Effects of hip muscle activation on the stiffness and energy absorption of the trochanteric soft tissue during impact in sideways falls.

The trochanteric soft tissue attenuates impact force or absorbs impact energy during a fall on the hip (thereby helps to reduce a risk of hip fracture). While the benefits should be affected by contractions of muscles spanning the hip joint, no information is available to date. We examined how the stiffness (force attenuation capacity) and energy absorption of the trochanteric soft tissue were affected by hip muscle activation during a fall. Thirteen healthy young individuals (5 males, 8 females) participated in the pelvis release experiment. Falling trials were acquired with three muscle contraction conditions: 0-20% ("relaxed"), 20-50% ("moderate"), and 60-100% ("maximal") of the maximal voluntary isometric contraction of the gluteus medius muscle. During trials, we measured real-time force and deformation behaviour of the trochanteric soft tissue. Outcome variables included the stiffness and energy absorption of the soft tissue. The stiffness and energy absorption ranged from 56.1 to 446.9 kN/m, and from 0.15 to 2.26 J, respectively. The stiffness value increased with muscle contraction, and 59% greater in "maximal" than "relaxed" condition (232.2 (SD = 121.4) versus 146.1 (SD = 49.9)). However, energy absorption decreased with muscle contraction, and 58.9% greater in "relaxed" than "maximal" condition (0.89 (SD = 0.63) versus 0.56 (SD = 0.41)). Our results provide insights on biomechanics of the trochanteric soft tissue ("natural" padding device) during impact stage of a fall, suggesting that soft tissues' protective benefits are largely affected by the level of muscle contraction.

Effect of fall characteristics on the severity of hip impact during a fall on the ground from standing height.

The magnitude of hip impact force during a fall on the ground (i.e., concrete surface) from standing height was determined. We found that this force decreases up to 59%, depending on how they land on the ground. INTRODUCTION: We determined the magnitude of hip impact force that humans may experience in the event of a fall from standing height on the ground, in order to examine how the hip impact force was affected by characteristics of a fall. METHODS: Twenty subjects mimicked a typical older adults' falls on a mat. Trials were acquired with three initial fall directions: forward, sideways, and backward. Trials were also acquired with three knee positions at the time of hip impact: knee together, knee on the mat, and free knee. During falls, attenuated vertical hip impact forces and corresponding depression of the mat were measured via a force plate placed under the mat and motion capture system, respectively. Using a mass-spring model, actual hip impact force and body stiffness during a fall on the ground were estimated. RESULTS: Hip impact force averaged 4.0 kN (SD = 1.7). The hip impact force was associated with knee condition (F = 25.6, p < 0.005), but not with fall direction (F = 0.4, p = 0.599). Compared with "knee on the mat," hip impact force averaged 59% and 45% greater in "free knee" and "knee together," respectively (4.6 versus 2.9 kN, p < 0.005; 4.3 versus 2.9 kN, p < 0.005). However, the hip impact force did not differ between "free knee" and "knee together (4.6 versus 4.3 kN, p = 0.554). CONCLUSION: Our results suggest that hip fracture risk during a fall decreases substantially, depending on how they land on the ground, informing the development of safe landing strategies to prevent fall-related hip fractures in older adults.

Soft tissue stiffness over the hip increases with age and its implication in hip fracture risk in older adults.

Risk of hip fracture depends on the bone strength as well as the impact force delivered to the proximal femur during falls, and femoral soft tissue may help to reduce the hip fracture risk by attenuating the impact force. Femoral soft tissue stiffness was measured from a large sample, and compared how this was affected by age, gender and site. One hundred fifty healthy individuals (fifty-two young (aged between 19 and 29), forty-eight middle-aged (30-64), and fifty old (over 65)) participated. Each age group included an equal number of males and females. Using an automated hand-held indentation device, soft tissue stiffness was measured over twelve sites with respect to the greater trochanter (GT). For both left and right hips, the stiffness was associated with age (p < 0.0005), gender (p < 0.0005), and site (p < 0.0005). On average, the stiffness was 26% greater in older than young adults (321.5 versus 254.3 N/m). On average across twelve sites, the regression analysis indicated that the stiffness increases 1.33 N/m every year ("soft tissue stiffness over the hip = 1.33*age + 221.8"; R = 0.518, p < 0.0005). Furthermore, the stiffness was 18% greater in male than female (308.8 versus 262.6 N/m), and differed across twelve sites over the hip, being greatest (424.2 N/m) at the GT, and least (206.3 N/m) at the superior gluteal region. The results provide insights into the shock absorbing property of soft tissue over the hip, and inform the improvement of fall-related injury prevention interventions (i.e., hip protector, safe landing strategies) in older adults.

