Responders were defined as those achieving a 30% or greater reduction in Interstitial Cystitis Symptom Index score from baseline to study end point (week 32 or last observation carried forward).
Results: A positive correlation at baseline was observed between sleep scores Wortmannin price and Short Form-12 physical and mental components (r = 0.43 and 0.37, respectively, p <0.0001). Patients showed statistically significant improvement in Interstitial Cystitis Symptom
Index and sleep scores by week 32. Responders (48, 43%) had a mean change in sleep score of 11.8 +/- 22.4 while nonresponders (64, 57%) had a mean change of 1.6 +/- 15.7 (p = 0.0055 between groups). The reduction in Interstitial Cystitis Symptom Index score correlated with improvement in sleep score from baseline to study end point (r = -0.33, p = 0.0003). At the study end point responders demonstrated a significant improvement in the Short Form-12
physical component compared with baseline (p <0.0001).
Conclusions: Reduction in interstitial cystitis symptoms find more may be associated with patient reported improvement in sleep and quality of life.”
“To improve the thermostability of Trichoderma reesei xylanase 2 (Xyn2), the thermostabilizing domain (A2) from Thermotoga maritima XynA were engineered into the N-terminal region of the Xyn2 protein. Elafibranor supplier The xyn2 and hybrid genes were successfully expressed in Pichia pastoris using the strong methanol inducible alcohol oxidase 1 (AOX1)
promoter and the secretion signal sequence from S. cerevisiae (alpha-factor). The transformants expressed the hybrid gene produced clearly increased both the thermostability and substrate-binding capacity compared to the corresponding strains expressed the native Xyn2 gene. The activity of the hybrid enzyme was highest at 65 degrees C that was 10 degrees C higher than the native Xyn2. The hybrid enzyme was stable at 60 degrees C and retained more than 85% of its activity after 30-min incubation at this temperature. The hybrid enzyme was highly specific toward xylan and analysis of the products from birchwood xylan degradation confirmed that the enzyme was an endo-xylanase with xylobiose and xylotriose as the main degradation products. These attributes should make it an attractive applicant for various applications. Our results also suggested that the N-terminal domain A2 is responsible for both the thermostability and substrate-binding capacity of T. maritima XynA.”
“Purpose: Recent studies have suggested a defect in phosphate balance as a significant underlying cause of calcium urolithiasis.
Therefore, it is crucial to understand the ultimate causes of ongoing axonal dysfunction and find effective measures to prevent axon loss. Our findings related
to functional deficit and functional recovery of axons from a demyelinating insult are important preliminary steps towards understanding this issue. Cuprizone diet for 3-6 wks triggered extensive corpus callosum (CC) demyelination, reduced axon conduction, and resulted in loss of axon structural integrity including nodes of Ranvier. Replacing cuprizone diet with normal diet led to regeneration of myelin, but did find more not fully reverse the conduction and structural deficits. A shorter 1.5 wk cuprizone diet also caused demyelination of the CC, with minimal loss of axon structure and nodal organization. Switching to normal diet led to remyelination and restored callosal axon conduction to normal levels. Our findings suggest the existence
of a critical window of time for remyelination, beyond which demyelinated axons become damaged beyond the point of repair and permanent functional loss follows. Moreover, initiating remyelination early within the critical period, before prolonged demyelination-induced axon damage ensues, will improve functional axon recovery and inhibit disease progression. Published by Elsevier Ltd on behalf of IBRO.”
“Ebola virus VP35 contains a C-terminal cluster of basic amino acids required for double-stranded RNA ( dsRNA) binding and inhibition of interferon regulatory factor 3 (IRF3). VP35 also blocks Idasanutlin in vitro protein kinase R (PKR) activation; however, the responsible domain has remained undefined. Here we show that the IRF inhibitory domain of VP35 mediates the inhibition of PKR and enhances the synthesis of coexpressed proteins. In contrast to dsRNA binding and IRF inhibition, alanine substitutions of at
least two basic amino acids are required to abrogate PKR inhibition and enhanced protein expression. Moreover, we show that PKR activation is not only blocked but reversed by Ebola virus infection.”
“Male rats that copulate to ejaculation with female rats bearing an odor show a learned preference to ejaculate selectively with females that bear the odor. This conditioned ejaculatory preference reflects an association between Citarinostat concentration the odor and the reward state induced by ejaculation. Although little is known about the neuronal mechanisms that mediate this form of learning, convergence of genitosensory and olfactory inputs occurs in both hypothalamic and cortical regions, notably within primary olfactory (piriform) cortex, which may be involved in the encoding or storage of the association. The present study contrasted the ability of genital investigations, mounts, intromissions, ejaculations, and a sexually conditioned olfactory stimulus, to enhance evoked synaptic field potentials in the piriform cortex. Rats in the Paired group underwent conditioning trials in which they copulated with sexually receptive females bearing an almond odor.
