Amygdala AVPR1A mediates susceptibility to chronic social isolation in females.

Females are more sensitive to social exclusion, which could contribute to their heightened susceptibility to anxiety disorders. Chronic social isolation stress (CSIS) for at least 7 weeks after puberty induces anxiety-related behavioral adaptations in female mice. Here, we show that Arginine vasopressin receptor 1a ( Avpr1a )-expressing neurons in the central nucleus of the amygdala (CeA) mediate these sex-specific effects, in part, via projections to the caudate putamen. Loss of function studies demonstrate that AVPR1A signaling in the CeA is required for effects of CSIS on anxiety-related behaviors in females but has no effect in males or group housed females. This sex-specificity is mediated by AVP produced by a subpopulation of neurons in the posterodorsal medial nucleus of the amygdala that project to the CeA. Estrogen receptor alpha signaling in these neurons also contributes to preferential sensitivity of females to CSIS. These data support new therapeutic applications for AVPR1A antagonists in women.

Pathway-specific contribution of parvalbumin interneuron NMDARs to synaptic currents and thalamocortical feedforward inhibition.

Prefrontal cortex (PFC) is a site of information convergence important for behaviors relevant to psychiatric disorders. Despite the importance of inhibitory GABAergic parvalbumin-expressing (PV+) interneurons to PFC circuit function and decades of interest in N-methyl-D-aspartate receptors (NMDARs) in these neurons, examples of defined circuit functions that depend on PV+ interneuron NMDARs have been elusive. Indeed, it remains controversial whether all PV+ interneurons contain functional NMDARs in adult PFC, which has major consequences for hypotheses of the pathogenesis of psychiatric disorders. Using a combination of fluorescent in situ hybridization, pathway-specific optogenetics, cell-type-specific gene ablation, and electrophysiological recordings from PV+ interneurons, here we resolve this controversy. We found that nearly 100% of PV+ interneurons in adult medial PFC (mPFC) express transcripts encoding GluN1 and GluN2B, and they have functional NMDARs. By optogenetically stimulating corticocortical and thalamocortical inputs to mPFC, we show that synaptic NMDAR contribution to PV+ interneuron EPSCs is pathway-specific, which likely explains earlier reports of PV+ interneurons without synaptic NMDAR currents. Lastly, we report a major contribution of NMDARs in PV+ interneurons to thalamus-mediated feedforward inhibition in adult mPFC circuits, suggesting molecular and circuit-based mechanisms for cognitive impairment under conditions of reduced NMDAR function. These findings represent an important conceptual advance that has major implications for hypotheses of the pathogenesis of psychiatric disorders.

Parallel Social Information Processing Circuits Are Differentially Impacted in Autism.

Parallel processing circuits are thought to dramatically expand the network capabilities of the nervous system. Magnocellular and parvocellular oxytocin neurons have been proposed to subserve two parallel streams of social information processing, which allow a single molecule to encode a diverse array of ethologically distinct behaviors. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons in male mice, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next use novel multiple feature selection tools in Fmr1-KO mice to provide direct evidence that normal functioning of the parvocellular but not magnocellular oxytocin pathway is required for autism-relevant social reward behavior. Finally, we demonstrate that autism risk genes are enriched in parvocellular compared with magnocellular oxytocin neurons. Taken together, these results provide the first evidence that oxytocin-pathway-specific pathogenic mechanisms account for social impairments across a broad range of autism etiologies.

Oxytocin-dependent reopening of a social reward learning critical period with MDMA.

