The effects of rehabilitation on the biomechanics of patients with athletic groin pain.

This study sought to investigate the kinematic and kinetic variables that change in patients with athletic groin pain (AGP) after a successful exercise intervention. The kinematic and kinetic measures of subjects with AGP (n = 65) that completed a lateral hurdle hop, pre and post an exercise rehabilitation program were compared to a control group of matched uninjured individuals (n = 50). Analysis of Characterising Phases was used to identify differences in kinematic and kinetic measures between the groups. AGP subjects returned to pain-free participation in sport in a median time of 9.14 weeks (5.14-29.0). In total 18 different biomechanical variables were significantly different between the AGP group and the uninjured group pre-rehabilitation. Of these, seven variables were no longer significantly different between the AGP group post-rehabilitation and the uninjured group. These seven variables may represent the factors most related to return to play in this cohort and are potential targets for rehabilitation.

Is stiffness related to athletic groin pain?

Athletic groin pain (AGP) is a common injury prevalent in field sports. One biomechanical measure that may be of importance for injury risk is stiffness. To date, [corrected] however, stiffness has not been examined in AGP. The primary aim was to determine whether AGP affects vertical and joint stiffness and if so, whether successful rehabilitation is associated with a change in stiffness. Sixty-five male patients with AGP and fifty male controls were recruited to this study. Assessment included a biomechanical examination of stiffness during a lateral hurdle hop test. Subjects with AGP were tested pre- and post-rehabilitation, while controls were tested once. AGP subjects were cleared for return to play in a median time of 9.14 weeks (5.14-29.0). Stiffness was significantly different at pre-rehabilitation in comparison with controls for three [corrected] of the ten stiffness values examined: ankle plantar flexor, knee extensor, hip abductor, and vertical stiffness (P <  .05, D = 0.38-0.81). [corrected]. Despite clearance for return to play, of these four variables, only hip abductor stiffness changed significantly from pre- to post-rehabilitation (P = .05, D = 0.36) [corrected] to become non-significantly different to the uninjured group (P = .23, D = 0.23). [corrected]. These findings suggest that hip abductor stiffness may represent a target for AGP rehabilitation. Conversely, given the clearance for return to play, the lower sagittal plane and vertical stiffness in the AGP group in comparison with the uninjured controls likely represents either a compensatory mechanism to reduce the risk of further injury or a consequence of neuromuscular detraining.

Does the amount of lower extremity movement variability differ between injured and uninjured populations? A systematic review.

Movement variability during repetitive performance of a dynamic activity (eg, running, jumping, kicking) is considered an integral characteristic of optimal movement execution; however, its relationship with musculo-skeletal injury is not known. The primary aim of this study was to review published comparison trials to determine whether movement variability differs between uninjured controls and subjects with a lower limb musculo-skeletal injury. A systematic search of online databases; MEDLINE, Sports Discus, Scopus, and Web of Science was conducted from July to November 2016. Studies were selected if they (a) included participants with a lower limb injury, (b) compared injured participants to uninjured controls, (c) examined movement variability for at least one dependent variable, and (d) provided a statistical between-group comparison when comparing measures of movement variability. Studies were excluded if they (a) investigated neurological disorders, (b) examined musculo-skeletal injury in the upper extremity or spine, and (c) used nonlinear measures to examine variability (ie, complexity). A significant difference between injured and uninjured populations was reported in 73% of the included studies, and of these, 64% reported greater movement variability in the injured group. This is the first systematic review with a best-evidence synthesis investigating the association between movement variability and musculo-skeletal injury. Findings suggest that movement variability in those with a musculo-skeletal injury differs from uninjured individuals. Interestingly, there was an overall trend toward greater movement variability being associated with the injured groups, although it should be noted that this trend was not consistent across all subcategories (eg, injury type). For a clearer insight into the clinical application of variability, greater methodological homogeneity is required and prospective research is recommended.

Crystal chemistry and single-phase synthesis of Gd3+ substituted Co-Zn ferrite nanoparticles for enhanced magnetic properties.

