Control of water intake by a pathway from the nucleus of the solitary tract to the paraventricular hypothalamic nucleus.

Several brain areas have been shown to participate in thirst and control of fluid intake. An understanding of how these circuits interact, and their roles in the activation, maintenance, and termination of fluid intake remains incomplete. Central glucagon-like peptide-1 (GLP-1) receptor activation appears to be an important part of the termination of drinking, but the site(s) of action for this suppression has not yet been determined. In an attempt to use GLP-1 responsiveness as a means to screen targets of hindbrain cells that participate in the termination of thirst and the resultant water intake, we injected the GLP-1 receptor agonist exendin-4 (Ex-4) into three brain areas known to express GLP-1 receptors, and measured subsequent water intake. Ex-4 reduced water consumption when injected into the paraventricular hypothalamic nucleus (PVH) and nucleus of the solitary tract (NTS), but not when injected into the nucleus accumbens (NAc). Using the effective response after injection into the PVH as a guide, we examined the connection between the NTS - the site of endogenous central GLP-1 production - and the PVH. Retrograde tracing combined with Fos immunohistochemistry suggested intake-induced activity in PVH-projecting NTS cells. To test the hypothesis that this pathway is important in the termination of drinking, we chemogenetically activated PVH-projecting hindbrain cells. Interestingly, activation of this population of cells increased water intake, calling into question the heterogeneity of the pathway with respect to the control of fluid intake. Taken together, we conclude that the PVH is a site of action for GLP-1 receptor activation in the inhibition of water intake, but suspect that endogenous GLP-1 in NTS-to-PVH projections may be counterbalanced by a parallel pathway that either activates or maintains already activated water intake.

Post-combat adaptation: improving social support and reaching constructive growth.

BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder, a commonly researched mental health outcome associated with trauma, does not develop in the majority of survivors. More common trajectories of adaptation include resilience, and posttraumatic growth (PTG). The objectives of the current study were to: (1) describe posttrauma adaptation profiles in a sample of Israeli male military veterans (N = 448); and (2) to explore the protective factors that promote constructive PTG within two profiles of posttrauma adaptation. METHODS: The study used secondary data to estimate latent profile mixture models and a series of logistic regression analyses. RESULTS: Demographic controls, combat related variables, endorsement of coping strategies, and reports of improvement in social support were not significant predictors of constructive growth in the resilient class. However, those in the struggling growth subset of the sample who reported improvement in perceived social support increased the odds of reaching constructive growth. CONCLUSION: These findings highlight the importance of tailored clinical interventions that account for more complex profiles of posttrauma adaptation; and further, provide evidence that adaptation takes place over time. Finally, these findings call for future research to continue to explore the quality of PTG and the contexts in which protective factors promote positive adaptation.

Zoological institution participation in a West Nile Virus surveillance system: implications for public health.

OBJECTIVE: To identify attributes of zoological institutions and surveillance system factors that were associated with participation in the West Nile Virus Surveillance System for Zoological Institutions in the USA, and to assess the potential effectiveness of zoos as a novel data source for surveillance of emerging infectious zoonoses. STUDY DESIGN: Retrospective. METHODS: The number of specimens submitted between August 2001 and December 2006 for West Nile virus testing was determined for each institution. Descriptive statistics were used to summarize the distribution of number of specimens submitted and features of the institutions. Student's t-test was used to assess potential associations between institutional and animal collection characteristics and the total number of specimens submitted by each institution. RESULTS: Factors associated with institutional participation include: submitting specimens for specific purposes of serosurvey testing, sentinel surveillance, vaccine titre checks, vaccine effectiveness, submitting specimens for multiple reasons, and communication with public health. CONCLUSION: Understanding how zoo and surveillance system characteristics are associated with participation in this surveillance effort may enhance public health efforts and the design of future zoological surveillance efforts.

Dual-energy CT angiography of pelvic and lower extremity arteries: dual-energy bone subtraction versus manual bone subtraction.

