Intrathecal morphine in combination with bupivacaine as pre-emptive analgesia in posterior lumbar fusion surgery: a retrospective cohort study.

BACKGROUND: The purpose of this study was to evaluate the efficacy of intrathecal morphine (ITM) in combination with bupivacaine as pre-emptive analgesia in patients undergoing posterior lumbar fusion surgery. This is in comparison with traditional opioid analgesics such as intravenous (IV) morphine. METHODS: Two groups were identified retrospectively. The first (ITM group) included patients who had general anaesthesia (GA) with low-dose spinal anaesthesia prior to induction using 1-4 mls of 0.25% bupivacaine and 0.2 mg ITM. 1 ml of 0.25% bupivacaine was administered per hour of predicted surgery time, up to a maximum of 4 ml. The insertion level for the spinal anaesthetic corresponded to the spinal level of the iliac crest line and the level at which the spinal cord terminated. The control group had GA without any spinal anaesthesia. Patients were instead administered opioid analgesia in the form of IV morphine or diamorphine. The primary outcome was the consumption of opioids administered intraoperatively and in recovery, and over the first 48 h following discharge from the post-anaesthesia care unit (PACU). Total opioid dose was measured, and a morphine equivalent dose was calculated. Secondary outcomes included visual analogue scale (VAS) pain scores in recovery and at day two postoperatively, and the length of stay in hospital. RESULTS: For the ITM group, the median total amount of IV morphine equivalent administered intraoperatively and in recovery, was 0 mg versus 17 mg. The median total amount morphine equivalent, administered over the first 48 h following discharge from PACU was 20 mg versus 80 mg. Both are in comparison with the control group. The median length of stay was over 1 day less and the median VAS for pain in recovery was 6 points lower. No evidence was found for a difference in the worst VAS for pain at day two postoperatively. CONCLUSION: ITM in combination with bupivacaine results in a significantly decreased use of perioperative opioids. In addition, length of hospital stay is reduced and so too is patient perceived pain intensity. Trial registration The study was approved by the ethics committee at The Robert Jones and Agnes Hunt Orthopaedic Hospital as a service improvement project (Approval no. 1617_004).

Interweaving of reactive oxygen species and major neurological and psychiatric disorders.

Reactive oxygen species are found to be having a wide range of biological effects ranging from regulating functions in normal physiology to alteration and damaging various processes and cell components causing a number of diseases. Mitochondria are an important organelle responsible for energy production and in many signalling mechanisms. The electron transport chain in mitochondria, where oxidative phosphorylation takes place, is also coupled with the generation of reactive oxygen species (ROS). Changes in normal homeostasis and overproduction of reactive oxygen species by various sources are found to be involved in multiple neurological and major neurodegenerative diseases. This review summarises the role of reactive oxygen species and the mechanism of neuronal loss in major neuronal disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, and schizophrenia.

3D printing in pharmaceuticals: An emerging technology full of challenges.

Although in its infancy, when compared with the other sectors, year 2005 marked the rapid evolution of 3 Dimensional printing (3DP) technologies in pharma sector with a huge potential in the dosage form designing and personalisation of the medication. 3DP is an innovative and highly promising way for the instant manufacturing in contrast with the tailored made conventional manufacturing. Various 3DP technologies are categorized into the various areas on the basis of the type of material used, deposition techniques and the solidification/fusion techniques. 3DP technologies have multiple pharmaceutical applications including formulation of the precise and unique dosage forms, medical research, personalization of medicine, tissues engineering and surgical application. In the present article, we have accentuated the comparative merits and demerits of various 3DP technologies used in the pharmaceutical sector. An insight in to the challenges, apropos availability and the choice of the excipients, as well as the printer, regulatory and safety concern of the product is provided.

Experimental characterization and theoretical analysis of cell tip oscillations in directional solidification.