A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC).

BACKGROUND: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes. CONCLUSION: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation. CLINICALTRIALSGOV IDENTIFIER: NCT01029418.

Bioactivity of proteins isolated from Lactobacillus plantarum L67 treated with Zanthoxylum piperitum DC glycoprotein.

Lactobacilli in the human gastrointestinal tract have beneficial effects on the health of their host. To enhance these effects, the bioactivity of lactobacilli can be fortified through exogenous dietary or pharmacological agents, such as glycoproteins. To elucidate the inductive effect of Zanthoxylum piperitum DC (ZPDC) glycoprotein on Lactobacillus plantarum L67, we evaluated the radical-scavenging activity, anti-oxidative enzymes (SOD, GPx and CAT), growth rate, ATPase activity and ß-galactosidase activity of this strain. When Lact. plantarum L67 was treated with ZPDC glycoprotein at different concentrations, the intensities of a few SDS-PAGE bands were slightly changed. The amount of a 23 kDa protein was increased upon treatment with increasing concentrations of ZPDC glycoprotein. The results of this study indicate that the radical-scavenging activity for O2(-) and OH¯, but not for the DPPH radical, increased in a concentration-dependent manner after treatment with ZPDC glycoprotein. The activation of anti-oxidative enzymes (SOD, GPx and CAT), growth rate and ß-galactosidase activity also increased in a concentration-dependent manner in response to ZPDC glycoprotein treatment, whereas ATPase activity was decreased. In summary, ZPDC glycoprotein stimulated an increase in the bioactivity of Lact. plantarum L67. Significance and impact of the study: This study demonstrated that Lactobacillus plantarum L67 possesses anti-oxidative activity. This strain of lactic bacteria has been known to have various probiotic uses, such as yogurt starters and dietary additional supplements. We found, through this experiment, that the protein has a strong anti-oxidative character, and the activity can be enhanced by treatment with Zanthoxylum piperitum DC (ZPDC) glycoprotein. This study may be application of Lact. plantarum L67 treated by ZPDC glycoprotein in yogurt fermentation. It could be one of the avenues of minimizing yogurt postacidification during storage. In addition, it can be manufactured and incorporated in food products without losing viability and functionality of Lact. plantarum L67.

The proteins (12 and 15 kDa) isolated from heat-killed Lactobacillus plantarum L67 induces apoptosis in HT-29 cells.

A number of scientific studies have revealed that Lactobacillus strains have beneficial bioactivities in the gastrointestinal tract. In this study, the production of intracellular reactive oxygen species (ROS) and the amounts of intracellular calcium, protein kinase C activity, cytochrome c, Bid, Bcl-2, Bax and the apoptosis-mediated proteins [caspase-8, caspase-3 and poly ADP ribose polymerase (PARP)] were evaluated to understand the induction of programmed cell death in HT-29 cells by Lactobacillus plantarum L67. The results obtained from this study indicated that the relative intensities of the apoptotic-related factors (intracellular ROS and intracellular calcium) and of apoptotic signals (Bax and t-Bid) increased with increasing concentrations of the membrane proteins isolated from heat-killed L. plantarum L67, whereas the relative intensities of cytochrome c, Bcl-2, caspase-8, caspase-3 and PARP decreased. This study determines whether proteins (12 and 15 kDa) isolated from heat-killed L. plantarum L67 induce programmed cell death in HT-29 cells. Proteins isolated from L. plantarum L67 can stimulate the apoptotic signals and then consequently induce programmed cell death in HT-29 cells. The results in this study suggest that the proteins isolated from L. plantarum L67 could be used as an antitumoural agent in probiotics and as a component of supplements or health foods.

Physical, chemical, and biological methods for the removal of arsenic compounds.

