Transforming growth factor beta-3 localization in the corneal response to epithelial-stromal injury and effects on corneal fibroblast transition to myofibroblasts.

The purpose of this study was to evaluate the localization of TGF beta-3 in situ in unwounded rabbit corneas and corneas that had epithelial-stromal injuries produced by photorefractive keratectomy (PRK) in rabbits and to evaluate the in vitro effects of TGF beta-3 compared to TGF beta-1 on alpha-smooth muscle actin (α-SMA) protein expression and myofibroblast development in corneal fibroblasts. Forty-eight New Zealand white rabbits underwent either -3 diopter (D) or -9D PRK and were studied from one to eight weeks (four corneas in each group at each time point) after surgery with immunohistochemistry for TGF beta-3, laminin alpha-5, and alpha-smooth muscle actin (α-SMA). Rabbit corneal fibroblasts were treated with activated TGF beta-1 and/or TGF beta-3 at different concentrations and duration of exposure and studied with immunocytochemistry for myofibroblast development and the expression of α-SMA using Jess automated Western blotting. TGF beta-3 was detected at high levels in the stroma of unwounded corneas and corneas at one to eight weeks after -3D or -9D PRK, as well as in the epithelium and epithelial basement membrane (EBM). No difference was noted between corneas that healed with and without myofibroblast-mediated fibrosis, although TGF beta-3 was commonly associated with myofibroblasts. TGF beta-3 effects on corneal fibroblasts in vitro were similar to TGF beta-1 in stimulating transition to α-SMA-positive myofibroblasts and promoting α-SMA protein expression. The corneal stromal localization pattern of TGF beta-3 protein in unwounded corneas and corneas after epithelial-stromal injury was found to be higher and different from TGF beta-1 and TGF beta-2 reported in previous studies. TGF beta-3 had similar effects to TGF beta-1 in driving myofibroblast development and α-SMA expression in corneal fibroblasts cultured in medium with 1% fetal bovine serum.

6-Pin Technique Joshi External Stabilization System Fixation for Proximal Humerus Fractures - A Case Series.

Introduction: Proximal humerus fractures account for 4-5% of the fractures in long bones with a bimodal distribution. A wide spectrum of options are available in its management ranging from conservative to total shoulder replacement. We aim to demonstrate a minimally invasive simple 6-pin technique in the management of proximal humerus fracture using Joshi external stabilization system (JESS). Case Report: We report the results of ten patients (M: F = 4:6) with proximal humerus fractures of age range between 19 and 88 years managed with the 6-pin technique JESS under regional anesthesia. Of the included patients, 4, 3, and 3 cases belonged to Neer Type II, III, and IV, respectively. On analysis of outcomes based on the Constant-Murley score, we noted excellent outcomes and good outcomes in 6 (60%), and 4 (40%) patients, respectively, at 12 months. Fixator was removed after the radiological union between 8 and 12 weeks. Complications noted include pin tract infection in 1 (10%) and malunion in 1 (10%) case. Conclusion: JESS fixation by 6-pin technique remains a viable minimally invasive cost-effective treatment option in the management of proximal humerus fractures.

Comparison of Automated and Traditional Western Blotting Methods.

Traditional Western blotting is one of the most used analytical techniques in biological research. However, it can be time-consuming and suffer from a lack of reproducibility. Consequently, devices with different degrees of automation have been developed. These include semi-automated techniques and fully automated devices that replicate all stages downstream of the sample preparation, including sample size separation, immunoblotting, imaging, and analysis. We directly compared traditional Western blotting with two different automated systems, iBind™ Flex, which is a semi-automated system designed to perform the immunoblotting, and JESS Simple Western™, a fully automated and capillary-based system performing all steps downstream of sample preparation and loading, including imaging and image analysis. We found that a fully automated system can save time and importantly offer valuable sensitivity. This is particularly beneficial for limited sample amounts. The downside of automation is the cost of devices and reagents. Nevertheless, automation can be a good option to increase output and facilitate sensitive protein analyses.

Management of mangled hand injuries with JESS fixator in a tertiary care hospital in North East India: A prospective study.