A critical period is a developmental epoch during which the nervous system is expressly sensitive to specific environmental stimuli that are required for proper circuit organization and learning. Mechanistic characterization of critical periods has revealed an important role for exuberant brain plasticity during early development, and for constraints that are imposed on these mechanisms as the brain matures1. In disease states, closure of critical periods limits the ability of the brain to adapt even when optimal conditions are restored. Thus, identification of manipulations that reopen critical periods has been a priority for translational neuroscience2. Here we provide evidence that developmental regulation of oxytocin-mediated synaptic plasticity (long-term depression) in the nucleus accumbens establishes a critical period for social reward learning. Furthermore, we show that a single dose of (+/-)-3,4-methylendioxymethamphetamine (MDMA) reopens the critical period for social reward learning and leads to a metaplastic upregulation of oxytocin-dependent long-term depression. MDMA-induced reopening of this critical period requires activation of oxytocin receptors in the nucleus accumbens, and is recapitulated by stimulation of oxytocin terminals in the nucleus accumbens. These findings have important implications for understanding the pathogenesis of neurodevelopmental diseases that are characterized by social impairments and of disorders that respond to social influence or are the result of social injury3.

Gating of social reward by oxytocin in the ventral tegmental area.

The reward generated by social interactions is critical for promoting prosocial behaviors. Here we present evidence that oxytocin (OXT) release in the ventral tegmental area (VTA), a key node of the brain's reward circuitry, is necessary to elicit social reward. During social interactions, activity in paraventricular nucleus (PVN) OXT neurons increased. Direct activation of these neurons in the PVN or their terminals in the VTA enhanced prosocial behaviors. Conversely, inhibition of PVN OXT axon terminals in the VTA decreased social interactions. OXT increased excitatory drive onto reward-specific VTA dopamine (DA) neurons. These results demonstrate that OXT promotes prosocial behavior through direct effects on VTA DA neurons, thus providing mechanistic insight into how social interactions can generate rewarding experiences.

Investigation of the antigen antibody reaction between anti-bovine serum albumin (a-BSA) and bovine serum albumin (BSA) using piezoresistive microcantilever based sensors.

A new microsensor application based on piezoresistive microcantilever technology has been used to study the interaction of anti-bovine serum albumin (a-BSA) with bovine serum albumin (BSA). A thin layer of BSA attached to a glass slide was used as the active sensing layer for the detection of a-BSA in solution. This design produced a large, consistent cantilever deflection when exposed to the analyte. In this system, the cantilever deflection is measured as a simple resistance change in the piezoresistive channel within the cantilever. In a second set of experiments, 3:1 BSA:PEO protein/polymer blended substrates were used as the active sensing layer for the detection of a-BSA in an aerosol delivery. A distinct signature for the analyte, separate from the water vapor carrier, is obtained for this system.

Exploring the structure of a hydrogen cyanide polymer by electron spin resonance and scanning force microscopy.

Aqueous solutions of potassium cyanide and ammonium hydroxide are known to yield a heterogeneous cyanide polymer, containing paramagnetic sites and biologically significant substructures including polypeptides. Here, such solutions were used to prepare various samples of polymer for study by X-band and W-band electron spin resonance (ESR), scanning electron microscopy (SEM), and scanning force microscopy (SFM). Elemental composition of a typical sample of the polymer was C-35.2%, N-38.47%, 0-14.51%, and H-4.13%, exposing the polymer to 6M HCl hydrolyzed portions of the polymer and released glycine and traces of other amino acids. The X-band ESR spectra consist of a single slightly asymmetric line centered at g = 2.003; spin concentration measurements made at X-band using a nitroxide radical standard yield approximate radical concentrations of 10(18) spins/gm. W-band ESR indicates the presence of a single rhombic paramagnetic site with g(x) = 2.0025, g(y) = 2.0030, and g(z) = 2.0048 and the possibility of small 14N hyperfine splittings. The ESR spin echo studies yield a longitudinal relaxation time, Tl of 75 microS and a short-phase memory relaxation time, Tm, of about 300 nS. Scanning electron microscopy studies of the polymer show that it is made of ellipsoidal particles about one micron in size. The particles tend to clump together when suspended in aqueous solution. The particles disperse and dissolve in dimethyl sulfoxide (DMSO); when these solutions dry on microscope slides, optical microscopy shows a branched island morphology for the polymer. This morphology is reminiscent of snowflakes and is identified as dendritic. Phase contrast SFM of the dendritic arms show a striking segregation and ordering of various components of the polymer. Paramagnetic sites are conserved in the series of steps leading to dendritic structures.

