Quantification of angiogenesis in estrogen receptor-positive and negative breast carcinoma

Background

The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.

Methods

This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).

Results

The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).

Conclusion

ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.

     

Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

Background

Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone.

Methods

We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts.

Results

Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003).

Conclusions

Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.

     

Analysis of p53 expression in partial hydatidiform mole and hydropic abortion

Background

Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterized by abnormal trophoblast tissue. Molar and non-molar hydropic placental changes are the most common forms of GTD. Differential diagnosis of GTD is sometimes problematic. Recently, p53 expression was identified as a good marker for distinguishing GTD types.

Aims

Comparison of p53 expression in partial hydatidiform mole (PHM) and hydropic abortion.

Methods

In this prospective cross-sectional study, molar and non-molar hydropic pregnancy specimens were collected. Immunohistochemical staining, based on the Labeled Streptavidin Biotin (LSAB) technique, was carried out on multiple 4 mm paraffin block sections prepared from formalin-fixed trophoblastic tissues. Polymer-based Envision was used to assess p53 tumor suppressor protein immunoreactivity. p53 expression was then compared between both groups.

Results

In the study, 40 patients were included: 20 with confirmed PHM and 20 with hydropic pregnancy. p53 protein was positive in 60% of patients with PHM and 25% of patients with hydropic pregnancy. The p53 positive rate was significantly higher in patients with PHM (p = 0.027). Moreover, patients with PHM had a significantly high grade of staining (p<0.001).

Conclusion

Our findings indicate that immunohistochemical analysis of p53 protein can be used to distinguish PHM and hydropic pregnancy.

     

Bioelectrical phase angle values in a clinical sample of ambulatory rehabilitation patients

Background

Phase angle (PhA) is derived from the resistance and reactance measurements obtained from bioelectric impedance analysis (BIA) and is considered indicative of cellular health and membrane integrity. This study measured PhA values of rehabilitation patients and compared them to reference values, measures of functional ability and serum C-reactive protein (CRP) levels to explore their utility as a clinical tool to monitor disease progression and treatment efficacy.

Methods

This cross-sectional observational study was conducted on 215 ambulatory rehabilitation patients aged 20 – 94 years. All participants had been hospitalised for a stroke, orthopaedic or other condition resulting in a functional limitation. PhA was derived from BIA analysis and functional ability characterised using the Functional Independence Measure (FIM), timed up and go (TUG) and maximal quadriceps strength (MQS). Serum levels of CRP were also collected.

Results

Stroke patients had the highest PhA (5.3°) followed by elective orthopaedic surgery (5.0°) with the other group (4.3°) significantly lower than both previous categories (p < 0.001). Ambulatory rehabilitation patients' PhA values were dependent on age and sex (p < 0.001), lower than published age matched healthy reference values (p ≤ 0.05) and similar to other hospitalised or sick groups, but also higher than values reported in critically ill patients. Patients with CRP values less than 10 mg.L^-1 had significantly (p = 0.005) higher mean PhA values. Furthermore, the highest functional status quartiles had significantly higher PhAs (p ≤ 0.04) for the FIM, MQS and TUG measures.

Conclusion

The results suggest that the phase angles of rehabilitation patients are between those of healthy individuals and seriously ill patients, thereby supporting claims that PhA is indicative of general health status. Phase angles are a potentially useful indicator of functional status in patients commencing an ambulatory rehabilitation program with a normal hydration status.

     

Women with large breasts are at an increased risk of advanced breast cancer

Background

The risk of nodal metastasis is higher in women with bigger breast. It is not clear if this increase is due to the size of the breast (largely related to obesity) or is the result of larger tumour size at presentation (due to delayed diagnosis). It is hypothesised that women with large breasts are more likely to have node positive disease mainly attributable to their breast size.

Patients and methods

One hundred and twenty consecutive patients who underwent mastectomy during the year 2004 and 2005 for primary breast cancers in a large Teaching Hospital were included in the study. Patient's variable and tumour variable were collected and analysed by SPSS^® computer programme.

