Impact of cannabinoids on synapse markers in an SH-SY5Y cell culture model.

Patients suffering from schizophrenic psychosis show reduced synaptic connectivity compared to healthy individuals, and often, the use of cannabis precedes the onset of schizophrenic psychosis. Therefore, we investigated if different types of cannabinoids impact methylation patterns and expression of schizophrenia candidate genes concerned with the development and preservation of synapses and synaptic function in a SH-SY5Y cell culture model. For this purpose, SH-SY5Y cells were differentiated into a neuron-like cell type as previously described. Effects of the cannabinoids delta-9-THC, HU-210, and Anandamide were investigated by analysis of cell morphology and measurement of neurite/dendrite lengths as well as determination of methylation pattern, expression (real time-qPCR, western blot) and localization (immunocytochemistry) of different target molecules concerned with the formation of synapses. Regarding the global impression of morphology, cells, and neurites appeared to be a bit more blunted/roundish and to have more structures that could be described a bit boldly as resembling transport vesicles under the application of the three cannabinoids in comparison to a sole application of retinoic acid (RA). However, there were no obvious differences between the three cannabinoids. Concerning dendrites or branch lengths, there was a significant difference with longer dendrites and branches in RA-treated cells than in undifferentiated control cells (as shown previously), but there were no differences between cannabinoid treatment and exclusive RA application. Methylation rates in the promoter regions of synapse candidate genes in cannabinoid-treated cells were in between those of differentiated cells and untreated controls, even though findings were significant only in some of the investigated genes. In other targets, the methylation rates of cannabinoid-treated cells did not only approach those of undifferentiated cells but were also valued even beyond. mRNA levels also showed the same tendency of values approaching those of undifferentiated controls under the application of the three cannabinoids for most investigated targets except for the structural molecules (NEFH, MAPT). Likewise, the quantification of expression via western blot analysis revealed a higher expression of targets in RA-treated cells compared to undifferentiated controls and, again, lower expression under the additional application of THC in trend. In line with our earlier findings, the application of RA led to higher fluorescence intensity and/or a differential signal distribution in the cell in most of the investigated targets in ICC. Under treatment with THC, fluorescence intensity decreased, or the signal distribution became similar to the dispersion in the undifferentiated control condition. Our findings point to a decline of neuronal differentiation markers in our in vitro cell-culture system under the application of cannabinoids.

Autologous non-vascularized fibula with compression plating in the management of aseptic complex non-union of long bones.

BACKGROUND: The surgical treatment of non-union of long bones are challenging especially when bones are osteoporotic or there is a large bone gap due to repeated surgeries and implant failures. Plate with intramedullary fibula provides a stable construct as fibula acts as a second implant with better anchorage and high pull-out strength. The aim of our study is to present our experience of treating complex non-union of long bones using compression plating (LCPs/DCPs) in combination with autologous non-vascularized fibular graft (ANVFG). MATERIAL AND METHODS: 10 cases of complex non-union of long bones (tibia, femur, humerus) treated with debridement, decortication followed by intramedullary fibular strut grafting and rigid osteosynthesis by LCPs/DCPs were included in this study. DASH score and LEFS score was used for upper limb and lower limb functional assessment. RESULTS: All patients had clinico-radiological union with a mean time of 11.4 months. Pre-operative mean DASH and LEFS score was 45.9±2.1 and 20.6±2.03 At the last follow-up, mean DASH and LEFS score was 19.8±1.1 and 60.6±2.6. CONCLUSION: Compression plating with ANVFG is a viable option for treating complex non-union of long bones. Intramedullary fibula acting as a second implant provides mechanical stability and support biological healing with its osteogenic property at the non-union site.

From Trauma to Triumph: Navigating the Complexities of a Central Hip and Ipsilateral Knee Dislocation with Associated Fractures.

