Non-invasive perfusion MR imaging of the human brain via breath-holding.

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3 T and 7 T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3 T vs. 8.5 at 7 T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20-40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.

Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma

Purpose Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance. Methods In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan–Meier was performed to determine the prognostic significance. Results High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010). Conclusion Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field (AU)

Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma.

PURPOSE: Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance. METHODS: In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan-Meier was performed to determine the prognostic significance. RESULTS: High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010). CONCLUSION: Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field.

Understanding salt tolerance mechanism using transcriptome profiling and de novo assembly of wild tomato Solanum chilense.

Soil salinity affects the plant growth and productivity detrimentally, but Solanum chilense, a wild relative of cultivated tomato (Solanum lycopersicum L.), is known to have exceptional salt tolerance. It has precise adaptations against direct exposure to salt stress conditions. Hence, a better understanding of the mechanism to salinity stress tolerance by S. chilense can be accomplished by comprehensive gene expression studies. In this study 1-month-old seedlings of S. chilense and S. lycopersicum were subjected to salinity stress through application of sodium chloride (NaCl) solution. Through RNA-sequencing here we have studied the differences in the gene expression patterns. A total of 386 million clean reads were obtained through RNAseq analysis using the Illumina HiSeq 2000 platform. Clean reads were further assembled de novo into a transcriptome dataset comprising of 514,747 unigenes with N50 length of 578 bp and were further aligned to the public databases. Genebank non-redundant (Nr), Viridiplantae, Gene Ontology (GO), KOG, and KEGG databases classification suggested enrichment of these unigenes in 30 GO categories, 26 KOG, and 127 pathways, respectively. Out of 265,158 genes that were differentially expressed in response to salt treatment, 134,566 and 130,592 genes were significantly up and down-regulated, respectively. Upon placing all the differentially expressed genes (DEG) in known signaling pathways, it was evident that most of the DEGs involved in cytokinin, ethylene, auxin, abscisic acid, gibberellin, and Ca2+ mediated signaling pathways were up-regulated. Furthermore, GO enrichment analysis was performed using REVIGO and up-regulation of multiple genes involved in various biological processes in chilense under salinity were identified. Through pathway analysis of DEGs, "Wnt signaling pathway" was identified as a novel pathway for the response to the salinity stress. Moreover, key genes for salinity tolerance, such as genes encoding proline and arginine metabolism, ROS scavenging system, transporters, osmotic regulation, defense and stress response, homeostasis and transcription factors were not only salt-induced but also showed higher expression in S. chilense as compared to S. lycopersicum. Thus indicating that these genes may have an important role in salinity tolerance in S. chilense. Overall, the results of this study improve our understanding on possible molecular mechanisms underlying salt tolerance in plants in general and tomato in particular.

Transcriptional regulation-mediating ROS homeostasis and physio-biochemical changes in wild tomato (Solanum chilense) and cultivated tomato (Solanum lycopersicum) under high salinity.

Salinity intrusion is one of the biggest problems in the context of sustainable agricultural practices. The major concern and challenge in developing salt-resistance in cultivated crops is the genetic complexity of the trait and lack of natural variability for stress-responsive traits. In this context, tomato wild relatives are important and have provided novel alleles for breeding abiotic stress tolerance including salt tolerance. We provide here a case study, involving tomato wild relative Solanum chilense and cultivated variety Solanum lycopersicum, carried out under high salt stress to investigate comparative transcriptional regulation mediating ROS homeostasis and other physiological attributes. Salt dependent oxidative stress in S. lycopersicum was characterized by a relatively higher H2O2 content, generation of O2 •-, electrolytic leakage and lipid peroxidation whereas reduced content of both ascorbate and glutathione. On the contrary, the robust anti-oxidative system in the S. chilense particularly counteracted the salt-induced oxidative damages by a higher fold change in expression profile of defense-related salt-responsive genes along with the increased activities of anti-oxidative enzymes. We conclude that S. chilense harbours novel genes or alleles for salt stress-related traits that could be identified, characterized, and mapped for its possible introgression into cultivated tomato lines.

DNA damage response proteins and its role in tumor progression of uveal melanoma with patient outcome.