Results

It was found that big breasted women (those patients with mastectomy weight greater than 800 g) had a significantly greater tumour size than those with smaller breasts (p = 0.019, Mann-Whitney test) but there was no significant difference in grade (Kendall's tau-b = 0.055, p = 0.57) or lymph node positivity (Kendall's tau-b = 0.011, p = 0.93) between the two groups. Although, the tumour size was significantly greater in those with lymph node metastases (p < 0.001) but mastectomy weight was not found to be significantly greater in those with lymph node metastases (p = 0.11). For patients with similar tumour sizes mastectomy weight was not significantly greater in those patients with lymph node metastases (p = 0.28).

Conclusion

It is concluded that increased incidence of lymph node positivity at presentation big-breasted women is because of larger size of the primary tumour and not due to the size of the breast alone.

     

Impact of transduction towards the proliferation and migration as well as the transduction efficiency of human umbilical cord-derived late endothelial progenitor cells with nine recombinant adeno-associated virus serotypes

Objectives

To evaluate the transduction efficiency of human umbilical cord-derived, late endothelial progenitor cells late (HUCB-late EPCs) with nine recombinant adeno-associated virus (rAAV) serotypes and the ability of proliferation and migration of the cells after transduction.

Results

rAAV2 and rAAV6 showed a greater ability than other serotypes to transduce late EPCs (P < 0.05). After transduction, cell proliferation ability weakened (P < 0.05), but the ability of migration to stromal cell-derived factor (SDF-1) unchanged.

Conclusion

There is an advantage of choosing the optimal rAAV serotype as a gene vector to alter the biologic characteristics of late EPCs.

     

The influence of obesity on calf blood flow and vascular reactivity in older adults

Objective

To determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity.

Methods

Eighty-seven individuals who were 60 years of age or older (age = 69 ± 7 yrs; mean ± SD) were grouped into normal weight (BMI < 25; n = 30), overweight (BMI ≥ 25 and < 30; n = 28), or obese (BMI ≥ 30; n = 29) categories. Calf blood flow (BF) was assessed by venous occlusion strain-gauge plethysmography at rest and post-occlusive reactive hyperemia.

Results

Post-occlusive reactive hyperemia BF was lower (p = 0.038) in the obese group (5.55 ± 4.67 %/min) than in the normal weight group (8.34 ± 3.89 %/min). Additionally, change in BF from rest to post-occlusion in the obese group (1.93 ± 2.58 %/min) was lower (p = 0.001) than in the normal weight group (5.21 ± 3.59 %/min), as well as the percentage change (75 ± 98 % vs. 202 ± 190 %, p = 0.006, respectively). After adjusting for age, prevalence in hypertension and calf skinfold thickness, change in BF values remained lower (p < 0.05) in obese subjects compared to the normal weight subjects. Lastly, the absolute and percentage change in BF were significantly related to BMI (r = -0.44, p < 0.001, and r = -0.37, p < 0.001, respectively) and to waist circumference (r = -0.36, p = 0.001, and r = -0.32, p = 0.002).

Conclusion

Obesity and abdominal adiposity impair vascular reactivity in older men and women, and these deleterious effects on vascular reactivity are independent of conventional risk factors.

     

Peak systolic velocity Doppler of middle cerebral artery in small for gestational age (SGA) fetus

Background

Small for gestational age (SGA) has high frequency which increases the risk of long-term adverse outcomes. Thus the aim of this study was to evaluate peak systolic velocity Doppler of middle cerebral artery (MCA) in SGA fetus in order to find appropriate method to diagnosis SGA sooner.

Materials and Methods

This prospective longitudinal study was conducted on 90 pregnant women with a diagnosis of SGA fetus and 90 pregnant women with normal fetus. Then MCA and umbilical artery assessment were performed for all subjects and compared between two groups.

Results

Doppler assessment showed that umbilical artery PI was significantly higher in SGA group as compared to normal group (1.11±0.37 vs 0.98±0.18, P = 0.003), while MCA PI was significantly lower in SGA group (1.77±0.44 vs 1.92±0.47, P = 0.028). On the other hand, PSV did not differ between the groups (P = 0.592). Moreover, we found that PSV was more in SGA group by grouping maternal age (<27 years) (P = 0.006), and gestational age (>34 weeks) (P<0.001).

Conclusion

The results of this study suggest that MCA PI decreased significantly in SGA fetuses, while UA PI increased in this group. Moreover, PSV increased in this group when evaluated in different subgroups (based on maternal age and gestational age).

