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Wider application of heat recovery ventilation in residential buildings brings attention to knowledge and regulatory gaps which call for research and other actions. In many technical questions there is no consensus in national regulations of EU Member States (MS). This applies for instance for air flow rates, i.e. how much ventilation is needed, restrictions of the use of some heat exchangers types, connection of cooker hoods to ventilation system and placement of exhaust air devices. While European standards are well detailed in these aspects for non-residential ventilation, there is very limited information available for residential ventilation systems. Recent European Guidebook REHVA GB No 25 has made an attempt to collect evidence based best practice technical solutions and design principles for residential ventilation. In this paper a recent evidence and common assumptions behind REHVA airflow rate selection procedure is discussed. Best practice solutions and open research questions related to cooker hood connection to heat recovery and compensation to enable balanced operation of ventilation in an airtight building are analyzed. The paper summarizes existing evidence in these questions and defines open research questions for future residential ventilation research agenda.

Background. Gastrointestinal dysfunction is one of the most common non-motor symptoms in Parkinson's disease (PD). The exact mechanisms behind these symptoms are not clearly understood. Studies in the well-established 6-hydroxydopamine (6-OHDA) lesioned rats of PD have shown altered contractility in isolated circular and longitudinal smooth muscle strips of distal colon. Contractile changes in proximal colon and distal ileum are nevertheless poorly studied. Moreover, segments may serve as better tissue preparations to understand the interplay between circular and longitudinal smooth muscle. This study aimed to compare changes in contractility between isolated full-thickness distal colon muscle strips and segments, and extend the investigation to proximal colon and distal ileum in the 6-OHDA rat model. Methods. Spontaneous contractions and contractions induced by electrical field stimulation (EFS) and by the non-selective muscarinic agonist methacholine were investigated in strip and/or segment preparations of smooth muscle tissue from distal and proximal colon and distal ileum in an in vitro organ bath comparing 6-OHDA-lesioned rats with Sham-operated animals. Key Results. Our data showed increased contractility evoked by EFS and methacholine in segments, but not in circular and longitudinal tissue strips of distal colon after central 6-OHDA-induced dopamine denervation. Changes in proximal colon segments were also displayed in high K+ Krebs-induced contractility and spontaneous contractions. Conclusions. This study further confirms changes in smooth muscle contractility in distal colon and to some extent in proximal colon, but not in distal ileum in the 6-OHDA rat model of PD. However, the changes depended on tissue preparation. [ABSTRACT FROM AUTHOR]

Today, monotherapy is the most common pharmacological treatment option for patients suffering from overactive bladder (OAB). Recent reports have indicated potential benefits of combination therapy, using a muscarinic antagonist and a β3‐adrenoceptor agonist. This may be of particular interest for therapy‐resistant patients with OAB and concomitant cystitis. The objective of the current study was to assess how combination therapy affects bladder parameters in health and cystitis and if the efficacy of the drugs can be linked to altered release of nitric oxide (NO). Rats were pretreated with either a combination of the muscarinic antagonist tolterodine and β3‐selective adrenoceptor agonist mirabegron or saline for 10 days. Forty‐eight hours prior to assessing micturition parameters in a metabolic cage, the rats were intraperitoneally injected with cyclophosphamide, causing cystitis, or saline. Urine samples were collected and analyzed for NO content. Bladder contractile properties were assessed in an organ bath setup. Induction of cystitis led to bladder overactivity. Combination therapy normalized bladder parameters. Both induction of cystitis and drug treatment increased the release of NO. The innate contractile properties of the bladder were unaffected by combination therapy. This study demonstrates positive effects of combination drug therapy on symptoms of OAB, possibly indicating it to be a good option for treatment of OAB during concomitant cystitis. It remains to be determined if increased release of NO is crucial for successful pharmacological treatment of bladder overactivity during cystitis. [ABSTRACT FROM AUTHOR]

Background: Urinary problems, including urinary frequency, urgency, and nocturia are some of the non-motor symptoms that correlate most with poor quality of life in Parkinson's disease. However, the mechanism behind these symptoms is poorly understood, in particular regarding peripheral bladder pathophysiology following dopamine degeneration. Objective: In this study, we compared the contractile responsiveness of urinary bladder from the 6-OHDA unilateral rat model of Parkinson's disease with that of normal untreated animals. Methods: The contractility of the urinary detrusor muscle was evaluated in bladder strip preparations using electrical field stimulation, and muscarinic and purinoceptor stimulations in an vitro organ bath setup. Results: Our data show that the overall contractile response following electrical field stimulation was significantly higher (43% at maximum contraction by 20-40 Hz stimulation) in the 6-OHDA-lesioned rats as compared to control animals. This increase was associated with a significant increase in the cholinergic contractile response, where the muscarinic agonist methacholine produced a 44% (at 10-4 Mconcentration) higher response in the 6-OHDA-treated rats as compared to controls with a significant left-shift of the dose response. This indicates an altered sensitivity of the muscarinic receptor system following the specific central 6-OHDA-induced dopamine depletion. In addition a 36% larger contraction of strips from the 6-OHDA animals was also observed with purinoceptor activation using the agonist ATP (5×10-3 M) during atropine treatment. Conclusions: Our data shows that it is not only the central dopamine control of the micturition reflex that is altered in Parkinson's disease, but also the local contractile function of the urinary bladder. The current study draws attention to a mechanism of urinary dysfunction in Parkinson's disease that has previously not been described. [ABSTRACT FROM AUTHOR]

