Fall prevention in community-dwelling adults with mild to moderate cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment (CI) increases an individual's risk of falls due to the role cognition plays in gait control. Older adults with dementia fall 2-3 times more than cognitively healthy older adults and 60-80% of people with dementia fall annually. Practitioners require evidence-based fall prevention best practices to reduce the risk of falls in cognitively impaired adults living in the community. METHODS: We conducted a systematic review and meta-analysis to identify the effectiveness of primary and secondary fall prevention interventions in reducing falls and fear of falling, and improving gait, balance, and functional mobility. We searched 7 databases for fall prevention interventions involving community-dwelling adults ≥50 years with mild to moderate CI. Reviewers screened citations, extracted data, and assessed risk of bias and certainty of evidence (GRADE). We assessed statistical and methodological heterogeneity and performed a meta-analysis of studies including subgroup analysis based on intervention and risk of bias groupings. RESULTS: Five hundred nine community-dwelling adults (mean age 67.5 to 84.0 years) with mild to moderate CI from 12 randomized or clinical controlled trials (RCTs/CCTs) were included in this review. Eight studies were exercise interventions, 3 were multifactorial, and 1 provided medication treatment. Fall prevention interventions had significant effects of medium magnitude on fear of falling (standardized mean difference (SMD) -0.73 [- 1.10, - 0.36]), balance (SMD 0.66 [0.19, 1.12]), and functional mobility measured as Timed Up and Go test (SMD -0.56 [- 0.94, - 0.17]) and significant effects of small magnitude on gait control (SMD 0.26 [0.08, 0.43]) all with moderate certainty of evidence. The meta-analysis showed no significant effects for falls (number of events or falls incidence). Sub-analysis showed that exercise and low risk of bias studies remained significant for balance and perceived risk of falls. CONCLUSION: The effect of fall prevention interventions on direct outcomes, such as falls, remains unclear in cognitively impaired individuals. Exercise interventions are effective at improving fall risk factors, however, high quality studies with longer follow-up and adequate sample sizes are needed to determine their effectiveness on falls directly. There remains a gap in terms of effective fall prevention interventions for older adults with CI.

Applying the RE-AIM implementation framework to evaluate fall prevention interventions in community dwelling adults with cognitive impairment: a review and secondary analysis.

BACKGROUND: Cognitive impairment (CI) is a risk factor for falls due to environmental or living settings, balance, gait and vision impairments, as well as medications. While previous systematic reviews have focused on the effectiveness of fall prevention programs in adults with cognitive impairment, very limited information is available on their implementation. This review examines what aspects of fall prevention interventions for community-dwelling adults with CI have been reported using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to support successful implementation. METHODS: We examined the included studies from our systematic review, which searched 7 databases for primary and secondary fall prevention interventions involving community-dwelling adults ≥50 years with mild to moderate CI. Reviewers screened citations and extracted data for study characteristics and the 5 dimensions (62 criteria) of the RE-AIM framework. RESULTS: Twelve randomized or clinical controlled trials (RCTs/CCTs) consisting of 8 exercise interventions, 3 multifactorial interventions, and 1 medication treatment were included in the review. Only 4 of 62 criteria were reported by all 12 included studies and 29 criteria were not reported by any of the studies. Five of the included studies reported on 20 or more of the 62 possible RE-AIM criteria and 3 of these studies self-identified as "feasibility" studies. While Reach was the best-reported construct by the included studies, followed by Effectiveness and Implementation, the criteria within the Adoption and Maintenance constructs were rarely mentioned by these studies. In general, there was also wide variation in how each of the criteria were reported on by study authors. CONCLUSION: Based on the reporting of RE-AIM components in this review, we are unable to make connections to successful intervention components and thus practice-based recommendations for fall prevention in those with CI. The lack of detail regarding implementation approaches greatly limits the interpretation and comparisons across studies to fully inform future research efforts.

Kinetic separation and characterization of three sugar transport modes in Caco-2 cells.