     

Are the effects of a non-drug multimodal activation therapy of dementia sustainable? Follow-up study 10 months after completion of a randomised controlled trial

Background

Little is known about the long-term success of non-drug therapies for treating dementia, especially whether the effects are sustained after therapy ends. Here, we examined the effects of a one-year multimodal therapy 10 months after patients completed the therapy.

Methods

This randomised, controlled, single-blind, longitudinal trial involved 61 patients (catamnesis: n?=?52) with primary degenerative dementia in five nursing homes in Bavaria, Germany. The highly standardised intervention, MAKS, consisted of motor stimulation, practice of activities of daily living (ADLs), and cognitive stimulation. Each group of 10 patients was treated for 2 h, 6 days a week for 12 months. Control patients received standard nursing home care. At baseline, at the end of therapy (month 12), and 10 months thereafter (month 22), cognitive functioning was assessed using the cognitive subscale of the Alzheimer’s Disease Assessment Scale, and the ability to perform ADLs was assessed using the Erlangen Test of Activities of Daily Living.

Results

During the therapy phase, the MAKS patients maintained their cognitive function and ability to carry out ADLs. After the end of therapy, both the control and the MAKS groups deteriorated in both their cognitive function (control, p?=?0.02; MAKS, p?<?0.001) and their ability to carry out ADLs (control, p?<?0.001; MAKS, p?=?0.001). However, in a confound-adjusted multiple regression model, the ability of the MAKS group to perform ADLs remained significantly higher than that of the control group even 10 months after the end of therapy (H₀: β_MAKS?+?β_{MAKS month 22}?=?0; χ²?=?3.8568, p?=?0.0496). Cohen’s d for the difference between the two groups in ADLs and cognitive abilities 10 months after the end of therapy was 0.40 and 0.22, respectively.

Conclusions

A multimodal non-drug therapy of dementia resulted in stabilisation of the ability to perform ADLs, even beyond the end of therapy. To prevent functional decline for as long as possible, therapy should be performed continuously until the benefit for the patient ends. Follow-up studies on larger numbers of patients are needed to definitively confirm these results.

Trial registration

http://www.isrctn.com Identifier: ISRCTN87391496

     

Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men

Background

Obesity is associated with both impaired testosterone production and a chronic state of low grade inflammation. Previously it was believed that this inflammation was mediated by a decline in the immunosuppressive action of testosterone. However, more recently an alternative hypothesis (GELDING theory) has suggested that inflammation originating from the passage of intestinal bacteria into the circulation (metabolic endotoxaemia) may actually be the cause of impaired testicular function in obese men. The aim of this study is to investigate if metabolic endotoxaemia, as quantified by serum Lipopolysaccharide Binding Protein (LBP), is associated with impaired testicular endocrine function.

Methods

A total of 50 men aged between 21 and 50 years (mean 35.1?±?6.8 years) were assessed for adiposity (BMI, waist circumference and % body fat using bio-impedance), inflammatory status (serum CRP, IL-1β, IL-6, TNFα and LBP) and testicular endocrine function (serum testosterone, estradiol, AMH, LH and FSH). Statistical analysis was performed using Pearson correlation analysis, with log transformation of data where appropriate, and multi-variate regression.

Results

Overall increasing adiposity (% body fat) was positively associated with metabolic endotoxaemia (LBP, r?=?0.366, p?=?0.009) and inflammation (CRP r?=?0.531, p?<?0.001; IL-6 r?=?0.463, p?=?0.001), while also being negatively correlated with serum testosterone (r?=??0.403, p?=?0.004). Serum testosterone levels were significantly negatively correlated with inflammation (CRP r?=??0.471, p?=?0.001; IL-6 r?=??0.516, p?<?0.001) and endotoxaemia (LBP) after adjusting for serum LH levels (p?=??0.317, p?=?0.03). Furthermore, serum IL-6 was negatively associated with AMH levels (r?=??0.324, p?=?0.023), with a negative trend between LBP and AMH also approaching significance (r?=??0.267, p?=?0.064).

Conclusions

Obesity and its associated metabolic endotoxaemia helps initiate a pro-inflammatory state characterised by raised serum IL-6 levels, which in turn is correlated with impairment of both Leydig (testosterone) and Sertoli cell function (AMH). These results open up the potential for new treatments of obesity related male hypogonadism that focus on preventing the endotoxaemia associated chronic inflammatory state.