Rare earth (RE) ions are known to improve the magnetic interactions in spinel ferrites if they are accommodated in the lattice, whereas the formation of a secondary phase leads to the degradation of the magnetic properties of materials. Therefore, it is necessary to solubilize the RE ions in a spinel lattice to get the most benefit. In this context, this work describes the synthesis of Co-Zn ferrite nanoparticles and the Gd3+ doping effect on the tuning of their magnetic properties. The modified sol-gel synthesis approach offered a facile way to synthesize ferrite nanoparticles using water as the solvent. X-ray diffraction with Rietveld refinement confirmed that both pure Co-Zn ferrite and Gd3+ substituted Co-Zn ferrite maintained single-phase cubic spinel structures. Energy dispersive spectroscopy was used to determine the elemental compositions of the nanoparticles. Field and temperature dependent magnetic characteristics were measured by employing a vibration sample magnetometer in field cooled (FC)/zero field cooled (ZFC) modes. Magnetic interactions were also determined by Mössbauer spectroscopy. The saturation magnetization and coercivity of Co-Zn ferrite were improved with the Gd3+ substitution due to the Gd3+ (4f7)-Fe3+ (3d5) interactions. The increase in magnetization and coercivity makes these Gd3+ substituted materials applicable for use in magnetic recording media and permanent magnets.

Athletic groin pain (part 2): a prospective cohort study on the biomechanical evaluation of change of direction identifies three clusters of movement patterns.

BACKGROUND: Athletic groin pain (AGP) is prevalent in sports involving repeated accelerations, decelerations, kicking and change-of-direction movements. Clinical and radiological examinations lack the ability to assess pathomechanics of AGP, but three-dimensional biomechanical movement analysis may be an important innovation. AIM: The primary aim was to describe and analyse movements used by patients with AGP during a maximum effort change-of-direction task. The secondary aim was to determine if specific anatomical diagnoses were related to a distinct movement strategy. METHODS: 322 athletes with a current symptom of chronic AGP participated. Structured and standardised clinical assessments and radiological examinations were performed on all participants. Additionally, each participant performed multiple repetitions of a planned maximum effort change-of-direction task during which whole body kinematics were recorded. Kinematic and kinetic data were examined using continuous waveform analysis techniques in combination with a subgroup design that used gap statistic and hierarchical clustering. RESULTS: Three subgroups (clusters) were identified. Kinematic and kinetic measures of the clusters differed strongly in patterns observed in thorax, pelvis, hip, knee and ankle. Cluster 1 (40%) was characterised by increased ankle eversion, external rotation and knee internal rotation and greater knee work. Cluster 2 (15%) was characterised by increased hip flexion, pelvis contralateral drop, thorax tilt and increased hip work. Cluster 3 (45%) was characterised by high ankle dorsiflexion, thorax contralateral drop, ankle work and prolonged ground contact time. No correlation was observed between movement clusters and clinically palpated location of the participant's pain. CONCLUSIONS: We identified three distinct movement strategies among athletes with long-standing groin pain during a maximum effort change-of-direction task These movement strategies were not related to clinical assessment findings but highlighted targets for rehabilitation in response to possible propagative mechanisms. TRIAL REGISTRATION NUMBER: NCT02437942, pre results.

Stressful life events, hopelessness, and suicidal intent in patients admitted with attempted suicide in a tertiary care general hospital.

BACKGROUND: Suicide is a psychiatric emergency. Stressors in life and social variables (like marital status, family, and social support) are among the determinants of suicide. Hopelessness and suicidal intent are among the psychological variables that have shown promise in the prediction of suicide. AIMS AND OBJECTIVES: To assess stressful life events, hopelessness, suicidal intent, and sociodemographic variables in patients of attempted suicide. MATERIALS AND METHODS: Fifty consecutive patients admitted with attempted suicide were interviewed. Presumptive Stressful Life Event Scale, Beck Hopelessness Scale, and Beck Suicidal Intent Scale were used along with a semistructured pro forma for interview. Data were analyzed with statistical tests. RESULTS: Sixty-six percent of the participants were females, 72% were less than 30 years of age. Sixty-six percent of the patients had stressful life event score between 101 and 200 with the mean score of 127. The stressful life event score in those who considered they are in need of psychiatric help was significantly high. Most of the patients had mild (34%) and moderate (40%) degrees of hopelessness, and the mean score was 9.64. The mean suicidal intent in the participants was 25.14, when correlated with hopelessness score significant positive correlation was found. CONCLUSION: Lethality of the attempt increases with the increase in hopelessness.

Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes.

CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31-87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2-24) for the 14-day dosing schedule and 6 (1-24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS.

Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides.

