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Cells in the medial preoptic area (mPOA), arcuate nucleus (ARC), and ventromedial nucleus (VMN) that possess estrogen receptor alpha (ER alpha) mediate estradiol feedback to regulate endocrine and behavioral events during the estrous cycle. A percentage of ER alpha cells located in the ARC and VMN express somatostatin (SST) and are activated in response to estradiol. The aims of the present study were to investigate the location of c-Fos, a marker for activation, in cells containing ER alpha or SST at various times during the follicular phase and to determine whether lipopolysaccharide (LPS) administration, which leads to disruption of the luteinizing hormone (LH) surge, is accompanied by altered ER alpha and/or SST activation patterns. Follicular phases were synchronized with progesterone vaginal pessaries, and control animals were killed at 0, 16, 31, and 40 h (n = 4-6/group) after progesterone withdrawal (PW [time 0]). At 28 h, other animals received LPS (100 ng/kg) and were subsequently killed at 31 h or 40 h (n = 5/group). Hypothalamic sections were immunostained for c-Fos and ER alpha or SST. LH surges occurred only in control ewes with onset at 36.7 ± 1.3 h after PW; these animals had a marked increase in the percentage of ER alpha cells that colocalized c-Fos (%ER alpha/c-Fos) in the ARC and mPOA from 31 h after PW and throughout the LH surge. In the VMN, %ER alpha/c-Fos was higher in animals that expressed sexual behavior than in those that did not. SST cell activation in the ARC and VMN was greater during the LH surge than in other stages in the follicular phase. At 31 or 40 h after PW (i.e., 3 or 12 h after treatment, respectively), LPS decreased %ER alpha/c-Fos in the ARC and the mPOA, but there was no change in the VMN compared to that in controls. The %SST/c-Fos increased in the VMN at 31 h after PW (i.e., 3 h after LPS) with no change in the ARC compared to controls. These results indicate that there is a distinct temporal pattern of ER alpha cell activation in the hypothalamus during the follicular phase, which begins in the ARC and mPOA at least 6-7 h before the LH surge onset and extends to the VMN after the onset of sexual behavior and LH surge. Furthermore, during the surge, some of these ER alpha-activated cells may be SST-secreting cells. This pattern is markedly altered by LPS administered during the late follicular phase, indicating that the disruptive effects of this stressor are mediated by suppressing ER alpha cell activation at the level of the mPOA and ARC and enhancing SST cell activation in the VMN, leading to the attenuation of the LH surge.

Intraosseous lines are a reliable and rapid tool for obtaining vascular access in emergency situations, particularly in children. Their use is recommended when intravenous access cannot be easily secured and there is a need for fluid or pharmacological resuscitation. Training in this technique is included in the Advanced Trauma Life Support (ATLS) and Advanced Paediatric Life Support course (APLS) provider courses. The objective of this study is to analyse the national use of intraosseous lines in paediatric trauma in England and Wales. Data has been collected from the Trauma Audit and Research Network (TARN) group longitudinally over 14 years from 1988 to 2002. From 23,489 paediatric trauma cases, intraosseous lines were used in only 129 patients. Compared with the remainder of the paediatric data, we found that these were the younger (1-6 years), more severely injured patients (higher ISS, lower GCS, higher head, thorax, and abdominal AIS). The mortality of these patients was high at 64% compared with 4% overall. IO line use was greater in general than in Paediatric hospitals, perhaps due to good intravenous access skills in paediatric centres. We recommend that intraosseous line use should be a skill available to everybody involved in paediatric trauma resuscitation, particularly those who may not have refined paediatric intravenous cannulation skills.

The objective of the current study was to examine how periadolescent nicotine exposure affects dendritic morphology of medium spiny neurons from the nucleus accumbens shell. Male Long-Evans hooded rats were chronically administered nicotine or saline for a period extending from postnatal day 22 (p22) to p69. Nicotine and saline administration was via subcutaneously implanted osmotic pumps. At p144, 75 days after conclusion of nicotine administration, brains were processed for Golgi-Cox staining. Medium spiny neurons from the nucleus accumbens shell were digitally reconstructed. It was found that neurons from nicotine-treated animals possessed significantly longer dendrites and a greater number of dendritic segments than control animals. A branch order analysis indicated that differences in dendritic length and segment number were most pronounced in third and fourth order segments. A subsequent behavioral experiment suggests that the observed anatomical changes are associated with enduring psychomotor differences. These findings indicate that periadolescent exposure to nicotine can result in long-lasting structural changes in the nucleus accumbens shell and are consistent with behavioral data suggesting that adolescent nicotine exposure may result in vulnerability to nicotine addiction in adulthood.

The flight activity of the apple leaf midge, Dasineura mali (Kieffer), was determined in the field and laboratory. Males and females began emerging at the onset of the photophase. In the field, delta-shaped traps baited with 6 virgin females caught males exclusively, with the most abundant catches on the ground as compared to those at 1 and 2 m. Most males were captured at 1100 hours and males remained in the vegetation under the trees throughout the day. Sweep netting revealed that conspecifics mate in the vegetation under orchard trees in the morning hours, and females move from the ground to the orchard canopy to oviposit at 1000 hours. Gas chromatographic-electroantennographic detection (GC-EAD) analyses indicated the presence of an electrophysiologically active compound in solid phase microextraction (SPME) effluvial collections and pheromone gland extractions from virgin females.