Experiments performed in DECLIC-DSI on board the International Space Station evidenced oscillatory modes during the directional solidification of a bulk sample of succinonitrile-based transparent alloy. The interferometric data acquired during a reference experiment, V_{p}=1 µm/s and G=19 K/cm, allowed us to reconstruct the cell shape and thus measure the cell tip position, radius, and growth velocity evolution, in order to quantify the dynamics of the oscillating cells. This study completes our previous reports [Bergeon et al., Phys. Rev. Lett. 110, 226102 (2013)10.1103/PhysRevLett.110.226102; Tourret et al., Phys. Rev. E 92, 042401 (2015)10.1103/PhysRevE.92.042401; Pereda et al., Phys. Rev. E 95, 012803 (2017)10.1103/PhysRevE.95.012803] with, to our knowledge, the first complete monitoring of the geometric cell tip characteristics variations in bulk samples. The evolution of the shape, velocity, and position of the tip of the oscillating cells is associated with an evolution of the concentration field, inaccessible experimentally but mediating the diffusive interactions between the cells. The experimental results are supported by 3D phase-field simulations which evidence the existence of transversal solute fluxes between neighboring cells that play a fundamental role in the oscillation dynamics. The dynamics of oscillation of an individual cell is analyzed using a theoretical model based on classical equations of solidification through the calculation of the phase relationships between oscillation of the different tip characteristics.

Spinal navigation for minimally invasive thoracic and lumbosacral spine fixation: implications for radiation exposure, operative time, and accuracy of pedicle screw placement.

PURPOSE: Navigation is emerging as a useful adjunct in percutaneous, minimally invasive spinal surgery (MIS). The aim of this study was to compare C-Arm navigated, O-Arm navigated and conventional 2D-fluoroscopy assisted MIS thoracic and lumbosacral spine fixation techniques in terms of operating time, radiation exposure and accuracy of pedicle screw (PS) placement. METHODS: Retrospective observational study of 152 consecutive adults who underwent MIS fixations for spinal instability: 96 2D-fluoroscopy assisted, 39 3D-C-Arm navigated and 27 using O-Arm navigated. RESULTS: O-Arm navigation significantly reduced PS misplacement (1.23%, p) compared to 3D-C-Arm navigation (7.29%, p = 0.0082) and 2D-fluoro guided placement (5.16%, p = 0379). 3D-C-Arm navigation was associated with lower procedural radiation exposure of the patient (0.4 mSv) than O-Arm navigation (3.24 mSv) or 2D-fluoro guidance (1.5 mSv). Operative time was comparable between three modalities. CONCLUSIONS: O-Arm navigation provides greater accuracy of percutaneous instrumentation placement with an acceptable procedural radiation dose delivered to the patients and comparable operative times. These slides can be retrieved under Electronic Supplementary material.

Advanced magnetic resonance imaging and neuropsychological assessment for detecting brain injury in a prospective cohort of university amateur boxers.

BACKGROUND/AIM: The safety of amateur and professional boxing is a contentious issue. We hypothesised that advanced magnetic resonance imaging and neuropsychological testing could provide evidence of acute and early brain injury in amateur boxers. METHODS: We recruited 30 participants from a university amateur boxing club in a prospective cohort study. Magnetic resonance imaging (MRI) and neuropsychological testing was performed at three time points: prior to starting training; within 48 h following a first major competition to detect acute brain injury; and one year follow-up. A single MRI acquisition was made from control participants. Imaging analysis included cortical thickness measurements with Advanced Normalization Tools (ANTS) and FreeSurfer, voxel based morphometry (VBM), and Tract Based Spatial Statistics (TBSS). A computerized battery of neuropsychological tests was performed assessing attention, learning, memory and impulsivity. RESULTS: During the study period, one boxer developed seizures controlled with medication while another developed a chronic subdural hematoma requiring neurosurgical drainage. A total of 10 boxers contributed data at to the longitudinal assessment protocol. Reasons for withdrawal were: logistics (10), stopping boxing (7), withdrawal of consent (2), and development of a chronic subdural hematoma (1). No significant changes were detected using VBM, TBSS, cortical thickness measured with FreeSurfer or ANTS, either cross-sectionally at baseline, or longitudinally. Neuropsychological assessment of boxers found attention/concentration improved over time while planning and problem solving ability latency decreased after a bout but recovered after one year. CONCLUSION: While this neuroimaging and neuropsychological assessment protocol could not detect any evidence of brain injury, one boxer developed seizures and another developed a chronic sub-dural haematoma.