BACKGROUND: The role of DNA damage response (DDR) proteins is poorly understood in uveal melanoma. ATR belongs to one of those proteins that induce DDR by arresting the cell cycle which leads to DNA repair. ATR is localized at position 23 on the same chromosome 3 where BAP1 is located at position 21.1 which is a known poor prognostic marker of UM. The aim of our study is to detect the expression of ATR at the protein and RNA levels and determine its prognostic significance. METHODS: Expression of nuclear ATR was investigated on sixty-nine UM patients. Formalin-fixed paraffin-embedded choroidal melanoma samples were taken to evaluate the expression of ATR. Fifty samples were also validated by real-time PCR. Results of both protein and mRNA were then correlated with clinicopathological parameters. To determine the prognostic significance, Kaplan-Meier and multivariate analyses were performed. RESULTS: Loss of ATR protein was seen in 72% cases which was statistically significant with epithelioid cell type (p = 0.005), tumor thickness (p = 0.016), mitotic figures (p = 0.001) and BAP1 loss (p < 0.001). At the transcriptional level loss of ATR was seen in 76% cases which were statistically significant with metastasis (p = 0.046), staging (0.044) and loss of BAP1 (p = 0.022). On multivariate analysis loss of ATR and tumor staging came out to be independent prognostic parameters. CONCLUSION: Our data suggest that ATR might serve as a potential prognostic marker in UM patients and could serve as a potential therapeutic target.

Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome.

PURPOSE: Uveal melanoma (UM) is the most common intraocular cancer with a high mortality rate that requires new research in the field of prevention and treatment. c-REL is a member of the nuclear factor κB (NF-κB) transcription factor family and an emerging regulator of tumorigenesis. Therefore, the objective of the study is to evaluate the constitutive expression of c-REL in uveal melanoma patients and its prognostic significance. METHODS: Detection of c-REL expression was carried out by immunohistochemistry in all 75 patients, and qRT-PCR performed on 58 fresh cases of uveal melanoma along with IL-6 status. Immunoblot was performed to validate immunohistochemistry results. Expression of c-REL protein correlated with clinicopathological parameters and overall survival of patients. RESULTS: Immunohistochemistry results revealed nuclear expression of the c-REL protein (56%) in our cases. Out of 75 cases, 31 cases showed nuclear expression, and 11 cases had cytoplasmic expression. qRT-PCR showed upregulation of the REL gene in 56.89% cases at the transcriptional level. There was a statistically significant difference in the overall survival of patients with c-REL nuclear immunopositivity (p = 0.0048). On multivariate analysis, scleral invasion and c-REL nuclear expression found to be an independent prognostic factor (p < 0.05) CONCLUSIONS: To the best of our knowledge, this was the first study reporting the expression of the c-REL protein in uveal melanoma. Strong nuclear immunoexpression of c-Rel suggests NFκB pathway activation which might be involved in the progression of the disease. Differential expression of c-REL protein may be used as an attractive target for the development of anticancer strategies.

Development of recombinant nucleocapsid protein-based indirect enzyme-linked immunosorbent assay for sero-survey of porcine reproductive and respiratory syndrome.

BACKGROUND AND AIM: Porcine reproductive and respiratory syndrome (PRRS) is a disease endemic in many countries and is of economic importance. India was free from PRRS until the first outbreak was reported from a North-East Indian state in 2013. Since then, disease outbreaks have been reported from North-East India and the pilot study conducted earlier showed that it is gradually spreading to the rest of India. Considering there are no locally developed population screening tests available for PRRS and imported diagnostic/screening tests are expensive, the present study was aimed at developing recombinant nucleocapsid (rN) protein-based indirect enzyme-linked immunosorbent assay (iELISA). MATERIALS AND METHODS: The rN protein of PRRS virus (PRRSV) was produced following standard cloning, expression, and purification procedures. Using this antigen, iELISA was optimized for the detection of serum antibodies to PRRSV. The sensitivity and specificity of the test were assessed by comparing it with a commercial PRRSV antibody detection kit. RESULT: A total of 745 serum samples from ten different states of India were screened using the developed iELISA. The iELISA had a relative specificity of 76.18% and sensitivity of 82.61% compared to the commercial ELISA (Priocheck PRRSV ELISA kit, Thermo Fisher Scientific, USA). CONCLUSION: The iELISA, which deployed rN protein from Indian PRRSV, was found to be suitable in the serological survey and may be a useful tool in future disease surveillance programs.