Use of addictive substances by human juveniles and adolescents is common, including use to intoxication and progression from one drug to other drugs. Until quite recently, animal studies have not addressed the periadolescent period as a time of special vulnerability to substance abuse. For ethanol (EtOH), the most studied drug in periadolescent animals, it has become clear that effects of alcohol are similar in some ways, but different in others, compared to the effects seen in adult animals. Sparse data suggest that this conclusion may apply to other drugs as well. Recent work in rats indicates that periadolescent substance use may disrupt normal pubertal development, and may induce stronger effects on systems subserving plasticity and cognition than in adults. Animal data also indicate that some drugs may produce altered subsequent sensitivity to the same or a different drug, changes in adult cognitive capabilities, and even CNS damage. It is now clear that there can be no presumption that all studies of abusable substances carried out in adult animals will generalize readily to periadolescents. Some data suggest that continuing developmental changes in receptor expression may underlie age-related changes in drug effects. However, the biological characteristics of periadolescence which predispose toward consumption to intoxication, and the mechanisms underlying drug progression and persisting drug effects, still remain to be well defined.

Gunshot wounds that traverse the mediastinum frequently cause serious injury to the cardiac, vascular, pulmonary, and digestive structures contained within. Most patients present with unstable vital signs signifying the need for emergency operation. An occasional patient will present with stable vital signs. Work-ups for such a patient may range from surgical exploration to radiographic and endoscopic testing to mere observation. We report our experience with diagnostic work-up of the stable patient with a transmediastinal gunshot wound. All stable patients who present to our urban level I trauma center following a transmediastinal gunshot wound undergo diagnostic work-up consisting of chest radiograph, cardiac ultrasound, angiography, esophagoscopy, barium swallow, and bronchoscopy. The work-up is dependent on the trajectory of the missile. Information on these patients is kept in a prospective database maintained by the trauma attending physicians. This database was analyzed and comparisons were made using Student's t-test and the Fisher exact c2 as appropriate. Over a 68-month period, 50 stable patients were admitted following a transmediastinal gunshot wound. All of these patients had a chest radiograph followed by one or more of the above tests. 8 patients (16%) were found to have a mediastinal injury (4 cardiac, 3 vascular, and 1 tracheo-esophageal) requiring urgent operation (group 1). The remaining 42 patients (84%) did not have a mediastinal injury (group 2). There was no difference between groups with respect to blood pressure, pulse, respiratory rate, pH, base deficit, or initial chest tube output. There was one death in each group, and three complications in group 2. Patients may appear stable following a transmediastinal gunshot wound, even when they have life-threatening injuries. There is no difference in vital signs, blood gas, or hemothorax to indicate which patients have serious injuries. We advocate continued aggressive work-up of these patients to avoid missing an injury with disastrous consequences.

Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi–Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in 3D. Spine density was also measured at both time points. Our morphometric results show (1) the formation of new dendritic branches and spines 1 day following nicotine exposure, (2) new dendritic branches, but not spine density, remains relatively stable for at least 21 days, (3) the co-administration of SCH-23390 completely blocked nicotine-induced dendritic remodeling of MSNs at both early and late time points, suggesting the formation of new dendritic branches in response to nicotine is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Overall this study provides new insight into how nicotine influences the normal trajectory of adolescent brain development and demonstrates a persistent form of nicotine-induced neuroplasticity in the NAcc shell that develops rapidly and is D1DR dependent.

Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety-like behavior on single-trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety-like behavior in rats divided into high-anxiety and low-anxiety groups. Baclofen decreased locomotor behavior in high-anxiety rats. Baclofen alone failed to produce differences in anxiety-like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High- and low-anxiety groups also showed differences in single-trial nicotine-induced place preference. Only high-anxiety rats formed place preference to nicotine, while rats in the low-anxiety group formed no conditioned place preference. These results suggest that among adolescents, high-anxiety individuals are more likely to show preference for nicotine than low-anxiety individuals. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1352–1364, 2014.

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIs with reduced off-target activity (hERG IC5018 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 μM) and topo IV (IC50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.

Long-Evans hooded rats were given 5% alcohol (EtOH), 10% EtOH or tap water as sole fluid from postnatal day 21 (P21) to P70. The 10% EtOH group drank 26% less and 10% EtOH males gained 7.6% less weight than the tap water control group. There were no significant consumption or weight differences between 5% EtOH and control subjects. At P105, 35 days after the conclusion of alcohol dosing, we conducted several behavioral tests. Males in the 10% group drank 67.8% more alcohol than controls in a two-bottle preference test. On a DRL-20-s operant reinforcement schedule, a difficult timing task dependent upon limbic structures, subjects in the 10% group had higher barpress rates, while those in the 5% group had lower barpress rates than controls. On this task, 10% females received fewer reinforcements, while both 5% and 10% males earned more reinforcements than controls. Efficiency ratios were lowest for 10% females and highest for 5% males. Males in the 5% group had shorter latencies than controls to find the platform in a Morris water maze and were significantly more likely than controls to initially find the platform. These data suggest that EtOH consumption during periadolescent development may have long-lasting neurobehavioral effects.

The objective of this study was to determine prospectively which risk factors require cardiac monitoring for blunt cardiac injury (BCI) following blunt chest trauma. All patients who sustained blunt chest trauma had an electrocardiogram (ECG) on admission to our urban level I trauma center. Those with ST segment changes, dysrhythmias, hemodynamic instability, history of cardiac disease, age > 55 years, or a need for general anesthesia within 24 hours (group 1) were admitted to the intensive care unit (ICU) for 24 hours where they were subjected to serial ECGs, creatinine phosphokinase (CPK) assays, and echocardiography (ECHO). Those with only mechanism for BCI, i.e., none of the above risk factors (group 2), were admitted to a nonmonitored bed and had a follow-up ECG 24 hours later. A series of 315 patients were admitted with blunt chest trauma during a 17-month period; 144 patients were in group 1 and 171 in group 2. Overall, 22 patients were diagnosed as BCI (+BCI), defined as evolving ST segment changes, dysrhythmias, a CPK-MB index of > 2.5, or hemodynamic instability. Of the 18 +BCI patients in group 1, all were symptomatic (i.e., none was included solely for a cardiac history, age, or need for general anesthesia). Six of these patients required treatment for dysrhythmias, hypotension, or pulmonary edema; one of whom died. Four patients with +BCI were in group 2 and had ECG changes at 24 hours; none of these four had any sequelae from their +BCI. None of the ECHOs demonstrated abnormal wall motion. Patients who sustain blunt chest trauma with a normal ECG, normal blood pressure, and no dysrhythmias on admission require no further intervention for BCI. Patients with ST segment changes, dysrhythmias, or hypotension following blunt chest trauma should be monitored for 24 hours, as this subgroup occasionally requires further treatment for complications of BCI. ECHO adds nothing as a screening test.