The bleeding source was assumed to be the choroid plexus Nepicastat datasheet metastasis in the trigone of the right lateral ventricle (following second admission).
INTERVENTION: Surgery was performed using a navigation-assisted system. The tumor was entirely removed, including some choroid plexus tissue. A ventriculoperitoneal shunt was also performed to treat the hydrocephalus. Histopathological examination revealed brain metastasis
from papillary thyroid carcinoma. Postoperatively, the patient showed good recovery, with nausea and vomiting improved, and gait disturbance diminished. The patient was discharged from the hospital one month later.
CONCLUSION: Choroid plexus metastasis from papillary thyroid carcinoma is very rare, and this is the first case of intraventricular hemorrhage reported.”
“Nanomaterials, including single-walled carbon nanotubes (SWCNT), are being developed for a variety of commercial products. However, adverse health effects attributed to these new materials are not well understood. Recent reports showed that exposure of mice to dispersed SWCNT (DSWCNT) produced a rapid and progressive interstitial lung fibrosis without persistent inflammation. To understand the mechanism underlying this unusual fibrogenicity of DSWCNT,
the present investigation focused on the direct bioactivity of DSWCNT using a cell culture of lung fibroblasts that represent PD173074 chemical structure a major cell type resident in the lung interstitium and responsible for the production of collagen matrix. At concentrations relevant to those used in vivo, in vitro exposure of lung fibroblasts to DSWCNT stimulated cell proliferation and induced collagen production without producing Cepharanthine cell damage. One of the major matrix metalloproteinases (MMP), MMP-9, which is known to be involved in lung fibrosis, was also elevated by DSWCNT treatment both in vitro and in vivo. Taken together, these results suggest that
direct stimulation of fibroblasts by DSWCNT translocated into the interstitium may play a significant role in DSWCNT-induced lung fibrosis. Our data also suggest that the dispersion status and/or size of the SWCNT structures is a critical factor in determining nanoparticle fibrogenicity and that MMP-9 may be involved in the fibrogenic process. The results obtained may aid in the development of in vitro models for rapid screening of the potential fibrogenicity of carbon nanotubes, which are lacking and urgently needed.”
“OBJECTIVE: Detachable endovascular coils have become a common treatment strategy for carotid cavernous sinus aneurysms (CCAs), but previously unrecognized postprocedure complications may emerge as longer follow-up data are accumulated.
Pure neuronal cultures, derived from foetal BALB/c mice cortices, were provoked into injury Selonsertib manufacturer by oxygen and glucose deprivation (OGD). Cultures were exposed to either nitrogen hypoxia or noble gas hypoxia in balanced salt solution devoid of glucose for 90 min. The cultures were allowed to recover
in normal culture medium for a further 24 h in nitrogen or noble gas. The effect of noble gases on cell reducing ability in the absence of OGD was also investigated. Cell reducing ability was quantified via an MITT assay and expressed as a ratio of the control. The OGD caused a reduction in cell reducing ability to 0.56 +/- 0.04 of the control in the absence of noble gas (p < 0.001). Like xenon (0.92 +/- 0.10; p < 0.001), neuroprotection was Afforded by argon (0.71 +/- 0.05; A-1210477 solubility dmso p < 0.01). Neon and krypton did not have a protective effect under our experimental conditions. Helium had a detrimental effect on the cells. In the absence of OGD, krypton reduced the reducing ability of uninjured cells to 0.84 +/- 0.09 (p < 0.01), but argon showed an improvement in reducing ability to 1.15 +/- 0.11 (p < 0.05). Our data suggest that the cheap and widely available noble gas argon may have potential as a neuroprotectant
for the future. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Resting frontal electroencephalographic (EEG) alpha-asymmetry was measured in 16 participants to predict affective responses to musical stimuli. Three affective musical stimuli either expressing neutral, positive or negative mood were evaluated by the subjects concerning “”expressed mood”" and “”level of enjoyment”". The results show that individuals with relatively higher medroxyprogesterone alpha power over right frontal electrode sites rated all stimuli more positive than participants with relatively higher alpha power over left frontal electrode sites. On the “”expressed mood”" scale, the valence of the stimuli did not influence
the difference between the ratings of left- and right-active individuals. On the “”enjoyment”" scale, the largest difference between the ratings of left- and right-active individuals emerged in the negative condition. The results are specific to the alpha frequency band. In line with previous studies, these results suggest that resting frontal alpha-asymmetry reflects a person’s predisposition to respond affectively. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Background Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty; oral regimens could enable shorter hospital stays. We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty.