Introduction: Central hip dislocations are rare orthopedic injuries, and their concomitant occurrence with ipsilateral knee dislocations is an even rarer phenomenon. We present a unique case of central hip dislocation along with ipsilateral knee dislocation and additional fractures involving the lateral condyle of the left tibia and patella. This complex injury pattern resulted from a severe road traffic accident, necessitating operative management to address the multiple musculoskeletal injuries. Ultimately, femoral head avascular necrosis (AVN) developed, leading to the need for total hip replacement (THR). Case Report: A 28-year-old male was involved in a high-impact road traffic accident, leading to central hip dislocation, ipsilateral knee dislocation, and fractures of the lateral condyle of the left tibia and patella. The patient was promptly assessed, and operative intervention was initiated. Closed reduction and internal fixation with K-wires were performed for the fractures of the lateral condyle of the left tibia and patella. For the central hip dislocation, open reduction was achieved using a 9-hole RECON plate. Following the procedures, a long leg slab was applied for 6 weeks to facilitate optimal healing.Postoperatively, at the 6-week mark, K-wires were removed, and the patient commenced physiotherapy with partial weight-bearing permitted. However, during the rehabilitation phase, the patient reported instability in his left knee. Magnetic resonance imaging revealed an avulsion fracture of the posterior cruciate ligament (PCL) from its tibial attachment site and a complete anterior cruciate ligament (ACL) tear. It was observed that the femoral head had developed AVN. This complication necessitated further intervention, leading to the performance of a THR. Discussion: This case underscores the challenges and complexities associated with managing central hip dislocation and ipsilateral knee dislocation with multiple fractures. The post-operative instability of the knee, diagnosed as an avulsion fracture of the PCL and complete ACL tear, necessitated additional intervention. The patient subsequently underwent PCL reconstruction using a semitendinosus graft, highlighting the importance of a comprehensive approach to address the diverse musculoskeletal injuries resulting from high-impact trauma. Conclusion: The successful management of central hip dislocation and ipsilateral knee dislocation with associated fractures requires a multidisciplinary approach, incorporating timely surgical intervention, rigorous rehabilitation, and vigilant post-operative monitoring to address potential complications. This case emphasizes the need for ongoing clinical assessment and imaging studies to identify and manage secondary injuries that may manifest during the recovery phase. In addition, it highlights the development of femoral head AVN, ultimately leading to the necessity for THR.

Polidocanol sclerotherapy for the treatment of aneurysmal bone cyst, with or without pathological fractures: A prospective, comparative study.

Introduction: Polidocanol sclerotherapy in the treatment of aneurysmal bone cysts (ABCs) with or without pathological fractures has been a topic of debate. While some studies recommend intralesional curettage as the preferred treatment, others suggest intralesional sclerosants as an effective alternative. Material and methods: This study evaluates the use of polidocanol-based percutaneous sclerosant therapy in 28 patients with ABCs, of which 8 patients had pathological fracture. The patients received injections every four weeks based on clinical and radiological evaluation of the cyst, and the study assessed the results and complications of the treatment. Results: In group A (without pathological fractures), 14 out of 17 (82.4 %) lesions healed without any significant residual lesion. Three out of 17 (17.6 %) patients required further surgical intervention and were treated by curettage and bone grafting, definitively. Minor local inflammatory reaction was observed in 3 patients, which resolved without intervention within 3-4 days. In group B, all the 8 patients (100 %) with pathological fracture in their lesions healed as Grade 1 healing, without any significant residual lesion. One patient developed an episode of anesthesia related complication (delayed recovery) which resolved within an hour, without any residual effect. At final follow up, no recurrence was seen in any patient. Conclusion: The study concludes that polidocanol sclerotherapy is an effective treatment option for patients with ABCs, with or without pathological fractures, and has the potential to become the new treatment of choice for pathological fractures due to its low invasiveness, low morbidity, and affordability. However, further research is needed to confirm the efficacy of polidocanol sclerotherapy in larger patient populations and to compare its effectiveness with other treatment options.

Orthopaedic problems in the blind.

Background: Blindness is a common problem in every society and country. The problem ranges from complete blindness to partially sighted in the affected population. India has close to 12 million visually impaired people. Orthopaedic problems are not uncommon in blind. Orthopaedic Surgeons though had been aware of the postural and gait abnormalities in blind but very few published studies have systematically focused on the effect of blindness on the development of posture and gait. Methods: Case Control study done for the orthopaedic evaluation of the blind and partially sighted individuals. The study population included 242 students of Ahmadi School for the Blind, Aligarh Muslim University, Aligarh (India), as the cases and another matched set of 250 non-blind children. All the children were assessed for the orthopaedic problems like degree of ligamentous laxity, spinal alignment, foot morphology and alignment of hips, knees and ankles. Standing posture and gait were also examined and recorded. Ligamentous laxity was assessed according to the method adopted by Beighton et al.10 Chi-square test was applied using IBM SPSS 23.0. Results: 139 children (57.4 %) were found to have laxity of the ligaments. 72 children (29.7 %) had spine deformities, out of which kyphosis was present in 34 (47.2 %), scoliosis in 23 (31.9 %), lordosis in 13 (18.0 %), and meningomyelocele in 2 (2.9 %) children. 119 children (49.1 %) had foot deformities. 37 children (15.2 %) had knee deformity. 22 children (9.0 %) showed evidence of cerebral palsy. 216 children (89.2 %) had varying degrees of postural abnormalities. The data was statistically significant when compared with the control group (P < 0.05). Conclusion: Blindness causes a wide range of complicated sensory and motor problems that frequently forces people into isolation. Blind rehabilitation requires an interdisciplinary approach. Orthopaedic problems are quite common in blind individuals and should be dealt separately.