This study was undertaken to confirm the safety and efficacy of diagnostic peritoneal lavage (DPL) for trauma patients. A prospectively maintained database of all DPLs performed in the past 75 months was analyzed. A red blood cell count of 100,000/mm(3) was considered positive for injury in blunt trauma; 10,000/mm(3) was considered positive for peritoneal penetration in penetrating trauma. Information relative to type of injury, DPL result, laparotomy result and complications, was analysed to determine if DPL was more or less suited to any specific indication or type of patient. Over a 75 month period, 2501 DPLs were performed at our urban level I trauma center. The overall sensitivity, specificity and accuracy for the above thresholds were 95, 99 and 98%. The majority (2409, 96%) were performed using percutaneous or "closed" seldinger technique. Ninety-two (4%) were performed using open technique because of pelvic fractures, previous scars and pregnancy. Open DPL was less sensitive than closed DPL in patients who sustained blunt trauma (90 vs 95%) but slightly more sensitive in determining penetration (100 vs 96%). Overall, there were 21 complications (0.8%). There was no difference in complication rate between open and closed DPL. In conclusion, DPL remains a highly accurate, sensitive and specific test with an extremely low complication rate. It can be performed either open or closed with comparable results. We recommend its use in the evaluation of both blunt and penetrating trauma.

Anthropomorphic carotid bifurcation flow phantoms that incorporate different stenotic geometries within the internal carotid artery have been developed. This technique produces high-fidelity, life-size vascular flow models that are compatible with magnetic resonance techniques. The models, in conjunction with a computer-controlled flow pump, address the need for a complex vascular geometry that can be used to verify magnetic resonance angiography (MRA) techniques that quantify stenosis severity and blood flow. Stenotic geometries, with up to 80% diameter reduction, have been fabricated in two different phantom materials. Plastic phantoms provide a durable, rigid geometry where the absolute dimensions of the model are well known. Agar gel phantoms provide tissue-like signal (T1, T2) up to the lumen boundary and are also compatible with ultrasound techniques. In this paper the technique to produce vascular flow phantoms is outlined and the compatibility of these phantoms with MRA techniques is demonstrated. J. Magn. Reson. Imaging 1999;10:533-544.

To determine whether cocaine administration during a developmental period corresponding to middle and late childhood results in enduring changes in behavior, we injected rats with 5 or 20 mg/kg/d of cocaine s.c. from weaning (postnatal day 21; P21) through P60; controls included uninjected and vehicle-injected controls. The 20-mg/kg dose resulted in a transient, male-limited weight reduction for the last 10 days of dosing, which rapidly recovered to normal after dosing ceased. Approximately 5 months later, the subjects were given a brief battery of behavioral tests. Female 20-mg subjects received fewer reinforcements than control subjects in a DRL-20 task. Female subjects also displayed altered patterns of cocaine-stimulated changes in open-field activity. No significant lasting effects were seen in males. These data suggest that the central nervous system retains sufficient plasticity into later development to produce long-lasting functional changes in response to drug administration and that cocaine consumption during the rat equivalent of childhood produces very long lasting plastic changes in behavior.

We investigated the utility of maternal cotinine concentration as a predictor of preterm and small-for-gestational-age (SGA) deliveries. Subjects were randomly selected from antenatal clinics, and their serum cotinine concentrations at approximately 16 weeks' gestation were compared with self-reports of smoking. The value of these measures in predicting preterm and SGA deliveries was examined, using likelihood ratios and logistic regression, for 845 women with singleton, live births. Smoking status alone (defined by self-report or cotinine) only weakly predicted preterm or SGA delivery. Self-reported moderate/high smoking (top 15% of smokers) had a likelihood ratio (LR) of 2 and a positive predictive value (PPV) of 17%. In contrast, moderate/high cotinine concentration (top 15% of smokers) had an LR of 5 and a PPV of 33%. The predictive value of cotinine was independent of associated maternal characteristics. Cotinine concentration may therefore be a useful predictor of poor pregnancy outcome, and should be considered as a screening tool.

The performance of a simple colorimetric assay for urinary nicotine metabolites to assess smoking status in diabetic subjects (n = 251) was investigated. Several variations of the colorimetric assay and a qualitative extraction procedure were evaluated in comparison with a cotinine immunoassay as the “gold standard.” Among these, the best overall performance was achieved with the qualitative test (sensitivity 95%; specificity 100%). The quantitative measurement of total nicotine metabolites performed less well (sensitivity 92%; specificity 97%) but could be improved by incorporating a blank extraction (sensitivity 98%; specificity 98%). Allowance for diuresis appeared to offer no advantage over the other methods. These results support previous findings regarding the use of these colorimetric procedures in nondiabetic subjects and, contrary to other recent observations, their performance was not impaired in diabetic patients.

