Transfer of acquired practical skills from dry lab into live surgery using the avatera robotic system: An experimental study.

OBJECTIVE: To evaluate the transfer of the practical skills of robot-assisted surgery acquired in the dry-lab into a real live experimental setting for performing upper and lower urinary tract surgeries. MATERIAL AND METHODS: An in vivo experimental study design was utilized. Six urology trainees and fellows; two 2nd year trainees with no previous exposure to laparoscopic surgery (Group 1), two 4th year residents with medium exposure to laparoscopic surgery (Group 2) and two fellows trained to perform laparoscopic surgeries (Group 3) performed ureteral reimplantation into the bladder, pyeloplasty, and radical nephrectomy on three female pigs under general anesthesia. Prior to performing the requested procedures, each participant completed 10-14 h dry-lab robotic training acquiring skills in basic surgical tasks, such as suturing, cutting and needle passage. The recorded variables were the successful completion of the procedures, the console time, and the time to perform different steps and major complications. RESULTS: All procedures were completed successfully by all groups except the pyeloplasty by group 1 which was complicated by bleeding from the renal vein, and the procedure was abandoned. Group 3 achieved shorter console time for all successfully completed procedures and for separate surgical steps compared to all groups, followed by Group 2. The slowest group for all procedures and steps analyzed was Group 3. CONCLUSIONS: Although further clinical evidence is needed, the robotic-assisted urological procedures and the most challenging steps could be performed safely and effectively after proper training in the dry lab under mentor supervision according to our study.

European Association for Endoscopic Surgery (EAES) consensus on Indocyanine Green (ICG) fluorescence-guided surgery.

BACKGROUND: In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community. METHODS: An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021. RESULTS: A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications. CONCLUSIONS: Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.

Serious gaming and virtual reality in the multimodal training of laparoscopic inguinal hernia repair: a randomized crossover study.

BACKGROUND: The aim of this study was to assess the transferability of surgical skills for the laparoscopic hernia module between the serious game Touch Surgery™ (TS) and the virtual reality (VR) trainer Lap Mentor™. Furthermore, this study aimed to collect validity evidence and to discuss "sources of validity evidence" for the findings using the laparoscopic inguinal hernia module on TS. METHODS: In a randomized crossover study, medical students (n = 40) in their clinical years performed laparoscopic inguinal hernia modules on TS and the VR trainer. TS group started with "Laparoscopic Inguinal Hernia Module" on TS (phase 1: Preparation, phase 2: Port Placement and Hernia Repair), performed the module first in training, then in test mode until proficiency was reached. VR group started with "Inguinal Hernia Module" on the VR trainer (task 1: Anatomy Identification, task 2: Incision and Dissection) and also performed the module until proficiency. Once proficiency reached in the first modality, the groups performed the other training modality until reaching proficiency. Primary endpoint was the number of attempts needed to achieve proficiency for each group for each task/phase. RESULTS: Students starting with TS needed significantly less attempts to reach proficiency for task 1 on the VR trainer than students who started with the VR trainer (TS = 2.7 ± 0.6 vs. VR = 3.2 ± 0.7; p = 0.028). No significant differences for task 2 were observed between groups (TS = 2.3 ± 1.1 vs. VR = 2.1 ± 0.8; p = 0.524). For both phases on TS, no significant skill transfer from the VR trainer to TS was observed. Aspects of validity evidence for the module on TS were collected. CONCLUSION: The results show that TS brought additional benefit to improve performances on the VR trainer for task 1 but not for task 2. Skill transfer from the VR trainer to TS could not be shown. VR and TS should thus be used in combination with TS first in multimodal training to ensure optimal training conditions.

Robotic-assisted cholecystectomy is superior to laparoscopic cholecystectomy in the initial training for surgical novices in an ex vivo porcine model: a randomized crossover study.