Established prognostic tools in patients with myelodysplastic syndromes (MDS) were largely derived from untreated patient cohorts. Although azanucleosides are standard therapies for higher-risk (HR)-MDS, the relative prognostic performance of existing prognostic tools among patients with HR-MDS receiving azanucleoside therapy is unknown. In the MDS Clinical Research Consortium database, we compared the prognostic utility of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Prognostic Scoring System (MDAPSS), World Health Organization-based Prognostic Scoring System (WPSS) and the French Prognostic Scoring System (FPSS) among 632 patients who presented with HR-MDS and were treated with azanucleosides as the first-line therapy. Median follow-up from diagnosis was 15.7 months. No prognostic tool predicted the probability of achieving an objective response. Nonetheless, all five tools were associated with overall survival (OS, P=0.025 for the IPSS, P=0.011 for WPSS and P<0.001 for the other three tools). The corrected Akaike Information Criteria, which were used to compare OS with the different prognostic scoring systems as covariates (lower is better) were 4138 (MDAPSS), 4156 (FPSS), 4196 (IPSS-R), 4186 (WPSS) and 4196 (IPSS). Patients in the highest-risk groups of the prognostic tools had a median OS from diagnosis of 11-16 months and should be considered for up-front transplantation or experimental approaches.

PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).

A pharmacodynamic study of sorafenib in patients with relapsed and refractory acute leukemias.

We report the results of a phase I dose escalation trial of the multikinase inhibitor sorafenib in relapsed and refractory acute leukemia patients using an intermittent dosing regimen. Fifteen patients with advanced leukemia (12 with acute myeloid leukemia, 2 with acute lymphoblastic leukemia, 1 with biphenotypic) and a median age of 63 (range 37-85) years were enrolled and treated on a dose escalation trial. Toxicities >or=grade 3 were present in 55% of cycles and the maximum tolerated dose (MTD) was determined to be 400 mg b.i.d. x 21 days in a 28-day cycle. Plasma inhibitory assays of kinase targets extracellular signal-regulated kinase (ERK) and FLT3-internal tandem duplication (ITD) showed excellent target inhibition, with FLT3-ITD silencing occurring below the MTD. The N-oxide metabolite of sorafenib seemed to be a more potent inhibitor of FLT3-ITD than the parent compound. Despite marked ex vivo FLT-3 ITD inhibition, no patients met the criteria for complete or partial response in this monotherapy study. Out of 15 patients, 11 experienced stable disease as best response. Although sorafenib showed only modest clinical activity as a single agent in this heavily treated population, robust inhibition of FLT3 and ERK suggests that there may be a potential important role in combination therapies.

p21(WAF1/CIP1) induction by 5-azacytosine nucleosides requires DNA damage.

Decitabine (DAC) and 5-azacitidine have recently been approved for the treatment of myelodysplastic syndrome. The pharmacodynamic effects of DAC and 5-azacitidine outside their known activity as inhibitors of DNA methyltransferases (DNMTs) require further investigation. The purpose of this study was to investigate the effect of DAC on the expression of p21(WAF1/CIP1), a gene with a putative CpG island surrounding its promoter region. Promoter methylation analysis of p21(WAF1/CIP1) in leukemia cells revealed the absence of CpG methylation. However, DAC upregulated p21(WAF1/CIP1) expression in a dose-dependent manner (ED(50)=103.34 nM) and induced G2/M cell cycle arrest in leukemia cells. Sequential application of DAC followed by different histone deacetylase inhibitors induced expression of p21(WAF1/CIP1) synergistically. Upregulation of p21(WAF1/CIP1) paralleled DAC-induced apoptosis (ED(50)=153 nM). Low doses of DAC induced gamma-H2AX expression (ED(50)=16.5 nM) and upregulated p21(WAF1/CIP1) in congenic HCT 116 colon cancer cells in a DNMT-independent and p53-dependent fashion. Inhibition of p53 transactivation by pifithrin-alpha or the kinase activity of ATM by either the specific ATM inhibitor KU-5593 or caffeine abrogated p21(WAF1/CIP1) upregulation, indicating that DAC upregulation of p21(WAF1/CIP1) was p53- and ATM-dependent in leukemia cells. In conclusion, DAC upregulates p21(WAF1/CIP1) in DNMT-independent manner via the DNA damage/ATM/p53 axis.

Azacitidine prolongs overall survival and reduces infections and hospitalizations in patients with WHO-defined acute myeloid leukaemia compared with conventional care regimens: an update.