Background: To determine which patients need a "one-shot" intravenous pyelogram (IVP) before laparotomy for penetrating abdominal trauma. Study Design: Over a 15-month period, 240 laparotomies were performed for penetrating trauma at our urban level I trauma center. Prospectively collected data included clinical suspicion of genitourinary injury, results of preoperative IVP, intraoperative findings, and operative decisions influenced by the IVP. Results: Preoperative IVP was performed in 175 patients (73%). Of these, 71 (41%) had suspicion of a renal injury based on the presence of a flank wound or gross hematuria. The IVP was believed to influence operative decisions in six patients, all in this group. Each of these six patients had either a shattered kidney or a renovascular injury and had a nephrectomy performed with the knowledge that a normal functioning kidney was present on the contralateral side. No patient without a flank wound or gross hematuria had an IVP that was judged to be helpful intraoperatively. Preoperative IVP was helpful only in patients with flank wounds or gross hematuria. Nephrectomy was performed in two additional patients who did not undergo IVP, both of whom presented in shock. Conclusions: Routine preoperative IVP is not necessary in all patients undergoing laparotomy for penetrating trauma. The number of IVPs can be safely reduced by 60% if the indications are narrowed to include only those stable patients with a flank wound or gross hematuria.

Background: It has previously been shown that 98% of gunshot wounds that penetrate the peritoneal cavity cause injuries that require surgical repair. Many gunshot wounds in the vicinity of the abdomen (GSWA) may actually be tangential and not penetrate the peritoneal cavity at all. Patients with such wounds may not require laparotomy. It is important to determine which patients with a potential tangential GSWA actually have penetration of the peritoneal cavity to minimize negative laparotomies. This study was undertaken to determine the sensitivity, specificity, and accuracy of diagnostic peritoneal lavage (DPL) in the determination of peritoneal penetration for patients who sustain GSWA. Methods: DPI, was performed for all patients who had sustained a GSWA in whom peritoneal penetration was unclear, i.e., patients whose GSWA appeared to be tangential, thoraco-abdominal, or transpelvic and for whom a clear indication for laparotomy (shock, peritonitis, etc.) did not exist. Our threshold for a positive DPL, was 10,000 red blood cells (RBC)/mm 3 . A prospective data base was kept with information on the location of the wound, DPI, result, findings at laparotomy, and outcome. Results: During a 4-year period, 429 consecutive DPLs were performed for GSWA at our urban Level I trauma center. One hundred fifty DPLs were positive, with more than 10,000 RBC/ mm 3 . Six of these patients were found to have no peritoneal penetration at laparotomy (false-positive). The remaining 144 patients with positive DPLs were found to have operative injuries (true-positive). Of the 279 patients with DPL counts less than 10,000 RBC/mm 3 , 2 developed indications for laparotomy and were found to have intraperitoneal injuries (false-negative). The remaining 277 patients had no peritoneal injuries (true-negative). This was demonstrated either by laparotomy done for another indication In = 7) or by uneventful inpatient observation for 24 hours In = 270). The sensitivity, specificity, and accuracy of DPL in determining peritoneal penetration in GSWA is therefore 99, 98, and 98%, respectively. Conclusion: For patients who sustain GSWA for whom peritoneal penetration is unclear, DPL is a sensitive, specific, and accurate test to determine the need for laparotomy. It remains our test of choice when confronted with these patients.

A typical Data Structures (CS 2) course covers a wide variety of topics: elementary algorithm analysis; data structures including dynamic structures, trees, tables, graphs, etc. ; large programming projects; and more advanced object-oriented concepts. Integrating these topics into assignments is a challenging task; educators often duplicate work done by others in re-inventing such assignments. At the same time, these assignments and large programs take time to develop and are often changed from semester to semester to preclude cheating. We report on a project that provides modules containing many kinds of programming and lab assignments which can be re-used across semesters with accessible and exciting application-oriented materials. Our project is a collaboration between a research and teaching oriented private university, a teaching oriented public university, and a teaching oriented historically black university. This helps ensure that the modules will be accessible to nearly all student populations. The modules developed are available electronically as hyper-text documents.

Adolescents have an increased vulnerability to nicotine and anxiety may play a role in the development of nicotine abuse. One possible treatment for anxiety disorders and substance abuse is the GABAB agonist, baclofen. The aim of the present study was to determine the effect of anxiety-like behavior on single-trial nicotine conditioned place preference in adolescent rats, and to assess the action of baclofen. Baclofen was shown to have effects on locomotor and anxiety-like behavior in rats divided into high-anxiety and low-anxiety groups. Baclofen decreased locomotor behavior in high-anxiety rats. Baclofen alone failed to produce differences in anxiety-like behavior, but nicotine and baclofen + nicotine administration were anxiolytic. High- and low-anxiety groups also showed differences in single-trial nicotine-induced place preference. Only high-anxiety rats formed place preference to nicotine, while rats in the low-anxiety group formed no conditioned place preference. These results suggest that among adolescents, high-anxiety individuals are more likely to show preference for nicotine than low-anxiety individuals.

The Book of Mormon annals open in an ancient Near Eastern context. The archaeological-historical context is carefully outlined here within a systematic chronology that is tied to fixed, absolute dates of recorded astronomical events—particularly those from cuneiform eponym calendars. The resultant matrix allows those early Book of Mormon events to be understood in a rational, familiar, and meaningful way, i.e., in a biblical context. In addition, an excursus is devoted to understanding the Arabia of the Book of Mormon as the Lehite exiles must have known it. Throughout it is clear that the world depicted by the Book of Mormon dovetails remarkably well with what we know of the ancient Near East.

Background To demonstrate the safety and efficacy of 65°C (149°F) centrally administered intravenous fluid (CIVF) compared to conventional 40°C (104°F) CIVF in the treatment of hypothermia. Method Ten beagles (9–13 kg) were prospectively randomized to receive 65°C or 40°C CIVF. They were anesthetized and data were collected at baseline, during hypothermia, and after 1 and 2 hours of rewarming. The plasma free/total hemoglobin (PFHb/THb) was measured to detect hemolysis. Each subject was cooled to 30°C (86°F) and then received either 65 C or 40°C CIVF through a specialized catheter in the superior vena cava for 2 hours in addition to conventional rewarming techniques. All subjects survived 7 days, after which they were sacrificed and a complete autopsy was performed. Results The rewarming rate was 3.7°C/hr in the 65°C CIVF group and 1.75°C/hr in the 40°C CIVF group. Core temperatures were significantly different after 1 hour (33.4° ± 0.77° versus 31.7° ±0.57°, P Conclusion CIVF at 65°C is a safe and effective means of treating hypothermia.