Aims Cyclophosphamide-induced cystitis alterations have been reported to occur both at efferent and afferent level in the micturition reflex arc. In particular, the stretching of the bladder wall causing urothelial release of ATP has been proposed as one of the pivotal mechanisms causing these alterations. To evaluate functional changes at efferent and afferent levels of the micturition reflex following cyclophosphamide treatment we have applied a novel in situ half bladder rat model. Methods Male Sprague-Dawley rats were treated with either saline or cyclophosphamide (100 mg/kg), and stretch-, electric-, methacholine-, and ATP-induced responses were thereafter measured at 60-72 hr postinjection under pentobarbitone anesthesia. In the novel in situ half bladder model, the urinary bladder was prepared via a midline incision, where the two halves were separated all the way to the urethra as previously described. Results Following bladder stretch of 30-80 mN, of the half that was not used for tension measurement, the cyclophosphamide-treated animals evoked significant two- to threefold larger contractile responses as compared to saline-treated control animals. A sensitization of the afferent arm was shown in cyclophosphamide-treated animals, since afferent stimulation evoked similar responses as in control animals despite that the efferent pelvic nerve stimulation displayed a lower contraction-frequency relationship in cyclophosphamide-treated animals. Atropine reduced the stretch(reflex)-evoked contraction by up to 50% in control and 75-80% in cyclophosphamide-treated rats. Subsequent addition of PPADS further reduced the contractions. Conclusion The micturition reflex response is increased following cyclophosphamide-induced cystitis, as compared to control. The likely cause is sensitization at mechanosensor level in the micturition arc, which overrides the decrement of the efferent cholinergic effects. Neurourol. Urodynam. 34:375-380, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim P301 S MAPT transgenic mice ( P301 S mice) are a widely used model of frontotemporal dementia and parkinsonism linked to chromosome 17 with tau pathology ( FTDP-17-tau). However, a systematic correlation between cognitive deficits and cellular tau pathology at different ages is still missing. Therefore, our study investigated memory deficits of P301 S mice in relation to pathological tau species and dendritic spine pathology throughout adulthood. Methods We analysed P301 S mice behaviourally with the novel open field, rotarod, and Morris water maze tests to measure deficits in locomotion, balance and cognition, respectively; immunohistochemically with different tau antibodies for specific tau species; and with Golgi staining for dendritic spine pathology. Results We confirmed the occurrence of locomotor deficits at an age of 5 months and newly report memory deficits from 2.5 months of age onwards. At this early age, MC1 and CP13, but not AT180 immunoreactivity, was prominent in the hippocampus of P301 S mice. Neuronal cell loss in the hippocampus of P301 S mice was not observed to occur till 6 months of age. However, there was a significant reduction in the density of dendritic spines from young adulthood onwards in hippocampal pyramidal neurones. Conclusion In P301 S mice, memory deficits precede the onset of locomotor dysfunction and coincide with the appearance of conformationally changed, S202-phosphorylated tau and reduced spine density in the absence of neuronal cell loss in the hippocampus. Our finding provides insights into the toxic effects of different tau species in vivo and may facilitate the development of new therapies against neurodegenerative tauopathies. [ABSTRACT FROM AUTHOR]

Objective: The P301S mutation in exon 10 of the tau gene causes a hereditary tauopathy. While mitochondrial complex I inhibition has been linked to sporadic tauopathies. Piericidin A is a prototypical member of the group of the piericidins, a class of biologically active natural complex I inhibitors, isolated from streptomyces spp. with global distribution in marine and agricultural habitats. The aim of this study was to determine whether there is a pathogenic interaction of the environmental toxin piericidin A and the P301S mutation. Methods: Transgenic mice expressing human tau with the P301S-mutation (P301S+/+) and wild-type mice at 12 weeks of age were treated subcutaneously with vehicle (N = 10 P301S+/+, N = 7 wild-type) or piericidin A (N = 9 P301S+/+, N = 9 wild-type mice) at a dose of 0.5 mg/kg/d for a period of 28 days via osmotic minipumps. Tau pathology was measured by stereological counts of cells immunoreative with antibodies against phosphorylated tau (AD2, AT8, AT180, and AT100) and corresponding Western blot analysis. Results: Piericidin A significantly increased the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S+/+ mice, but only to a variable and mild extent in wild-type mice. Furthermore, piericidin A led to increased levels of pathologically phosphorylated tau only in P301S+/+ mice. While we observed no apparent cell loss in the frontal cortex, the synaptic density was reduced by piericidin A treatment in P301S+/+ mice. Discussion: This study shows that exposure to piericidin A aggravates the course of genetically determined tau pathology, providing experimental support for the concept of gene-environment interaction in the etiology of tauopathies. [ABSTRACT FROM AUTHOR]

