Ordering of water molecules between phospholipid bilayers visualized by coherent anti-Stokes Raman scattering microscopy

We demonstrate ordered orientation of the hydration water at the surface of phospholipid bilayers by use of coherent anti-Stokes Raman scattering (CARS) microscopy, a highly sensitive vibrational imaging method recently developed. We investigated negatively charged POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine) and neutral POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) multilamellar onions dispersed in deuterated dodecane. The imaging contrast based on the CARS signal from the H2O stretching vibration shows a clear dependence on the excitation field polarization. Our results provide direct experimental evidence that water molecules close to the phospholipid bilayer surface are ordered with the symmetry axis along the direction normal to the bilayer. Moreover, the amount of ordered water molecules depends on the lipid polar group. The spectral profile for the inter-lamellar water shows that the water molecules bound to the bilayer surface are less hydrogen-bonded and exhibit a higher vibrational frequency than bulk water.     

Engineering asymmetric vesicles

Vesicles are bilayers of lipid molecules enclosing a fixed volume of aqueous solution. Ubiquitous in cells, they can be produced in vitro to study the physical properties of biological membranes and for use in drug delivery and cosmetics. Biological membranes are, in fact, a fluid mosaic of lipids and other molecules; the richness of their chemical and mechanical properties in vivo is often dictated by an asymmetric distribution of these molecules. Techniques for vesicle preparation have been based on the spontaneous assembly of lipid bilayers, precluding the formation of such asymmetric structures. Partial asymmetry has been achieved only with chemical methods greatly restricting the study of the physical and chemical properties of asymmetric vesicles and their use in potential applications for drug delivery. Here we describe the systematic engineering of unilamellar vesicles assembled with two independently prepared monolayers; this process produces asymmetries as high as 95%. We demonstrate the versatility of our method by investigating the stability of the asymmetry. We also use it to engineer hybrid structures comprised of an inner leaflet of diblock copolymer and an independent lipid outer leaflet.     

Relationship of clinical symptoms and substance use in schizophrenia patients on conventional versus atypical antipsychotics

A large body of research documents the high prevalence and devastating consequences of substance abuse among individuals diagnosed with schizophrenia. One prominent theory of the high rate of comorbidity between these disorders is that substance abuse in schizophrenia is an attempt to self-medicate psychiatric symptoms including negative symptoms and depression as well as side effects including extrapyramidal reactions (EPR). Consistent with this notion, novel antipsychotic medications, which have been shown to reduce negative and depressive symptoms while exhibiting a lower propensity to cause EPR, have been associated with reduced substance abuse in patients with schizophrenia. To further explore the self-medication hypothesis as it relates to the mechanism by which atypical antipsychotics reduce substance abuse, we compared schizophrenia patients with a history of substance abuse medicated with either conventional (n = 35) or atypical (n = 35) antipsychotics. Patients with schizophrenia who did not have a history of substance abuse who were on conventional (n = 23) vs. atypical antipsychotics (n = 29) were also examined. Assessments included the Positive and Negative Symptom Scale, Hamilton Rating Scale for Depression, Simpson-Angus, and Abnormal Involuntary Movement Scale. Compared with conventional medications, atypical antipsychotic drugs were associated with reduced levels of substance use (primarily alcohol). Interestingly, however, in substance-abusing patients there were no significant differences between patients on conventional vs. atypical agents with respect to positive or negative symptoms, depression, or EPR. These data suggest that theories related to self-medication of symptoms and side effects do not appear to account for the difference in rates of substance use found in schizophrenia patients on atypical vs. conventional antipsychotic medications.     

Antithrombin-independent anticoagulation by hypersulfated low-molecular-weight heparin

Low-molecular-weight heparin (LMWH) inhibits the activity of the intrinsic factor X activation complex, a property that persists when LMWH is rendered low affinity (LA) for antithrombin, but is reduced when it is N-desulfated. When LA-LMWH is hypersulfated (sLA-LMWH), its potency against intrinsic tenase is increased and it acquires inhibitory activity against prothrombinase. sLA-LMWH functions by interfering with the association of enzyme and cofactor in both activation complexes. In a rabbit carotid artery thrombosis prevention model, sLA-LMWH is superior to LMWH. Because of its low affinity for antithrombin and multiple sites of action, sLA-LMWH may prove to be safer and more effective than other anticoagulants.     

Induction of a brainstem correlate of conditioned taste aversion expression: role of the pontine parabrachial nucleus

Increases in Fos-like immunoreactivity (FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) are seen following the expression of a conditioned taste aversion (CTA). In studies limited to behavioral assessment, the pontine parabrachial nucleus (PBN) has been demonstrated to play a critical role in the acquisition, but not the expression, of CTAs. To better define the role of the PBN in taste aversion learning, the present study examined the effects of PBN lesions on FLI in iNTS in animals with lesions placed either before or after CTA training. As is the case with behavioral expression of a CTA, timing of PBN lesions was found to be critical. Lesions placed prior to conditioning blocked evidence of conditioning, including both taste rejection and FLI in iNTS. Lesions placed after conditioning, but before testing, did not interfere with either taste rejection or FLI. These results support and extend prior claims that PBN is critical for CTA acquisition but not expression. They also demonstrate that input from PBN to iNTS is not necessary for the FLI seen there during CTA expression.     

Sleep loss and fatigue in residency training: a reappraisal

Reduced sleep time is commonplace for many interns and residents. Recent studies, however, suggest that sleep loss and fatigue result in significant neurobehavioral impairments in healthy young adults. We reviewed studies addressing the effects of sleep loss on cognition, performance, and health in surgical and nonsurgical residents. We describe the effectiveness of countermeasures for sleepiness, including recent work-hour restrictions. A more complete understanding of the issues of sleep loss during residency training can inform innovative strategies to minimize the effects of sleepiness and fatigue on patient care and resident safety.      

COMPARISON OF RURAL AND URBAN CERTIFIED NURSE-MIDWIVES IN ARIZONA

A survey of certified nurse-midwives (CNMs) in Arizona was carried out in 1990 to provide data for maternity service planning in the state. Information was gathered on location and scope of CNM practice, barriers to practice, and the contribution of CNMs to maternity care. Demographic and clinical practice characteristics of urban and rural CNMs were also compared. Urban and rural CNMs are significantly different in terms of education (urban CNMs are much more likely to have master's degrees) and number of years since first certification (urban CNMs have been certified significantly longer). Rural midwives are more likely to be under the age of 40. Health services provided by urban and rural CNMs were compared with each other and with national data. Midwives in rural areas of Arizona are more likely to provide comprehensive nurse-midwifery services than are either urban Arizona midwives or U.S. midwives as a whole. Urban and rural CNMs described lack of physician backup as a major barrier to nurse-midwifery practice in rural areas. Lack of hospital privileges was another major obstacle noted by rural nurse-midwives. Arizona CNMs felt they could provide comprehensive, cost-effective maternity services in rural areas that would improve access to care, patient satisfaction, and maternal and child health outcomes.