A systematic review: the appraisal of the effects of metformin on lipoprotein modification and function.

AIMS: Metformin is a commonly prescribed anti-hyperglycaemic pharmacological agent, and it remains a staple in the management of type II diabetes. In addition to metformin's glucose lowering effects, research has indicated that metformin inhibits glycation-mediated and oxidative modification of lipoprotein residues. The purpose was to discuss the effects of metformin as it relates to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) modification. MATERIALS AND METHODS: The purpose was to conduct a narrative and pragmatic review on the effects of metformin as it pertains to HDL and LDL modification. RESULTS: High-density lipoprotein (HDL) concentration is a quantitative measure and therefore does not provide insight into its function, which is a qualitative property. Dysfunctional HDLs are unable to carry out functions normally associated with HDL because they can be modified by glycating agents. Metformin may counteract HDL dysfunction by abating HDL modification. Reductions in HDL modification may improve reverse cholesterol transport ability and thus possibly diminish cardiovascular risk. Similarly, metformin-mediated attenuations in LDL modification may reduce their atherogenic potency. CONCLUSION: Metformin may partially ameliorate HDL dysfunction and reduce LDL modification by inhibiting alpha-dicarbonyl-mediated modification of apolipoprotein residues; consequently, the results are salient because cardiovascular disease incidence may be reduced given that reverse cholesterol transport activity predicts risk, and modified LDL are proatherogenic.

Does NEMO/IKKgamma protein have a role in determining prognostic significance in uveal melanoma?

Purpose: Uveal melanoma, although a rare form of cancer, is the most common primary malignancy of the eye in adults. Nuclear factor-kapaB (NF-kapaB) is a transcription factor that transactivates genes involved in the regulation of cell growth, apoptosis, angiogenesis, and metastasis, but the molecular mechanisms that negatively regulate NF-kapaB activation are not fully understood. NF-kapaB can also be activated by DNA damage pathway through NEMO protein. Therefore, the objective of this study is to elucidate the role of NEMO/IKKgamma protein in uveal melanoma patients. Methods: Seventy-five formalin-fixed paraffin-embedded prospective tissues of uveal melanoma were included in the present study. These cases were reviewed and investigated for the expression of NEMO/IKKgamma protein by immunohistochemistry and validated by western blotting along with the qRT-PCR for mRNA expression. Expression levels were correlated with the clinicopathological parameters and patients’ outcome. Results: Immunohistochemistry showed cytoplasmic expression of NEMO/IKKgamma expression in only 22 out of 75 (29.33%) cases. This result was confirmed by western blotting, and correlated well with the immunohistochemical expression of NEMO/IKKgamma protein (48 kDa). In addition, downregulation of this gene was found in 87.93% of the cases when compared with the normal tissues. On statistical analysis, loss of NEMO/IKKgamma protein was correlated with neovascularization, high mitotic count, and presence of vascular loop (p < 0.05). There was less overall survival rate with low expression of NEMO/IKKgamma protein in patients with uveal melanoma. Conclusion: This was the first study suggesting the relevant role of NEMO/IKKgamma protein, and highlights the prognostic significance with outcome in uveal melanoma patients. This protein might be used as a screening biomarker in these patients after large-scale validation and translational studies

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Does NEMO/IKKγ protein have a role in determining prognostic significance in uveal melanoma?

PURPOSE: Uveal melanoma, although a rare form of cancer, is the most common primary malignancy of the eye in adults. Nuclear factor-κB (NF-κB) is a transcription factor that transactivates genes involved in the regulation of cell growth, apoptosis, angiogenesis, and metastasis, but the molecular mechanisms that negatively regulate NF-κB activation are not fully understood. NF-κB can also be activated by DNA damage pathway through NEMO protein. Therefore, the objective of this study is to elucidate the role of NEMO/IKKγ protein in uveal melanoma patients. METHODS: Seventy-five formalin-fixed paraffin-embedded prospective tissues of uveal melanoma were included in the present study. These cases were reviewed and investigated for the expression of NEMO/IKKγ protein by immunohistochemistry and validated by western blotting along with the qRT-PCR for mRNA expression. Expression levels were correlated with the clinicopathological parameters and patients' outcome. RESULTS: Immunohistochemistry showed cytoplasmic expression of NEMO/IKKγ expression in only 22 out of 75 (29.33%) cases. This result was confirmed by western blotting, and correlated well with the immunohistochemical expression of NEMO/IKKγ protein (48 kDa). In addition, downregulation of this gene was found in 87.93% of the cases when compared with the normal tissues. On statistical analysis, loss of NEMO/IKKγ protein was correlated with neovascularization, high mitotic count, and presence of vascular loop (p < 0.05). There was less overall survival rate with low expression of NEMO/IKKγ protein in patients with uveal melanoma. CONCLUSION: This was the first study suggesting the relevant role of NEMO/IKKγ protein, and highlights the prognostic significance with outcome in uveal melanoma patients. This protein might be used as a screening biomarker in these patients after large-scale validation and translational studies.