Experimental observation of oscillatory cellular patterns in three-dimensional directional solidification.

We present a detailed analysis of oscillatory modes during three-dimensional cellular growth in a diffusive transport regime. We ground our analysis primarily on in situ observations of directional solidification experiments of a transparent succinonitrile 0.24wt% camphor alloy performed in microgravity conditions onboard the International Space Station. This study completes our previous reports [Bergeon et al., Phys. Rev. Lett. 110, 226102 (2013)10.1103/PhysRevLett.110.226102; Tourret et al., Phys. Rev. E 92, 042401 (2015)10.1103/PhysRevE.92.042401] from an experimental perspective, and results are supported by additional phase-field simulations. We analyze the influence of growth parameters, crystal orientation, and sample history on promoting oscillations, and on their spatiotemporal characteristics. Cellular patterns display a remarkably uniform oscillation period throughout the entire array, despite a high array disorder and a wide distribution of primary spacing. Oscillation inhibition may be associated to crystalline disorientation, which stems from polygonization and is manifested as pattern drifting. We determine a drifting velocity threshold above which oscillations are inhibited, thereby demonstrating that inhibition is due to cell drifting and not directly to disorientation, and also explaining the suppression of oscillations when the pulling velocity history favors drifting. Furthermore, we show that the array disorder prevents long-range coherence of oscillations, but not short-range coherence in localized ordered regions. For regions of a few cells exhibiting hexagonal (square) ordering, three (two) subarrays oscillate with a phase shift of approximately ±120^{∘} (180^{∘}), with square ordering occurring preferentially near subgrain boundaries.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

OBJECTIVE: A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. METHOD: A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. RESULTS: Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. CONCLUSION: Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

Comparison of IOL power calculation formulae for pediatric eyes.

PurposeTo evaluate and compare the accuracy of modern intraocular lens (IOL) power calculation formulae in pediatric eyes and compare prediction error (PE) obtained with manufacturer's vs personalized lens constant.Patients and methodsAn observational case study was conducted in 117 eyes (117 patients) undergoing pediatric cataract surgery with IOL implantation. PE was calculated as predicted refraction minus actual postoperative refraction, and absolute PE as absolute difference independent of the sign, (APE)=predicted refraction minus actual postoperative refraction. This was done for each formula using manufacturer's and personalized lens constant. Further, PE and APE were evaluated according to axial length (AL).ResultsMean age of children was 2.97 years. About 66/117 eyes (56.4%) were below 2 years of age. Using Holladay 2, Holladay 1, Hoffer Q, and SRK/T formulae with manufacturer's lens constant, mean PE was 0.36, 0.41, 0.69, and 0.28 diopter (D), respectively. With personalized lens constant, it was 0.16, 0.15, 0.50, and -0.12 D, respectively. Difference in mean PE between the formulae was statistically significant (P<0.0001). SRK/T and Holladay 2 formulae had the least PE, both with manufacturer's and personalized constant. For eyes with AL<20 mm, SRK/T and Holladay 2 formulae gave the least PE. Personalizing the lens constant led to a decrease in mean PE in all formulae, except the Hoffer Q formula. However, personalizing the lens constant did not significantly improve the APE. At least 21% eyes had an APE of >2 D with all formulae, even with personalized lens constants.ConclusionIn pediatric eyes, SRK/T and the Holladay 2 formulae had the least PE. Personalizing the lens formula constant did reduce the PE significantly for all formulae except Hoffer Q. In extremely short eyes (AL<20 mm), SRK/T and Holladay 2 formulae gave the best PE.

Intraocular lens exchange for high myopia in pseudophakic children.