Arsenic is a toxic metalloid which is widely distributed in nature. It is normally present as arsenate under oxic conditions while arsenite is predominant under reducing condition. The major discharges of arsenic in the environment are mainly due to natural sources such as aquifers and anthropogenic sources. It is known that arsenite salts are more toxic than arsenate as it binds with vicinal thiols in pyruvate dehydrogenase while arsenate inhibits the oxidative phosphorylation process. The common mechanisms for arsenic detoxification are uptaken by phosphate transporters, aquaglyceroporins, and active extrusion system and reduced by arsenate reductases via dissimilatory reduction mechanism. Some species of autotrophic and heterotrophic microorganisms use arsenic oxyanions for their regeneration of energy. Certain species of microorganisms are able to use arsenate as their nutrient in respiratory process. Detoxification operons are a common form of arsenic resistance in microorganisms. Hence, the use of bioremediation could be an effective and economic way to reduce this pollutant from the environment.

Investigation of toxin genes among methicillin-resistant Staphylococcus aureus strains isolated from a tertiary hospital in Malaysia.

Staphylococcus aureus is a persistent human pathogen responsible for a variety of infections ranging from soft-tissue infections to bacteremia. It produces a variety of virulence factors which are responsible for specific acute staphylococcal toxaemia syndromes. The objective of this study was to determine the prevalence of a repertoire of toxin genes among Malaysian MRSA strains and their genetic diversity by PCR-RFLP of coa gene. One hundred eighty-eight strains (2003, 2004, 2007 and 2008) of methicillin-resistant S. aureus (MRSA) were screened for 20 genes encoding for extracellular virulence determinant (sea, seb, sec, sed, see, seg, seh, sei, sej, tst, eta, etb, etd) and adhesins (cna, etb, fnbA, fnbB, hlg, ica, sdrE). The genetic relatedness of these strains was determined by PCR-RFLP of coa gene and agr grouping. Majority of the strains were tested positive for efb and fnbA (96% each), ica (78%) and hlg (59%) genes. A total of 101 strains were positive for at least one type of staphylococcal enterotoxin genes with sea being the predominant. Genes for seb, sed, see, seh, sej, eta and etb were not detected in any of the MRSA strains. The prevalence of sea, sec and ica among strains isolated in 2008 was increased significantly (p< 0.05) compared to 2003. Most of the strains were of agr type I (97.5%) followed by agr type II (1.2%) and agr type III (0.6%). All sea, sei and tst gene-positive strains were of agr type I. The only etd positive strain was agr type III. PCR-RFLP of coa produced 47 different patterns. The number of strains with virulence factors (sea, sec and ica) had increased over the years. No direct correlation between PCR-RFLP- coa profiles and virulotypes was observed.

ermA, ermC , tetM and tetK are essential for erythromycin and tetracycline resistance among methicillin-resistant Staphylococcus aureus strains isolated from a tertiary hospital in Malaysia.

The objective of this study was to determine the expression and transferability of tetracycline and erythromycin resistance among 188 MRSA strains from a Malaysian tertiary hospital. The minimum inhibitory concentrations (MICs) for oxacillin, erythromycin, tetracycline and ciprofloxacin ranged from 4 to 512 µg/ml, 0.25 to 256 µg/ml, 0.5 to 256 µg/ml and 0.5 to 512 µg/ml, respectively. Tetracycline-resistant strains showed co-resistance towards ciprofloxacin and erythromycin. There was a significant increase (P<0.05) of high-level tetracycline (≥MIC 256 µg/ml) and erythromycin (≥MIC 128 µg/ml) resistant strains in between the years 2003 and 2008. All erythromycin-resistant strains harboured ermA or ermC gene and all tetracycline-resistant strains harboured tetM or tetK gene. The blaZ was detected in all MRSA strains, whereas ermA, tetM, ermC, tetK and msrA genes were detected in 157 (84%), 92 (49%), 40 (21%), 39 (21%) and 4 (2%) MRSA strains, respectively. The blaZ, tetM, ermC and tetK genes were plasmid-encoded, with ermC gene being easily transmissible. Tn5801-like transposon was present in 78 tetM-positive strains. ermA and tetM genes were the most prevalent erythromycin and tetracycline resistance determinants, respectively, in MRSA strains. The association of resistance genes with mobile genetic elements possibly enhances the spread of resistant traits in MRSA.