BACKGROUND: Robotic-assisted surgery (RAS) potentially reduces workload and shortens the surgical learning curve compared to conventional laparoscopy (CL). The present study aimed to compare robotic-assisted cholecystectomy (RAC) to laparoscopic cholecystectomy (LC) in the initial learning phase for novices. METHODS: In a randomized crossover study, medical students (n = 40) in their clinical years performed both LC and RAC on a cadaveric porcine model. After standardized instructions and basic skill training, group 1 started with RAC and then performed LC, while group 2 started with LC and then performed RAC. The primary endpoint was surgical performance measured with Objective Structured Assessment of Technical Skills (OSATS) score, secondary endpoints included operating time, complications (liver damage, gallbladder perforations, vessel damage), force applied to tissue, and subjective workload assessment. RESULTS: Surgical performance was better for RAC than for LC for total OSATS (RAC = 77.4 ± 7.9 vs. LC = 73.8 ± 9.4; p = 0.025, global OSATS (RAC = 27.2 ± 1.0 vs. LC = 26.5 ± 1.6; p = 0.012, and task specific OSATS score (RAC = 50.5 ± 7.5 vs. LC = 47.1 ± 8.5; p = 0.037). There were less complications with RAC than with LC (10 (25.6%) vs. 26 (65.0%), p = 0.006) but no difference in operating times (RAC = 77.0 ± 15.3 vs. LC = 75.5 ± 15.3 min; p = 0.517). Force applied to tissue was similar. Students found RAC less physical demanding and less frustrating than LC. CONCLUSIONS: Novices performed their first cholecystectomies with better performance and less complications with RAS than with CL, while operating time showed no differences. Students perceived less subjective workload for RAS than for CL. Unlike our expectations, the lack of haptic feedback on the robotic system did not lead to higher force application during RAC than LC and did not increase tissue damage. These results show potential advantages for RAS over CL for surgical novices while performing their first RAC and LC using an ex vivo cadaveric porcine model. REGISTRATION NUMBER: researchregistry6029.

Functional outcomes after laparoscopic versus robotic-assisted rectal resection: a systematic review and meta-analysis.

Surgical resection is crucial for curative treatment of rectal cancer. Through multidisciplinary treatment, including radiochemotherapy and total mesorectal excision, survival has improved substantially. Consequently, more patients have to deal with side effects of treatment. The most recently introduced surgical technique is robotic-assisted surgery (RAS) which seems equally effective in terms of oncological control compared to laparoscopy. However, RAS enables further advantages which maximize the precision of surgery, thus providing better functional outcomes such as sexual function or contience without compromising oncological results. This review was done according to the PRISMA and AMSTAR-II guidelines and registered with PROSPERO (CRD42018104519). The search was planned with PICO criteria and conducted on Medline, Web of Science and CENTRAL. All screening steps were performed by two independent reviewers. Inclusion criteria were original, comparative studies for laparoscopy vs. RAS for rectal cancer and reporting of functional outcomes. Quality was assessed with the Newcastle-Ottawa scale. The search retrieved 9703 hits, of which 51 studies with 24,319 patients were included. There was a lower rate of urinary retention (non-RCTs: Odds ratio (OR) [95% Confidence Interval (CI)] 0.65 [0.46, 0.92]; RCTs: OR[CI] 1.29[0.08, 21.47]), ileus (non-RCTs: OR[CI] 0.86[0.75, 0.98]; RCTs: OR[CI] 0.80[0.33, 1.93]), less urinary symptoms (non-RCTs mean difference (MD) [CI] - 0.60 [- 1.17, - 0.03]; RCTs: - 1.37 [- 4.18, 1.44]), and higher quality of life for RAS (only non-RCTs: MD[CI]: 2.99 [2.02, 3.95]). No significant differences were found for sexual function (non-RCTs: standardized MD[CI]: 0.46[- 0.13, 1.04]; RCTs: SMD[CI]: 0.09[- 0.14, 0.31]). The current meta-analysis suggests potential benefits for RAS over laparoscopy in terms of functional outcomes after rectal cancer resection. The current evidence is limited due to non-randomized controlled trials and reporting of functional outcomes as secondary endpoints.