Extranodal Diffuse Large B-Cell Lymphoma (DLBCL) Presenting as Diffuse Joint Pain: A Diagnostic Dilemma.

Diffuse Large B-Cell Lymphoma (DLBCL) of bone is a rare presentation of Non-Hodgkin Lymphoma (NHL), which remains asymptomatic or present late in clinical course as bone pain or pathological fracture. We report a case of a 15-year-old male child presenting with diffuse joint pain and swelling over his left shoulder and elbow, associated with B symptoms. Radiological examination revealed lytic lesions in multiple bones along with collection along the left iliopsoas and hip joint, suggestive of infective etiology. The diagnostic dilemma was resolved on biopsy, which confirmed DLBCL involving bones and soft tissue.

A clinic-epidemiological study of 148 patients of pemphigus at Lady Reading Hospital, Peshawar: a case series.

A seven-year retrospective study was held at the Department of Dermatology, Lady Reading Hospital, Peshawar, between 2013 to 2020 to determine the demography and clinical features of pemphigus. Among 148 patients included in this study 88 (58%) were females and 60 (40%) were males with a female to male ratio of 1.46:1. Average age at onset of the disease was 38±12 years (range 14-75 years). On the basis of Autoimmune Bullous Skin Disorder Score (ABSIS), 14 (9.3%) patients had mild disease, 58 (38.7%) had moderate disease, and 76 (50.7%) patients had severe disease. In total, 144 (96%) patients had pemphigus vulgaris, 3 (2%) patients had pemphigus foliaceous and 1 (0.7%) patient had paraneoplastic pemphigus. Severe pemphigus was more frequently associated with multiple relapses (p=0.00). This study shows poor prognostic factors like severe pemphigus vulgaris associated with multiple relapses. Five years of follow-up shows that complete remission on minimal therapy was achieved more in patients who received Rituximab.

Augmentation of elastic stable intramedullary nail with external fixator in the management of comminuted shaft femur fracture in adolescents.

BACKGROUND: The management of adolescent femur fractures continues to evolve and remains controversial. Currently, operative fixation methods are favoured, offering options such as external fixator, flexible and locked intramedullary nailing, compression and locked plating. Our study aims to introduce a novel approach for treating adolescent femoral shaft fractures by combining an external fixator with an elastic stable intramedullary nail. MATERIAL AND METHODS: We included 32 patients aged 11-16 years with femoral shaft fractures treated using an external fixator augmented elastic intramedullary nail at our institution from August 2015 to January 2019. RESULTS: All patients achieved bony union. We analysed patient's results both clinically and radiologically. On average, the surgery took 77.34 minutes to complete with an average time to union of 13.9 weeks. External fixator and elastic nail removal took an average of 3.59 months and 26.5 months, respectively. At the final follow-up, knee range of motion averaged 131.88 degrees. According to the Flynn criteria, functional outcomes were excellent in 18 patients, satisfactory in 11 patients and poor in 3 patients. Pin site infection occurred in 3 patients, malunion in 4 patients, limb length shortening < 1 cm in 3 patients, distal nail tip prominence and knee stiffness in 3 patients. CONCLUSION: The management of femur fractures in adolescents using an elastic nail augmented with an external fixator is a minimally invasive procedure that provide secure fracture stabilization and predictable outcomes.

Methylation pattern and mRNA expression of synapse-relevant genes in the MAM model of schizophrenia in the time-course of adolescence.