The Houdini effect--an unusual case of blunt abdominal trauma resulting in perforative appendicitis.

We present a unique case of perforative appendicitis that occurred in an adult following blunt abdominal trauma. This case represents the first such reported case from Ireland. It also represents a modern practical example of Laplace's theory of the effect of increased pressure on colonic wall tension leading to localized perforation, and serves to highlight not only the importance in preoperative imaging for blunt abdominal trauma, but also the importance of considering appendiceal perforation.

Adenoma malignum of the uterine cervix: ultrasonographic findings in 11 patients.

OBJECTIVE: To evaluate the ultrasonographic features of adenoma malignum, a minimal deviation adenocarcinoma of the uterine cervix. METHODS: Eighteen consecutive patients with pathologically confirmed adenoma malignum were enrolled in this study at two institutions. Preoperative ultrasound examination was performed and the results were available in 11 patients. We analyzed retrospectively the gray-scale ultrasound findings for the following morphologic characteristics: cervical enlargement, as well as size, location and ultrasonographic characteristics of lesions. In five patients we also evaluated Doppler features with regard to intralesional vascularity. RESULTS: The cervix was enlarged in 73% (8/11) of cases. The mean greatest tumor diameter was 4.2 (range, 2.5-6.8) cm. In five (45%) cases, the cervix was completely infiltrated by the tumor. At gray-scale ultrasound examination, three (27%) tumors were multilocular lesions, four (36%) were multilocular lesions with solid components and four (36%) were solid lesions. In the multilocular lesions with or without a solid component, locules tended to be 1 cm or less in average diameter (86%, 6/7 cases) and there tended to be 11-20 in number (57%, 4/7 cases). In most (57%, 4/7) cases the locular fluid was homogeneously hypoechoic. Most (75%, 3/4) solid lesions manifested heterogeneous echogenicity. The five (100%) tumors examined with Doppler manifested moderate or abundant color content on color or power Doppler. CONCLUSIONS: Adenoma malignum can appear sonographically as solid, multilocular and multilocular solid cervical lesions. Awareness of its clinical and ultrasonographic features might improve diagnosis before surgery.

Triple-vessel mesenteric ischaemia presenting with gastric ulceration.

We present an unusual presentation of chronic mesenteric ischaemia in a patient with recurrent gastric ulceration that highlights both the importance of recognition of ischaemia as a possible aetiology in those refractory to conventional treatment and the success of percutaneous transluminal mesenteric angioplasty in these cases.

Gun shot-101: an 8-year review of gunshot injuries in an Irish teaching hospital from a general surgical perspective.

BACKGROUND: Gun-related crime offences have increased in the Republic of Ireland steadily over the past number of years. Regional trauma units are witnessing unprecedented numbers of injuries in the Republic of Ireland with limited prior experience. AIMS: Eight-year retrospective study analysing demographic data, management and outcome of firearm-related injuries. RESULTS: Patients who experience gunshot injuries in this region are statistically likely to be young, male and unemployed with a single shotgun injury to an extremity. Post-operative survival rates of 100% for those who undergo an exploratory laparotomy. CONCLUSION: Ireland has comparable survival outcomes to other international centres with similar patient demographics due to timely and appropriate operative intervention. These results serve to provide a template for further patient management.

Differentiating blood samples from scrapie infected and non-infected hamsters by detecting disease-associated prion proteins using Multimer Detection System.

This communication describes the application of a modified sandwich enzyme-linked immunosorbent assay (ELISA), termed Multimer Detection System (MDS) for the detection of disease-associated multimeric forms of the prion protein (PrPd) in hamster blood. PrPd was detected in plasma of prion-affected hamsters while MDS revealed no PrPd in identically-treated plasma of healthy animals. This is the first report of a single ELISA- based immune detection of PrPd from blood samples.

Protein tyrosine phosphatase epsilon is a negative regulator of FcepsilonRI-mediated mast cell responses.