Aims The search for new animal models to investigate both efferent and afferent levels of the micturition reflex, to better understand urinary dysfunctions, is of great importance. Therefore in this study we developed and characterized, by comparisons with a conventional whole bladder model, a novel in situ model. Methods The urinary bladder was carefully prepared and separated, via a midline incision, into two halves all the way to the urethra in pentobarbitone and medetomidine anesthetized male rats. The separated bladder halves (with no direct connection) were immobilized with ligatures to the underlying tissue. The tension could thereafter be recorded at one side, while the other half was occasionally stretched in order to evoke an afferent signal. Also, injections of ATP and methacholine and electric nerve stimulation were employed. Results Ipsilateral stretch of 30 and 50 mN induced a force-dependent contractile response on the contralateral side. Moreover, electrical stimulation of efferent pelvic nerve fibers, and intravenous injections of methacholine and ATP, evoked dose-dependent contractions, resembling responses observed in the whole bladder model. Here, the threshold frequency at electrical stimulation of the efferent fibers was <2 Hz and the maximum response appeared at 10-20 Hz, while afferent stimulation had a threshold of 5-10 Hz with the maximum response at 40 Hz. Conclusions In the current study we show that stimulation of afferents at one side of the bladder induces, via impulses from the central nervous system, contractions from the other side. This novel model enables quantitative comparisons of changes occurring within the micturition reflex arc in bladder disorders. Neurourol. Urodynam. 33:550-557, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In vivo gene transfer using viral vectors is an emerging therapy for neurodegenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the [11C]raclopride [(S)-(-)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-6-methoxybenzamide] micro-positron emission tomography (PET) technique to demonstrate that delivery of the tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) enzymes using anrAAV5vector normalizes the increased [11C]raclopride binding in hemiparkinsonian rats. Importantly, we show in vivo by microPET imaging and postmortem by classical binding assays performed in the very same animals that the changes in [11C]raclopride after viral vector-based enzyme replacement therapy is attributable to a decrease in the affinity of the tracer binding to the D2 receptors, providing evidence for reconstitution of a functional pool of endogenous dopamine in the striatum. Moreover, the extent of the normalization in this non-invasive imaging measure was highly correlated with the functional recovery in motor behavior. The PET imaging protocol used in this study is fully adaptable to humans and thus can serve as an in vivo imaging technique to followTH+GCH1 gene therapy in PD patientsandprovideanadditionalobjectivemeasuretoapotentialclinicaltrialusingrAAVvectorstodeliver ʟ-3,4-dihydroxyphenylanalineinthebrain. [ABSTRACT FROM AUTHOR]

Clinical trials in patients with Parkinson's disease have shown that transplants of fetal mesencephalic dopamine neurons can form a new functional innervation of the host striatum, but the clinical benefits have been highly variable: some patients have shown substantial recovery in motor function, whereas others have shown no improvement and even a worsening in the 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinetic side effects. Differences in the composition of the grafted cell preparation may contribute to these discrepancies. In particular, the number of serotonin neurons contained in the graft can vary greatly depending on the dissection of the fetal tissue. Importantly, serotonin neurons have the ability to store and release dopamine, formed from exogenously administered L-DOPA. Here, we have evaluated the effect of transplants containing serotonin neurons, or a mixture of dopamine and serotonin neurons, on L-DOPA-induced dyskinesias in 6-hydroxydopamine-lesioned animals. As expected, dopamine neuron-rich grafts induced functional recovery, accompanied by a 60% reduction in L-DOPA-induced dyskinesia that developed gradually over the first 10 weeks. Rats with serotonin-rich grafts with few dopamine neurons, in contrast, showed a progressive worsening of their L-DOPA-induced dyskinesias over time, and no functional improvement. The antidyskinetic effect of dopamine-rich grafts was independent of the number of serotonin neurons present. We conclude that serotonin neurons in the grafts are likely to have a detrimental effect on L-DOPA-induced dyskinesias in cases in which the grafts contain no or few dopamine neurons. [ABSTRACT FROM AUTHOR]