Quasi-experimental pilot study to improve mobility and balance in recurrently falling nursing home residents by voluntary non-targeted side-stepping exercise intervention.

BACKGROUND: Side-stepping is a potential exercise program to reduce fall risk in community-dwelling adults in their seventies, but it has never been tested in nursing home residents. This was a pilot quasi-experimental study to examine the feasibility and potential mobility and balance benefits of an intervention based on voluntary non-targeted side-stepping exercises in nursing home residents who fall recurrently. METHODS: Twenty-two participants were recruited and non-randomly assigned to an intervention group ([Formula: see text]11, side-stepping exercises, STEP) participating in an 8-week protocol and to a control group ([Formula: see text]11, usual physiotherapy care, CTRL). They were clinically assessed at 4-time points: baseline, after 4 and 8 weeks, and after a 4-week follow-up period (usual physiotherapy care). Statistical differences between time points were assessed with a Friedman repeated measures ANOVA on ranks or a one-way repeated measures ANOVA. RESULTS: Compared to baseline, significant benefits were observed in the STEP group at 8 weeks for the Timed Up and Go ([Formula: see text]0.020) and 6-minute walking test ([Formula: see text]0.001) as well as for the Berg Balance Scale ([Formula: see text]0.041) and Mini motor test ([Formula: see text]0.026). At follow-up, the Tinetti Performance Oriented Mobility Assessment and Berg Balance Scale significantly worsened in the STEP group ([Formula: see text]0.009 and [Formula: see text]0.001, respectively). No significant differences were found between the groups at the same time points. CONCLUSIONS: Our intervention was feasible and improved mobility and balance after almost 8 weeks. Studies with larger samples and randomized control trials are needed to consolidate our preliminary observations and confirm the deterioration of some tests when side-stepping exercises are discontinued. TRIAL REGISTRATION: Identifier: ISRCTN13584053. Retrospectively registered 01/09/2022.

Fine adaptive precision grip control without maximum pinch strength changes after upper limb neurodynamic mobilization.

Before and immediately after passive upper limb neurodynamic mobilizations targeting the median nerve, grip ([Formula: see text]) and load ([Formula: see text]) forces applied by the thumb, index and major fingers (three-jaw chuck pinch) were collected using a manipulandum during three different grip precision tasks: grip-lift-hold-replace (GLHR), vertical oscillations (OSC), and vertical oscillations with up and down collisions (OSC/COLL/u, OSC/COLL/d). Several parameters were collected or computed from [Formula: see text] and [Formula: see text]. Maximum pinch strength and fingertips pressure sensation threshold were also examined. After the mobilizations, [Formula: see text] max changes from 3.2 ± 0.4 to 3.4 ± 0.4 N (p = 0.014), d[Formula: see text] from 89.0 ± 66.6 to 102.2 ± 59.6 [Formula: see text] (p = 0.009), and d[Formula: see text] from 43.6 ± 17.0 to 56.0 ± 17.9 [Formula: see text] ([Formula: see text]0.001) during GLHR. [Formula: see text] SD changes from 0.9 ± 0.3 to 1.0 ± 0.2 N (p = 0.004) during OSC. [Formula: see text] peak changes from 17.4 ± 8.3 to 15.1 ± 7.5 N ([Formula: see text]0.001), [Formula: see text] from 12.4 ± 6.7 to 11.3 ± 6.8 N (p = 0.033), and [Formula: see text] from 2.9 ± 0.4 to 3.00 ± 0.4 N (p = 0.018) during OSC/COLL/u. [Formula: see text] peak changes from 13.5 ± 7.4 to 12.3 ± 7.7 N (p = 0.030) and [Formula: see text] from 14.5 ± 6.0 to 13.6 ± 5.5 N (p = 0.018) during OSC/COLL/d. Sensation thresholds at index and thumb were reduced (p = 0.001, p = 0.008). Precision grip adaptations observed after the mobilizations could be partly explained by changes in cutaneous median-nerve pressure afferents from the thumb and index fingertips.

Timed Up and Go and Six-Minute Walking Tests with Wearable Inertial Sensor: One Step Further for the Prediction of the Risk of Fall in Elderly Nursing Home People.