Analysis of peptides synthesized in the presence of SAz-1 montmorillonite and Cu(2+) exchanged hectorite.

We have investigated the synthesis of oligopeptides containing glycine and tyrosine in the presence of the clay minerals montmorillonite (non-exchanged, SAz-1) and Cu(2+) exchanged hectorite. In both cases, homopolymers of the two amino acids are formed, as are mixed peptides. In the case of Cu(2+) hectorite, mixed oligopeptides up to trimers are detected in small amounts. For montmorillonite, heterogeneous oligopeptides up to hexamers are detected. Our experiments indicate montmorillonite is more effective in promoting oligopeptide formation than Cu(2+) hectorite. Analysis of the oligopeptide sequences formed on the montmorillonite surfaces indicates preferential synthesis of certain Gly-Tyr sequences over others.

Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2.

BACKGROUND: This study was performed to determine the incidence of central venous device-related blood stream infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2 (IL-2). METHODS: The records of 160 consecutive patients treated at the University of Wisconsin Hospital and Clinics, between June 1990 and June 1997, with moderate dose continuous-infusion IL-2 (IL-2 [1.5-3.0 x 10(6) U/m(2)/day] Hoffman-LaRoche, Nutley, NJ or IL-2 [4.5 x 10(6) U/m(2)/day] Chiron Corporation, Berkley, CA) were reviewed retrospectively. The majority of patients had metastatic melanoma (78 patients) or renal cell carcinoma (70 patients). All of the patients had a surgically implanted central venous device placed before starting IL-2 therapy; 89% of these were cuffed Hickman catheters. Eighty-four patients received 1 mg of warfarin per day as prophylaxis against device-related thrombosis; none received periinsertion prophylactic antibiotics. RESULTS: Twenty-one patients (13%) developed central venous device-related bloodstream infection (DRBSI) during the study period, a rate of 2 DRBSI per 1000 device-days. DRBSIs were associated with the type of immunotherapy given with IL-2 (P = 0.01) and with thrombosis (odds ratio, 4.1; 95% confidence interval, 1.5-11.4; P = 0.008) but not with patient gender, type of cancer, duration of the central device, or site of device placement. Twenty-six patients (16%) developed central venous device-related thrombosis (DRT) during immunotherapy. Low dose warfarin did not appear to prevent thrombosis. Device-related thrombosis was associated with DRBSI but not with patient gender, type of cancer, type of device, duration or location of device, or concomitant immunotherapy. CONCLUSIONS: Central venous DRBSI and DRT are significant complications that can occur during moderate dose continuous-infusion IL-2 therapy. The risk of DRBSI appears lower than the risk reported with high dose IL-2 therapy by previous investigators. The risk of DRT appears to be higher than the risk reported for patients with similar devices but not given IL-2. Low dose warfarin did not prevent DRT when started after device placement.

The interaction of biological molecules with clay minerals: a scanning force microscopy study.

We have used the technique of scanning force microscopy (SFM) to investigate the reaction of both amino acids and activated nucleotides in the presence of the clay mineral Cu(II)-exchanged hectorite. Using simulated prebiotic heating and wetting cycles, we have shown that the clay mineral acts to adsorb, concentrate, and subsequently catalyze the polymerization of these biological monomers into short peptides and oligonucleotides. The presence of the Cu(II) cations within the clay intergallery regions, and at surface step edges and cracks, is crucial for the observed reactions to occur. Clay minerals such as hectorite may have thus played an important role in the evolution of biologically viable molecules on the prebiotic earth.

Examples of Hartmann-Hahn match conditions for CP/MAS between two half-integer quadrupolar nuclei.