Endoscopic versus surgical treatment for infected necrotizing pancreatitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare outcomes of endoscopic and surgical treatment for infected necrotizing pancreatitis (INP) based on results of randomized controlled trials (RCT). BACKGROUND: Treatment of INP has changed in the last two decades with adoption of interventional, endoscopic and minimally invasive surgical procedures for drainage and necrosectomy. However, this relies mostly on observational studies. METHODS: We performed a systematic review following Cochrane and PRISMA guidelines and AMSTAR-2 criteria and searched CENTRAL, Medline and Web of Science. Randomized controlled trails that compared an endoscopic treatment to a surgical treatment for patients with infected walled-off necrosis and included one of the main outcomes were eligible for inclusion. The main outcomes were mortality and new onset multiple organ failure. Prospero registration ID: CRD42019126033 RESULTS: Three RCTs with 190 patients were included. Intention to treat analysis showed no difference in mortality. However, patients in the endoscopic group had statistically significant lower odds of experiencing new onset multiple organ failure (odds ratio (OR) confidence interval [CI] 0.31 [0.10, 0.98]) and were statistically less likely to suffer from perforations of visceral organs or enterocutaneous fistulae (OR [CI] 0.31 [0.10, 0.93]), and pancreatic fistulae (OR [CI] 0.09 [0.03, 0.28]). Patients with endoscopic treatment had a statistically significant lower mean hospital stay (Mean difference [CI] - 7.86 days [- 14.49, - 1.22]). No differences in bleeding requiring intervention, incisional hernia, exocrine or endocrine insufficiency or ICU stay were apparent. Overall certainty of evidence was moderate. CONCLUSION: There seem to be possible benefits of endoscopic treatment procedure. Given the heterogenous procedures in the surgical group as well as the low amount of randomized evidence, further studies are needed to evaluate the combination of different approaches and appropriate timepoints for interventions.

Implementation of feeding guidelines in infants at risk of intestinal failure.

OBJECTIVE: To implement feeding guidelines to reduce advancement time and the incidence of parenteral nutrition-associated liver disease (PNALD) among intestinal surgical infants requiring parenteral nutrition (PN). STUDY DESIGN: Feeding guidelines with higher initial enteral nutrition (EN) volume and specific advancement criteria were implemented for surgical infants aged <6 months. Preimplementation and postimplementation outcomes were compared. RESULTS: There were 57 preimplementation and 33 postimplementation infants. The initial EN volume improved from 10 to 20 ml kg(-1) day(-1) (P<0.001). Time to reach 50% of goal calories from EN decreased by a median of 6 days (P=0.012) without a change in necrotizing enterocolitis incidence after resuming feeding. PNALD incidence decreased from 70% to 48% (P=0.046), and median peak direct bilirubin (DB) decreased from 5.6 to 2.3 mg dl(-1) (P=0.011). CONCLUSION: Feeding guideline implementation with higher initial feeding volume was well tolerated and resulted in faster achievement of 50% goal EN calories. PNALD incidence and peak DB were reduced.

Monitoring anti-angiogenic therapy in colorectal cancer murine model using dynamic contrast-enhanced MRI: comparing pixel-by-pixel with region of interest analysis.

Sorafenib is a multi-kinase inhibitor that blocks cell proliferation and angiogenesis. It is currently approved for advanced hepatocellular and renal cell carcinomas in humans, where its major mechanism of action is thought to be through inhibition of vascular endothelial growth factor and platelet-derived growth factor receptors. The purpose of this study was to determine whether pixel-by-pixel analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is better able to capture the heterogeneous response of Sorafenib in a murine model of colorectal tumor xenografts (as compared with region of interest analysis). MRI was performed on a 9.4 T pre-clinical scanner on the initial treatment day. Then either vehicle or drug were gavaged daily (3 days) up to the final image. Four days later, the mice were again imaged. The two-compartment model and reference tissue method of DCE-MRI were used to analyze the data. The results demonstrated that the contrast agent distribution rate constant (K(trans)) were significantly reduced (p < 0.005) at day-4 of Sorafenib treatment. In addition, the K(trans) of nearby muscle was also reduced after Sorafenib treatment. The pixel-by-pixel analysis (compared to region of interest analysis) was better able to capture the heterogeneity of the tumor and the decrease in K(trans) four days after treatment. For both methods, the volume of the extravascular extracellular space did not change significantly after treatment. These results confirm that parameters such as K(trans), could provide a non-invasive biomarker to assess the response to anti-angiogenic therapies such as Sorafenib, but that the heterogeneity of response across a tumor requires a more detailed analysis than has typically been undertaken.