Assessing the risk of fall in elderly people is a difficult challenge for clinicians. Since falls represent one of the first causes of death in such people, numerous clinical tests have been created and validated over the past 30 years to ascertain the risk of falls. More recently, the developments of low-cost motion capture sensors have facilitated observations of gait differences between fallers and nonfallers. The aim of this study is twofold. First, to design a method combining clinical tests and motion capture sensors in order to optimize the prediction of the risk of fall. Second to assess the ability of artificial intelligence to predict risk of fall from sensor raw data only. Seventy-three nursing home residents over the age of 65 underwent the Timed Up and Go (TUG) and six-minute walking tests equipped with a home-designed wearable Inertial Measurement Unit during two sets of measurements at a six-month interval. Observed falls during that interval enabled us to divide residents into two categories: fallers and nonfallers. We show that the TUG test results coupled to gait variability indicators, measured during a six-minute walking test, improve (from 68% to 76%) the accuracy of risk of fall's prediction at six months. In addition, we show that an artificial intelligence algorithm trained on the sensor raw data of 57 participants reveals an accuracy of 75% on the remaining 16 participants.

Sensitization of a human ovarian cancer cell line to temozolomide by simultaneous attenuation of the Bcl-2 antiapoptotic protein and DNA repair by O6-alkylguanine-DNA alkyltransferase.

Temozolomide is an alkylating agent that mediates its cytotoxic effects via O(6)-methylguanine (O(6)-meG) adducts in DNA. O(6)-alkylguanine-DNA-alkyltransferase (MGMT) can repair such adducts and therefore constitutes a major resistance mechanism to the drug. MGMT activity can be attenuated in vitro and in vivo by the pseudosubstrate O(6)-(4-bromothenyl)guanine (PaTrin-2, Patrin, Lomeguatrib), which in clinical trials is in combination with temozolomide. Resistance to cytotoxic agents can also be mediated by the Bcl-2 protein, which inhibits apoptosis and is frequently up-regulated in tumor cells. Attenuation of Bcl-2 expression can be affected by treatment of cells with the antisense oligonucleotide, oblimersen sodium (Genasense), currently in phase III clinical trials in combination with the methylating agent dacarbazine. Using a human ovarian cancer cell line (A2780) that expresses both Bcl-2 and MGMT, we show that cells treated with active dose levels of either oblimersen (but not control reverse sequence or mismatch oligonucleotides) or PaTrin-2 are substantially sensitized to temozolomide. Furthermore, the exposure of oblimersen-pretreated cells to PaTrin-2 leads to an even greater sensitization of these cells to temozolomide. Thus, growth of cells treated only with temozolomide (5 microg/mL) was 91% of control growth, whereas additional exposure to PaTrin-2 alone (10 micromol/L) or oblimersen alone (33 nmol/L) reduced this to 81% and 66%, respectively, and the combination of PaTrin-2 (10 micromol/L) and oblimersen (33 nmol/L) reduced growth to 25% of control. These results suggest that targeting both Bcl-2 with oblimersen and MGMT with PaTrin-2 would markedly enhance the antitumor activity of temozolomide and merits testing in clinical trials.

Dual repair modulation reverses Temozolomide resistance in vitro.

Temozolomide is an alkylating agent that mediates its cytotoxic effects via O(6)-methylguanine (O(6)-meG) adducts in DNA and their recognition and processing by the postreplication mismatch repair system (MMR). O(6)-meG adducts can be repaired by the DNA repair protein O(6)-alkylguanine-DNA-alkyltransferase (MGMT), which therefore constitutes a major resistance mechanism to the drug. Resistance to Temozolomide can also be mediated by loss of MMR, which is frequently mediated by methylation of the hMLH1 gene promoter. Methylation of hMLH1 can be reversed by treatment of cells with 5-aza-2'-deoxycytidine, while the MGMT pseudosubstrate O(6)-(4-bromothenyl)guanine (PaTrin-2) can deplete MGMT activity. Using a drug-resistant cell line which expresses MGMT and has methylated hMLH1, we show that while either of these treatments can individually sensitize cells to Temozolomide, the combined treatment leads to substantially greater sensitization. The increased sensitization is not observed in matched MMR proficient cells.