Cross section data for electron impact electronic excitation of electronically excited states of H2 are computed using fixed-nuclear R-matrix calculations. Specifically, there is a focus on ...transitions from the quasi-metastable excited states a Σ g + 3 and c Π u 3 . Data are compared with known theoretical data where available. Our calculations suggest that the published cross sections are generally too large in the low energy (<20 eV) collision region. The effect of shifting the electronic excitation thresholds to those given by essentially exact calculations is tested.
We present benchmark integrated and differential cross-sections for electron collisions with H2 using two different theoretical approaches, namely, the R-matrix and molecular convergent ...close-coupling. This is similar to comparative studies conducted on electron-atom collisions for H, He and Mg. Electron impact excitation to the b3Σu+, a3Σg+, B1Σu+, c3Πu, EF1Σg+, C1Πu, e3Σu+, h3Σg+, B′1Σu+ and d3Πu excited electronic states are considered. Calculations are presented in both the fixed nuclei and adiabatic nuclei approximations, where the latter is shown only for the b3Σu+ state. Good agreement is found for all transitions presented. Where available, we compare with existing experimental and recommended data.
Abstract Modulation of excessive glutamatergic transmission within the basal ganglia is considered as an alternative approach to reduce l -Dopa-induced dyskinesias (LIDs) in Parkinson's disease (PD). ...In this study receptor binding autoradiography of 3 HMPEP, a metabotropic glutamate receptor 5 (mGluR5) selective radioligand, was used to investigate possible changes in mGluR5 in the basal ganglia of l -Dopa-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys having developed LIDs compared to animals in which LIDs was prevented by adjunct treatments. LIDs were associated with an increase of mGluR5 specific binding in the posterior putamen and pallidum (+41% and +56%) compared to controls. By contrast, prevention of dyskinesias was associated with an important decrease of mGluR5 specific binding in these areas (−37% and −48%) compared with dyskinetic animals. Moreover, an upregulation (+34%) of mGluR5 receptor binding was seen in the anterior caudate nucleus of saline treated MPTP monkeys. This study is the first to provide evidence that enhanced mGluR5 specific binding in the posterior putamen and pallidum may contribute to the pathogenesis of LIDs in PD.
To document discharge locations for geriatric patients treated for a hip fracture before and during the COVID pandemic and subsequent changes in outcomes seen between each cohort.
Retrospective ...cohort study.
Academic medical center.
Two matched cohorts of 100 patients with hip fracture treated pre-COVID (February-May 2019) and during COVID (February-May 2020).
Discharge location and COVID status on admission. Discharge locations were home (home independently or home with health services) versus facility subacute nursing facility (SNF) or acute rehabilitation facility.
Readmissions, inpatient and 1-year mortality, and 1-year functional outcomes (EQ5D-3L).
In COVID+ patients, 93% (13/14) were discharged to a facility, 62% (8/13) of whom passed away within 1 year of discharge. Of COVID+ patients discharged to an SNF, 80% (8/10) died within 1 year. Patients discharged to an SNF in 2020 were 1.8x more likely to die within 1 year compared with 2019 (
= 0.029). COVID- patients discharged to an SNF in 2020 had a 3x increased 30-day mortality rate and 1.5x increased 1-year mortality rate compared with 2019. Patients discharged to an acute rehabilitation facility in 2020 had higher rates of 90-day readmission. There was no difference in functional outcomes.
All patients, including COVID- patients, discharged to all discharge locations during the onset of the pandemic experienced a higher mortality rate as compared with prepandemic. This was most pronounced in patients discharged to a skilled nursing facility in 2020 during the early stages of the pandemic. If this trend continues, it suggests that during COVID waves, discharge planning should be conducted with the understanding that no options eliminate the increased risks associated with the pandemic.
III.