Schizophrenia is highly heritable and aggregating in families, but genetics alone does not exclusively explain the pathogenesis. Many risk factors, including childhood trauma, viral infections, migration, and the use of cannabis, are associated with schizophrenia. Adolescence seems to be the critical period where symptoms of the disease manifest. This work focuses on studying an epigenetic regulatory mechanism (the role of DNA methylation) and its interaction with mRNA expression during development, with a particular emphasis on adolescence. The presumptions regarding the role of aberrant neurodevelopment in schizophrenia were tested in the Methyl-Azoxy-Methanol (MAM) animal model. MAM treatment induces neurodevelopmental disruptions and behavioral deficits in off-springs of the treated animals reminiscent of those observed in schizophrenia and is thus considered a promising model for studying this pathology. On a gestational day-17, adult pregnant rats were treated with the antimitotic agent MAM. Experimental animals were divided into groups and subgroups according to substance treatment (MAM and vehicle agent [Sham]) and age of analysis (pre-adolescent and post-adolescent). Methylation and mRNA expression analysis of four candidate genes, which are often implicated in schizophrenia, with special emphasis on the Dopamine hypothesis i.e., Dopamine receptor D2 (Drd2), and the "co-factors" Disrupted in schizophrenia 1 (DISC1), Synaptophysin (Syp), and Dystrobrevin-binding protein 1 (Dtnbp1), was performed in the Gyrus cingulum (CING) and prefrontal cortex (PFC). Data were analyzed to observe the effect of substance treatment between groups and the impact of adolescence within-group. We found reduced pre-adolescent expression levels of Drd2 in both brain areas under the application of MAM. The "co-factor genes" did not show high deviations in mRNA expression levels but high alterations of methylation rates under the application of MAM (up to ~20%), which diminished in the further time course, reaching a comparable level like in Sham control animals after adolescence. The pre-adolescent reduction in DRD2 expression might be interpreted as downregulation of the receptor due to hyperdopaminergic signaling from the ventral tegmental area (VTA), eventually even to both investigated brain regions. The notable alterations of methylation rates in the three analyzed co-factor genes might be interpreted as attempt to compensate for the altered dopaminergic neurotransmission.

Ex vivo, in vitro, and in silico approaches to unveil the mechanisms underlying vasorelaxation effect of Mentha Longifolia (L.) in porcine coronary artery.

OBJECTIVE: Mentha (M.) longifolia (L.) is traditionally used for various ailments. The current study was intended to explore the underlying vasorelaxation mechanisms of M. longifolia. MATERIAL AND METHODS: Aqueous-methanol extract from the aerial parts of M. longifolia was prepared and subjected to activity-guided fractionation. The vasorelaxant activity was performed using porcine coronary arteries with intact and denuded endothelium. In-vitro PDE inhibitory activity of the active fraction was carried out using the radio-enzymatic assay. The active fraction was also subjected to GCMS. Docking and molecular dynamic simulation studies were also performed RESULT: We had observed that aqueous-methanolic extract induced relaxation in the coronary artery in a dose-dependent manner when the endothelium was intact and denuded. n-butanol fraction (MLB) has produced a maximum effect, and it was selected for mechanistic studies. MLB has significantly enhanced the relaxation produced by cAMP and cGMP, elevating atrial natriuretic peptide, sodium nitroprusside, isoproterenol, and forskolin. The pre-treatment with MLB inhibited the contractile response produced by KCl, U46619, and CaCl2 in without endothelium rings. MLB has non-selectively inhibited the PDE isoforms. GCMS analysis of MLB has revealed the presence of menthol, thymol, and carvacrol in the active fraction. Docking and molecular dynamic simulation studies have indicated that thymol can be a competitive inhibitor for PDE1. CONCLUSION: It is postulated that an n-butanol fraction of Mentha longifolia produced endothelium-independent relaxation due to increased levels of cAMP and cGMP caused by the inhibition of various PDEs.

Single-stage versus two-stage reconstruction in chronic multi ligament knee injury.