     

The efficacy and feasibility of total reconstruction versus nontotal reconstruction of the pelvic floor on short-term and long-term urinary continence rates after radical prostatectomy: a meta-analysis

Background

Recently, total pelvic floor reconstruction (TR) has been the treatment of choice for improving urinary incontinence (UI) after radical prostatectomy (RP). However, the superiority of TR with respect to urinary continence recovery following RP remains controversial. This study identified the effect of TR versus nonTR of the pelvic floor on short-term and long-term continence rates after RP.

Methods

A literature search was performed in November 2017 using the PubMed, Embase, and Web of Science databases. Only comparative research or clinical studies reporting urinary continence outcomes was included in the meta-analysis, and the quality of evidence was evaluated using the 2011 Level of Evidence for therapy research.

Results

We analyzed ten studies reporting urinary continence rates after RP at one or more postoperative time points (1, 2, 4, 12, 24, and 52 weeks). TR was associated with significantly better urinary continence outcomes at 1 week (OR 2.76, 95% CI 1.58–4.84, P?<?0.001), 2 weeks (OR 2.57, 95% CI 1.74–3.80, P?<?0.001), 4 weeks (OR 2.61, 95% CI 1.56–4.38, P?<?0.001), 12 weeks (OR 4.33, 95% CI 2.01–9.33, P?<?0.001), 24 weeks (OR 3.83, 95% CI 1.54–9.55, P?=?0.004), 52 weeks (OR 4.10, 95% CI 1.80–9.38, P?<?0.001) after RP. There was no difference in the rate of complications between the two arms (OR 0.54, 95% CI 0.19–1.54, P?=?0.25).

Conclusions

Compared with nonTR, TR is significantly and positively associated with a return to continence but not with complication rate in men following RP, suggesting that TR may be useful for decreasing the urinary incontinence rate after surgery.

     

Usefulness of selected laboratory markers in ulcerative colitis

Introduction

This study aimed to compare the accuracy of selected laboratory markers in assessing disease activity in patients with ulcerative colitis (UC). The analysis included serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ, hsCRP, peripheral regulatory T cells, as well as fecal calprotectin and lactoferrin.

Patients and methods

A group of 45 adults with UC was enrolled in the study. Disease activity was assessed using the Mayo endoscopic index, while for clinical activity scoring, the Clinical Activity Index (CAI) was used. Concentrations of markers investigated were estimated by means of flow cytometry and enzyme-linked immunosorbent assays: the results were correlated with both indices.

Results

The study demonstrated that both fecal markers, i.e. calprotectin (r = 0.880, P<0.001) and lactoferrin (r = 0.799, P<0.001) correlated closely with the Mayo endoscopic score, and might be used to evaluate the severity of UC in the clinical setting. The correlation of these markers with CAI was also significant, with r = 0.831 for calprotectin (P<0.001) and r = 0.672 for lactoferrin (P<0.05). As for the other markers investigated, only IL-6 (r = 0.598, P<0.001), IL-17A (r = 0.587, P<0.005), and TNF-α (r = 0.701, P<0.001) correlated closely with the Mayo endoscopic index. The correlation of the markers with CAI was also significant, though weaker, with r = 0.525 for IL-6 (P<0.001), r = 0.587 for IL-17A (P<0.05), and r = 0.624 for TNF-α (P<0.001).

Discussion

Despite the fact, that UC is generally considered to be an IL-13-driven, Th2-like type of disease, markers of inflammation such as serum interleukin (IL)-6, IL-17, TNF-α, fecal calprotectin and lactoferrin might be useful in assessing disease activity.

     

MiR-338-3p inhibits TNF-α-induced lipogenesis in human sebocytes

Objective

To suppress TNF-α-induced lipogenesis in sebocytes (associated with acne development) with microRNA-338-3p (miR-338-3p) and to explore the underlying mechanisms.

Results

TNF-α increased lipid droplet formation in sebocytes which were used as in vitro model of inflammation-induced acne. Flow cytometry and TLC assays validated that miR-338-3p could suppress TNF-α-induced lipid droplet formation, down-regulate the expression of PREX2a, and inactivate AKT signaling in sebocytes. In addition, suppression of AKT activity by the PI3 K and AKT inhibitors diminished TNF-α-induced lipogenesis. PREX2a siRNA mimics the effects of miR-338-3p on AKT phosphorylation and lipogenesis. PREX2a overexpression consistently restored lipogenesis and AKT phosphorylation attenuated by miR-338-3p.