NR2B antagonists have received considerable attention in recent years. In this class of excitatory amino acid receptor antagonists NR2B antagonists have shown efficacy in neuroprotection, ...anti-hyperalgesic and anti-Parkinson animal models. Several groups are involved in developing these compounds as therapeutic agents and evaluating newer therapeutic targets for these agents. Until recently benzylpiperidine and phenylpiperidine templates, which were based on the structures of Ifenprodil and Eliprodil, formed the basis of most SAR in this area. A few chemical leads in this class such as CP-101,606, Ro25,6981 and PD0196860 have been identified as possible development leads which have generated significant interest in this area. In addition to the efforts of Pfizer (Parke-Davis), Roche and E.Merck, several other industrial and academic research groups have continued to work in the NR2B area and recently Merck and Roche have reported new chemical leads as NR2B antagonists with significantly different biaryl templates. These new advances have raised hope, for potential success of the NR2B antagonists as new therapeutic agents, for the treatment of several pathophysiological indications.
To evaluate the incidence and clinical outcomes of cell-free DNA results suspicious for maternal malignancy on prenatal cell-free DNA screening with single-nucleotide polymorphism (SNP)-based ...technology.
This retrospective cohort study included data from SNP-based, noninvasive prenatal screening samples from a commercial laboratory from January 2015 to October 2021. Maternal plasma was screened for trisomy 21, 18, and 13; monosomy X; and triploidy. Cases were considered suspicious for maternal malignancy if retrospective bioinformatics and visual inspection of the SNP plot were suggestive of multiple maternal copy number variants across at least two of the tested chromosomes. Clinical follow-up on patients was obtained by contacting individual referring clinician offices by telephone, facsimile, or email.
A total of 2,004,428 noninvasive prenatal screening samples during the study period met criteria for inclusion in the analysis. Of these, 38 samples (0.002% or 1 in 52,748, 95% CI 1:74,539-1:38,430) had SNP-plot results that were suspicious for maternal malignancy. Maternal health outcomes were obtained in 30 of these patients (78.9%); eight were lost to follow-up. Maternal malignancy or suspected malignancy was identified in 66.7% (20/30) of the 30 patients with clinical follow-up provided by the clinic. The most common maternal malignancies were lymphoma (n=10), breast cancer (n=5), and colon cancer (n=3).
Results suspicious for maternal malignancy are rare with SNP-based noninvasive prenatal screening (1:53,000), but two thirds of patients who had a noninvasive prenatal screening result concerning for malignancy in this study had a cancer diagnosis. Investigation for malignancy should be recommended for all pregnant patients with this type of result.
This study was funded by Natera, Inc.
4-4-(4-Benzylpiperidin-1-yl)but-1-ynylphenol (8) and 4-3-(4-benzylpiperidin-1-yl)prop-1-ynylphenol (9) are potent NR1a/2B receptor antagonists (IC50 values 0.17 and 0.10 μM, respectively). ...Administered intraperitoneally, they both potentiated the activity of l-DOPA in the unilaterally 6-hydroxydopamine-lesioned (6-OHDA) rat, a model of Parkinson's disease. However, compound 9 was not active orally, likely due to rapid first-pass metabolism of the phenol moiety. The phenol was replaced by several bicyclic heterocyclic systems containing an NH group to function as a H-bond donor in the hope that these would be less likely to undergo rapid metabolism. In general, indoles, indazoles, benzotriazoles, indolones, and isatins gave analogues with weaker NR1a/2B activity than the parent phenols, while benzimidazolones and benzimidazolinones gave equipotent or more potent analogues. The preference for a para arrangement between the H-bond donor and the linking acetylene moiety was confirmed, and a propyne link was preferred over a butyne link. Substitution on the benzyl group or a 4-hydroxyl group on the piperidine had little effect on NR1a/2B potency; however, 4-hydroxypiperidines demonstrated slightly improved selectivity for NR1a/2B receptors versus α-1 adrenergic and dopamine D2 receptor affinity. From this study, 5-3-(4-benzylpiperidin-1-yl)prop-1-ynyl-1,3-dihydrobenzoimidazol-2-one (46b) was identified as a very potent, selective NR1a/2B receptor antagonist (IC50 value 0.0053 μM). After oral administration at 10 and 30 mg/kg, 46b potentiated the effects of l-DOPA in the 6-OHDA-lesioned rat and seemed to have improved oral bioavailability but lower brain penetration compared to phenol 9.