Pregnant Long-Evans hooded rats were dosed with 5, 10, 20, or 40 mg/kg/d cocaine from GD7 through GD20; pairfed/vehicle-injected, and uninjected controls were included. At birth, representative pups from each litter were killed by decapitation and serum assayed for prolactin and growth hormone via radioimmunoassay. Prolactin levels were significantly reduced on P1 in offspring which had been dosed prenatally with 20 or 40 mg/kg/d, while growth hormone levels were significantly lower than control levels in the 5 and 10 mg/kg/d animals. Pairfed/vehicle controls did not differ from uninjected controls on levels of either hormone. These endocrine changes associated with cocaine dosing may affect subsequent development of the organism.

Pregnant Long-Evans hooded rats were dosed with 1, 5, or 10 mg/kg per day naloxone from gestational day 7 (GD7) through GD20. The control groups included both uninjected animals and injected animals pairfed to the 10-mg dose animals. At birth, all litters were culled to four males and four females, and fostered to undosed surrogate dams. Prenatal naloxone exposure produced changes in body weight development, pain sensitivity, and motor behavior in the offspring. Five and 10 mg/kg naloxone increased adult body weights in females only, as did the pairfeeding condition. The 10 mg/kg naloxone altered pain sensitivity (in males only) as measured by the tail flick test. Animals in the 1 mg/kg dose condition habituated more rapidly than uninjected (UN) subjects in the open field, and showed less activity than UNs as they matured. Bar pressing rates were reduced in the 10 mg/kg dose males in a visual discrimination task, while 10 mg/kg males and females showed reduced bar pressing rates on differential reinforcement of low rates of responding (DRL). These findings confirm that prenatal exposure to naloxone alters some aspects of neurobehavioral development in the rat, and are consistent with the hypothesis that 1 mg/kg prenatally may increase opiate function in offspring, while 10 mg/kg prenatally may decrease opiate functioning in the offspring.

For 3 yr (1989–1991) we examined effects of different integrated pest management (IPM) programs on populations of mites in an apple orchard in Nova Scotia, Canada. The stage 1 IPM program involved pest monitoring and application of insecticides (phosmet, pirimicarb, Bacillus thuringiensis var. kurstaki Berliner + one-tenth the recommended rate of cypermethrin) known to be harmless or slightly harmful to the phytoseiid predator Typhlodmmus pyri Scheuten. With the stage 2 program, most insecticide applications were replaced by alternatives such as insecticidal soap, insect pathogens, and insect growth regulators. In stage 1 and stage 2 plots, apple scab, Venturia inaequalis (Cke.) Wint., was controlled either with captan, a fungicide that is harmless to phytophagous mites and T. pyri , or with metiram, a fungicide that is slightly harmful to phytophagous mites and moderately harmful to T. pyri . In June and July 1989, densities of European red mite, Panonychus ulmi (Koch), and apple rust mite, Aculus schlechtendali (Nalepa), were too high (maximum 7.6 to > 100 per leaf) to be controlled by the low numbers of T. pyri (

a b s t r a c t The insular cortex has emerged as a novel target for nicotine addiction research. One unresolved question about the insular cortex is whether its neurons exhibit nicotine-induced dendritic remodeling similar to other brain regions implicated in nicotine addiction. To test this question, Long-Evans rats were admin- istered nicotine via osmotic pump for two weeks. Thirty-seven days following the end of nicotine dosing, rats were sacrificed for Golgi-Cox staining and pyramidal neurons from the rostral agranular insular cor- tex were digitally reconstructed in three dimensions. Results from morphometric analyses revealed an increased complexity of dendrites in the insular cortex following nicotine. Increases were found for both total dendrite length and number of bifurcations. Sholl analyses revealed these changes depended on the distance from the soma, with the most prominent changes distributed at distal points along the dendritic tree. A follow-up comparison of length and bifurcation measurements from Sholl analyses suggested that new dendritic branches, rather than growth of existing dendrites, most likely contributed to overall changes in complexity. No change in dendrite morphology was found for apical dendrites. Together, these results show the insular cortex is a target for neuroplasticity following nicotine exposure.

Three different methods for estimating the percentage of reduction in the diameter of the internal carotid artery (ie, stenosis) have been proposed in the literature. Further comparisons of the methods were carried out with the intent of recommending a current standard for determining the percentage of stenosis from angiograms. Angiograms from 112 patients were obtained. For each angiogram, stenosis was estimated in the manner of the European Carotid Surgery Trial (ECST method), the North American Symptomatic Carotid Endarterectomy Trial (NASCET method), and by a method using the common carotid artery lumen diameter (CC method). Although there is much discrepancy among the estimates of stenosis arising from the three different methods for any particular patient, it is possible to predict (on average) the percentage of stenosis from one method to another. The relationship between the NASCET and CC methods is linear, with a mean ratio of distal internal carotid artery to common carotid diameter of 0.62 (SD of 0.11). The variability in the diameter of the common carotid artery lumen stabilizes only beyond 2.5 common carotid diameter units (approximately 20 to 30 mm by conventional angiography) proximal to the bifurcation. Unexpectedly, the relationships between both the ECST and NASCET methods and ECST and CC methods were parabolic (P < .001). The reasons underlying these departures from linearity are uncertain. The comparability of our results with those reported in the literature regarding the CC and NASCET methods provides further evidence of the reproducibility of methods measuring anatomic features that can be visualized on an angiogram. Disease of the internal carotid artery is one of the important causes of ischemic symptoms. Measuring the narrowest portion of the internal artery relative to the normal portion of the same artery, well beyond the bulb, is a logical method. Moreover, benefits of carotid endarterectomy for patients with 70% to 99% stenosis as determined by the NASCET method have been well established in a clinical trial. Converting from the NASCET method to the CC method, given that the CC method is neither superior nor easier to calculate, is not recommended.