PurposeThe purpose of this study was to examine the preoperative factors and postoperative outcomes following intraocular lens (IOL) exchange for high myopia in pseudophakic children.MethodsThe medical records of all patients undergoing IOL exchange for high myopia were retrospectively reviewed.ResultsA total of 15 eyes were identified that had undergone an IOL exchange for myopic shift. Average age of cataract extraction (CE) was 5.4 months. In all, 10/15 had a unilateral cataract. IOL exchange usually occurred at an average of 6 years following cataract surgery. The average spherical equivalent (SE) of the refractive error at that time was -9.6 D. Following IOL exchange, SE was -1.3 D. A two-line reduction in best-corrected visual acuity was observed in 1/13 of our patients for whom pre- and post-exchange data were available. The average axial length (AL) of the eye undergoing the IOL exchange was 24.0 mm, average AL in the non-operative eye was 22.1 mm. On average, the operative eyes grew 4.4 mm and the non-operative eyes 3.02 mm. No adverse events were seen in the operative eyes.ConclusionYounger age at the time of CE creates a greater likelihood of AL elongation and predisposes a child to myopic shift. IOL exchange should be considered an option to reduce anisometropia and associated aniseikonia to improve visual outcomes. Successful visual rehabilitation and predictable post-exchange refractions were seen with our patients.

Secondary intraocular lens implantation following infantile cataract surgery: intraoperative indications, postoperative outcomes.

PurposeThe purpose of this study was to determine the long-term complications and outcomes of secondary intraocular lens (IOL) implantation in patients with congenital cataracts.Patients and MethodsThe medical records of children operated for secondary IOL implantation surgery between 2000 and 2014 were retrospectively reviewed. Those who had undergone their initial congenital cataract surgery before 7 months of age were included and were analyzed for intra- and postoperative factors and postoperative refractive outcomes. We focused on three complications: visual axis opacification (VAO), glaucoma, and IOL exchange after at least 1 year of follow-up.ResultsA total of 49 eyes of 49 patients were analyzed for intraoperative indications. Of those, 37 eyes of 37 patients had at least 1 year of follow-up and were analyzed for postoperative outcomes. The mean age at secondary implantation was 55.2±21.6 months. At secondary implantation, 69.4% of eyes were implanted in the capsular bag, 28.6% in the sulcus, and 2.0% that were angle-supported. There was no significant correlation between the site of secondary IOL implantation and age at implantation (P=0.216). The mean follow-up after implantation was 57.6±33.6 months. The rate of VAO was 5.4%, the rate of glaucoma occurring after secondary implantation was 16.2%, and the rate of IOL exchange was 2.7%. The median visual acuity at final follow-up was 20/40. For patients with unilateral cataracts it was 20/60 and for bilateral patients it was 20/30.ConclusionsThe secondary IOL implantation in children is a relatively safe procedure associated with low rates of postoperative complications. Visual outcomes are acceptable and are better for bilateral patients than for unilateral patients.

Visual acuity and its predictors after surgery for bilateral cataracts in children.

PurposeThe objective of this study was to investigate preoperative factors associated with postoperative visual acuity outcomes and to develop a model to predict visual acuity prognosis.MethodsA retrospective study was conducted by reviewing clinical charts of pediatric patients who underwent bilateral cataract surgery by a single surgeon (MEW) at the Storm Eye Institute. A multiple logistic regression model was constructed to predict the odds of poor postoperative visual acuity, that is, worse than 20/40, based on age at surgery, gender, primary intraocular lens (IOL) placement, ethnicity, and preoperative nystagmus.ResultsA sample size of 157 children (314 eyes) was investigated with median duration of follow-up of 6.4 years. A total of 78% of children with bilateral cataract had postoperative visual acuity of 20/40 or better. The presence of preoperative nystagmus was highly correlated with poor postoperative visual acuity (OR=6.0; 95% CLs, 2.5-14.1; P-value<0.0001). Children of age <1 year at time of cataract extraction (OR=3.2; 95% CLs, 1.4-7.6; P-value=0.0073), male gender (OR=2.3; 95% CLs, 1.1-4.5; P-value=0.02), the absence of primary IOL placement (OR=3.0; 95% CLs, 1.05-8.4; P-value=0.04), and non-Caucasian ethnicity (OR=2.0; 95% CLs, 1.02-4.03; P-value 0.0447) were associated with poor visual acuity postoperatively.ConclusionsSatisfactory visual outcomes occurred in 78% of children operated on for bilateral cataracts. Preoperative nystagmus, age <1 year at time of cataract extraction, absence of primary IOL placement, male gender, and non-Caucasian ethnicity, were all factors associated with poor postoperative visual acuity.