Heterokaryon assays confirmed that UL3 was capable of shuttling between the nucleus and the cytoplasm. These results demonstrate that the UL3 protein is a novel HSV-1 encoded nucleocytoplasmic shuttling protein. (C) 2011 Elsevier B.V. All rights reserved.”
“Fuelled by new sequencing technologies, epigenome
mapping projects are revealing epigenomic variation at all levels of biological complexity, from species to cells. Comparisons of methylation profiles among species reveal evolutionary conservation of gene body methylation patterns, pointing to the fundamental role of epigenomes in gene regulation. At the human population level, epigenomic AZD1480 changes provide footprints of the effects of genomic variants within the vast nonprotein-coding fraction of the genome, and comparisons of the epigenomes of parents and their offspring point to quantitative epigenomic parent-of-origin effects confounding
classical Mendelian genetics. At the organismal level, comparisons of epigenomes from diverse cell types Bafilomycin A1 provide insights into cellular differentiation. Finally, comparisons of epigenomes from monozygotic twins help dissect genetic and environmental influences on human phenotypes and longitudinal comparisons reveal aging-associated epigenomic drift. The development of new bioinformatic frameworks for comparative epigenome analysis is putting epigenome maps within the reach of researchers across a wide spectrum of biological disciplines.”
“Background Selleck Venetoclax and objective: Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens. (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect
of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues.
Methods: Rats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking.
Results: The reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3 mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3 mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5 mg/kg) but not with mecamylamine (3 mg/kg) or scopolamine methobromide (1 mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior.
(C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
a dimensionless index normally used to evaluate changes in the shape of the airflow pattern entering and leaving a whole-body flow plethysmograph as an animal breathes. The index is sensitive to changes in the distribution of area under the waveform during exhalation and increases in a nonlinear selleck compound fashion as the normalized area increases near the beginning of the curve. Enhanced pause (Penh) has been used to evaluate changes in pulmonary function and as a method to evaluate airway reactivity. However, the use of Penh to assess pulmonary function has been challenged (Bates et al., 2004; Lundblad et al., 2002; Mitzner et al., 2003; Mitzner & Tankersley, 1998; Petak et al., 2001; Sly et al., 2005). The objective of this study was to show how Penh of the thorax and plethysmograph flow patterns are related. That relationship is used to describe the conditions under which whole-body plethysmograph Penh measurements can be used to detect changes in sR(aw).”
“Visual cortical areas in the two hemispheres interact via the
corpus callosum, but the precise role of the callosal pathway in visual processing remains controversial. find more Here we have investigated the function of transcallosal projections in human primary visual cortex (V1). Visual evoked potentials (VEPs) triggered by grating stimuli of different contrasts were recorded before and after functional inactivation of the occipital cortex of one hemisphere via off-line low-frequency repetitive transcranial magnetic stimulation (rTMS; 0.5 Hz stimulation for 20 min). VEPs were recorded in V1 before (TO), immediately after (T1) and 45′ following the completion Pyruvate dehydrogenase of rTMS (T2). We found that low-frequency rTMS had an inhibitory effect on VEPs amplitudes at all contrasts in the treated side. Remarkably, reduction of VEP amplitudes in the inhibited hemisphere at T1 was accompanied by an increase in VEP amplitudes in the contralateral side only
at mid-high contrasts (50-90%). This disinhibitory effect was observed with both central and hemifield stimulation. No changes in VEP amplitudes were observed when rTMS was applied to a cortical site more anterior with respect to V1. These data provide the first evidence that a mechanism of transcallosal inhibition dampens neural responses at high contrasts in human visual cortex. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Coarse, fine, and ultrafine particulate matter (PM) fractions possess different physical properties and chemical compositions and may produce different adverse health effects. Studies were undertaken to determine whether or not gene expression patterns may be used to discriminate among the three size fractions.
A number of tau kinases, such as c-jun N-terminal kinase (JNK), glycogen-synthase kinase-3 beta (GSK3 beta), and casein kinase 1 (CK1), have been reported to be Selleck JQ-EZ-05 markers of granulovacuolar degeneration. In addition, cyclin-dependent kinase 5 (CDK5), which phosphorylates tau, has been shown to be abundantly expressed in neurofibrillary tangles in the hippocampus.