A turbine flow sensor for MR flow experiments has been evaluated using reference volume-flow rate measurements obtained using an electromagnetic (EM) flow meter measurements and simultaneous phase contrast (PC) MR acquisitions. After calibration, the device was found to have accuracy (compared with the EM flow meter), linearity, and precision of better than +/- 1%, +/- 3.5%, 3.5%, respectively, in constant flow mode (0 to 30 ml s-1). The frequency response of the flow sensor was flat (within +/- 10%) up to 13.9 Hz. Volume-flow rate measurements on constant and simulated physiologic flow waveforms were in close agreement with both the electromagnetic (EM) flow meter and the gated MR PC estimates.

Work in our laboratory has revealed autonomic and/or behavioral sensitivity of mice, rats, and a domestic fowl to extremely-low-frequency (ELF) or nominally static magnetic (B) fields at flux densities between 250 and 1700 FT (rms). To extend our work, an automated exposure and data-acquisition system was used with the technique of conditional suppression to assess behavioral sensitivity to time-varying B fields. Each of five rats was exposed aperiodically to a B field during 3 min warning periods that terminated in a brief electric shock. The difference between rates of lever pressing during B-field warning periods and rates during immediately antecedent, 3 min control periods was analyzed at frequencies of 7, 16, 30, 60, and 65.1 Hz. To produce equivalent induced voltages in the rat at each frequency, graded flux densities were established that ranged from 1900 FT at 7 Hz to 200 FT at 65.1 Hz. Analysis of differences in lever-pressing rates revealed that in a given session of testing the rats would increasingly suppress responding when exposed to a B field, but this trend was independent of frequency. This experiment provides evidence of behavioral sensitivity by a mammal to an ELF magnetic field. 01994 Wiley-Liss, Inc.*

A total of 26 patients with locally advanced bladder cancer received chemotherapy consisting of cisplatin, methotrexate and vinblastine. Radical cystectomy was performed in 24 of 26 patients (92%) receiving neoadjuvant therapy, with a pathological complete response in 6 (23%) and pathological partial response in 1 (4%) for an overall response rate of 35% (95% confidence limits 17 to 56%). The overall median survival time is currently undefined. Of the patients 15 (58%) are alive with a median followup of 48.6 months. Response rates from this neoadjuvant chemotherapy appear to be similar to those reported with methotrexate, vinblastine, doxorubicin and cisplatin, and may represent a therapeutically equivalent regimen but neither may be curative in the majority of the patients.

The influence of nutrient limitation on the quality of Scenedesmus acutus as food for Daphnia obtusa is examined. The nature and degree of nutrient limitation greatly influences the rate at which Daphnia converts Scenedesmus biomass into herbivore biomass. From high to low quality, Scenedesmus food is ranked moderately N limited, severely N limited, and severely P limited. Even a very high concentration (3 mg DW.liter-I) of low quality food yields slow Daphnia growth, and it appears that no amount of low quality food would support rapid Daphnia growth. Food-limited animals display lowered intercepts of length-weight regressions (prereproductive females), reduced rates of biomass gain (both males and females), increased ages at first reproduction, lowered clutch sizes, increased mortality, and lowered reproductive rate. The N and P contents and the N : P ratio of Scenedesmus all vary considerably under N and P limitation, while the N content (and possibly P content) of Daphnia is less variable and the N: P ratio of Daphnia is essentially constant. Clearance and feeding rates are lower on severely P-limited cells than on severely N-limited cells. These results indicate that the mineral nutrition of their algal food may influence the demographics of zooplankton herbivores to a degree not before realized.

HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H inhibitors.

KEY WORDS dendrites; prefrontal cortex; infralimbic; adolescent; cerebral hemi-spheres; functional laterality; Sprague–Dawley rats; developmentABSTRACT This study investigated the dendritic morphology of neurons located inthe right and left basolateral amygdala (BLA) and infralimbic (IL) cortex followingchronic nicotine exposure during adolescence or adulthood. Sprague–Dawley rats wereadministered subcutaneous injections of nicotine (0.5 mg/kg; free base) or saline threetimes per week for 2 weeks (six total injections). The dose period began on either post-natal day (P) 32 (adolescent) or P61 (adult). Twenty days following the end of dosing,brains were processed for Golgi-Cox staining, and dendrites from principal neurons inthe BLA and pyramidal neurons in the IL were digitally reconstructed in three dimen-sions. Morphometric analysis revealed a contrasting pattern of BLA dendritic morphol-ogy between the adolescent and adult pretreatment groups. In the adult control group,basilar dendritic length did not differ with respect to hemisphere. Nicotine induced ro-bust hemispheric asymmetry by increasing dendritic length in the right hemisphereonly. In contrast, adolescent nicotine exposure did not produce significant alteration ofbasilar dendritic morphology. There was, however, an indication that nicotine eliminateda naturally existing hemispheric asymmetry in the younger cohort. At both ages, nico-tine produced a reduction in complexity of the apical tree of principal neurons. Chronicnicotine did not affect the dendritic morphology of pyramidal neurons from the IL in ei-ther age group, indicating another dimension of anatomical specificity. Collectively, thesedata implicate the BLA as a target for lasting neuroplasticity associated with chronicnicotine exposure. Further, hemispheric differences in dendritic morphology were uncov-ered that depended on the age of nicotine exposure, a finding that underscores the im-portance of considering laterality when investigating neurodevelopmental effects of drugexposure. Synapse 64:754–764, 2010.

