A randomised controlled trial of prehabilitation in patients undergoing elective cardiac surgery.

The feasibility, safety and efficacy of prehabilitation in adult patients awaiting elective cardiac surgery are unknown. A total of 180 participants undergoing elective cardiac surgery were allocated randomly to receive either standard pre-operative care or prehabilitation, consisting of pre-operative exercise and inspiratory muscle training. The primary outcome was change in six-minute walk test distance from baseline to pre-operative assessment. Secondary outcomes included change in inspiratory muscle strength (maximal inspiratory pressure); sarcopenia (handgrip strength); quality of life and compliance. Safety outcomes were pre-specified surgical and pulmonary complications and adverse events. All outcomes were assessed at baseline; at pre-operative assessment; and 6 and 12 weeks following surgery. Mean (SD) age was 64.7 (10.2) years; 33/180 (18%) were women. In total, 65/91 (71.4%) participants who were allocated to prehabilitation attended at least four of eight supervised in-hospital exercise classes; participants aged > 50 years were more likely than younger participants to attend (odds ratio (95%CI) of 4.6 (1.0-25.1)). Six-minute walk test was not significantly different between groups (mean difference (95%CI) -7.8 m (-30.6-15.0), p = 0.503) in the intention-to-treat analysis. Subgroup analyses based on tests for interaction indicated improvements in six-minute walk test distance were larger amongst sarcopenic patients in the prehabilitation group (p = 0.004). Change in maximal inspiratory pressure from baseline to all time-points was significantly greater in the prehabilitation group, with the greatest mean difference (95%CI) observed 12 weeks after surgery (10.6 cmH2 O (4.6-16.6) cmH2 O, p < 0.001). There were no differences in handgrip strength or quality of life up to 12 weeks after surgery. There was no significant difference in postoperative mortality (one death in each group), surgical or pulmonary complications. Of 71 pre-operative adverse events, six (8.5%) were related to prehabilitation. The combination of exercise and inspiratory muscle training in a prehabilitation intervention before cardiac surgery was not superior to standard care in improving functional exercise capacity measured by six-minute walk test distance pre-operatively. Future trials should target patients living with sarcopenia and include inspiratory muscle strength training.

Aberrant heterodimerization of keratin 16 with keratin 6A in HaCaT keratinocytes results in diminished cellular migration.

Keratin filaments form obligatory heterodimers consisting of one type I and one type II keratin that build the intermediate filaments. In keratinocytes, type II keratin 6 (K6) interacts with type I keratin 16 (K16). We previously showed that the intermediate filament protein K16 is up-regulated in aged human skin. Here, we report that there is an obvious imbalance of K16 to K6 mRNA in in vivo and in vitro aging, which possibly leads to cellular effects. To unveil a possible biological function of K16 overexpression we investigated the migration potential of keratinocytes having up-regulated K16 expression in vitro. Two cell lines were established by transfection of human keratinocytes (HaCaT cells) with K16 or control vectors and subsequent fluorescence-activated cell sorting. By performing migration assays we were able to show a 90% reduction in the migration ability of the K16-overexpressing keratinocytes. In addition, a delay in wound closure associated with K16-overexpressing cells was shown by scratch assays. Transient overexpression of K6A in K16-overexpressing keratinocytes partially corrected the cell-migration defect. By real-time PCR we excluded co-regulation of the annotated interaction partner, K6, in the K16 cell line. Finally, we observed a decreased level of tyrosine phosphorylation in K16-overexpressing cells. Taken together, these data highlight the possibility of a physiological role for K6/K16 heterodimers in keratinocyte cell migration, in addition to the heterodimer's known functions in cell differentiation and mechanical resilience.

Differential cytotoxicity of trace metals in cisplatin-sensitive and -resistant human ovarian cancer cells.

Cellular resistance of cisplatin is related to various factors such as membrane transformations, changes in cellular transport systems, and an increased efflux of cisplatin by the tumor cells. Deficiencies of one or more trace metals can affect normal physiological functions, leading to altered enzymatic activities and a reduction in immune responses. This in vitro investigation was undertaken to study and determine the differential cytotoxicity of certain trace metals in human ovarian cancer cells that were sensitive and resistant to cisplatin. Standard cytotoxicity assays were performed using the neutral red assay. In general, the cisplatin-resistant cells exhibited an increased resistance to the externally supplied trace metals. For both cell lines the rank order of cytotoxicity from greatest to least with the non-essential metals was Cd2+ > Bi3+, and for the macrometals, Ca2+ > K+ > Mg2+. The transition metals and selenium exhibited a slight difference between the two cell lines with respect to the order of cytotoxicity. The cisplatin-sensitive cells had a rank order of V5+ > Se6+ > Cu2+ > Zn2+ > Fe3+, from greatest to least toxicity. The cisplatin-resistant cells had a rank order of Cu2+ > V5+ > Se6+ > Zn2+ > Fe3+. Since trace metals have various functions in maintaining normal health, these results provide key baseline cytotoxicity data and show that, in general, cytotoxic resistance to the trace metals tested followed a pattern similar to cellular cisplatin resistance.

The cytotoxic interaction of inorganic trace elements with EDTA and cisplatin in sensitive and resistant human ovarian cancer cells.

Cisplatin (CDDP)-sensitive and -resistant human ovarian cells were studied in vitro with the objective of enhancing CDDP cytotoxicity by the addition of a metal and the chelate ethylenediaminetetraacetic acid (EDTA), to the CDDP. Chelateable elements, such as bismuth, calcium, cadmium, copper, iron, magnesium, selenium, vanadium, and zinc, when added to CDDP and in the presence of EDTA increased the cytotoxicity of the CDDP as compared to CDDP treatment alone.

Effects of serum zinc supplementation on pica behavior of persons with mental retardation.

Although pica is one of the most frequently observed eating dysfunctions among people with mental retardation, it is significantly underreported in the literature. Of 806 institutionalized adults with mental retardation in the present study, 15.5% exhibited pica. Prevalence estimates from previous studies have ranged from 25.8% to 3%. Fifty-four percent of the pica group had serum zinc levels below normal range, whereas 7% of the control group had serum zinc levels below the normal range. After supplementation with chelated zinc, residents had significant reductions in pica. Data indicated zinc as a possible adjunct to other treatment approaches.

Screening for selected trace elements in single cell populations by energy dispersive X-ray fluorescence spectrometry.

An adaptation of the thin film approach to energy dispersive X-ray fluorescence spectrometry (EDXRF) is described, which provides for a screening analysis for Fe, Ni, Cu, Zn, Se, and Cd in K-562 leukemic cells incubated in various metal-enhanced cultures. Valuable quantitative and semiquantitative data can be obtained on as few as 400,000 cells.

Trace element status of some commercial smokeless tobaccos.

Baseline conditions for sample handling, processing, chemical extraction, and chemical analysis of chewing tobacco were established. The chemical solubility patterns for cadmium, copper, nickel, selenium, and zinc in several commercial brands of chewing tobacco were determined. Five extractants were used: water with pH value of 3.0, pH value of 5.4, and pH value of 6.5; amylase (0.1%); and methanol (99.9%). The bulk of the total cadmium, copper, nickel, and zinc in the tobacco samples was in a tightly bound form not extracted to any appreciable degree by the solvents used. Selenium was below detectable limits for each of the extractants. It has been reported that copper and zinc may counter the carcinogenic effects of cadmium and nickel. The extractants solubilized a greater amount of copper and zinc than cadmium and nickel from the total metal present in the chewing tobacco.