diaphragm treated with 2% SDS for 48 h showed complete acellularity and orderly arranged collagen fibers. The SEM confirmed preservation of collagen structure and integrity. The DNA content was significantly (P < 0.05) reduced in BDM (33.12 ± 5.40 ng/mg) as compared to the native diaphragm (443.96 ± 162.60 ng/mg). DNA extracts from BDM show considerable removal of DNA material, with absence of DNA band in agarose gel. The FTIR spectrum of BDM has shown all characteristic transmittance peaks of bovine skin collagen indicating preserved collagen structure. Six cattle with BDM implant recovered uneventfully and remained sound at least upto 6 months. Hemato-biochemical and antioxidant findings were unremarkable. Bubaline diaphragm matrix shows excellent repair efficiency and biocompatibility for abdominal hernia repair in cattle without complications.

Multicystic Lesion in Jaws: A Rare Case Report on Gorlin-Goltz Syndrome

Background and Objectives: Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder, which is characterized by multiple odontogenickeratocysts (OKC) and basal cell carcinomas, skeletal, dental, ophthalmic and neurological abnormalities.Material and Methods: Thirteen years old male patient came with swelling of left maxilla obliterating buccal vestibule with pus discharge for 1 month. The orthopantomograph and computed tomography scan demonstrated multiple lytic lesions in maxilla and mandible.  Incisional biopsy was suggestive of odontogenickeratocyst (OKC). Besides multiple OKCs; bifid ribs, palmer pits and hypertelorism were present supporting for the diagnosis as Gorlin-Goltz Syndrome.Results: The classical treatment of KCOT with enucleation with curettage or resection would have resulted in significant morbidity. Therefore we first decompressed and then enucleated the cysts.Conclusion: Gorlin-Goltz syndrome is a rare entity and the multiple KCOT can be managed with decompression followed by enucleation.

Ethnomedicinal, phytochemical and pharmacological updates on Hygrophila auriculata (Schum.) Hiene: an overview / 中西医结合学报

This article explores the most recent evidence-based information on ethnomedicinal, phytochemical and pharmacological understanding of Hygrophila auriculata for the treatment of various diseases and health conditions. Various ethnomedicinal writings suggest the use of the plant or its parts for the treatment of jaundice, oedema, gastrointestinal ailments, diarrhoea, dysentery, urinogenital disorder, gall stones, urinary calculi, kidney stone, leucorrhoea, rheumatism, tuberculosis, anaemia, body pain, constipation, skin disease, and as an aphrodisiac. The plant has been reported to contain flavonoids (apigenin, luteolin, ellagic acid, gallic acid and quercetin), alkaloids (asteracanthine and asteracanthicine), triterpenes (lupeol, lupenone, hentricontane and betulin), sterols (stigmasterol and asterol), minerals, amino acids, fatty acids, aliphatic esters and essential oils. Extracts and bioactive compounds from the plant have been found to possess antimicrobial, anthelmintic, antitermite, nephroprotective, hepatoprotective, central nervous system protective, antitumour, antidiabetic, anticataract, antioxidant, haematopoietic, diuretic, antinociceptive, anti-inflammatory, antipyretic, antimotility, aphrodisiac, neuroprotection, anti-endotoxin and anti-urolithiatic activities. For this paper, we reviewed patents, clinical studies, analytical studies and marketed formulations from the earliest found examples from 1887 to the end of 2017.

Cone beam- computed tomography as an indispensable tool in the management of radiculous premolar: a case report

Background: Internal anatomy of maxillary first premolars is particularly multifaceted on account of the variation in number of roots and canal configuration. Maxillary first premolars with 3 roots are called as small molar or "radiculous" because of their similar anatomy to the maxillary first molars. The most demanding step in endodontic treatment is identification and proper access to pulp canals of certain teeth with atypical canal configurations. Methods of identification of such premolars can be by various aides. Case Presentation: The present case describes the application of Cone Beam-Computed Tomography in the diagnosis of extra root with extra canal in a three rooted maxillary right first premolar. Conclusions: Proper knowledge of the anatomical variations is a must for an endodontist to make a treatment successful. Utilizing the latest technology along with the traditional concepts can surely rule out the inaccuracy in the treatment involved in such cases.