Hartmann-Hahn match conditions for n2 --> M2 CP/MAS between two quadrupolar nuclei, spin-lock signal as a function of effective nutation frequency, and the correlation of effective nutation frequency and radiofrequency field strength are reported for three samples: sodium diborate (Na2B4O7), aluminum boride (AlB2), and lithiump aluminate (LiAlO2). Radiofrequency field strengths used for CP/MAS are both greater and less than the sample spinning speed of 10 kHz, resulting in the observation of both zero-quantum and double-quantum matches, which have signals of opposite sign. The match conditions for Na2B4O7 are as expected from published theory and CP/MAS experiments on spins 12 and n2 (n = 3 or 5) with quadrupole frequencies (omegaQ) large compared to the radiofrequency field strength of the CP contact pulse, consisting mainly of sideband matches at one and two times the sample spinning frequency, and the correlation of effective nutation frequency and radiofrequency field strength supports the conclusion that omegaQ is large for both 11B and 23Na. Aluminum-27 in AlB2 may have either small or intermediate omegaQ, and 7Li in LiAlO2 is proposed to have intermediate omegaQ in relation to the radiofrequency field strength, and both have curves of the spin-lock signal as a function of effective nutation frequency with central minima, differing from those of the nuclei with large omegaQ. The sign of the CP/MAS signal for AlB2 and LiAlO2 appears to vary with the CP field strengths for the two nuclei so that positive or negative signals cannot be consistently correlated with zero- or double-quantum matches. However, it is possible to assign at least some of the matches as close to integral multiples of the sample spinning frequency, and some of these are matches at greater than two times the sample spinning frequency.

The synergy of health promotion practice/research/education.

Many nurses are concerned about the lack of connection among nursing practice, research and education. However, the assumption that nursing practice, research, and education represent separate domains or activities that need to be linked, may well contravene the relational synergy they share. This paper describes a project that sought to illustrate, and further explore, the synergistic, iterative relationship of health promoting practice/research/education. The project revealed how this synergy lives out within the daily practice of frontline practitioners and how the researched knowledge practitioners bring forth through their practice can transform care.

Site-specific prebiotic oligomerization reactions of glycine on the surface of hectorite.

Condensation reactions of the amino acid glycine on the surface of Cu(II)-exchanged hectorite are investigated using the technique of scanning force microscopy. Prebiotic conditions are simulated using alternate wetting and heating cycles. Concentration, immobilization, and subsequent polymerization resulting in glycine oligomers are seen to occur primarily at step edges or faults in the topmost layer. Condensation reactions also occur within tiny micropores or defects in the topmost layer. These reactions are facilitated by the availability of intergallery metal cations at the step edges or pores in the surface region.

Outcome measures after standardized pain management strategies in postoperative patients in the neonatal intensive care unit.

Written guidelines based on current research on infant pain assessment and management were developed by an interdisciplinary team in a neonatal intensive care unit of a regional medical center. Charts for infants who had undergone abdominal surgery were reviewed to compare patient outcomes before and after use of this pain management protocol. With the standardization of pain management strategies, the following improvements were noted: decreased length of time to extubation, decreased length of stay, better fluid management, and reduced side effects of narcotics. Additional benefits included improved pain management documentation, decreased cost, and decreased nursing time.

Traumatic duodenal rupture and avulsion of the ampulla of Vater.

Duodenal injury following blunt abdominal trauma is uncommon. The severity of injury can vary from an intramural haematoma to a duodenal rupture with associated transection of the pancreatic duct. A case of duodenal rupture with avulsion of the ampulla of Vater is presented and discussed.

The operative aetiology and types of adhesions causing small bowel obstruction.

Postoperative adhesions account for 64-79% of admissions with small bowel obstruction (SBO). The aim of this study was to identify the operative procedures and the types of adhesions that cause SBO. A retrospective analysis of all patients with an admission diagnosis of acute adhesive SBO between January 1982 and December 1990 was performed. One hundred and nineteen patients had 144 admissions with an initial diagnosis of acute SBO due to adhesions. The previous operations were: appendicectomy 23.3%; colorectal resection 20.8%; gynaecological surgery 11.7%; upper gastrointestinal (gastric, biliary or splenic) surgery 9.2%; small bowel surgery 8.3%; and more than one previous abdominal operation 23.6%. Sixty-one admissions required surgery to relieve the SBO. Eighteen patients had strangulated small bowel. All but two of these patients had a single band adhesion causing the SBO and associated strangulation. Band adhesions were commonly found following appendicectomy, colorectal resections or gynaecological operations. Seventeen of the 21 patients with previous surgery for a colorectal malignancy had benign adhesions causing the SBO, while four of the six patients with either previous ovarian or previous gastric carcinoma had recurrent malignancy causing the SBO. Five patients had previously undiagnosed carcinomas (three ovarian and two caecal) as the cause of the SBO.