Modulation of mast-cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase epsilon (PTPepsilon; Ptpre) plays key regulatory roles during mast-cell activation mediated by the high-affinity IgE receptor (FcepsilonRI). Bone marrow-derived mast cells (BMMC) from Ptpre(-/-) mice exhibited enhanced FcepsilonRI-induced Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca(2+) mobilization revealed that the absence of PTPepsilon leads to increased phosphorylation of the linker for activation of T cells and SH2 domain-containing leucocyte phosphoproteins of 76 kDa, but not Grb2-associated binder-2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTPepsilon. In the event, Syk but not Lyn was hyperphosphorylated in PTPepsilon-deficient BMMC. Thus, PTPepsilon most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP-76 and linker of activated T cells and mobilization of Ca(2+). Consistent with the in vitro data, antigen- and IgE-mediated passive systemic anaphylactic reactions were augmented in Ptpre(-/-) mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell-autonomous signalling events. These data suggest that PTPepsilon negatively regulates FcepsilonRI-mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions.

Antioxidative activity of glycoprotein isolated from Geranium sibiricum Linne.

Glycoprotein from Geranium sibiricum Linne (GSL) with 18 kDa was isolated and it consists of carbohydrate moiety (10.45%) and protein moiety (89.55%). The GSL glycoprotein was characterised by its radical scavenging activity under various experimental conditions. When GSL glycoprotein was treated with deactivation agents (pronase E or NaIO(4)), its scavenging activity decreased in both cases. It has optimal and maximal activity in acidic, neutral pH (up to pH 9), and up to 85 degrees C. Also, its activity reduced in the case of Ca(2+) and Mn(2+), with the exception of the Mg(2+) case. Its activity in the presence of Mn(2+) declined more than in the case of the Ca(2+). Also, GSL glycoprotein (500 microg mL(-1)) has antioxidative effects on hydroxyl and superoxide anion radicals in cell-free systems, and GSL glycoprotein (200 microg mL(-1)) significantly protected from cytotoxicity in the GO (100 mU mL(-1))-treated Chang liver cells for 4 h.

Inhibitory effect of ZPDC glycoprotein on the expression of inflammation-related cytokines through p38 MAP kinase and JNK in lipopolysaccharide-stimulated RAW 264.7 cells.

OBJECTIVE: This study was carried out to investigate the anti-inflammatory potentials of 24 kDa glycoprotein isolated from Zanthoxylum piperitum DC fruit (ZPDC glycoprotein) in lipopolysaccharide (LPS)-stimulated murine macrophage cell line (RAW 264.7 cells). MATERIAL AND METHODS: RAW 264.7 cells were treated with ZPDC glycoprotein (50-200 microg/ml) in presence of LPS (2 microg/ml). The changes of the levels of inflammation-related factors were determined by using Western blot, EMSA, and RT-PCR. RESULTS: ZPDC glycoprotein has inhibitory effects on the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK), on the DNA binding activity of activator protein-1 (AP-1), and on the expression of c-Jun and c-Fos in LPS-stimulated RAW 264.7 cells. Interestingly, the DNA binding activity of AP-1 was attenuated by treatment with inhibitors of p38 MAP kinase and JNK. In addition, ZPDC glycoprotein (200 microg/ml) not only diminished the production of superoxide anion, hydrogen peroxide, and nitric oxide, but also suppressed the expression of pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha) and proteins (iNOS, COX-2, and MMP-9) in LPS- stimulated RAW 264.7 cells. CONCLUSIONS: The present study demonstrates that ZPDC glycoprotein is a natural anti-oxidant and one of the modulators of pro-inflammatory signal transduction pathways in RAW 264.7 cells.

A review of neonatal attendances out of hours in a Dublin maternity hospital.

UNLABELLED: BACKGROUND All neonates have free open access to the Baby Clinic at the maternity hospitals in Dublin for assessment of neonatal health issues. Through observation, however there is an increase in number of neonates attending the hospital outside the Baby Clinic hours. AIMS: To determine the number of neonates attending the acute neonatal service out of hours and to identify the percentage of neonates treated as true emergency. METHODS: Retrospective chart review over a twelve-month period. RESULTS: Seven hundred and thirty-two neonates attended the hospital out of hours. The majority were diagnosed with gastrointestinal problems (228/31%), jaundice (101/13.7%), respiratory problems (82/11.1%) and skin disorders (79/10.7%). Only 106 (14.4%) attendances warranted admissions. CONCLUSIONS: A large number of neonatal attendances did not require acute assessment out of hours and were managed by reassurance and maternal education. A centralized phone-in-triage system was suggested to relieve the strain on the acute neonatal service.