CDK5 has a unique staining pattern, and therefore, has the potential to be a novel marker for granulovacuolar degeneration. In this study, we investigated the ability of CDK5 to be a marker for granulovacuolar degeneration using immunohistochemical analysis. Four Alzheimer’s disease cases, three myotonic dystrophy (MyD) cases, and three control cases were subjected to immunohistochemistry and immunofluorescent techniques using anti-CDK5, anti-charged multivesicular body protein 2B (CHMP2B), anti-pSmad2/3, anti-ubiquitin (Ub), anti-phospho-TDP-43
4-Hydroxytamoxifen order and AT8 antibodies. Some CDK5-positive granules were morphologically similar to granulovacuolar degeneration intraluminal granules, and these granules overlapped with those immunopositive for pSmad2/3, Ub and phospho-TDP-43 established granulovacuolar degeneration markers. Moreover, CDK5-positive granulovacuolar degeneration and phosphorylated tau colocalized in pyramidal neurons in Alzheimer’s disease and MyD cases. The numbers of CDK5-positive granules showed an inverse relationship with the degree of mature neurofibrillary tangles in each cell, as was the case
with CHMP2B-positive granulovacuolar degeneration granules and neurofibrillary tangles. The presence of tau kinases including CDK5 in granulovacuolar degeneration might implicate that granulovacuolar degeneration is structurally involved in tau modification. NeuroReport 23: 867-872 (C) 2012 Wolters Kluwer Health | Lippincott Williams secondly & Wilkins.”
“The prevalence of glomerular hyperfiltration in type 2 diabetic patients varies widely. Here we studied whether glomerular hyperfiltration in diabetic nephropathy in type 2 patients is related to renal structural changes and predicts the functional development of diabetic nephropathy. Thirty normo- or microalbuminuric type 2 diabetic patients having a renal biopsy were followed every 6 months for a mean of 6.2 years. The glomerular filtration rate (GFR) at the time of biopsy, determined by iohexol clearance, correlated with filtration surface per glomerulus, but no other quantitative microscopic morphometric parameter. The filtration surface was positively associated with the decrease in GFR during the first year but not associated in subsequent years following the renal biopsy. The GFR showed a statistically significant linear decrease in 9 of the 30 patients; however, slopes of the regression lines were almost zero in 11 patients. The GFR increased and decreased in a parabolic manner in two patients.
76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64,p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p < 0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p < 0.0001).
Conclusions. Offspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death.”
“Auditory Selleckchem 4SC-202 extinction and spatio-temporal order judgment (STOJ) were assessed in patients with acquired brain damage by systematically manipulating onset times in bilateral stimulation
under free-field conditions. We tested the hypothesis that extinction will be reduced by increasing stimulus onset asynchrony. Two groups of patients with right-hemisphere (RH, n = 17) or left-hemisphere (LH, n = 17) damage were investigated in comparison to Lonafarnib manufacturer a healthy control group (n = 12). The patients were recruited
based on previously diagnosed impairments: auditory discrimination deficits with (RHE/LHE) or without extinction (RH0/LH0) due to cortical and/or subcortical temporo-parietally centred lesions. Stimuli were presented bilaterally in the acoustic free-field, with an onset asynchrony of +/- 30 to +/- 150 ms, or unilaterally, from speakers located +/- 60 degrees. Low frequency (LF) and high frequency (HF) stimuli were used to address spatial auditory processing in the horizontal plane based on the two main cues of interaural time and interaural
intensity differences, respectively. The subjects’ task was to indicate whether they perceived one (left or right) or two stimuli (left and right), and in the case of two make an STOJ (left or right first). Temporal asynchrony significantly reduced extinction in those patients that previously exhibited extinction for bilateral-simultaneous stimulation (RHE/LHE). In addition, their error rates in STOJ were higher than the controls’. A number of patients with no previous signs of extinction in bilateral-simultaneous stimulation (RH0/LH0) also showed impaired STOJ: in RH0 patients this was specific to ipsilesional-leading stimuli, whilst in LH0 patients no side-specific effect was observed. The data support the notion of differential roles for the two hemispheres in spatio-temporal Amrubicin auditory perception and are discussed with respect to prevalent models of extinction and its possible long-term reduction. (C) 2012 Elsevier Ltd. All rights reserved.”
“Over the last few decades, comparative cognitive research has focused on the pinnacles of mental evolution, asking all-or-nothing questions such as which animals (if any) possess a theory of mind, culture, linguistic abilities, future planning, and so on. Research programs adopting this top-down perspective have often pitted one taxon against another, resulting in sharp dividing lines.
Future research should establish whether the observed relationship of depressive symptoms to ET-1 level mediates the link between depression and survival.”