A simple electronic device to detect location or to track locomotion of small animals is described. The device is based on anantenna effect—it responds to a change in capacitance as the body of the animal passes between an antenna and one of a series of contact plates. A digital address system is incorporated that is capable of electronically polling the contact plates according to instructions from a data-acquisition system (DAS). Any DAS capable of generating an address of two bits or more and of reading a one-bit data line may be employed. The device is ideal for mazes or other apparatus in which the exclusion of stereotypical behaviors is desired.

p70 ribosomal S6 kinase (p70S6K) is a downstream effector of the mTOR signaling pathway involved in cell proliferation, cell growth, cell-cycle progression, and glucose homeostasis. Multiple phosphorylation events within the catalytic, autoinhibitory, and hydrophobic motif domains contribute to the regulation of p70S6K. We report the crystal structures of the kinase domain of p70S6K1 bound to staurosporine in both the unphosphorylated state and in the 3′-phosphoinositide-dependent kinase-1-phosphorylated state in which Thr-252 of the activation loop is phosphorylated. Unphosphorylated p70S6K1 exists in two crystal forms, one in which the p70S6K1 kinase domain exists as a monomer and the other as a domain-swapped dimer. The crystal structure of the partially activated kinase domain that is phosphorylated within the activation loop reveals conformational ordering of the activation loop that is consistent with a role in activation. The structures offer insights into the structural basis of the 3′-phosphoinositide-dependent kinase-1-induced activation of p70S6K and provide a platform for the rational structure-guided design of specific p70S6K inhibitors.

Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.

The first known sex pheromone for the family Miridae is reported for the mullein bug,Campylomma verbasci (Meyer) (Heteroptera: Miridae). Extracts of and Porapak Q-trapped volatiles from females were attractive to males in field bioassays. Butyl butyrate and hexyl butyrate were the predominant compounds in the females' volatiles, but these compounds previously had been found to be inactive when released alone or in combination. Butyl butyrate in combination with an isolated trace chemical, (E)-crotyl butyrate (which was inactive alone), rivaled the attraction elicited by five live females. When synthetic butyl butyrate and (E)-crotyl butyrate in a 16: 1 ratio were released at 91 or 183 μg/day, they comprised an effective attractant for male bugs.

Objective: To determine if patients who present with a history of loss of consciousness who are neurologically intact (minimal head injury) should be managed with head computed tomography (CT), observation, or both. Methods: We prospectively studied patients who presented to our urban Level I trauma center with a history of loss of consciousness after blunt trauma and a Glasgow Coma Scale score of 15. All patients underwent CT of the head and were subsequently admitted for 24 hours of observation. Results: A total of 1,170 patients with minimal head injury were studied during a 35-month period. All patients had Glasgow Coma Scale scores of 15 on arrival and had a history of either loss of consciousness or amnesia to the event. Two hundred forty-seven patients (21.1%) were intoxicated with drugs or alcohol on admission; 39 patients (3.3%) had abnormalities detected by CT, including 18 intracranial bleeds; 21 patients (1.8%) had changes in therapy as a direct result of their CT results, including 4 operative procedures. No patient with negative CT results deteriorated during the subsequent observation period. Conclusion: CT is a useful test in patients with minimal head injury because it may lead to a change in therapy in a small but significant number of patients. Subsequent hospital observation adds nothing to the CT results and is not necessary in patients with isolated minimal head injury.

Male mullein bugs, Campylamma verbasci (Meyer), were captured in 27 traps baited with live females in the fall within 10 apple orchards in the Okanagan Valley, British Columbia. When the catches of males from 14 September to 13 October 1987 were compared with limb tap samples of nymphs in the following spring, the relationships in the trap trees ( r 2 = 0.61) and trees adjacent to the trap trees ( r 2 = 0.56) were significant. Similar positive relationships occurred for four shorter trapping intervals but not for the final interval from 3 to 13 October, when trap catches were low. These results suggest that when a synthetic pheromone is available for this mirid, prediction of economic injury levels may be made in the fall, 6-8 mo before egg hatch. Limb tap sampling in the spring could then be concentrated in orchards with the highest probability of damage to the crop.

Cozart Bioscience Limited has developed novel lateral flow technology that allows the detection of drugs of abuse in biological fluids and suspect powders. This paper describes the application of this technology for the detection of 3,4-methylenedioxymethamphetamine (MDMA) in oral fluid. Samples (N = 370) were obtained from the analytical laboratory at Cozart Bioscience Limited following their routine analysis for drugs of abuse. Oral fluid samples were screened for the presence of MDMA and methamphetamine using the Cozart® RapiScan System (CRS) and then confirmed for the presence of amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA, and MBDB) by gas chromatography-mass spectrometry (GC-MS). In addition to the detection of MDMA and methamphetamine, the CRS cross-reacts with high levels of amphetamine to give a positive result. One hundred and twenty-one samples screened positive using the CRS. Six of these samples were confirmed negative for MDMA and methamphetamine, but contained very high levels of amphetamine. Employing a screening cutoff of 45 ng/mL for the CRS and a confirmation cutoff of 30 ng/mL for GC-MS, the sensitivity, specificity, and accuracy were 96.6, 96.8, and 96.8%, respectively. When applying the Substance Abuse and Mental Health Services Administration recommended confirmation cutoff for amphetamines of 50 ng/mL, the sensitivity, specificity, and accuracy increased marginally to 98.3, 96.9, and 97.3%, respectively.