Introduction: Mangled hand injuries have proved to be a tough challenge for both the patients and surgeons alike. Severe bony and soft tissue injuries necessitate the requirement of a multidisciplinary approach. Materials: In our tertiary care facility, a prospective study was done on the use of the Joshi's external stabilization system (JESS) fixator in the treatment of 31 instances with mangled hand injuries from November 2019 to November 2020. The cases were evaluated for functional outcome at the end of 12 months of follow up. Results: 31 cases of mangled hand injuries with 43 fractures were treated with the said intervention. The mean age of the patients was 33.7 ± 4.2 years and almost 90% patients were males. Machinery injuries were the most frequent type of injury (55%). Cases were intervened at an emergency basis within 24 h of the injury. Functional evaluation was done by Modified Mayo Wrist Score with an average score of 84 ± 10. Good results were seen in about 60% of cases and there were no Poor results. Conclusion: The application of JESS fixator for the prompt treatment of mangling hand injuries yielded satisfactory results in the working population with an early return to function. The strict adherence to the principles of ligamentotaxis, appropriate wound care and post-operative physiotherapy are other variables in the final outcome of such injuries. Level of evidence: II.

Comparison of Supersaturation Outputs from Different Programs and Their Application in Testing Correspondence with Kidney Stone Composition.

Introduction: Relative supersaturation (SS) for calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA) has been used for assessing urinary crystallization and estimated by programs, including EQUIL, Joint Expert Speciation System (JESS), and Lithorisk. We compared outputs from these programs and their correspondence with stone composition. Materials and Methods: SS of CaOx, CaP, and UA, using EQUIL, JESS, and Lithorisk were calculated from stone-forming patients. Pearson correlation coefficients were used to ascertain the correspondence between the outputs. Fractional regression models evaluated the relationship between SS and the percentage of each compound in the stones. Results: Two hundred eleven patients were included. Pearson correlation coefficients for CaOx (r ≥ 0.96), CaP (r ≥ 0.99), and UA SS (r ≥ 0.99) showed a high correspondence between all programs. We observed a significant correspondence between CaOx SS and the percentage of CaOx dihydrate in the stone (p < 0.001), as well as between the percentage of brushite and apatite and CaP SS. UA SS showed the strongest correspondence with the percentage of UA in the stones (p < 0.001). Conclusions: Good correlation between EQUIL, JESS, and Lithorisk was observed and good correspondence with stone composition. The magnitude of the association demonstrated by fractional regression models supports evidence for applying SS in clinical practice.

Lauric acid ameliorates lipopolysaccharide (LPS)-induced liver inflammation by mediating TLR4/MyD88 pathway in Sprague Dawley (SD) rats.

BACKGROUND: Lipopolysaccharide (LPS) is an endotoxin that leads to inflammation in many organs, including liver. It binds to pattern recognition receptors, that generally recognise pathogen expressed molecules to transduce signals that result in a multifaceted network of intracellular responses ending up in inflammation. Aim In this study, we used lauric acid (LA), a constituent abundantly found in coconut oil to determine its anti-inflammatory role in LPS-induced liver inflammation in Sprague Dawley (SD) rats. METHOD: Male SD rats were divided into five groups (n = 8), injected with LPS and thereafter treated with LA (50 and 100 mg/kg) or vehicle orally for 14 days. After fourteen days of LA treatment, all the groups were humanely killed to investigate biochemical parameters followed by pro-inflammatory cytokine markers; tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß. Moreover, liver tissues were harvested for histopathological studies and evaluation of targeted protein expression with western blot and localisation through immunohistochemistry (IHC). RESULTS: The study results showed that treatment of LA 50 and 100 mg/kg for 14 days were able to reduce the elevated level of pro-inflammatory cytokines, liver inflammation, and downregulated the expression of TLR4/NF-κB mediating proteins in liver tissues. CONCLUSION: These findings suggest that treatment of LA has a protective role against LPS-induced liver inflammation in rats, thus, warrants further in-depth investigation through mechanistic approaches in different study models.

Results of JESS (Joshi's External Stabilizing System) in Relapsed, Neglected and Neurogenic Clubfoot in an Age Group of 2-10 Years.