BACKGROUND: Multi ligament knee injury (MLKI) refers to the disruption of at least 2 of the 4 major knee ligaments. These injuries are managed in single and two-stage surgeries however, treatment guidelines for best practice are unsettled. There is no study in the literature that compares single and two-stage surgery for the management of chronic multiligament knee injury. Therefore, the aim of this study was to compare the functional outcome between single-stage and two-stage surgical fixation in chronic multi-ligament knee injury. METHODS: Twenty seven patients with chronic MLKI with at least 2 years of follow up were included. Fourteen patients underwent reconstruction of torn ligaments in a single-stage operation (Group I) and 13 patients underwent reconstruction of torn ligaments in two stages (Group II). Assessment of clinical outcome was done with IKDC knee score, TEGNER LYSHOLM knee score, range of movement and laxity tests (Anterior drawer test, Lachman, Posterior drawer test, pivot shift test, dial test, varus and valgus stress test). RESULTS: At final follow up, there was no significant difference in post-operative IKDC knee scores in group I and group II (84.7±7.1 and 81.4±8.4 respectively, p=0.3) and Lysholm scores (85.8±8.3 and 80.9±8.3 respectively, p=0.1), range of movement (133.2±5.7 and 131.5±6.6 respectively, p=0.5) and all the patients regained full extension. At the final follow up 12/14 patients (85.7%) in group I and 11/13 patients (84.6%) in group II had a negative/grade 1 anterior drawer test (p=0.6), 14/14 (100%) in group I and 13/13 (100%) patients had negative/grade 1 lachman test (p=0.6), 13/14 patients (92.8%) in group I and 13/13 patients (100%) patients in group II had negative/grade 1 pivot shift test (p=0.4), 9/10 patients (90%) in group I and 12/13 patients (92.3%) in group II had negative/grade 1 posterior drawer (p=0.6), 6/6 patients (100%) in group I and 6/7 patients (85.7%) in group II had negative/grade 1 dial test (p=0.3), 5/6 patients (83.3%) in group I and 5/7 patients (71.4%) in group II had negative/grade 1 varus stress test (p=0.4), 6/7 patients (85.7%) in group I and 7/7 patients (100%) in group II had negative/grade 1 valgus stress test (p=0.1). CONCLUSION: Chronic MLKI managed by single stage and two stage reconstruction provides similar functional outcomes. LEVEL OF EVIDENCE: Level III Retrospective Cohort Study.

Pharmacological exploration of anti-arthritic potential of terbutaline through in-vitro and in-vivo experimental models.

Terbutaline have been reported to have anti-inflammatory activity. Present study aimed to check the anti-arthritic activity of terbutaline. The drug was tested using in vitro models (bovine serum albumin denaturation, egg albumin denaturation and HRBC membrane stabilization) and in vivo (formaldehyde induced arthritis). Results of bovine serum albumin denaturation assay illustrated that terbutaline inhibited 89.54±0.46% denaturation at 6400µg/ml concentration. Terbutaline resulted in dose dependent impediment of protein denaturation in egg albumin denaturation assay with 74.40±0.72% inhibition at concentration of 6400µg/ml. Terbutaline also showed protection of HRBC membrane against hypotonic stress in a dose dependent manner, with maximum 76.45±0.62% prevention at 6400µg/ml concentration. Results of formaldehyde induced arthritis model showed that paw volume was significantly declined by terbutaline with maximum percentage inhibition at 10th day of study period which implies immune inhibitory potential of terbutaline. Findings of present study concluded that terbutaline has arthritis reducing potential possible through inhibitory effects on synthesis and release of inflammatory mediators as well as limiting the formation of autoantigen. Thus, terbutaline might be the potential candidate for use in treatment of arthritis.

Knowledge, Attitude, Practice, Behavior and Risk Perception of COVID-19 Pandemic among Medical and non-Medical University Students.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) pandemic has substantially affected students around the globe due to the closure of educational institutes. However, student involvements and contributions are important in combating the disease; for this reason, the current study was designed to assess the knowledge-attitude-practice (KAP), preventive behavior, and risk perception among university students. METHODS: A cross-sectional survey-based study was conducted among medical and non-medical university students, from April 1 to June 30, 2020. The 68-item questionnaire was used to evaluate responses using statistical approaches (Student's t-test, regression-analysis, and co-relation analysis) by considering a P-value <0.05 as statistically significant. RESULTS: A total of 503 university students (medical and nonmedical) were selected, where majority of participants were females (83%) and 64.5% were of age ranged from 16 to 21 years old. The participants (80%) reported good disease knowledge with a mean score of 12.06 ± 1.75, which substantially higher among medical students (P < 0.05). Most of the respondents (72%) believed that COVID-19 will be effectively controlled through precautionary measures. In correlation subgroup analysis, a significant relationship (P = 0.025) between knowledge and positive attitude were indicated. Fear and knowledge of COVID-19 emerged as strong predictors (P < 0.001) of preventive behaviors towards disease. CONCLUSION: This study demonstrated satisfactory knowledge, positive attitudes, and suitable practices among students toward COVID-19. University students can be involved in public education to aid the health authorities in achieving the targets of educational campaigns with maximum population coverage.

