The gait and balance of patients with diabetes can be improved: a randomised controlled trial

Item does not contain fulltextAIMS/HYPOTHESIS: Gait characteristics and balance are altered in diabetic patients. Little is known about possible treatment strategies. This study evaluates the effect of a specific training programme on gait and balance of diabetic patients. METHODS: This was a randomised controlled trial (n=71) with an intervention (n=35) and control group (n=36). The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening (twice weekly over 12 weeks). Controls received no treatment. Individuals were allocated to the groups in a central office. Gait, balance, fear of falls, muscle strength and joint mobility were measured at baseline, after intervention and at 6-month follow-up. RESULTS: The trial is closed to recruitment and follow-up. After training, the intervention group increased habitual walking speed by 0.149 m/s (p<0.001) compared with the control group. Patients in the intervention group also significantly improved their balance (time to walk over a beam, balance index recorded on Biodex balance system), their performance-oriented mobility, their degree of concern about falling, their hip and ankle plantar flexor strength, and their hip flexion mobility compared with the control group. After 6 months, all these variables remained significant except for the Biodex sway index and ankle plantar flexor strength. Two patients developed pain in their Achilles tendon: the progression for two related exercises was slowed down. CONCLUSIONS/INTERPRETATION: Specific training can improve gait speed, balance, muscle strength and joint mobility in diabetic patients. Further studies are needed to explore the influence of these improvements on the number of reported falls, patients' physical activity levels and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT00637546 FUNDING: This work was supported by the Swiss National Foundation (SNF): PBSKP-123446/1/1 maart 201

Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

INTRODUCTION: ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients. METHODS: We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks. RESULTS: No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients. CONCLUSION: Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development

Valley splitting of single-electron Si MOS quantum dots

Silicon-based metal-oxide-semiconductor quantum dots are prominent candidates for high-fidelity, manufacturable qubits. Due to silicon's band structure, additional low-energy states persist in these devices, presenting both challenges and opportunities. Although the physics governing these valley states has been the subject of intense study, quantitative agreement between experiment and theory remains elusive. Here, we present data from an experiment probing the valley states of quantum dot devices and develop a theory that is in quantitative agreement with both this and a recently reported experiment. Through sampling millions of realistic cases of interface roughness, our method provides evidence that the valley physics between the two samples is essentially the same.J.K.G. gratefully acknowledges support from the Sandia National Laboratories Truman Fellowship Program, which is funded by the Laboratory Directed Research and Development (LDRD) program. This work was performed, in part, at the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science. C.H.Y. and A.S.D. acknowledge support from the Australian Research Council (CE11E0001017), the U.S. Army Research Office (W911NF-13-1-0024) and the NSW Node of the Australian National Fabrication Facility. A.R. acknowledges support from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 654712 (SINHOPSI)

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185(c-erbB-2) levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185(c-erbB-2) and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells

Clinical factors associated with a conservative gait pattern in older male veterans with diabetes

<p>Abstract</p> <p>Background</p> <p>Patients with diabetes and peripheral neuropathy are at higher risk for falls. People with diabetes sometimes adopt a more conservative gait pattern with decreased walking speed, widened base, and increased double support time. The purpose of this study was to use a multivariate approach to describe this conservative gait pattern.</p> <p>Methods</p> <p>Male veterans (mean age = 67 years; SD = 9.8; range 37–86) with diabetes (n = 152) participated in this study from July 2000 to May 2001 at the Veterans Affairs Medical Center, White River Junction, VT. Various demographic, clinical, static mobility, and plantar pressure measures were collected. Conservative gait pattern was defined by visual gait analysis as failure to demonstrate a heel-to-toe gait during the propulsive phase of gait.</p> <p>Results</p> <p>Patients with the conservative gait pattern had lower walking speed and decreased stride length compared to normal gait. (0.68 m/s v. 0.91 m/s, <it>p </it>< 0.001; 1.04 m v. 1.24 m, <it>p </it>< 0.001) Age, monofilament insensitivity, and Romberg's sign were significantly higher; and ankle dorsiflexion was significantly lower in the conservative gait pattern group. In the multivariate analysis, walking speed, age, ankle dorsiflexion, and callus were retained in the final model describing 36% of the variance. With the inclusion of ankle dorsiflexion in the model, monofilament insensitivity was no longer an independent predictor.</p> <p>Conclusion</p> <p>Our multivariate investigation of conservative gait in diabetes patients suggests that walking speed, advanced age, limited ankle dorsiflexion, and callus describe this condition more so than clinical measures of neuropathy.</p

Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin

The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from “classical swine H1N1” virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s–1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population

MS4a4B, a CD20 Homologue in T Cells, Inhibits T Cell Propagation by Modulation of Cell Cycle

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK) and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cell

Why Do Situational Interviews Predict Performance? Is it Saying How You Would Behave or Knowing How You Should Behave?

Purpose: The present study examined two theoretical explanations for why situational interviews predict work-related performance, namely (a) that they are measures of interviewees’ behavioral intentions or (b) that they are measures of interviewees’ ability to correctly decipher situational demands. Design/Methodology/Approach: We tested these explanations with 101 students, who participated in a 2-day selection simulation. Findings: In line with the first explanation, there was considerable similarity between what participants said they would do and their actual behavior in corresponding work-related situations. However, the underlying postulated mechanism was not supported by the data. In line with the second explanation, participants’ ability to correctly decipher situational demands was related to performance in both the interview and work-related situations. Furthermore, the relationship between the interview and performance in the work-related situations was partially explained by this ability to decipher situational demands. Implications: Assessing interviewees’ ability to identify criteria might be of additional value for making selection decisions, particularly for jobs where it is essential to assess situational demands. Originality/Value: The present study made an effort to open the ‘black box’ of situational interview validity by examining two explanations for their validity. The results provided only moderate support for the first explanation. However, the second explanation was fully supported by these results

Heterogeneity within the Asian American community

BACKGROUND: Educational interventions are grounded on scientific data and assumptions about the community to be served. While the Pan Asian community is composed of multiple, ethnic subgroups, it is often treated as a single group for which one health promotion program will be applicable for all of its cultural subgroups. Compounding this stereotypical view of the Pan Asian community, there is sparse data about the cultural subgroups' similarities and dissimilarities. The Asian Grocery Store based cancer education program evaluation data provided an opportunity to compare data collected under identical circumstances from members of six Asian American cultural groups. METHODS: A convenience sample of 1,202 Asian American women evaluated the cultural alignment of a cancer education program, completing baseline and follow-up surveys that included questions about their breast cancer knowledge, attitudes, and screening behaviors. Participants took part in a brief education program that facilitated adherence to recommended screening guidelines. RESULTS: Unique recruitment methods were needed to attract participants from each ethnic group. Impressions gained from the aggregate data revealed different insights than the disaggregate data. Statistically significant variations existed among the subgroups' breast cancer knowledge, attitudes, and screening behaviors that could contribute to health disparities among the subgroups and within the aggregate Pan Asian community. CONCLUSION: Health promotion efforts of providers, educators, and policy makers can be enhanced if cultural differences are identified and taken into account when developing strategies to reduce health disparities and promote health equity