BACKGROUND: Joshi's External Stabilization System (JESS) is an external fixator based methodology to correct different deformities of club foot using differential distraction. MATERIAL AND METHODS: 31 difficult clubfeet feet in 24 patients who were neglected, neurogenic or relapsed were treated using JESS between July 2013 to June 2015 with an average follow-up of 4. 2 years. There were 16 males and 8 females in an age group of 2-10 years. 30 feet belonged to the severe and most severe group as per the Dimeglio Scoring System. All patients achieved correction of all components of the clubfoot. RESULTS: However, one patient required tibialis anterior transfer for dynamic forefoot adduction at the end of treatment. The mean total duration in JESS fixation was 69.5 days/foot (range 44-123 days) and the mean time to achieve correction within JESS averaged 52 days. The deformities improved from a mean Dimeglio score of 14.06 to 2.93. The objective radiological assessment of the deformities revealed improvements in the talocalcaneal angle on AP view from 16.39° to 34.52° and on lateral view from 15.97° to 33.03°. The Talo-1st metatarsal angle (AP view) improved from 35.29° to 7°. Complications included 11 cases of superficial pin tract infection, two instances of pin loosening and a case of pin cut out. There were three cases of 1st metatarsophalangeal dislocation that were managed by reversing the process of distraction. CONCLUSION: JESS is an effective method for managing difficult clubfeet.

Multimodal treatment including standard chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for the Ewing sarcoma family of tumors in Japan: Results of the Japan Ewing Sarcoma Study 04.

BACKGROUND: The survival rate in patients with Ewing sarcoma family of tumors (ESFT) in Japan was reported to be < 50% in the 1990s. The Japan Ewing Sarcoma Study Group was established to improve the prognosis of ESFT in Japan. The aim of this phase II trial was to determine the efficacy and safety of multimodal treatment for nonmetastatic ESFT. PROCEDURE: Patients with ESFT aged < 30 years were eligible for participation. The chemotherapy regimen consisted of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) repeating every 21 days for 52 weeks. Local treatment included surgery and/or radiation therapy (0-55.8 Gy) based on the margin of resection and histologic response. The primary endpoint was progression-free survival (PFS) at three years. The study was designed to test whether the lower limit of the 90% confidence interval for PFS would exceed the threshold of 60%. The planned sample size was 53 patients, allowing for 10% of patients being ineligible. RESULTS: Of the 53 patients screened for entry, seven were deemed ineligible. Forty-six patients were considered as the per-protocol set and were used for the efficacy analysis. Three-year PFS was 71.7% (0.59-0.81). Estimated five-year PFS and overall survival were both 69.6%. Although no previously unknown adverse event was reported, three patients developed secondary malignancies (acute lymphoblastic leukemia, myelodysplastic syndrome, and osteosarcoma, one patient each). CONCLUSIONS: Multimodal treatment with standard VDC-IE chemotherapy improved the prognosis for patients with ESFT in Japan, although statistical confirmation of efficacy compared to historical control was not achieved.

Transradial, Transscaphoid, Transcapitate, Perilunate Dislocation; A Case Report and Approach to the Patient.

Carpal injuries are uncommon and are mainly seen in the younger age group. The incidence is unclear as many of the cases go undiagnosed. A 22-year-old male patient coming to the hospital after road traffic accidentwith head, face and left wrist injury. After immediate primary management the patient was taken up for a definitive procedure 4 days after the injury. Scaphoid fracture was fixed with the help of Herbert's screw via the dorsal approach. The base of the first metacarpal was fixed with the help of JESS fixator and the distal end radius was fixed with the help of K-wires.  The scapholunate and lunato triquetral ligaments were repaired. The whole construct was stabilized with the help of an external fixator. Postoperative period was uneventful. The external fixator was removed after 4 weeks and patient had a good functional outcome with the patient related wrist evaluation score coming out to be 11 at the end of the third month. This uncommon case of Transradial, Trans scaphoid, transcapitate, and perilunate dislocation was managed successfully with no postoperative complications and a good functional outcome.

Management of Proximal Tibia Fractures Using Wire Based Circular External Fixator.