Design of a computationally efficient observer-based distributed fault detection and isolation scheme in second-order networked control systems.

This paper presents a novel directional observer-based fault detection and isolation scheme for second-order networked control systems (NCS). The directional unknown input observer (UIO) tool is exploited to study the problem of distributed fault detection and isolation (FDI). Two design schemes with global and partial/local network models are proposed to solve the distributed FDI problem. Thresholds are computed for the application of the proposed schemes in a noisy environment. In addition, the salient features of the proposed schemes are that both fault detection and fault isolation are achieved in a single step using a single observer. The schemes are applied to power system models to validate their results. A detailed comparison with existing FDI schemes is also provided, which clearly shows the effectiveness of the proposed scheme in terms of computational requirements.

Prediction of peroneus longus graft diameter for anterior cruciate ligament reconstruction by inframalleolar harvest and from anthropometric data.

BACKGROUND: The literature is gradually drifting towards a graft of larger diameter for successful ACL reconstruction. There is no published literature regarding the anthropometric predictors for the diameter of the peroneus longus tendon (PLT) graft obtained in ACL reconstruction through the inframalleolar approach. METHODS: Fifty-two patients were finally evaluated for anthropometric parameters to predict quadrupled PLT graft diameter in ACL reconstruction using the inframalleolar technique. Intraoperative quadrupled PLT graft diameter was correlated to the patient's anthropometric data such as age, height, weight, duration of injury, and BMI. We used regression analysis in a stepwise manner to ascertain anthropometric indices associated with the graft diameter. RESULTS: This study included 46 males and six females. Mean age was 28.2 ± 7.4 years, mean height was 172.7 ± 2.8 cm, mean weight was 75.6 ± 3.4 kg, mean BMI was 25.3 ± 0.9 kg/m2, mean duration of injury was 9.2 ± 3.9 months, and mean graft diameter was 9.3 ± 0.4 mm. Positive correlation with graft diameter was found only with height (r = 0.6, P < 0.01) and weight (r = 0.4, P < 0.01). On analysing through linear regression, height and weight had significant association with graft diameter, and we formulated the following prediction equation: PLT graft diameter (mm) = 0.083 × height (cm) + 0.011 × weight (kg) -5.854. CONCLUSION: Patients' characteristics, including height and weight, have a significant correlation with quadrupled PLT graft diameter and the average diameter of graft is > 9 mm through this approach.

Role of Huntington procedure as a limb salvage surgery for complex gap nonunion of tibia in children.

BACK GROUND: Complex gap nonunion of tibia following open fractures and osteomyelitis with pathological fractures in children is a treatment challenge with unpredictable outcome. Treatment options available are bone transport, bone grafting, induced membrane technique, allograft reconstruction and Huntington procedure (ipsilateral transposition of vascularized fibula). There is no consensus in the literature about which technique is optimal in the given situation. The purpose of the present study is to evaluate the role of Huntington procedure in the management of complex gap nonunion of tibia in paediatric patients. MATERIAL AND METHOD: Eighteen patients (11 males and 7 females) with a mean age of 8.4 years (range 3-12 years) having complex gap nonunion of tibia with an average bone defect of 6.6 cm (range 5-17 cm) were treated with Huntington procedure between June 2008 to December 2016. The mean follow-up was 4.3years (range 3.5-6 years). RESULT: Union was seen in all except one, with an average time to union being 11.5 weeks and13.8 weeks at proximal and distal tibio-fibular synostosis respectively. Revision plating was done in one patient with nonunion. Hypertrophy of fibula was seen in all patients. One patient developed 15° ankle varus and required corrective osteotomy. Ankle was fixed in equinus in three patients with a mean value of 13.3° (range 5°-25°). Lambrinaudi procedure was done to correct 25° fixed ankle equinus in one patient. Fixed flexion deformity of knee was seen in nine patients with a mean value of 9.7° (range 5°-20°). Two patients had iatrogenic foot drop; one recovered completely and one had only partial recovery. Shortening was seen in eight patients with a mean value of 3.5 cm (range 1-5 cm). At final evaluation 9 patients were very satisfied, 8 satisfied and 1 was dissatisfied. CONCLUSION: Huntington procedure is a useful limb salvage surgery for complex gap nonunion of tibia in children. However; further improvements in the surgical technique are needed to increase the patient satisfaction by reducing the risk of complications.