Conclusions

MiR-338-3p suppresses the TNF-α-induced lipogenesis in sebocytes by targeting PREX2a and down-regulating PI3K/AKT signaling.

     

Kinetic response of wild and mutant core codon 70 strains of HCV genotype 1b to pegylated interferon-α and ribavirin therapy

Background

Amino acid (aa) 70 substitution (R70Q/H) in the core protein of hepatitis C virus (HCV) genotype 1b has been shown to be one of the key factors in determining resistance for pegylated interferon-α plus ribavirin combination therapy (PEG-IFNα/RBV). But the exact mechanisms remain unclear. The aim of this study was to investigate the dynamic response of wild and mutant core codon 70 strains to PEG-IFNα/RBV treatment.

Methods

One hundred twelve Chinese patients with chronic HCV 1b infection were enrolled and received a standard protocol of 48 weeks of PEG-IFNα/RBV therapy and 24 consecutive weeks of follow-up. Serial blood samples were obtained at pretreatment baseline, and again at weeks 2, 4, 8, 12, and 24 during therapy for the quantification of 70R and 70Q/H strains. Dynamic characteristics and association with early virological response (EVR), sustained virological response (SVR) and IL28B genotypes were analyzed.

Results

Of the 112 patients enrolled in this study, 93.8 % (105/112) were infected with mixture of 70R and 70Q/H strains before treatment. The 70Q/H strain was dominant in 20.5 % of patients. 42.9 % of patients with dominant 70Q/H exhibited EVR versus 88.6 % of patients with dominant 70R (P?<?0.001). Furthermore, 35.0 % of patients with dominant 70Q/H exhibited SVR versus 77.4 % with dominant 70R (P?<?0.001). However, regardless of the dominant strain, virological response types or the IL28B SNP genotypes, 70Q/H strains always exhibited the same response to treatment as the 70R strains and the percentage of HCV harboring the 70Q/H substitution did not change significantly during treatment.

Conclusions

Although the ratio of 70Q/H to 70R is related to the virological response, 70Q/H strains always exhibited the same response as the 70R strains during PEG-IFNα/RBV treatment. Substitution of R70Q/H alone is not enough to lead to resistance to therapy. Positive selection for 70Q/H induced by IFNα was not observed.

     

Risk factors associated with 31-day unplanned readmission in 50,912 discharged patients after stroke in China

Background

Unplanned readmission within 31?days of discharge after stroke is a useful indicator for monitoring quality of hospital care. We evaluated the risk factors associated with 31-day unplanned readmission of stroke patients in China.

Methods

We identified 50,912 patients from 375 hospitals in 29 provinces, municipalities or autonomous districts across China who experienced an unplanned readmission after stroke between 2015 and 2016, and extracted data from the inpatients’ cover sheet data from the Medical Record Monitoring Database. Patients were grouped into readmission within 31?days or beyond for analysis. Chi-squared test was used to analyze demographic information, health system and clinical process-related factors according to the data type. Multilevel logistic modeling was used to examine the effects of patient (level 1) and hospital (level 2) characteristics on an unplanned readmission ≤31?days.

Results

Among 50,912 patients, 14,664 (28.8%) were readmitted within 31?days after discharge. The commonest cause of readmissions were recurrent stroke (34.8%), hypertension (22.94%), cardio/cerebrovascular disease (13.26%) and diabetes/diabetic complications (7.34%). Higher risks of unplanned readmissions were associated with diabetes (OR?=?1.089, P?=?0.001), use of clinical pathways (OR?=?1.174, P?<?0.001), and being discharged without doctor’s advice (OR?=?1.485, P?<?0.001). Lower risks were associated with basic medical insurances (OR ranging from 0.225 to 0.716, P?<?0.001) and commercial medical insurance (OR?=?0.636, P?=?0.021), compared to self-paying for medical services. And patients aged 50?years old and above (OR ranging from 0.650 to 0.985, P?<?0.05), with haemorrhagic stroke (OR?=?0.467, P?<?0.001), with length of stay more than 7?days in hospital (OR ranging from 0.082 to 0.566, P?<?0.001), also had lower risks.