Barriers in conducting clinical trials in oncology in the developing world: A cross-sectional survey of oncologists.

BACKGROUND: Several obstacles impede oncologists from performing clinical trials in the developing world. This study aimed to identify these barriers in order of importance and suggest possible remedial measures. MATERIALS AND METHODS: Design - cross-sectional survey. Two part questionnaire capturing experience of oncologists in practice and conducting trials (Part 1) and perceived barriers pertaining to investigator (training, time), patient (strict follow-up protocol), infrastructure (funds) and professional environment (encouragement from seniors) (Part 2) were administered to oncologists in two different settings: (1) Online portal (Survey Monkey) (2) In person during a national conference (Best of American Society of Clinical Oncology). Responses were captured on a Likert scale (1-5). RESULTS: (436/3021) 14.04% responded. A total of 313 (71.8%) had experience in conducting trials, but these were mainly industry-sponsored or small nonpractice changing studies. Lack of patient follow-up was the most significant barrier (inter quartile range [IQR] 4-5) followed by inadequate training, time and funds (IQR 2-5) and lack of encouragement (IQR 2-4) in decreasing order of frequency. Lack of adequate training was a barrier across all specialties (113 [71.97%] radiation oncologists, 71 [60.68%] medical oncologists and 73 [71.56%] surgical oncologists). More than half of the respondents without experience in clinical trials worked in academic institutions (50.48%). They perceived time constraint as a barrier more than their counterparts into private practice (175/242 [72.31%] vs. 119/177 [66.47%] respectively). CONCLUSION: Inability to maintain patient follow-up, lack of protected time and funds, inadequate training were the most significant barriers. Most of these can be addressed.

Oscillatory cellular patterns in three-dimensional directional solidification.

We present a phase-field study of oscillatory breathing modes observed during the solidification of three-dimensional cellular arrays in microgravity. Directional solidification experiments conducted onboard the International Space Station have allowed us to observe spatially extended homogeneous arrays of cells and dendrites while minimizing the amount of gravity-induced convection in the liquid. In situ observations of transparent alloys have revealed the existence, over a narrow range of control parameters, of oscillations in cellular arrays with a period ranging from about 25 to 125 min. Cellular patterns are spatially disordered, and the oscillations of individual cells are spatiotemporally uncorrelated at long distance. However, in regions displaying short-range spatial ordering, groups of cells can synchronize into oscillatory breathing modes. Quantitative phase-field simulations show that the oscillatory behavior of cells in this regime is linked to a stability limit of the spacing in hexagonal cellular array structures. For relatively high cellular front undercooling (i.e., low growth velocity or high thermal gradient), a gap appears in the otherwise continuous range of stable array spacings. Close to this gap, a sustained oscillatory regime appears with a period that compares quantitatively well with experiment. For control parameters where this gap exists, oscillations typically occur for spacings at the edge of the gap. However, after a change of growth conditions, oscillations can also occur for nearby values of control parameters where this gap just closes and a continuous range of spacings exists. In addition, sustained oscillations at to the opening of this stable gap exhibit a slow periodic modulation of the phase-shift among cells with a slower period of several hours. While long-range coherence of breathing modes can be achieved in simulations for a perfect spatial arrangement of cells as initial condition, global disorder is observed in both three-dimensional experiments and simulations from realistic noisy initial conditions. In the latter case, erratic tip-splitting events promoted by large-amplitude oscillations contribute to maintaining the long-range array disorder, unlike in thin-sample experiments where long-range coherence of oscillations is experimentally observable.

Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2 relaxometry and diffusion tensor imaging at 7T.