The question of sugar transport heterogeneity in the human intestinal Caco-2 cell line was addressed using alpha-methyl-D-glucose (AMG) and 2-deoxy-D-glucose (DG) as substrate analogues for D-glucose, the transport inhibitors phlorizin (PZ) and phloretin (PT), and NaCl or choline chloride uptake media. The data are compatible with the existence of three distinct pathways that can be isolated kinetically according to specific characteristics: 1) an "AMG-strict" system, strictly Na+ dependent and specific for AMG [Michaelis-Menten constant value (K(m)) = 2.0 +/- 0.3 mM] but sensitive to both PZ and PT, with PZ being more potent than PT, 2) a "DG-strict" system, strictly Na+ independent and specific for both DG (K(m) = 5.2 +/- 0.5 mM) and PT; and 3) a "DG/AMG-mixed" system, strictly Na+ dependent, with loose specificities for the glucose analogues DG (K(m) = 0.81 +/- 0.07 mM) and AMG (K(m) = 8.1 +/- 0.8 mM), and the inhibitors PZ and PT, but with PT being more potent than PZ. Since SGLT-1 obtained by polymerase chain reaction from either Caco-2 cells or normal human jejunum demonstrated identical transport properties when expressed in Xenopus laevis oocytes, we conclude that the "AMG-strict" system represents the expression of human SGLT-1 activity in this cell line. Moreover, Western blot analysis revealed that SGLT-1 is located exclusively in the apical membrane. In contrast, neither the nature nor the membrane location of both the DG-strict and DG/AMG-mixed pathways could be resolved unambiguously. Still it has been demonstrated that expression of the latter system is constitutive to all Caco-2 cells and that its Na+ dependence is not the consequence of H(+)-dependent transport activity. Aside from the presence of the DG/AMG-mixed system, a salient feature of Caco-2 cells is that the GLUT-3 protein is located exclusively in the brush-border membrane. Due to these limitations, it is concluded that the Caco-2 cell line cannot be considered as equivalent to either fetal colonic cells or normal enterocytes.

2-Deoxyglucose transport and metabolism in Caco-2 cells.

We investigated the kinetics of 2-deoxy-D-glucose (DG) uptake and metabolism in Caco-2 cells, because this human cell line may represent a valid enterocyte model to assess the dynamics between sugar transport and metabolism and hence to obtain insights into the factors involved during the intracellular phase of glucose absorption. When studied in 14-day-old monolayers, DG uptake is characterized by a lag phase with a time course matching the decrease in intracellular glucose concentrations, and no intracellular glucose 6-phosphate (G-6-P) can be detected at any time during incubation. After 1 h of preincubation of Caco-2 cells in substrate-free transport medium, however, steady-state DG uptake matches 2-deoxy-D-glucose 6-phosphate (DG-6-P) accumulation with undetectable levels of free DG. This complex behavior in DG uptake is linked to high hexokinase activity in Caco-2 cells, and the enzyme has a Michaelis-Menten constant K(m) for glucose that is typical of hexokinase type II (0.120 +/- 0.003 mM). Caco-2 cells also contain low-level glucose-6-phosphatase (G-6-Pase) activity, which may account for the leveling off in DG uptake, and the kinetics of DG transport may be attributed to the existence of a predominant pathway with a K(m) of 1.7 +/- 0.2 mM. Finally, analysis of the growth-related expression of DG transport and hexokinase activity clearly shows that DG uptake is lowest in postconfluent cells when hexokinase is at its highest levels. We thus conclude that 1) transport is the rate-limiting step during DG accumulation, 2) G-6-P is a potent inhibitor of hexokinase activity compared with DG-6-P, so that enzyme inhibition may have physiological relevance in diverting glucose from metabolism during its active reabsorption in the small intestine, and 3) low levels of G-6-Pase activity seem to exclude this enzyme, and hence the endoplasmic reticulum, as important factors during the intracellular phase of glucose transport.

Inhibition of IgE-mediated histamine release from human peripheral leukocytes by selective phosphodiesterase inhibitors.