Conditioned place preference (CPP) is often more effectively produced with nicotine using a biased procedure. Interpretation of results can be problematic, however, given that doses that produce CPP in rats have acute anxiolytic and residual anxiogenic effects. We tested three groups of male rats in a biased, 2-chambered apparatus. Over eight conditioning days, one group (paired group) received four alternating injections of nicotine paired with the non-preferred (white) chamber and of saline in the preferred (black) chamber. A second group (counterbalanced group) received two nicotine injections each paired with the black and white chambers, with saline pairings on alternate days. A third group (saline control) received saline injections paired with both chambers. Following conditioning, the paired group spent significantly more time in the initially non-preferred chamber relative to saline-treated controls, suggesting CPP. The counterbalanced group did not show a significant preference shift, providing evidence that the observed preference shift in the paired group was not due to a drug-induced unconditioned reduction in aversion. Although this finding is consistent with the notion that nicotine produced CPP through its rewarding effects, we cannot discount the possibility of a conditioned reduction in aversion to the non-preferred chamber. For the paired group, a negative correlation was found between time spent in the white chamber before conditioning and preference shift following conditioning, suggesting that animals showing greater initial aversion to a non-preferred context are more likely to form CPP.

Adolescent alcohol use is common and evidence suggests that early use may lead to an increased risk of later dependence. Persisting neuroadaptions in the amygdala as a result of chronic alcohol use have been associated with negative emotional states that may lead to increased alcohol intake. This study assessed the long-term impact of ethanol consumption on levels of several basolateral amygdala mRNAs in rats that consumed ethanol in adolescence or adulthood. Male Long-Evans rats were allowed restricted access to ethanol or water during adolescence (P28, n = 11, controls = 11) or adulthood (P80, n = 8, controls = 10) for 18 days. After a sixty day abstinent period, the brain was removed and sections containing the basolateral amygdala were taken. In situ hybridization was performed for GABA A α 1 , glutamic acid decarboxylase (GAD 67 ), corticotropin releasing factor (CRF), and N-methyl- d -aspartate (NMDA) NR2A mRNAs. A significant decrease was observed in GABA A α 1 , GAD 67 , and CRF, but not NR2A, mRNAs in adult rats that consumed ethanol in comparison to controls. No significant changes were seen in adolescent consumers of ethanol for any of the probes tested. A separate analysis for each probe in the piriform cortex ascertained that the changes after ethanol consumption were specific to the basolateral amygdala. These results indicate that chronic ethanol consumption induces age-dependent alterations in basolateral amygdala neurochemistry.

We examined the acute rewarding as well as the long-term psychomotor altering effects of nicotine in early adolescent and adult male Sprague-Dawley rats. Place conditioning was used to examine nicotine-induced reward after a single drug pairing. A single pairing of nicotine with the initially non-preferred side of the place conditioning apparatus produced a conditioned place preference (CPP) in early adolescent but not adult animals. One month later, animals were given a nicotine challenge and locomotor activity observed in the open field to characterize age differences in the lasting alterations resulting from this single injection. Adult rats showed tolerance to the locomotor depressant effects of a low dose of nicotine whereas adolescent rats showed tolerance to a higher dose. Regardless of treatment group, animals tested during adolescence responded to the nicotine challenge with less hypoactivity when compared with animals tested as adults. The present results are in agreement with previous studies showing that early adolescent rats are more sensitive to nicotine's rewarding effects and are in accord with studies showing a unique profile of neurobehavioral alterations following nicotine exposure when compared with adults. Such findings are extended here by showing that these differences are seen following only a single pretreatment dose and persist for at least one month after pretreatment.

Adolescent nicotine exposure is associated with long-term use, and it has been suggested that this vulnerability to addiction may relate to lasting anxiogenic effects of the drug. However, few studies have addressed long-term effects of adolescent nicotine, and fewer yet have compared adolescent to adult exposure. Male and female Long-Evans rats continuously received nicotine bitartrate or sodium tartrate via osmotic mini-pumps over 15 days either during adolescence (p28-42) or adulthood (p85-99). Initial nicotine dose (free base) was either low (1 mg/kg/day) or high (2 mg/kg/day). Open field behavior and fear conditioning were assessed in adulthood, 1 month post-dosing. Animals pretreated with nicotine during adolescence showed less center time in a novel open field than sham controls. Conversely, the two nicotine doses differentially affected fear conditioning. Animals pretreated with low nicotine during adolescence demonstrated superior acquisition of the task compared to sham control animals; however, unlike either high nicotine-pretreated or sham control animals, they failed to extinguish the learned behavior. In contrast, animals pretreated during adulthood did not behave significantly different from sham controls on either task. Overall, nicotine-pretreatment during adolescence induced effects on behaviors related to fear and anxiety in adulthood, while comparable pretreatment during adulthood failed to produce significant residual effects.

Research has shown that cigarette use during pregnancy can result in increased fetal mortality, sudden infant death syndrome, and behavioral and attentional disorders during childhood. Neurochemical and behavioral consequences of prenatal nicotine exposure have been well documented although few studies have examined long-term behavioral consequences that persist into adulthood. In this study, fifty-eight male and female Long-Evans rats were exposed to chronic nicotine prenatally and postnatally via subcutaneous infusions (0.96 mg/kg/day) in the dam. Nicotine exposure continued in the pups via maternal milk until the dams' osmotic mini-pumps became exhausted at approximately postnatal day (P) 11. At weaning, animals were group housed until behavioral testing at P60 to assess spatial learning and memory in the Morris water maze (MWM). Mild deficits in spatial learning were observed in nicotine-exposed females. These behavioral differences were accompanied by significant reduction in weight gain of nicotine-exposed females beginning at puberty, suggesting a hormonal interaction. Long-term effects of nicotine exposure were less striking in males. Nicotine-exposed males had significantly slower swim speeds than controls, but latency to reach the hidden platform was equal between groups by the conclusion of testing. Weight gain in males did not differ between groups as a result of prenatal nicotine exposure.