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Aims: Multifactorial falls prevention programmes (MFFPs) can prevent falls and fall-related injuries. We aimed to study MFFP patients' mortality compared with their sex-, age- and residence-matched population-based controls., Methods: This study is a Finnish single-centre retrospective register-based controlled cohort study of a total of 527 home-dwelling MFFP patients and their 3:1 age-, sex- and residence-matched population-based controls ( n = 1581), who had not attended the MFFP., Results: During the follow-up, the cumulative mortality of all patients was 40.4, and of controls 39.1 %. Hazard ratio was 0.82 (95% confidence interval 0.68 to 0.99), p = 0.041. Case patients had a 2.7 times greater risk to die due to accidents, but they had a lower risk to die due to dementia, compared with the control group. The 72-years-old or older participants had a lower mortality rate than the controls during follow-up., Conclusions: The MFFP seems to relate to a lower all-cause mortality when comparing MFFP patients with their age-, sex- and residence-matched controls. However, the MFFP did not seem to relate to a lower injury-related mortality. The relationship between the MFFP and lower all-cause mortality seemed to be strongest in the patients aged 72 years or older. Due to the study setting and population-based control group, it is difficult to draw solid conclusions and further studies are needed. A randomized controlled trial comparing the MFFP with standard care would give better insight on the effectiveness of a MFFP on mortality., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Objective: To assess the effectiveness and costs of intensive stroke rehabilitation and improvements in patient pathway in the city of Lahti and in Päijät-Häme region compared with other parts in Finland., Design: Retrospective benchmarking controlled trial., Patients: Three cohorts of Finnish community-dwelling patients (n = 94,749, n = 4,184, and n = 105,458) with ischaemic stroke between 2001 and 2019., Methods: This study is based on the PERFECT 2001-2019 database of ischaemic stroke patients. PERFECT indicators describe how the stroke patients recover. The difference-in-difference method was used in the main analysis., Results: Improved stroke rehabilitation in Lahti increased the share of patients discharged home (p = 0.005) and decreased the length of first institutional episode (-4 days, p = 0.006), the share of patients institutionalized (-5.1%, p = 0.001), and the costs of first institutional episode (€-2,085, p < 0.001) compared with the rest of Finland. Discharges to home increased 6.6 percentage points (p = 0.021) in Lahti compared with rest of Päijät-Häme. After 2013, the costs of first institutional episode per patient in Päijät-Häme decreased significantly compared with the rest of Finland (p < 0.001)., Conclusion: Investments in intensive stroke rehabilitation and patient pathway seem to provide both faster and better return to home for patients and reduced costs for the healthcare system.

Viral respiratory infections are a major cause of asthma exacerbations and can contribute to the pathogenesis of asthma. Major group human rhinovirus enters cells by binding to the cell surface molecule ICAM-1 that is present on epithelial and monocytic lineage cells. The focus of the resulting viral infection is in bronchial epithelia. However, previous studies of the cytokine dysregulation that follows rhinovirus infection have implicated monocytic lineage cells in establishing the inflammatory environment even though productive infection is not a result. We have determined that human alveolar macrophages and human peripheral blood monocytes release MCP-1 upon exposure to human rhinovirus 16 (HRV16). Indeed, we have found p38 MAPK activation in human alveolar macrophages within 15 min of exposure to HRV16, and this activation lasts up to 1 h. The targets of p38 MAPK activation include transcriptional activators of the MCP-1 promoter. The transcription factor ATF-2, a p38 MAPK substrate, is phosphorylated 45 min after HRV16 exposure. Furthermore, IkappaBalpha, the inhibitor of the transcription factor NF-kappaB, is degraded. Prevention of HRV16 binding was effective in blocking p38 MAPK activation, ATF-2 phosphorylation, and MCP-1 release. This is the first report of a relationship between HRV16 exposure, MCP-1 release and monocytic-lineage cells suggesting that MCP-1 plays a role in establishing the inflammatory microenvironment initiated in the human airway upon exposure to rhinovirus.

The activation of the Na+-H+ exchanger 1 (NHE1) and extracellular-signal regulated kinase (ERK) phosphorylation in Chinese hamster lung fibroblasts (CCL39) was characterized in response to the specific alpha1-adrenergic agonist, phenylephrine (PE). Addition of 100 micromol PE/L increased the steady-state intracellular pH (pHi) by 0.16 +/- 0.03 pH units, as well as increasing the phosphorylation of ERK. The response of NHE1 to PE in CCL39 cells was determined by the use of specific antagonists. Use of 2 specific chemical inhibitors of phosphoinositide-specific phospholipase C (PLC) reduced the ability of PE to activate either the exchanger or ERK. Studies were conducted in PLCbeta-deficient cell lines derived from parental CCL39 cells. NHE1 activity in both mutant cell lines was increased in response to phorbal esters or lysophosphatidic acid, whereas the addition of PE only caused a minimal change in either pHi or ERK phosphorylation. These results, combined with reconstitution experiments with exogenously expressed PLCbeta1, PLCbeta2, or PLCbeta3, revealed that stimulation of NHE1 activity by PE in CCL39 cells is a PLCbeta1-coupled event. Furthermore, the data indicate that alpha1-adrenergic signaling of PLCbeta is upstream of ERK activation. These data demonstrate that PLCbeta1 is primarily involved in the activation of NHE1 in CCL39 fibroblasts.

The sodium hydrogen exchanger isoform 1 (NHE1) is present in nearly all cells. Regulation of proton flux via the exchanger is a permissive step in cell growth and tumorgenesis and is vital in control of cell volume. The regulation of NHE1 by growth factors involves the Ras-extracellular signal regulated kinase (ERK) pathway, however, the mechanism for G protein-coupled receptor (GPCR) activation of NHE1 is not well established. In this report, the relationship between GPCRs, ERK, and NHE1 in CCL39 cells is investigated. We give evidence that two agonists, the specific alpha(1)-adrenergic agonist, phenylephrine and the water-soluble lipid mitogen, lysophosphatidic acid (LPA) activate NHE1 in CCL39 cells. Activation of ERK by phenylephrine and LPA occurs in a dose- and time-dependent manner. Optimal ERK activation was observed at 10 min and displayed a maximum stimulation at 100 microM phenylephrine and 10 microM LPA. alpha(1)-Adrenergic stimulation also led to a rise in steady-state pH(i) of 0.16+/-0.02 pH units, and incubation with LPA induced a 0.43+/-0.06 pH unit increase in pH(i). Phenylephrine-induced activation of NHE1 transport and ERK activity was inhibited by pretreating the cells with the MEK inhibitor PD98059. While only half of the LPA activatable exchange activity was abolished by PD98059 and U0126. To further demonstrate the specificity of the phenylephrine and LPA regulation of NHE1 and ERK, CCL39 cells were transfected with a kinase inactive MEK. The data indicate that ERK activation is essential for phenylephrine stimulation of NHE1, and that ERK and RhoA are involved in LPA stimulation of NHE1 by more than one mechanism. In addition, evidence of the convergence of these two pathways is shown by the loss of NHE1 activity when both pathways are inhibited and by the partial additivity of the two agonists on ERK and NHE1 activity. These studies indicate a direct involvement of ERK in the alpha(1)-adrenergic activation of NHE1 and a significant role for both ERK and RhoA in LPA stimulation of NHE1 in CCL39 fibroblasts.