Influence of sex hormone levels on gingival enlargement in adolescent patients undergoing fixed orthodontic therapy: A pilot study.

BACKGROUND: Sex hormones may be a modifying factor in the periodontal disease pathogenesis. AIM: The association between gingival enlargement and sex hormone levels in adolescent patients undergoing fixed orthodontic therapy needs to be determined. SETTINGS AND DESIGN: This study was conducted in the Department of Periodontology in association with the Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangaluru. MATERIALS AND METHODS: A pilot study was conducted on 21 adolescent patients between the age group of 13-19 years, who had undergone fixed orthodontic therapy for at least 3 months. Apicocoronally, the gingival enlargement was assessed by the index described by Miller and Damm. Miranda and Brunet index was used to assess gingival overgrowth in the buccal-lingual direction in the interdental papilla. Furthermore, the patients were assigned to two groups - Group 1-GE and Group 2-non-GE. Sex hormones assessed were estradiol and progesterone in females and testosterone in males in both groups. RESULTS: 57.1% of the study population had enlargement of the gingiva. The mean plaque score was 0.59 and 0.56, respectively, in both groups. A statistically significant relationship was found between estradiol and testosterone levels with gingival enlargement. However, a significant relationship was not obtained for progesterone levels with the gingival enlargement. CONCLUSION: Direct correlation between estradiol, testosterone, and gingival enlargement was seen.

Postoperative pain relief and functional outcome following total knee arthroplasty - a prospective comparative audit of three analgesic regimes.

Pain control plays a key role in joint-replacement -surgery. As a surgeon the challenge is to reduce pain to an acceptable level in the post-operative period. The aim of the study was to assess the efficacy of bolus -local anaesthesia, infusion in to the surgical site and nerve blocks with femoral nerve catheter and its functional outcome. A prospective audit of 114 patients undergoing total knee arthroplasty were carried out.The patients were divided in to three groups : Group 1 (n = 27) received a bolus injection of 20 ml 0.25% levobupivacaine + 10 ml 0.25%bupivacaine + adrenaline + 30 ml saline. Group 2 (n = 39) received a bolus injection as on group 1 with 240 ml 0.25% bupivacaine infusion and 5 ml/hour using a Pain Buster pump. Group 3 (n = 48) received 30 ml 0.125% levobupivacaine to femoral (3-in-1) block with 30 ml 0.25% levobupivacaine to -sciatic nerve and introduction of a femoral nerve catheter. All patients were prescribed paracetamol 1 g QDS, Oxycontin 20 mg BD and Ibuprofen post -operatively. Pain was assessed with a Visual Analog Scale (VAS). The incidence of PONV was measured by PONY intensity score. The mean post-op VAS score for Group 3 was 4. The demand of oxynorm and NSAID were minimal in Group 3. The mean in patient stay for Group 3 was 3.1 days. The PONV intensity score was > 50 for 9 (36%) in Group 1, 15 (40%) in Group 2 and 9 (20%) in Group 3. There was loss of 20-30 degrees of flexion movements in Group 3 in the first 4 to 6 days post-op. Our study demonstrated that Regime 3 with the use of nerve blocks and femoral nerve catheter has given the maximum pain relief and good functional outcome following total knee replacement.

Effectiveness of glucometer in screening diabetes mellitus using gingival crevicular blood.