Several phosphodiesterase (PDE) inhibitors with the capacity to inhibit the PDE IV isoenzyme produce dose-dependent inhibition of IgE-mediated histamine release (HR) from human peripheral leukocytes in vitro. Inhibition reached a maximum after 20 min of preincubation (IC30: 6-30 microM, IC50: 30-80 microM). Motapizone--a potent inhibitor of the isoenzyme PDE III--was much less effective, thus giving indirect evidence that PDE IV plays a predominant role in the control of cAMP cleavage in human basophils. The inhibiting effect of PDE-III/IV-selective compounds on IgE-mediated HR did not exceed the action of PDE-IV-selective inhibitors. The inhibition of anti-IgE-induced HR by zardaverine (a PDE-III/IV-inhibiting compound) was synergistically enhanced in the combined presence of forskolin or the recently synthesized histamine H2-agonist FRA 19).

Sensory innervation in the rim of the octopus sucker.

Anatomical components of afferent innervation in the rim of the octopus sucker are described. In the sensory epithelium under the smooth cuticle two associated ciliated receptor cell-types (presumably chemosensitive) occur in clusters. A third ciliated receptor cell-type under the toothed cuticle may be a mechanoreceptor. A non-ciliated receptor cell-type of unknown function, under the toothed culticle, is characterized by a microvillus-lined apical canal containing dense granular material. The axons of the latter two receptors go directly into large nerve tracts which run through the infundibular muscle and on to the ganglion of the sucker. The axons of the first cell-types terminated on interneurons either in the base of the epithelium or below the epithelium. All the interneurons of the basal region of the epithelium migrate centripetally and develop into encapsulated interneurons. Within the epithelium, fine fibers provide collateral contact among cluster receptors. Collateral interaction among basal and encapsulated interneurons occur in the infundibular plexus. The microanatomy of the rim of the sucker suggests that chemosensory cues are funneled into the interneurons where they are concentrated into integrated signals, while other sensory input is probably sent directly to the ganglia of the sucker and/or arm.

An unusual receptor in the octopus.

The epithelium of the rim of the octopus sucker in the site of several different types of primary receptors. One is a non-ciliated cell with unusual characteristics. (1) The surface of the cell is extremely irregular with finger-like extension of cytoplasm, especially far reaching in the basal region. (2) The slender neck contains a canal whose apical opening is in contact with the environment. This canal is lined with microvilli and contains granular material in an electron-dense matrix. (3) Patches of presumed glycogen granules occur throughout the cell, being especially abundant in the outer reaches of the cytoplasmic extensions. Their presence, together with numerous mitochondria and free ribosomes, indicate a high intrinsic metabolism. (4) Small fascicles of microtubules are randomly situated throughout the perikaryon. They gather into a coherent system of larger and larger bundles which ultimately enter the axon leading from the cell. This axon extends some distance in the basal region of the epithelium before crossing the subepithelial space to enter the infundibular muscle. Possible functions of this cell are discussed. On the basis of its specific position on the sucker and its intrinsic morphology we suggest that it is a mechanoreceptor involved in shape and/or negative pressure discrimination.

Fine structure of possible photoreceptor in cercariae of Schistosoma mansoni.

Two structures near the anterior end of cercariae of Schistosoma mansoni are interpreted as possible photoreceptors. Each appears to be ovoid and is composed of a thin cytoplasmic wall surrounding a cavity which contains lamellae. The lamellae are extensions of modified cilia which arise from the inner wall of the cavity.

The effect of dietary fat on lipogenesis in mammary gland and liver from lactating and virgin mice.

1. Virgin and lactating C(3)H mice maintained on laboratory chow were transferred to a high-fat (15% corn oil) or a fat-free diet 3 days before being killed. 2. The linoleate content of liver, mammary gland and milk was decreased in lactating mice given the fat-free diet but was increased in those fed on the high-fat diet. Changes in linoleate content and mammary gland followed a similar but much less marked trend in virgin animals. 3. Hepatic fatty acid synthesis in lactating and virgin mice fed on the fat-free diet was higher than in corresponding animals fed on either the chow or the high-fat diet. The lipogenic capacity of livers from mice fed on either the chow or the high-fat diet was greater in lactating than in virgin animals. These changes in hepatic lipogenic capacity were accompanied by alterations in the specific activities of certain enzymes involved in fat synthesis. 4. Mammary gland from virgin and lactating animals showed no such adaptation to dietary fat. Results indicate that fatty acid synthesis in neither mammary-gland parenchymal cells nor mammary-gland adipose cells can be influenced by dietary fat in the same way as in the hepatocyte.