The present study examines the change in water diffusion properties of the corpus callosum (CC) and the hippocampus, in response to prolonged hypobaric hypoxia (HH) stress, using in vivo magnetic resonance imaging (MRI) modalities such as T2 relaxometry and diffusion tensor imaging (DTI). Three groups of rats (n=7/group) were exposed to a simulated altitude of 6700m above sea level for the duration of 7, 14 and 21days, respectively. Data were acquired pre-exposure, post-exposure and after 1week of normoxic follow-up in each group. The increment in T2 values with no apparent diffusion coefficient (ADC) change in the CC after 7 and 14days of HH exposure indicated mixed (vasogenic and cytotoxic) edema formation. After 1week of normoxia, 7-day HH-exposed rats showed a decrease in ADC values in the CC, probably due to cytotoxic edema. A delayed decrease in ADC values was observed in the hippocampus after 1week normoxic follow-up in 7- and 14-day HH groups giving an insight of cytotoxic edema formation. Interestingly, 21-day HH-exposed rats did not show change in ADC values. The decrease in T2 values after 14 and 21days in the hippocampal region depicts iron deposition, which was confirmed by histopathology. This study successfully demonstrated the use of MRI modality to trace water diffusion changes in the brain due to prolonged HH exposure.

Medicarpin, a legume phytoalexin sensitizes myeloid leukemia cells to TRAIL-induced apoptosis through the induction of DR5 and activation of the ROS-JNK-CHOP pathway.

Tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent with cancer cell-selective cell death inducing effect. However, the major limitation in the usage of TRAIL as a chemotherapeutic agent is the development of TRAIL resistance in many cancer types including myeloid leukemia. In this study, we report for the first time that Medicarpin (Med), a naturally occurring phytoalexin sensitizes myeloid leukemia cells to TRAIL-induced apoptosis. Combination of Med and TRAIL induced significantly higher apoptosis compared with that of the individual treatments of either agent alone through activation of both the extrinsic and the intrinsic cell death pathways characterized by the activation of caspases 8, 9, 3, and 7. Med treatment downregulated antiapoptotic proteins (Survivin, Bcl2, Bcl-xL, XIAP, and c-FLIP), upregulated pro-apoptotic proteins (Bax, Cytochrome C, Smac/Diablo, Bid, truncated Bid (tBid), p-eIF2α, Bip, and CHOP (CCAAT-enhancer binding protein homologous protein)), induced G2/M cell-cycle arrest, and increased the expression of the functional TRAIL receptor DR5 through activation of the ROS-JNK-CHOP pathway. Gain and loss of function studies clearly indicated that DR5 expression was critical for Med-induced TRAIL sensitization. The Med-induced TRAIL sensitization did not involve the NFkB signaling pathway or redistribution of DR5 in lipid rafts. The concomitant treatment with Med and TRAIL showed robust apoptotic effects in primary myeloid leukemia cells but had no toxic effects in primary human peripheral blood mononuclear cells (PBMCs). In conclusion, our results suggest that Med sensitizes myeloid leukemia cells to TRAIL-induced apoptosis through the upregulation of DR5 through activation of the ROS-JNK-CHOP pathway.

A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-ß-catenin signaling.

Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[ß-D-apiofuranosyl-(1-6)-ß-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/ß-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/ß-catenin signaling to reduce phosphorylation of GSK3-ß and subsequent nuclear accumulation of ß-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in ß-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/ß-catenin mechanism. CAFG at 1 mg/kg(/)day dose in ovariectomy mice (human dose ∼0.081 mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair.

Diffusion tensor tractography in hypothyroidism and its correlation with memory function.

Diffusion tensor tractography (DTT) was performed to determine the microstructural changes in the white matter fibre tracts of hypothyroid patients compared to controls and to correlate these changes with memory dysfunction scores. DTT and Postgraduate Institute Memory Scale test were performed in eight hypothyroid patients and eight healthy controls. Diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was made between the patient group and controls. Pearson's correlation was performed between Memory Dysfunction score and DTI measures. Significant changes in DTI measures were observed in various white matter fibre tracts in hypothyroid patients compared to controls. In hypothyroid patients, an inverse correlation of Memory Dysfunction score with FA was observed in the right and left inferior fronto-occipital fasciculus, whereas a positive correlation with MD was observed in the right anterior thalamic radiation among all white matter tracts. These findings suggest that microstructural changes in white matter fibres may contribute to the underlying dysfunction in memory in hypothyroid patients.