Surgical Risk and Pathological Results of Emergency Resection in the Treatment of Acutely Obstructing Colorectal Cancers: A Retrospective Cohort Study.

PURPOSE: The treatment of acutely obstructing colorectal cancers is still a matter of debate. The prevailing opinion is that an immediate resection should be performed whenever possible. This study sought to determine whether immediate resection is safe and oncologically valid. METHODS: We completed a retrospective 2-center cohort study using the medical records of patients admitted for acutely obstructing colorectal cancer under the care of the Colorectal Team, Noble's Hospital, Isle of Man, and the Emergency Surgery Unit, Umberto I University Hospital, Rome, from March 2013 to May 2017. The primary endpoints were 90-day mortality and morbidity, reoperation rate, and length of stay. The secondary endpoints were status of margins, number of lymph nodes retrieved, and the rate of adequate nodal harvest. RESULTS: Sixty-three patients were retrospectively enrolled in the study. Mortality was associated with age > 80 years and Dukes B tumors. The length of hospital stay was shorter in patients who had their resection less than 24 hours from their admission, in those who had laparoscopic resection and in those with distal tumors. The number of lymph nodes retrieved and rate of R0 resections were similar to those reported in elective colorectal surgery and were greater in laparoscopic resections and in patients operated on within 24 hours, respectively. CONCLUSION: Immediate resection is a safe and reliable option in patients with acutely obstructing colorectal cancer.

Sliding mode control for a fractional-order non-linear glucose-insulin system.

By providing the generalisation of integration and differentiation, and incorporating the memory and hereditary effects, fractional-order modelling has gotten significant attention in the past few years. One of the extensively studied and utilised models to describe the glucose-insulin system of a human body is Bergman's minimal model. This non-linear model comprises of integer-order differential equations. However, comparison with the experimental data shows that the fractional-order version of Bergman's minimal model is a better representative of the glucose-insulin system than its original integer-order model. To design a control law for an artificial pancreas for a diabetic patient using a fractional-order model, different techniques, including feedback linearisation, have been applied in the literature. The authors' previous work shows that the fractional-order version of Bergman's model describes the glucose-insulin system in a better way than the integer-order model. This study applies the sliding mode control technique and then compares the obtained simulation results with the ones obtained using feedback linearisation.

DNA Methylation of the t-PA Gene Differs Between Various Immune Cell Subtypes Isolated From Depressed Patients Receiving Electroconvulsive Therapy.

BACKGROUND: Major depressive disorder (MDD) represents a tremendous health threat to the world's population. Electroconvulsive therapy (ECT) is the most effective treatment option for refractory MDD patients. Ample evidence suggests brain-derived neurotrophic factor (BDNF) to play a crucial role in ECT's mode of action. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are involved in BDNF production. HYPOTHESIS: The DNA methylation of gene regions encoding for t-PA and PAI-1 might be a suitable biomarker for ECT response prediction. METHODS: We withdrew blood from two cohorts of treatment-resistant MDD patients receiving ECT. In the first cohort (n = 59), blood was collected at baseline only. To evaluate DNA methylation changes throughout the treatment course, we acquired a second group (n = 28) and took blood samples at multiple time points. DNA isolated from whole blood and defined immune cell subtypes (B cells, monocytes, natural killer cells, and T cells) served for epigenetic analyses. RESULTS: Mixed linear models (corrected for multiple testing by Sidak's post-hoc test) revealed (1) no detectable baseline blood DNA methylation differences between ECT remitters (n = 33) and non-remitters (n = 53) in the regions analyzed, but (2) a significant difference in t-PA's DNA methylation between the investigated immune cell subtypes instead (p < 0.00001). This difference remained stable throughout the treatment course, showed no acute changes after ECT, and was independent of clinical remission. CONCLUSION: DNA methylation of both proteins seems to play a minor role in ECT's mechanisms. Generally, we recommend using defined immune cell subtypes (instead of whole blood only) for DNA methylation analyses.