Basic Salts with »Very Short« Hydrogen Bonds; the Crystal Structure of a-Picoline-N-oxide Hemihydrochloride Sesquihydrate (Dunlop\u27s Salt)

Type A acid salts of many simple carboxylic acids (HX) crystallise with anions, XHx-, which are symmetrical and which contain »very short« OHO-bonds with O . .. 0 less than 250 pm. Such compounds also reveal anomalous IR spectra. The Glasgow work on such crystal structures has benefited from a long collaboration with Hadzi\u27s spectroscopic group at Ljubljana. The importance of such joint studies in helping the understanding of strong hydrogen bonding is discussed. Some organic bases form analogous basic salts, which have similarly anomalous spectra. An example, discovered by Hadzi in 1962, is the hemihydrobromide of a.-picoline-N-oxide, B · 1/2HBr, where B = CoH7NO, for which he predicted the formula BHB+ Br-. Preliminary X-ray work confirmed this and the presence of a »very short« OHO-bond. Hitherto unpublished crystallographic work is summarised. Dunlop\u27s salt is the sesquihydrated hemihydrochloride of the same base. A careful X-ray study has been made (1040 reflexions; R = 3.70/o): B · 1/2HCl · 3/2H20 has a structure corresponding to BHB+ c1- · 3H20; the cation lies across a centre of symmetry, with O ... O = 241.4(3) pm. At one stage the salt was supposed to include a symmetrical ClHc1- anion; but our more precise work shows the anion to be c1- ... H-OH (or HO-H ... en symmetrised by disorder across a twofold axis of the crystal, with c1- ... O = = 297(1) pm. The spectrum of DSALT is almost identical with that of the hemihydrobromide

A carbamazepine-indomethacin (1:1) cocrystal produced by milling

An X-ray amorphous mixture of carbamazepine and indomethacin transforms upon annealing to produce a novel 1:1 cocrystal, whose structure has been determined from laboratory powder X-ray diffraction (PXRD) data

Functional status in ICU survivors and out of hospital outcomes: a cohort study

OBJECTIVES: Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. DESIGN: Single-center retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Ten thousand three hundred forty-three adults who received critical care from 1997 to 2011 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk-prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital discharge was associated with an increased odds of 90-day postdischarge mortality compared with patients with independent functional status (odds ratio, 7.63 [95% CI, 3.83-15.22; p < 0.001]). In patients who had at least 7 days of physical therapy treatment prior to hospital discharge (n = 2,293), the adjusted odds of 90-day postdischarge mortality in patients with marked improvement in functional status at discharge was 64% less than patients with no change in functional status (odds ratio, 0.36 [95% CI, 0.24-0.53]; p < 0.001). CONCLUSIONS: Lower functional status at hospital discharge in survivors of critical illness is associated with increased postdischarge mortality. Furthermore, patients whose functional status improves before discharge have decreased odds of postdischarge mortality.L30 TR001257 - NCATS NIH HH

Use of yeast artificial chromosomes (YACs) for studying control of gene expression: correct regulation of the genes of a human beta-globin locus YAC following transfer to mouse erythroleukemia cell lines.

We demonstrate that transfer of a yeast artificial chromosome (YAC) containing 230 kb of the human beta-globin locus into mouse erythroleukemia cells by fusion results in correct developmental regulation of the human beta-like globin genes. Additionally, we show that early after hybrid formation, human embryonic epsilon- and fetal gamma-globin genes are coexpressed with the adult beta gene but that after 10-20 weeks in culture, globin gene expression switches to predominantly adult. Thus, in contrast to shorter gene constructs, the globin genes of the beta-globin locus YAC are regulated like the chromosomal globin genes. These results indicate that transfer of YACs into established cell lines can be used for the analysis of the developmental control of multigenic and developmentally regulated human loci

The gastric acid pocket is attenuated in H. pylori infected subjects

Objective Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. Design We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. Results Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors &gt;1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p&lt;0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p&lt;0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p&lt;0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. Conclusions In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket

Maternofetal outcome of asymptomatic bacteriuria among pregnant women in a Nigerian Teaching Hospital