Azacitidine (AZA), as demonstrated in the phase III trial (AZA-001), is the first MDS treatment to significantly prolong overall survival (OS) in higher risk MDS pts ((2007) Blood 110 817). Approximately, one-third of the patients (pts) enrolled in AZA-001 were FAB RAEB-T (≥20-30% blasts) and now meet the WHO criteria for acute myeloid leukaemia (AML) ((1999) Blood 17 3835). Considering the poor prognosis (median survival <1 year) and the poor response to chemotherapy in these pts, this sub-group analysis evaluated the effects of AZA versus conventional care regimens (CCR) on OS and on response rates in pts with WHO AML.

The effects of continued azacitidine treatment cycles on response in higher risk patients with myelodysplastic syndromes: an update.

The international, phase III, multi-centre AZA-001 trial demonstrated azacitidine (AZA) is the first treatment to significantly extend overall survival (OS) in higher risk myelodysplastic syndromes (MDS) patients (Fenaux (2007) Blood110 817). The current treatment paradigm, which is based on a relationship between complete remission (CR) and survival, is increasingly being questioned (Cheson (2006) Blood108 419). Results of AZA-001 show CR is sufficient but not necessary to prolong OS (List (2008) Clin Oncol26 7006). Indeed, the AZA CR rate in AZA-001 was modest (17%), while partial remission (PR, 12%) and haematological improvement (HI, 49%) were also predictive of prolonged survival. This analysis was conducted to assess the median number of AZA treatment cycles associated with achievement of first response, as measured by IWG 2000-defined CR, PR or HI (major + minor). The number of treatment cycles from first response to best response was also measured.

Analysis on sliding helices and strands in protein structural comparisons: a case study with protein kinases.

Protein structural alignments are generally considered as 'golden standard' for the alignment at the level of amino acid residues. In this study we have compared the quality of pairwise and multiple structural alignments of about 5900 homologous proteins from 718 families of known 3-D structures. We observe shifts in the alignment of regular secondary structural elements (helices and strands) between pairwise and multiple structural alignments. The differences between pairwise and multiple structural alignments within helical and beta-strand regions often correspond to 4 and 2 residue positions respectively. Such shifts correspond approximately to "one turn" of these regular secondary structures. We have performed manual analysis explicitly on the family of protein kinases. We note shifts of one or two turns in helix-helix alignments obtained using pairwise and multiple structural alignments. Investigations on the quality of the equivalent helix-helix, strand-strand pairs in terms of their residue side-chain accessibilities have been made. Our results indicate that the quality of the pairwise alignments is comparable to that of the multiple structural alignments and, in fact, is often better. We propose that pairwise alignment of protein structures should also be used in formulation of methods for structure prediction and evolutionary analysis.

A method for optimising excision of the nail bed matrix.

This paper describes a useful way of ensuring complete surgical ablation of the germinal matrix of the nail bed by staining the proximal envelope with Bonney's Blue dye.

WITHDRAWN: Rice-based oral rehydration solution for treating diarrhoea.

BACKGROUND: Oral rehydration therapy is used to treat dehydration caused by diarrhoea. However the rehydration solution does not reduce stool loss or length of illness. A solution able to do this may lessen the use of ineffective diarrhoea treatments as well as improve morbidity and mortality related to diarrhoea. OBJECTIVES: The objective of this review was to assess the effects of rice-based oral rehydration salts solution compared with glucose-based oral rehydration salts solution on reduction of stool output and duration of diarrhoea in patients with acute watery diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Lilacs and the reference lists of relevant articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomized trials comparing standard World Health Organization oral rehydration solution with an experimental oral rehydration salts solution in which glucose (20 grams per litre) was replaced by 50-80 grams per litre of rice powder, with the electrolytes remaining unchanged. DATA COLLECTION AND ANALYSIS: Data were extracted independently by a statistician and a clinician. MAIN RESULTS: Twenty-two trials were included. Concealment of allocation was adequate in 15 of these trials. Irrespective of age, people with cholera who were given rice oral rehydration salts solution had substantially lower rates of stool loss than those given oral rehydration salts solution in the first 24 hours. Mean stool outputs in the first 24 hours were lower by 67 millilitres/kg of body weight (weighted mean difference -67.40, 95% confidence interval -94.26 to -41.53) in children, and by 51 millilitres/kg of body weight (weighted mean difference -51.07, 95% confidence interval -65.87 to -36.27) in adults. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only four millilitres/kg of body weight (weighted mean difference -4.29, 95% confidence interval -9.36 to 0.78). AUTHORS' CONCLUSIONS: Rice-based oral rehydration appears to be effective in reducing stool output in people with cholera. This effect was not apparent in infants and children with non-cholera diarrhoea.

Study of inheritance of diabetes mellitus in Western Indian population by pedigree analysis.