“Background Chronic kidney disease is characterised by low estimated glomerular fi ltration
rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modifi ed by diabetes is unknown.
Methods We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals selleck products with and without diabetes.
Findings We analysed data for 1 024 977 participants (128 505 with diabetes) from 30 general population and highrisk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and highrisk cohorts with data for all-cause mortality, 75 306 deaths occurred during a mean follow-up of 8.5 years (SD 5.0). In the 23 studies with data for cardiovascular mortality, 21 237 deaths occurred from cardiovascular disease during a mean follow-up of 9.2 years (SD 4.9). In the general and high-risk cohorts, mortality LB-100 purchase risks were 1.2-1.9 times higher for participants with diabetes than for those
without diabetes across the ranges of eGFR and albumin-tocreatinine ratio (ACR). With fi xed eGFR and ACR reference points in the diabetes and no diabetes Erythromycin groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1.73
m y [vs 95 mL/min per 1.73 m y], HR 1.35; 95% CI 1.18-1.55; vs 1.33; 1.19-1.48 and at ACR 30 mg/g [vs 5 mg/g], 1.50; 1.35-1.65 vs 1.52; 1.38-1.67). The overall interactions were not signifi cant. We identifi ed much the same fi ndings for ESRD in the chronic kidney disease cohorts.
Interpretation Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes.”
“Objective: To assess how clinical and psychological variables compare in their ability to predict coronary artery calcium (CAC) in a broad spectrum of subjects. Although prior studies reported contradictory findings on the association between psychological risk factors and CAC, psychological risk factors have not yet been compared with concurrent clinical corollary risk factors for their association to CAC measurements. Methods: We performed research CAC scans in three cohorts: 1,111 healthy volunteers; 138 asymptomatic patients; and 600 symptomatic patients.
IGF-1 receptor (IGF-1R) is aberrantly expressed by MMCs in association with a poor prognosis. In this study we show that insulin receptor (INSR) is increased throughout
normal plasma cell differentiation. INSR gene is also expressed by MMCs of 203/206 newly diagnosed patients. Insulin is an MGF as potent as IGF-1 at physiological concentrations and requires the presence of insulin/IGF-1 hybrid receptors, stimulating INSR(+)IGF-1R(+) MK-8931 solubility dmso MMCs, unlike INSR(+)IGF-1R(-) or INSR- IGF-1R(-) MMCs. Immunoprecipitation experiments indicate that INSR is linked with IGF-1R in MMCs and that insulin induces both IGF-1R and INSR phosphorylations and vice versa. In conclusion, we demonstrate for the first time that insulin is an MGF as potent as IGF-1 at physiological concentrations and its activity necessitates insulin/IGF-1 hybrid receptor activation.
selleck chemicals Further therapeutic strategies targeting the IGF/IGF-1R pathway have to take into account neutralizing the IGF-1R-mediated insulin MGF activity. Leukemia (2010) 24, 1940-1950; doi:10.1038/leu.2010.192; published online 16 September 2010″
“The present study employed dynamic causal modeling to investigate the effective functional connectivity between regions of the neural network involved in top-down letter processing. We used an illusory letter detection paradigm in which participants detected letters while viewing pure noise images. When participants detected letters, the response of the right middle occipital gyrus (MOG) in the visual cortex was enhanced by increased feed-backward connectivity from the left inferior frontal gyrus (IFG). In addition, illusory letter detection
increased feed-forward connectivity from the right MOG to the left inferior parietal lobules. Originating in the left IFG, this top-down letter processing network may facilitate the detection of letters by activating letter processing areas within the visual cortex. This activation in turns may highlight the visual features of letters and send letter information to activate the associated phonological gmelinol representations in the identified parietal region. (C) 2011 Elsevier Ltd. All rights reserved.”
“We previously described PASD1 as a new cancer testis antigen in multiple myeloma (MM) that is retained post-therapy, suggesting the use of vaccination strategies to induce anti-PASD1 immunity in a setting of minimal residual disease. We have focused on DNA fusion gene vaccines, coupling fragment C domain (DOM) of tetanus toxin with PASD1 sequence, and examined efficacy in Human Leukocyte Antigen (HLA)-A2 (HHD) transgenic mice using a human MM cell line expressing PASD1 protein and chimeric HLA-A2 class I molecules as target. DNA vaccines encoded two HLA-A2-restricted epitopes (p.DOM-PASD1(1), p.DOM-PASD1(2)) and full-length PASD1 (p.DOM-PASD1FL). p. DOM-PASD1(1) proved superior to p.