Introduction: Asymptomatic bacteriuria has been reported to be associated with adverse pregnancy outcome. This study sought to determine the prevalence and complications of asymptomatic bacteriuria amongst parturient in the University of Port Harcourt Teaching Hospital (UPTH).Methods: The study was a prospective cohort study involving 220 eligible antenatal attendees. Urine culture and sensitivity was conducted for each participant and the fetomaternal outcome between affected and unaffected women were compared and p value &lt;0.05 was considered significant.Results: Sixty-five of the participants had asymptomatic bacteriuria giving a prevalence of 29.5%. Twenty-three (35.4%) cultures yielded Klebsiella spp while Fifty-eight (89%) of the cultured organisms were sensitive to Nitrofurantoin. There was no statistical difference in the rate of prelabour rupture of membranes, preeclampsia, preterm delivery, birth asphyxia and low birth weight between affected and unaffected women.Conclusion: Contrary to widely held view, there was no significant increase in adverse pregnancy outcome amongst affected women.Keywords: Asymptomatic bacteriuria, prevalence, fetomaternal outcome, Port Harcour

‘We make them feel special’: The experiences of voluntary sector workers supporting asylum seeking and refugee women during pregnancy and early motherhood

Background or context: refugee and asylum seekers are over represented in maternal death data. Many asylum seeking and refugee women access maternity care infrequently, or not at all. Little is known about the role of voluntary sector workers in supporting pregnant refugees and asylum seekers. Objective: to explore the experiences of voluntary sector workers supporting asylum seeking and refugee women during pregnancy and early motherhood. Design: a qualitative descriptive study. Setting and participants: individual and focus group interviews in three large urban centres in North West England, United Kingdom. Findings: two main themes emerged. 'Literally through hell and back' reflected the experiences of suffering, abuse and loss recounted to the volunteers by many of the women they work with. 'Bridging the unacknowledged gap' related to the invisible processes undertaken by the workers as they enable the women they work with to over come their marginalised position. This included the difficulties of transience, and lack of enculturation, and to support them in accessing maternity care. Conclusion: voluntary sector workers supporting asylum seeking and refugee women strongly identified with the extreme suffering experienced by many of the women they work with. Through this contact, they become acutely aware of the gaps in provision for such women, and developed unique and innovative approaches to bridge this gap. These findings highlight the need for maternity health system to actively collaborate with, and learn from, voluntary agencies working in this field to improve the support offered to asylum seeking and refugee women

Stabilization of HPV16 E6 protein by PDZ proteins, and potential implications for genome maintenance

AbstractThe E6 protein from high-risk human papillomaviruses appears necessary for persistence of viral episomes in cells but the underlying mechanism is unclear. E6 has many activities, including its ability to bind and degrade PDZ domain-containing proteins, such as hScrib. However little is known about the role of these interactions for E6 function and the viral life cycle. We now show that the levels of expression of wild-type E6 are increased in the presence of hScrib whilst a mutant E6 protein lacking the PDZ-binding motif is found at lower levels as it is turned over more rapidly by the proteasome. This correlates with an inability of genomes containing this mutation to be maintained as episomes. These results show that E6 association with certain PDZ domain-containing proteins can stabilize the levels of E6 expression and provides one explanation as to how the PDZ-binding capacity of E6 might contribute to genome episomal maintenance

Basic Salts with »Very Short« Hydrogen Bonds; the Crystal Structure of a-Picoline-N-oxide Hemihydrochloride Sesquihydrate (Dunlop\u27s Salt)

Type A acid salts of many simple carboxylic acids (HX) crystallise with anions, XHx-, which are symmetrical and which contain »very short« OHO-bonds with O . .. 0 less than 250 pm. Such compounds also reveal anomalous IR spectra. The Glasgow work on such crystal structures has benefited from a long collaboration with Hadzi\u27s spectroscopic group at Ljubljana. The importance of such joint studies in helping the understanding of strong hydrogen bonding is discussed. Some organic bases form analogous basic salts, which have similarly anomalous spectra. An example, discovered by Hadzi in 1962, is the hemihydrobromide of a.-picoline-N-oxide, B · 1/2HBr, where B = CoH7NO, for which he predicted the formula BHB+ Br-. Preliminary X-ray work confirmed this and the presence of a »very short« OHO-bond. Hitherto unpublished crystallographic work is summarised. Dunlop\u27s salt is the sesquihydrated hemihydrochloride of the same base. A careful X-ray study has been made (1040 reflexions; R = 3.70/o): B · 1/2HCl · 3/2H20 has a structure corresponding to BHB+ c1- · 3H20; the cation lies across a centre of symmetry, with O ... O = 241.4(3) pm. At one stage the salt was supposed to include a symmetrical ClHc1- anion; but our more precise work shows the anion to be c1- ... H-OH (or HO-H ... en symmetrised by disorder across a twofold axis of the crystal, with c1- ... O = = 297(1) pm. The spectrum of DSALT is almost identical with that of the hemihydrobromide