To identify factors associated with food purchasing decisions and expenditure of South African supermarket shoppers across income levels.
Intercept surveys were conducted, grocery receipts collated ...and expenditure coded into categories, with each category calculated as percentage of the total expenditure. In-supermarket food quality audit and shelf space measurements of foods such as fruits and vegetables (F&V) (healthy foods), snacks and sugar-sweetened beverages (SSB) (unhealthy foods) were also assessed. Shoppers and supermarkets were classified by high-, middle- and low-income socio-economic areas (SEA) of residential area and location, respectively. Shoppers were also classified as "out-shoppers" (persons shopping outside their residential SEA) and "in-shoppers" (persons shopping in their residential SEA). Data were analysed using descriptive analysis and ANOVA.
Supermarkets located in different SEA in urban Cape Town.
Three hundred ninety-five shoppers from eleven purposively selected supermarkets.
Shelf space ratio of total healthy foods v. unhealthy foods in all the supermarkets was low, with supermarkets located in high SEA having the lowest ratio but better quality of fresh F&V. The share expenditure on SSB and snacks was higher than F&V in all SEA. Food secure shoppers spent more on food, but food items purchased frequently did not differ from the food insecure shoppers. Socio-economic status and food security were associated with greater expenditure on food items in supermarkets but not with overall healthier food purchases.
Urban supermarket shoppers in South Africa spent substantially more on unhealthy food items, which were also allocated greater shelf space, compared with healthier foods.
Benzopyranoxazine (+)-7 (PD 128907) is the most dopamine (DA) D3 receptor-selective agonist presently known. The only structural feature which distinguishes 7 from the analogous nonselective ...naphthoxazines is an oxygen atom in the 6-position. To extend this series of tricyclic DA agonists we used a classic bioisoster approach and synthesized thiopyran analogues of 7, which have a sulfur atom in the 6-position. We prepared trans-4-n-propyl-3,4,4a,10b-tetrahydro-2H,5H-1benzothiopyrano4,3-b-1,4-oxazin-9-ol (9, trans-9-OH-PTBTO), its enantiomers ((+)-9 and (−)-9), the racemic cis-analogue (10), and the racemic trans-sulfoxide (11) and studied the potency and selectivity for DA receptors of these compounds. As with other rigid DA agonists, the highest affinity for DA receptors resided in one of the enantiomers, in this case the (−)-enantiomer of 9. On the basis of a single-crystal X-ray analysis of a key intermediate, the absolute configuration of (−)-9 was found to be 4aS,10bR, which is homochiral with (+)-(4aR,10bR)-7. In contrast to (+)-7 however, (−)-9 displayed no selectivity for any of the DA receptors. In addition, it has affinity for 5HT1A receptors. (±)-cis-4-n-Propyl-3,4,4a,10b-tetrahydro-2H,5H-1benzothiopyrano4,3-b-1,4-oxazin-9-ol (10), which was expected to be inactive, displayed affinity and selectivity for the DA D3 receptor, whereas the sulfoxide 11 displayed some DA D3 selectivity, but with a lower affinity. Further pharmacological evaluation revealed that (−)-9 is a very potent full agonist at DA D2 receptors and a partial agonist at DA D3 receptors. The cis-analogue (±)-10 displayed the same profile, but with lower potency. These findings were confirmed in vivo: in reserpinized rats (−)-9 displayed short-acting activation of locomotor activity (DA D2 agonism) and also lower lip retraction and flat body posture, (5HT1A agonism). Compound (±)-10 had no effect on locomotor activity. In unilaterally 6-OH-DA lesioned rats, (−)-9 gave short-acting locomotor activation. Furthermore, in microdialysis studies in rat striatum, (−)-9 potently decreased DA release, confirming its activation of presynaptic DA D2 receptors.
PDF
