Methyl 4-(4-chloro­phen­yl)-1,2,3,3a,4,4a,5,12c-octa­hydro­benzo[f]chromeno[3,4-b]pyrrolizine-4a-carboxyl­ate

There are two mol­ecules in the asymmetric unit of the title compound, C26H24ClNO3. The dihedral angles between the naphthalene ring system and the chloro­phenyl substituent are 58.76 (9) and 51.59 (8)° in the two mol­ecules. In the pyrrolizine ring system, both the pyrrolidine rings adopt envelope conformations and the dihydro­pyran rings adopt half-chair conformations. In the pyrrolizine ring system of one of the mol­ecules, one of the C atoms is disordered over two positions with site occupancies of 0.69 (2) and 0.31 (2). The crystal packing is stabilized by weak intra­molecular C—H⋯O inter­actions and the crystal packing is stabilized by weak C—H⋯π inter­actions

Methyl 3-(4-chloro­phen­yl)-1-methyl-1,2,3,3a,4,11c-hexa­hydro­benzo[f]chromeno[4,3-b]pyrrole-3a-carboxyl­ate

In the title compound, C24H22ClNO3, the dihedral angle between the naphthalene ring system and the chloro­phenyl ring is 67.44 (4)°. The pyrrolidine and dihydro­pyran rings exhibit envelope and half chair conformations, respectively. In the crystal structure, weak C—H⋯π inter­actions are observed

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid

YesMulti-ionizable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallize ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ∼215 and ∼228 °C, while the glass transition temperatures of CHS-III and CS-III were ∼101 and ∼79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve noncongruently leading to high and sustainable drug solution concentrations in water at 25 and 37 °C, with the ciprofloxacin concentration of 58.8 ± 1.18 mg/mL after 1 h of the experiment at 37 °C. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically relevant properties, including molecular, solid state, and solubility characteristics.Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/ B1158

Multiplex ligation-dependent probe amplification versus karyotyping in prenatal diagnosis: the M.A.K.E. study

Abstract BACKGROUND: In the past 30 years karyotyping was the gold standard for prenatal diagnosis of chromosomal aberrations in the fetus. Traditional karyotyping (TKT) has a high accuracy and reliability. However, it is labor intensive, the results take 14-21 days, the costs are high and unwanted findings such as abnormalities with unknown clinical relevance are not uncommon. These disadvantages challenged the practice of karyotyping. Multiplex ligation-dependent probe amplification (MLPA) is a new molecular genetic technique in prenatal diagnosis. Previous preclinical evidence suggests equivalence of MLPA and traditional karyotyping (TKT) regarding test performance. METHODS/DESIGN: The proposed study is a multicentre diagnostic substitute study among pregnant women, who choose to have amniocentesis for the indication advanced maternal age and/or increased risk following prenatal screening test. In all subjects, both MLPA and karyotyping will be performed on the amniotic fluid sample. The primary outcome is diagnostic accuracy. Secondary outcomes will be maternal quality of life, women's preferences and costs. Analysis will be intention to treat and per protocol analysis. Quality of life analysis will be carried out within the study population. The study aims to include 4500 women. DISCUSSION: The study results are expected to help decide whether MLPA can replace traditional karyotyping for 'low-risk' pregnancies in terms of diagnostic accuracy, quality of life and women's preferences. This will be the first clinical study to report on all relevant aspects of the potential replacement

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping

Making subaltern shikaris: histories of the hunted in colonial central India

Academic histories of hunting or shikar in India have almost entirely focused on the sports hunting of British colonists and Indian royalty. This article attempts to balance this elite bias by focusing on the meaning of shikar in the construction of the Gond ‘tribal’ identity in late nineteenth and early twentieth-century colonial central India. Coining the term ‘subaltern shikaris’ to refer to the class of poor, rural hunters, typically ignored in this historiography, the article explores how the British managed to use hunting as a means of state penetration into central India’s forest interior, where they came to regard their Gond forest-dwelling subjects as essentially and eternally primitive hunting tribes. Subaltern shikaris were employed by elite sportsmen and were also paid to hunt in the colonial regime’s vermin eradication programme, which targeted tigers, wolves, bears and other species identified by the state as ‘dangerous beasts’. When offered economic incentives, forest dwellers usually willingly participated in new modes of hunting, even as impact on wildlife rapidly accelerated and became unsustainable. Yet as non-indigenous approaches to nature became normative, there was sometimes also resistance from Gond communities. As overkill accelerated, this led to exclusion of local peoples from natural resources, to their increasing incorporation into dominant political and economic systems, and to the eventual collapse of hunting as a livelihood. All of this raises the question: To what extent were subaltern subjects, like wildlife, ‘the hunted’ in colonial India

Characterization and social correlates of fecal testosterone and cortisol excretion in wild male Saguinus mystax

Reproductive success in male primates can be influenced by testosterone (T) and cortisol (C). We examined them in wild Saguinus mystax via fecal hormone analysis. Firstly, we wanted to characterize male hormonal status over the course of the year. Further we tested the influence of the reproductive status of the breeding female, social instability, and intergroup encounter rates on T levels, comparing the results with predictions of the challenge hypothesis (Wingfield et al., 1990). We also tested for interindividual differences in hormonal levels, possibly related to social or breeding status. We collected data during a 12-mo study on 2 groups of moustached tamarins at the Estación Biológica Quebrada Blanco in northeastern Peru. We found fairly similar T and C levels over the course of the year for all males. Yet an elevation of T shortly after the birth of infants, during the phase of ovarian inactivity of the group’s breeding female, was evident. Hormonal levels were not significantly elevated during a phase of social instability, did not correlate with intergroup encounter rates, and did not differ between breeding and nonbreeding males. Our results confirm the challenge hypothesis (Wingfield et al., 1990). The data suggest that reproductive competition inmoustached tamarins is not based on endocrinological, but instead on behavioral mechanisms, possibly combined with sperm competition.Deutsche Forschungsgemeinschaft (HE 1870/10-1,2