OBJECTIVES: To study the inheritance pattern of diabetes mellitus in Western Indian population by analysing the pedigree of diabetes patients. METHODS: 3,921 individuals from 300 families were interviewed for family history in this study, out of which 770 were diabetic individuals. Statistical analysis of the data was carried out using T-test and Chi-square test. RESULTS: 37% cases of Type 1 DM and 58% cases of Type 2 DM showed family history of the disease. Of the cases showing family history for diabetes, 92% in case of Type 1 DM and 59% in case of Type 2 DM showed family history of Type 2 DM with a decrease in age of onset in the successive generations. Both the parents, when diabetic conferred equal risk of inheriting diabetes in offspring. The sex ratio of offspring suffering from diabetes was not influenced when only one of the parents was diabetic. However it was observed that the male offspring were highly susceptible when both parents were diabetic (Chi-square value=4.55 with 1 d.f.). The age of onset of diabetes did not show significant correlation with whether one or both the parents were diabetic. However, it was noteworthy that in case of familial history of diabetes there was a decrease in the age of onset in successive generations. CONCLUSION: This study suggests that family history of diabetes results in predisposition to early onset of the disease in successive generations and a cluster of genes involved in Type 2 DM may show a parental effect for predisposition to Type 1 DM in the offspring in this set of Indian population.

Enrofloxacin pharmacokinetics in the European cuttlefish, Sepia officinalis, after a single i.v. injection and bath administration.

Enrofloxacin pharmacokinetics were studied in European cuttlefish, Sepia officinalis, after a single 5 mg/kg i.v. injection or a 2.5 mg/L 5 h bath. A pilot study with two animals was also performed following a 10 mg/kg p.o. administration. The concentration of enrofloxacin in hemolymph was assayed using high-performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived from compartmental methods. In the i.v. study, the terminal half-life (t(1/2)), apparent volume of distribution, and systemic clearance were respectively 1.81 h, 385 mL/kg, and 4.71 mL/min/kg. Following bath administration the t(1/2), peak hemolymph concentration (C(max)), and area under the curve to infinity (AUC(0-infinity)) were 1.01 h, 0.5 +/- 0.12 mug/mL, and 0.98 microg.h/mL, respectively. After oral administration, the t(1/2), C(max), and AUC(0-infinity) were 1.01 h, 10.95 microg/mL, 26.71 mug.h/mL, respectively. The active metabolite of enrofloxacin, ciprofloxacin, was not detected in any samples tested. The hemolymph concentration was still above minimum inhibitory concentration (MIC) values for shrimp and fish bacterial isolates at 6 h after i.v. administration, therefore, a dose of 5 mg/kg i.v. every 8-12 h is suggested for additional studies of efficacy. The C(max) value for the water bath was lower than for the i.v. study, but a bath of 2.5 mg/L for 5 h once to twice daily is suggested for additional studies to test efficacy against highly susceptible organisms. Although only two animals were used for the oral study, a dose of 10 mg/kg produced hemolymph concentrations of enrofloxacin that were in a range consistent with therapeutic efficacy in other species.

PRODOC: a resource for the comparison of tethered protein domain architectures with in-built information on remotely related domain families.

PROtein Domain Organization and Comparison (PRODOC) comprises several programs that enable convenient comparison of proteins as a sequence of domains. The in-built dataset currently consists of approximately 698 000 proteins from 192 organisms with complete genomic data, and all the SWISSPROT proteins obtained from the Pfam database. All the entries in PRODOC are represented as a sequence of functional domains, assigned using hidden Markov models, instead of as a sequence of amino acids. On average 69% of the proteins in the proteomes and 49% of the residues are covered by functional domain assignments. Software tools allow the user to query the dataset with a sequence of domains and identify proteins with the same or a jumbled or circularly permuted arrangement of domains. As it is proposed that proteins with jumbled or the same domain sequences have similar functions, this search tool is useful in assigning the overall function of a multi-domain protein. Unique features of PRODOC include the generation of alignments between multi-domain proteins on the basis of the sequence of domains and in-built information on distantly related domain families forming superfamilies. It is also possible using PRODOC to identify domain sharing and gene fusion events across organisms. An exhaustive genome-genome comparison tool in PRODOC also enables the detection of successive domain sharing and domain fusion events across two organisms. The tool permits the identification of gene clusters involved in similar biological processes in two closely related organisms. The URL for PRODOC is http://hodgkin.mbu.iisc.ernet.in/~prodoc.