AIM: To analyse the effect of dual-energy bone subtraction (DEBS) on the image quality of peripheral computed tomography (CT) angiograms. MATERIALS AND METHODS: Twenty patients underwent dual-energy CT angiography of the pelvic and lower extremity arteries using commercially available equipment. Two different methods of image processing were employed for each CT angiographic dataset: (1) DEBS, and (2) manual bone subtraction (MBS). Effects on vessel visibility and artificial vessel alterations were compared. RESULTS: Bone removal, and the resultant visibility of vessel segments, were significantly better with DEBS than with MBS (p=0.011). The overall frequency of vessel-related alterations was lower in MBS compared with DEBS (p=0.001). Specifically, in the 249 vessel segments with calcified plaques, MBS generated fewer vessel alterations than DEBS (p<0.001). In the 309 vessel segments without calcified plaques, there was no difference in vessel alteration between the two techniques (p=0.22). CONCLUSION: DEBS facilitates bone removal in peripheral CT angiography, but generates more vessel alterations, particularly in the presence of calcified plaque.

Intranuclear coccidiosis in tortoises: nine cases.

Chelonian intranuclear coccidiosis has been reported once, in two radiated tortoises (Geochelone radiata), and is apparently rare. We describe intranuclear coccidiosis diagnosed histologically in two radiated tortoises, three Travancore tortoises (Indotestudo forstenii), two leopard tortoises (Geochelone pardalis), one bowsprit tortoise (Chersina angulata), and one impressed tortoise (Manouria impressa). Infection was systemic and involved alimentary, urogenital, respiratory, lymphoid, endocrine, and integumentary systems. Trophozoites, meronts, merozoites, macrogametocytes, microgametocytes, and nonsporulated oocysts were seen histologically or by electron microscopy. Intracytoplasmic and extracellular stages of parasite development also were identified histologically. Sequencing of a coccidial 18S rRNA consensus polymerase chain reaction (PCR) product revealed a novel sequence that provided phylogenetic information and may be useful for further diagnostic test design. Intranuclear coccidiosis was associated with variable degrees of inflammation in all cases, was considered the cause of death in six tortoises, and was a substantial contributing factor to the cause of death in two tortoises.

Inhibition of proteolytic, serpinolytic, and progelatinase-b activation activities of periodontopathogens by doxycycline and the non-antimicrobial chemically modified tetracycline derivatives.

BACKGROUND: Tetracyclines, particularly doxycycline (Doxy), and their non-antimicrobial chemically-modified derivatives (CMTs) inhibit the activities of human matrix metalloproteinases (MMPs), and reduce the severity and progression of periodontal disease in animal models and humans. In this study, the effects of Doxy and CMT-1, -3, and -5 on proteolytic, serpinolytic, and progelatinase-B activation activities of potent periodontopathogens were studied. METHODS: The effect of Doxy and CMTs (0.5 to 50 microM) on proteolytic activities were investigated by incubating bacteria with chromogenic substrates or human serum albumin. A collagenolytic fraction of Porphyromonas gingivalis was used to evaluate the effect of these substances on collagenolytic (type I collagen) and serpinolytic (alpha1-proteinase inhibitor) activities. Lastly, the effect of Doxy on progelatinase-B (pro-MMP-9) activation by purified proteinases from P. gingivalis and Treponema denticola was investigated by SDS-PAGE/Western immunoblotting. RESULTS: Doxy and CMTs, except CMT-5 which lacks the structural elements required for cation chelation, inhibited Arg- and Lys-gingipain activities as well as collagenolytic activity of P. gingivalis. Doxy and CMTs did not markedly affect the chymotrypsin-like activity of T. denticola but inhibited its trypsin-like activity. In addition, degradation of human serum albumin by cells of P. gingivalis and T. denticola was strongly inhibited by Doxy and CMT-1. Doxy and CMT-1 also inhibited the inactivation of alpha1-proteinase inhibitor (serpinolytic activity) by a collagenolytic fraction of P. gingivalis. Lastly, Doxy prevented the latent to active conversion of human neutrophil progelatinase-B (pro-MMP-9) by Arg-gingipains A/B of P. gingivalis but not by the chymotrypsin-like proteinase of T. denticola. CONCLUSIONS: Data from this study suggest that Doxy and CMTs have the potential to inhibit the periodontopathogenic bacterial proteinases, which contribute to tissue destruction cascades during periodontitis directly and indirectly by triggering the host response.

Systems of spatial reference in human memory.