Host-Pathogen Interactions Between Phytophthora infestans and the Solanaceous Hosts Calibrachoa × hybridus, Petunia × hybrida, and Nicotiana benthamiana.

Late blight, caused by the pathogen Phytophthora infestans, is a devastating disease of potato and tomato, but can also damage other solanaceous hosts. To gain a better understanding of the interaction between P. infestans and these other hosts, the susceptibility of species in three solanaceous genera was investigated. Of the 10 Calibrachoa × hybridus cultivars tested, four were susceptible and six were resistant to the pathogen; susceptible cultivars supported only very limited growth of P. infestans. The majority of the Petunia × hybrida (petunia) cultivars were susceptible, although less so than susceptible potatoes or tomatoes. Two petunia cultivars displayed differential resistance, suggesting the presence of R genes against P. infestans. The hypersensitive response was present in susceptible, partially resistant, and resistant petunia-P. infestans interactions, but was predominant in the resistant interaction. Young petunias (3 weeks) were more susceptible than older petunias (7 weeks). Nicotiana benthamiana was susceptible to all four P. infestans isolates tested in the lab and became infected during a field epidemic. Several of these isolates were tested for the presence of the inf1 gene, and were found to have and express the gene in vitro. In addition, culture filtrate from these isolates contained 10-kDa proteins and also elicited the hypersensitive response in Nicotiana tabacum and N. benthamiana.

Tracking the concentration of heterotrophic plate count bacteria from the source to the consumer's tap.

The goal of this project was to quantify the concentration of heterotrophic plate count (HPC) bacteria within water reaching consumer's taps, and from the sources used by a major utility serving the City of Tucson, AZ. With this information, the amounts and sources of HPC bacteria consumed at the tap could be determined. Samples of water were collected on a monthly basis from two well fields, the CAVSARP recovery well field and Southern Avra Valley well field which serves as one of the groundwater sources for Tucson, AZ, and the distribution system which serves the same homes from which tap water was also tested. The average concentration of HPC in source waters within Southern Avra Valley Wells was 56 CFU/ml (range 1-1995/ml). From the CAVSARP recovery well field, corresponding values were 38 CFU/ml (1 to 502 CFU/ml). Unblended groundwater in the chlorinated distribution system averaged 22 CFU/ml (range 1-794). Blended water at the chlorinated distribution site averaged 47 CFU/ml (range 10-158). There was a major shift in the percentage of gram negative to gram-positive bacteria from the wells to the distribution system, to the tap. In the surface CAP source water, 76% of the bacteria were gram-negative compared to 27% gram-negative in the CAVSARP recovery wells. In contrast, Avra Valley wells contained 17% gram-negative bacteria. In both the Tucson groundwater distribution sites and blended distribution sites, the corresponding number of gram negative bacteria was 12%. Finally at the tap, only 0.2% of the bacteria were gram-negative. The average number of bacteria in household taps averaged 3072 HPC/ml and was equal or greater than 500 ml 68% of the time. This study shows that the number of HPC bacteria increases dramatically from the distribution system to the consumers tap. Thus, the major source of bacteria ingested by the average consumer in Tucson originates from bacteria within the household distribution system or the household tap, rather than from source waters or the distribution system. It is also clear that consumers' regularly consume more than 500 HPC/ml from drinking water taken from the household tap.