AIM: Study was carried out to evaluate the efficacy of a glucometer for screening diabetes using gingival crevicular blood and to compare the blood glucose levels in the gingival crevicular blood sample and blood sample collected by finger puncture method using glucometers. SUBJECTS AND METHODS: A total of 24 known diabetic patients who fulfilled the selection criteria were selected after obtaining their informed consent. Samples were collected from two sites, i.e., gingival crevice and fingertip which was measured using a self-monitoring device. STATISTICAL ANALYSIS USED: Karl Pearson correlation. RESULTS: This study revealed the existence of a positive correlation between gingival crevicular blood and capillary blood glucose level (r = 0.826), and gingival blood glucose level estimates 68.2% of capillary blood glucose level. Hence, based on the observations of the study using gingival crevicular blood glucose level, capillary blood glucose level may be estimated based on the following regression equation. Capillary blood glucose = 84.66 + 0.77x gingival crevicular blood glucose level. CONCLUSIONS: The intraoral sampling technique is safer, convenient, and cost-effective for the dental practitioner as the sample can be obtained during the routine periodontal examination. It can be concluded that with the regression equation based on the gingival crevicular blood glucose level, capillary blood glucose can be estimated.

Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars.

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

How safe is metabolic/diabetes surgery?

Although recent studies have shown the impressive antidiabetic effects of laparoscopic Roux-en-Y gastric bypass (LRYGB), the safety profile of metabolic/diabetes surgery has been a matter of concern among patients and physicians. Data on patients with type 2 diabetes who underwent LRYGB or one of seven other procedures between January 2007 and December 2012 were retrieved from the American College of Surgeons National Surgical Quality Improvement Program database and compared. Of the 66 678 patients included, 16 509 underwent LRYGB. The composite complication rate of 3.4% after LRYGB was similar to those of laparoscopic cholecystectomy and hysterectomy. The mortality rate for LRYGB (0.3%) was similar to that of knee arthroplasty. Patients who underwent LRYGB had significantly better short-term outcomes in all examined variables than patients who underwent coronary bypass, infra-inguinal revascularization and laparoscopic colectomy. In conclusion, LRYGB can be considered a safe procedure in people with diabetes, with similar short-term morbidity to that of common procedures such as cholecystectomy and appendectomy and a mortality rate similar to that of knee arthroplasty. The mortality risk for LRYGB is one-tenth that of cardiovascular surgery and earlier intervention with metabolic surgery to treat diabetes may eliminate the need for some later higher-risk procedures to treat diabetes complications.

The effect of total hip and hip resurfacing arthroplasty on vertical ground reaction force and impulse symmetry during a sit-to-stand task.

BACKGROUND: The aim of this study was to determine the influence of total hip arthroplasty and hip resurfacing arthroplasty on limb loading symmetry before, and after, hip reconstruction surgery during a sit-to-stand task. METHODS: Fourteen patients were recruited that were about to receive either a total hip prosthesis (n=7) or a hip resurfacing prosthesis (n=7), as well as matched controls. Patients performed a sit-to-stand movement before, 3 months after, and 12 months after surgery. Peak vertical ground reaction force and impulse were measured for each leg, from which ground reaction force and impulse symmetry ratios were calculated. FINDINGS: Before surgery, hip resurfacing patients showed a small asymmetry which was not different to normal for ground reaction force (0.88(0.28) vs. 1.00(0.11); p=0.311) or impulse (0.87(0.29) vs. 0.99(0.09); p=0.324) symmetry ratios. Total hip patients offloaded their affected hip by 30% in terms of impulse symmetry ratio (0.71(0.36) vs. 0.99(0.23); p=0.018). At 3 months following surgery asymmetries were seen that were different to normal in both hip resurfacing patients for ground reaction force (0.77(0.16); p=0.007), and total hip patients for ground reaction force (0.70(0.15); p=0.018) and impulse (0.72(0.16); p=0.011) symmetry ratios. By 12 months after surgery total hip patients regained a symmetrical loading pattern for both ground reaction force (0.95(0.06); p=0.676) and impulse (1.00(0.06); p=0.702) symmetry ratios. Hip resurfacing patients, however, performed the task by overloading their operated hip, with impulse symmetry ratio being larger than normal (1.16(0.16); p=0.035). INTERPRETATION: Physiotherapists should appreciate the need for early recovery of limb loading symmetry as well as subsequent differences in the responses observed with different prostheses.