Conclusions

Age, type of stroke, medical insurance status, type of discharge, use of clinical pathways, length of hospital stay and comorbidities were the most influential factors for readmission within 31?days.

     

Influence of venous emptying on the reactive hyperemic blood flow response

Background

Previous research indicates that venous emptying serves as a stimulus for vasodilation in the human forearm. This suggests the importance of recognizing the potential influence of venous volume on reactive hyperemic blood flow (RHBF) following occlusion. The purpose of this study was to examine the influence of venous emptying on forearm vascular function.

Methods

Forearm RHBF, venous capacitance and venous outflow were examined in 35 individuals (age = 22 ± 2 years), using mercury in-Silastic strain gauge plethysmography, at rest and following five minutes of upper arm occlusion using standard procedures (Control). In addition, the same measures were obtained following five minutes of upper arm occlusion preceded by two minutes of passive arm elevation (Pre-elevation).

Results

Average resting arterial inflow was 2.42 ± 1.11 ml·100 ml^-1·min^-1. RHBF and venous capacitance were significantly greater during Pre-elevation compared to Control (RHBF; Pre-elevation: 23.76 ± 5.95 ml·100 ml^-1 ·min^-1 vs. Control: 19.33 ± 4.50; p = 0.001), (venous capacitance; Pre-elevation: 2.74 ± 0.89 % vs. Control: 2.19 ± 0.97, p = 0.001). Venous outflow did not differ between the two conditions.

Conclusion

Venous emptying prior to upper arm occlusion results in a significant greater RHBF response and venous capacitance. Recognition of the influence of venous volume on RHBF is particularly important in studies focusing on arterial inflow, and also provides further evidence for the interplay between the venous and arterial system.

     

Hypoxia promotes the migration and invasion of human hepatocarcinoma cells through the HIF-1α–IL-8–Akt axis

Background

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. The 5-year survival rate remains low despite considerable research into treatments of HCC, including surgery, radiotherapy and chemotherapy. Many mechanisms within HCC still require investigation, including the influence of hypoxia, which has a crucial role in many cancers and is associated with metastasis. Hypoxia inducible factor-1α (HIF-1α) is known to regulate the expression of many chemokines, including interleukin-8 (IL-8), which is associated with tumor metastasis. Although many studies have reported that HIF-1α is associated with HCC migration and invasion, the underlying mechanisms remain unknown.

Methods

The expression level of HIF-1α was determined in HCC cells. The correlation of IL-8 and HIF-1α expressions was assessed via knockdown of HIF-1α. HCC cells were also used to assess the influence of HIF-1α on HCC cell migration and invasion. LY294002, an inhibitor of the Akt pathway, was used to confirm the associated signaling pathways.

Results

We observed a significant attenuation of cell migration and invasion after silencing of HIF-1α. Exogenously expressing IL-8 restored migration and invasion. Akt was found to be involved in this process.

Conclusion

Hypoxia promotes HCC cell migration and invasion through the HIF-1α–IL-8–Akt axis.

     

The relationship between lower limb muscle volume and body mass in ambulant individuals with bilateral cerebral palsy

Background

Individuals with cerebral palsy have smaller muscle volumes normalised to body mass than their typically developing peers. The aim of this study is to investigate the relationship between lower limb muscle volume and body mass in young people with bilateral cerebral palsy and their typically developing peers.

Methods

Twenty-five participants with bilateral cerebral palsy (aged 14.7±3.0 years, GMFCS level I-III) and 25 of their typically developing peers (aged 16.8±3.3 years) took part in this study. None of the participants had undergone orthopaedic surgery, botulinum toxin injections, or serial casting in the previous year. All participants underwent magnetic resonance imaging of both lower limbs. Nine major muscles of each lower limb were individually manually segmented and the muscle volumes calculated.

Results

Body mass and total lower limb muscle volume were significantly linearly related in both the cerebral palsy (R² = 0.75, p<0.001) and typically developing (R² = 0.77, p<0.001) groups. The slope of the relationship between muscle volume and body mass was significantly shallower in the cerebral palsy group compared to the typically developing group (p=0.007).

Conclusions

This cross-sectional study suggests that the increase in size of lower limb muscles relative to body mass is reduced in adolescents and young adults with cerebral palsy. Longitudinal studies are required to further investigate altered muscle growth trajectories in this group and their impact on long-term mobility.