Behavioral treatment of hypertensive heart disease in African Americans: rationale and design of a randomized controlled trial.

African Americans experience higher morbidity and mortality than Whites do as a result of hypertension and associated cardiovascular disease. Chronic psychosocial stress has been considered an important contributing factor to these high rates. The authors describe the rationale and design for a planned randomized controlled trial comparing Transcendental Meditation, a stress-reduction technique, with lifestyle education in the treatment of hypertension and hypertensive heart disease in urban African Americans. They pretested 170 men and women aged 20 to 70 years over a 3-session baseline period, with posttests at 6 months. Outcomes included clinic and ambulatory blood pressure, quality of life, left ventricular mass measured by M-mode echocardiography, left ventricular diastolic function measured by Doppler, and carotid atherosclerosis measured by beta-mode ultrasound. This trial was designed to evaluate the hypothesis that a selected stress reduction technique is effective in reducing hypertension and hypertensive heart disease in African Americans.

Analysis of pesticides by LC-electrospray-MS with postcolumn removal of nonvolatile buffers.

Liquid chromatographic (LC) separations for pesticides and many other compounds make use of nonvolatile buffers in the mobile phase. The coupling of LC with mass spectrometry (MS) does not allow the use of nonvolatile buffers. Substitution with volatile buffers is possible, but changes in chromatographic retention and resolution can result even if pH is held constant. The postcolumn removal of nonvolatile buffers using a commercially available ion suppressor is evaluated for the analysis of carbamate pesticides. The suppressor efficiently removes phosphate anions from an LC mobile phase. Most compounds show an increased signal by factors of 2-7 after postcolumn phosphate removal. The suppressor has little effect on the chromatographic parameters of some compounds, while serious negative effects are noted for others. Some compounds will give poor results due to adsorption or retention by the suppressor. The results indicate that such a device may be useful for the LC-MS analysis of some pesticides using nonvolatile buffers.

Discrimination and instructional comprehension: guided discretion, racial bias, and the death penalty.

This study links two previously unrelated lines of research: the lack of comprehension of capital penalty-phase jury instructions and discriminatory death sentencing. Jury-eligible subjects were randomly assigned to view one of four versions of a simulated capital penalty trial in which the race of defendant (Black or White) and the race of victim (Black or White) were varied orthogonally. Dependent measures included a sentencing verdict (life without the possibility of parole or the death penalty), ratings of penalty phase evidence, and a test of instructional comprehension. Results indicated that instructional comprehension was poor overall and that, although Black defendants were treated only slightly more punitively than White defendants in general, discriminatory effects were concentrated among participants whose comprehension was poorest. In addition, the use of penalty phase evidence differed as a function of race of defendant and whether the participant sentenced the defendant to life or death. The study suggest that racially biased and capricious death sentencing may be in part caused or exacerbated by the inability to comprehend penalty phase instructions.

Purification and chemical modifications of hemoglobin in developing hemoglobin based oxygen carriers.

The efficacy of blood substitutes, as a whole, has been readily demonstrated, in animals as well as clinical studies. It is well known that stroma free hemoglobin (SF-Hb) is very toxic, due to effects on renal and coagulation functions and vascular tone. Several modifications have been made to the hemoglobin tetramer in an attempt to eliminate its toxicity. Conjugation, cross-linking, polymerization, and recombinant technology have all been used to reduce toxicity, while aiming to optimize the therapeutic value of hemoglobin based blood substitutes. The remaining issue seems to be the hypertensive response seen in many hemoglobin solutions. The cause of the hypertensive response, and hence what chemical modifications are suitable to alleviate it are still under debate.

Evaluation of electrospray transport CID for the generation of searchable libraries.