Becoming a part of the community: implementing a public health vision in student health services.

Principles from public health and community health nursing provide an approach to student health services that enhances interdisciplinary collaboration and advocacy for access to care. Staff participation in the campus community requires administrative support, both in philosophy and in making outreach activities accessible to staff. Student health services at University of Maine's Cutler Health Center in Orono is implementing outreach and community involvement as ongoing aspects of the college health nursing role. Increased collaboration, visibility of nurses on campus, and improved community assessment and intervention are among the outcomes observed during the past 2 years. This article describes the principles that guide this approach and shares some community involvement experiences, including the response to a student suicide attempt, social support for students after a residence hall fire, and case management/consultation services.

The safety and duration of non-operative treatment for adhesive small bowel obstruction.

Small bowel obstruction (SBO) due to adhesions is often initially treated non-operatively but the safety and duration of non-operative treatment is controversial. The aims of this study were to assess the safety of non-operative treatment and determine the optimal duration of non-operative treatment in adhesive SBO. A retrospective analysis of patients admitted with a diagnosis of adhesive SBO following an initial period of non-operative treatment was performed. Patients whose condition resolved with non-operative treatment were compared with patients who required surgical intervention after an initial period of non-operative treatment. There were 123 admissions having an initial period of non-operative treatment. The SBO resolved in 85, the remaining 38 required surgical intervention. Complete resolution occurred within 48 h in 75 (88%) cases, the remaining 10 had resolved by 72 h. Thirty-one of 38 patients required surgical intervention for SBO more than 48 h duration after admission. The difference between cases resolving within 48 h and those requiring surgery after 48 h was significant (chi 2 = 113, P < 0.001). Three (2.4%) patients, initially treated non-operatively, had small bowel strangulation. All three were operated on within 24 h of admission when changes in clinical findings suggested small bowel strangulation may be present. There were no deaths in the group having an initial period of non-operative treatment. In the absence of any signs of strangulation, patients with an adhesive SBO can be managed safely with non-operative treatment. Most cases of adhesive SBO that will resolve, do so within 48 h of admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Open cholecystectomy: a control group for comparison with laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is rapidly becoming accepted as the best method for the treatment of symptomatic cholelithiasis. Randomized clinical trials comparing laparoscopic cholecystectomy with open cholecystectomy are unlikely to be performed. In order to compare these two operations, surgeons need an historical control group of patients who have undergone a conventional open cholecystectomy. The aim of this study was to document a control group of patients having an open cholecystectomy and compare them with patients having a laparoscopic cholecystectomy. This was achieved by a retrospective study of all patients who had an open cholecystectomy from January 1985 to December 1989. Four hundred and fifty-seven patients, 345 women and 112 men, had a cholecystectomy. Exploration of the common bile duct (ECBD) was performed in 59 (12.5%) cases. The mean operative duration was 73 min for cholecystectomy and 118 min for cholecystectomy and ECBD. The shortest mean postoperative stay was for an elective cholecystectomy (5.3 days) and the longest mean postoperative stay was for urgent admissions requiring ECBD (12.0 days). Operative dissection was difficult in 14.1% of elective cases and 51.8% of urgent cases. Ninety-seven (19.5%) patients had an additional procedure, unrelated to cholelithiasis, at the same operation; 44 did not require laparotomy, 31 had interval appendectomies, and 22 other cases required laparotomy in order to perform the additional procedure. All but one patient required postoperative narcotic analgesia. The mean duration of narcotic analgesia was 2.3 days. The complication rate was 35.2% for cholecystectomy and 62.5% for ECBD. If pulmonary atelectasis is excluded as a complication, these complication rates fell to 6.8% and 20.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)