Seven experiments examined the spatial reference systems used in memory to represent the locations of objects in the environment. Participants learned the locations of common objects in a room and then made judgments of relative direction using their memories of the layout (e.g., "Imagine you are standing at the shoe, facing the lamp; point to the clock"). The experiments manipulated the number of views that observers were allowed to experience, the presence or absence of local and global reference systems (e.g., a rectangular mat on which objects were placed and the walls of the room, respectively), and the congruence of local and global reference systems. Judgments of relative direction were more accurate for imagined headings parallel to study views than for imagined headings parallel to novel views, even with up to three study views. However, study views misaligned with salient reference systems in the environment were not strongly represented if they were experienced in the context of aligned views. Novel views aligned with a local reference system were, under certain conditions, easier to imagine than were novel views misaligned with the local reference system. We propose that learning and remembering the spatial structure of the surrounding environment involves interpreting the layout in terms of a spatial reference system. This reference system is imposed on the environment but defined by egocentric experience.

"Hidden" tongue jewellery.

Tongue piercing has many associated risks. This is a case report of a patient who, to avoid parental disapproval, hid the dorsal aspect of a lingual stud device. Subsequently, the dorsum repaired. The device could no longer be removed manually and warranted surgical removal. Despite being in situ for over two years, no further complications arose, but all efforts to obtain patient agreement for removal of the device failed.

Visual memories from nonvisual experiences.

Many common activities rely on spatial knowledge acquired from nonvisual modalities. We investigated the nature of this knowledge by having people look at a collection of objects on a desktop and manually reconstruct their arrangement, without vision, as though the display had been rotated by 0 degrees 45 degrees 90 degrees 135 degrees or 180 degrees relative to the view they could see. Performance on several measures of visual-spatial memory showed that participants had better visual memory for the view they had manually reconstructed than for the view they had studied visually for several minutes. These findings provide compelling new evidence that visual-spatial knowledge of very high fidelity can be acquired from nonvisual modalities, and reveal how, visual and nonvisual spatial information may even be confused in the brain.

Transcatheter interventions for the treatment of peripheral atherosclerotic lesions: part I.

Transcatheter endovascular procedures are increasingly used to treat symptomatic peripheral atherosclerosis. This two-part review identifies the existing evidence supportive of the application of transcatheter treatments for peripheral atherosclerotic lesions. The first part addresses the treatment of obstructive lesions that cause limb claudication and critical ischemia, renovascular hypertension and azotemia, and mesenteric ischemia. Studies were identified via a search of MEDLINE (January 1993 through April 1999) and reference lists of identified articles. When multicenter prospective randomized trials or other high-quality studies were unavailable, a preference was given to studies with at least 50 patients per treated group and a minimum mean follow-up duration of 6 months. Data presented in tables are proportionally weighted averages from included studies. For each application, the authors assessed the quality of evidence (QOE; efficacy, safety, and, where available, cost-effectiveness) and made recommendations with appropriate caveats. There is higher QOE supporting the more established treatments such as lower limb percutaneous transluminal angioplasty (PTA) with stent placement and thrombolysis. Treatments such as renal artery PTA and stent placement and mesenteric and brachiocephalic PTA are in wide use, but high QOE supporting general application is lacking. Blanket recommendations based on established efficacy and cost-effectiveness cannot be made. However, the use of transcatheter therapies can be supported in specific circumstances based on an expected reduction in procedure-related morbidity and/or mortality rates. It is hoped that the identification of deficiencies in the literature will inform and inspire critically needed research in this area.

Evaluating a support group for perinatal loss.

PURPOSE: This study attempted to determine if a support group intervention makes a difference in grief reactions of parents who have experienced a perinatal loss, and describes what parents perceived as being helpful and not helpful in handling the loss. DESIGN: A cross-sectional, retrospective, two-group research design was used. The independent variable was having attended or not having attended a perinatal loss support group. METHODS: A convenience sample of 121 participants (n = 67 in support groups; n = 51 not in support groups) was obtained from a mail survey to families who were on a perinatal loss support newsletter mailing list. The participants completed the Hogan Grief Reactions Checklist and a demographic questionnaire. RESULTS: There were no statistically significant differences in parents' grief reaction scores between the two groups, but there were some differences in grief scores by gender and ethnicity. In both groups, the parents perceived their spouse, their extended families, and their friends as "most helpful." Physicians were perceived as "least helpful." CLINICAL IMPLICATIONS: Grief is very individual, and not all individuals may benefit from a support group. When suggesting a support group or any intervention, timing and a caring approach are essential.

Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis.

OBJECTIVES: The therapeutic effects of doxycycline and other tetracyclines in the treatment of periodontitis involve, at least in part, mechanisms that are unrelated to their antimicrobial activity. Previous clinical studies have shown that doxycycline administered orally, at doses below those needed for antimicrobial efficacy, to human subjects with adult periodontitis resulted in significantly reduced collagenase activity in gingival crevicular fluid (GCF) and in extracts of inflamed gingival tissues. The purpose of the present study was to identify clinically effective dosing regimens using subantimicrobial dose doxycycline (SDD) as an adjunctive therapy in patients with adult periodontitis. MATERIAL AND METHODS: A total of 75 adult men and women qualified for enrollment into the three-part, placebo-controlled, double-blind, parallel-group study. Patients were stratified based on repeatedly exhibiting pathologic levels of periodontal attachment (ALv) and GCF collagenase activity at several appointments prior to baseline. Patients were administered a scaling and prophylaxis, then 1 of 5 treatment schedules for 12 weeks (part I), followed by a 12-week period of no drug therapy (part II), a second scaling and prophylaxis, and 12 additional weeks of treatment (part III). Primary determinants of efficacy included reductions in GCF collagenase activity and changes in relative ALv. RESULTS: 66 patients completed the 1st 12 weeks (part I) of the 3-part, 36-week study; 51 patients completed the entire 36-week study. From baseline to week 12 (part I), treatment with specially formulated SDD capsules (20 mg) 2x daily (1 x every 12 h) for up to 12 weeks was shown to significantly reduce GCF collagenase activity and to improve ALv, effects not seen in patients treated with placebo. Continuous drug therapy over the 12-week treatment period was needed to maintain and maximize the reduction in GCF collagenase and the improvement in ALv. Improvements in periodontal disease parameters occurred without the emergence of doxycycline-resistant micro-organisms. In patients administered an "on-off-on" regimen of SDD over 36 weeks (parts I-III), essentially no attachment loss occurred in patients receiving the highest of these SDD regimens (20 mg 2x daily during part I and 20 mg 1 x daily in part III), whereas patients administered placebo capsules experienced a mean attachment loss of approximately 0.8 mm at the 24- and 36-week time periods. CONCLUSIONS: Doxycycline administered at subantimicrobial doses led to improvements in disease parameters, with no apparent side effects, and appears to have significant potential as an oral adjunctive therapy in the long-term management of adult periodontitis.

Bleeding complications associated with the use of rt-PA versus r-PA for peripheral arterial and venous thromboembolic occlusions.

This article analyzes the early experience with alteplase (rt-PA) and reteplase (r-PA) to identify noteworthy differences in bleeding and to determine correlations with dosage, concomitant anticoagulation, and duration of infusion. A retrospective review of the medical records was unavailable for the initial 82 patients who were treated with either rt-PA (44) or r-PA (38) for peripheral arterial or venous occlusions after urokinase therapy. Successful recanalization was achieved in 31/44 (70%) of the patients treated with rt-PA and in 34/38 (89%) of the patients treated with r-PA. Significant bleeding was documented in 20/44 (45%) of the rt-PA-treated patients (including 14 transfusions) versus 3/38 (8%) of the r-PA-treated patients (3 transfusions). Concomitant anticoagulation with either preceding warfarin (international normalized ratio > 1.1) or a bolus of heparin at the outset of the infusion was associated with significant bleeding in 13/17 (76%) of the rt-PA-treated patients (including 9 transfusions) versus 0/17 in the r-PA-treated patients. No significant correlation between either mean dose or total dose and bleeding was shown for either drug. Early experience indicates that r-PA is at least as effective as rt-PA for the thrombolysis of peripheral arterial and venous occlusions. It also appears that r-PA is less likely than rt-PA to be associated with significant bleeding during such infusions, especially if the patient is concomitantly anticoagulated.

West Nile virus transmission and ecology in birds.