INTRODUCTION: Management of high grade proximal tibia or tibial plateau fractures is often associated with complications. The use of wire fixators for the definitive treatment of such fractures entails a minimally invasive technique of insertion that gives good fracture reduction and stability combined with minimal postoperative complications. AIM: To assess the outcome of treatment of such fractures by the use of Joshi's external stabilization system (JESS), which is a wire based, circular external fixator system. MATERIALS AND METHODS: A prospective, uncontrolled study was done using JESS on 20 consecutive patients of high energy fractures of the tibial plateau, classified according to the Schatzker's classification as type VI. RESULTS: In this series, road traffic accidents accounted for most of the injuries (n=12), while pedestrian accidents (n=4), injury due to fall from height (n=3) and injury due to fall while playing (n=1) were the other modes of injury. The mean patient age was 39.4 years. The mean follow up period was 24 weeks. In this study, using Knee society score evaluation, excellent results were seen in 12 patients (60%), good results were seen in 5 patients (25%), fair in 2 patients (10%) and bad in 1 patient (5%). Complications seen were, pin tract infections in two cases (10%) which resolved with dressings and oral antibiotics and one case of non-union (5%), in which the tibial plateau fracture extended into proximal 1/3 of the tibial shaft with severe comminution. No other complication was encountered. CONCLUSION: JESS is a simple, inexpensive and useful technique in the management of high grade tibial plateau fractures.

Comparative study of complete subtalar release and Joshi's external stabilization system in the management of neglected and resistant idiopathic clubfoot.

BACKGROUND: Various procedures have been used for the management of neglected and resistant clubfoot. The aim of our study was to assess the clinical and radiological correction by Joshi's external stabilization system (JESS fixator) and Simons subtalar release in resistant and neglected idiopathic congenital talipes equinovarus in children between the ages of 1 and 2 years. METHODS: A total of 50 resistant and neglected clubfeet were randomly divided into two equal groups of 25 feet each. Group I was treated with JESS fixator and group II was treated with complete subtalar release as described by Simons. Assessment of correction achieved was done both clinically and radiologically. Functional outcome was assessed with Ponseti scale. RESULTS: The change in clinical deformity and radiological correction of deformity were statistically significant within each group, but not significant when compared to each other. In group I excellent results were obtained in 17 (68%) and good in 8 (32%) of the feet. In group II, excellent results were found in 16 (64%) and good in 9 (36%) feet out of the 25 feet. Pin-site infections were seen in two cases in group I and serious skin problems occurred in two feet in group II. CONCLUSION: We conclude that there were no statistical significant differences between the outcomes of the two techniques in this short-term follow-up of 2.4 years. Thus, functional distraction using JESS can be utilized as an alternative method in cases of neglected and resistant clubfoot.

Management of radial clubhand with gradual distraction followed by centralization.

BACKGROUND: Treatment of radial clubhand has progressed over the years from no treatment to aggressive surgical correction. Various surgical methods of correction have been described; Centralization of the carpus over the distal end of the ulna has become the method of choice. Corrective casting prior to centralization is an easy and effective method of obtaining soft tissue stretching before any definitive procedure is undertaken. Moreover, it helps put the limb in a correct position. The outcome of deformity correction by serial casting / JESS distractor followed by centralization is discussed. MATERIALS AND METHODS: In a prospective study, of 17 cases with 18 radial clubhands of Heikel's Grade III and IV (with average age 11 months (range 20 days - 24 months) with M:F of 2.6:1, were treated by gradual soft tissue stretching using corrective cast (14 cases) and JESS distraction (4 cases), followed by centralization (16 cases) or radialization (2 cases) and tendon transfers. RESULTS: The average correction attained during the study was 71 degrees of radial deviation and 31 degrees of volar flexion. The average third metacarpal to distal ulna angle in anteroposterior and lateral view at final follow-up was 7 degrees in both views. Angle of movement at elbow showed a small increase from 99 degrees to 101 degrees during the follow-up period. However, the range of movement at fingers showed increase in stiffness during the follow-up. No injury occurred to the distal ulnar epiphysis during the operative intervention. The results at the final follow-up, at the end of 2 years were graded on the basis of the criteria of F.W. Bora, and of Bayne and Klug. Considering the criteria of F.W. Bora, satisfactory result was shown by nine of the 18 hands (50%) while 16 out of 18 hands (89%) showed good or satisfactory result based on deformity criteria of Bayne and Klug. CONCLUSION: The management of radial clubhand by gradual corrective cast or JESS distractor followed by centralization and tendon transfers in children is an acceptable method of treatment with consistently satisfactory results, both functional and cosmetic.