The ecology of the strain of West Nile virus (WNV) introduced into the United States in 1999 has similarities to the native flavivirus, St. Louis encephalitis (SLE) virus, but has unique features not observed with SLE virus or with WNV in the old world. The primary route of transmission for most of the arboviruses in North America is by mosquito, and infected native birds usually do not suffer morbidity or mortality. An exception to this pattern is eastern equine encephalitis virus, which has an alternate direct route of transmission among nonnative birds, and some mortality of native bird species occurs. The strain of WNV circulating in the northeastern United States is unique in that it causes significant mortality in exotic and native bird species, especially in the American crow (Corvus brachyrhynchos). Because of the lack of information on the susceptibility and pathogenesis of WNV for this species, experimental studies were conducted at the USGS National Wildlife Health Center. In two separate studies, crows were inoculated with a 1999 New York strain of WNV, and all experimentally infected crows died. In one of the studies, control crows in regular contact with experimentally inoculated crows in the same room but not inoculated with WNV succumbed to infection. The direct transmission between crows was most likely by the oral route. Inoculated crows were viremic before death, and high titers of virus were isolated from a variety of tissues. The significance of the experimental direct transmission among captive crows is unknown.

Transfer-appropriate processing (TAP) and repetition priming.

Transfer-appropriate processing (TAP), as applied to implicit memory, has tended to emphasize general forms of processing (e.g., perceptual or conceptual processing). In the present studies, the TAP principle was employed in a more specific manner in order to more precisely assess the relations between the processing engaged during first exposure and that engaged during second exposure to items. Thirteen experiments used a two-phase, cross-task design in which participants engaged in different combinations of seven specific intentional tasks between Phase 1 and Phase 2. Maximum repetition priming was found when tasks were the same in Phases 1 and 2. When Phase 1 and Phase 2 tasks differed, there were lesser, or no, repetition priming effects, depending on the particular combination of tasks. The results demonstrate the importance of the specific intentional processes engaged during repetition priming and the potential heuristic value of TAP, as a principle and methodology, for exploring the organization of memory and related process models.

Reteplase in the treatment of peripheral arterial and venous occlusions: a pilot study.

PURPOSE: Reteplase, a truncated mutant of tissue plasminogen activator, has been used successfully in the treatment of acute coronary occlusion, but, heretofore, it has not been investigated in the setting of peripheral vascular occlusion. Reteplase is a potential recombinant thrombolytic agent that may offer an appropriate alternative to currently employed plasminogen activators. MATERIALS AND METHODS: Over a 6-month period reteplase was used to treat peripheral vascular occlusions at five centers in the United States. The agent was used in peripheral arterial occlusion (n = 26, 70.3%) or venous occlusion (n = 11, 29.7%), in doses ranging from 0.5 to 2.0 U/h, infused directly into the thrombus. A lacing dose (4.3 +/- 0.9 U) was employed in 17 patients (45.9%), and 25 patients (67.6%) received concurrent heparin therapy in a subtherapeutic dose (n = 14, 37.8%) or as full therapeutic anticoagulation (n = 11, 29.7%). RESULTS: The 26 patients with arterial occlusions received a total dose of reteplase that averaged 20.5 U +/- 5.3 (mean +/- SEM), ranging from 3.5 to 82 U. The duration of infusion was 19.3 hours +/- 2.4 with a range of 0.2-36 hours. Complete dissolution of the occluding thrombus was achieved in 23 patients (88.5%). Hemorrhagic complications developed in eight patients (30.8%) and were major in five patients (19.2%). No patient experienced intracranial bleeding. Although there was no association between the dose regimen and thrombolytic efficacy, bleeding complications appeared to be more frequent as the dose was increased from 0.5 to 2.0 U/h. The 11 patients treated for deep venous thrombi received an average of 32.6 U +/- 7.4 of reteplase, ranging from 6 to 75 U over a mean length of time of 31.1 hours +/- 7.3 (range, 4-84 hours). Complete dissolution of thrombus occurred in eight patients (72.7%). Hemorrhagic complications developed in three patients (27.3%) and one of the episodes was major (9.1%). No patient experienced intracranial hemorrhage. CONCLUSIONS: Reteplase appears to be an acceptable alternative thrombolytic agent with a satisfactory safety and efficacy profile in the setting of peripheral arterial and venous occlusion. As such, it may provide an attractive alternative for the treatment of peripheral arterial and venous thrombotic occlusions. However, definitive conclusions must await the results of controlled comparisons of reteplase to other thrombolytic agents.