This paper reports the preliminary investigation of performance-based standard conditions that have been developed for electrospray ionization mass spectrometry. Using performance-based standard criteria, reproducible spectra can be obtained by CID in the electrospray-transport region and searched using a database created using the same performance criteria. To generate library-searchable mass spectra, the instrument was tuned to standard conditions that correspond to low, mid, and high fragmentation energies. The instrument was tuned using ion ratios relative to a given peak in a tune compound for each energy level. The library was evaluated using a set of 22 benzodiazepines. The CID libraries were found to be reproducible, both on the same instrument and on different instruments of the same type. Also, the libraries were found to be independent of flow rate and solvent system. The library was expanded to include 16 sulfonylurea herbicides and tested using spiked water samples. Performance of the library was tested over a concentration range of 2 orders of magnitude using sulfonylurea standards.

Ethics gap in surgery.

BACKGROUND: Discussion of ethical issues occurs much less often in the surgical than in the medical literature. The reasons for this "ethics gap" are unknown. METHODS: Our clinical faculty ranked the ethical and legal acceptability of four treatment options in two cases of surrogate decision making. Only one option in each case was ethically and legally unacceptable (treating despite objection by the surrogate decision maker). RESULTS: Surprisingly often, faculty mistakenly believed the ethically unacceptable option to be acceptable, and the legally unacceptable option to be acceptable. Surgeons were not ethically different from other physicians. Surgeons (19 of 31, 62%), however, were significantly (p < 0.05) more likely than internists (18 of 51, 35%) or pediatricians (4 of 18, 22%) to believe, mistakenly, that operating on the baby without parental consent was legally acceptable. CONCLUSIONS: This pilot study did not identify why the surgical literature contains a relative dearth of ethics discussion. Broader investigations are needed, because it is important that we understand the reasons for the gap. Surgeons' strong ethic of personal responsibility for patients' welfare should be transmitted to young trainees, a goal best achieved by discussing and writing about ethics. Moreover, our legal data suggest that a gap may also exist between surgeons and other physicians in understanding health law.

Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans.

BACKGROUND AND PURPOSE: African Americans suffer disproportionately higher cardiovascular disease mortality rates than do whites. Psychosocial stress influences the development and progression of atherosclerosis. Carotid intima-media thickness (IMT) is a valid surrogate measure for coronary atherosclerosis, is a predictor of coronary outcomes and stroke, and is associated with psychosocial stress factors. Stress reduction with the Transcendental Meditation (TM) program decreases coronary heart disease risk factors and cardiovascular mortality in African Americans. B-mode ultrasound is useful for the noninvasive evaluation of carotid atherosclerosis. METHODS: This randomized controlled clinical trial evaluated the effects of the TM program on carotid IMT in hypertensive African American men and women, aged >20 years, over a 6- to 9-month period. From the initially enrolled 138 volunteers, 60 subjects completed pretest and posttest carotid IMT data. The assigned interventions were either the TM program or a health education group. By use of B-mode ultrasound, mean maximum IMT from 6 carotid segments was used to determine pretest and posttest IMT values. Regression analysis and ANCOVA were performed. RESULTS: Age and pretest IMT were found to be predictors of posttest IMT values and were used as covariates. The TM group showed a significant decrease of -0.098 mm (95% CI -0. 198 to 0.003 mm) compared with an increase of 0.054 mm (95% CI -0.05 to 0.158 mm) in the control group (P=0.038, 2-tailed). CONCLUSIONS: Stress reduction with the TM program is associated with reduced carotid atherosclerosis compared with health education in hypertensive African Americans. Further research with this stress-reduction technique is warranted to confirm these preliminary findings.

Stress, stress reduction and hypercholesterolemia in African Americans: a review.

Psychological stress may directly contribute to the disproportionately high rates of coronary heart disease morbidity and mortality and its etiologic risk factors in African Americans. Specifically, acute and chronic stress have been shown to raise serum lipids and are associated with clinical coronary events. The mechanisms by which stress contributes to alterations in lipid levels are not fully known, but various pathways (ie, hormonal, dietary, etc) have been implicated. Traditional methods for reducing blood serum lipids include diet, drugs or both. These methods have been criticized because of issues of compliance, side effects, and cost. Because of these limitations, nondrug behavioral methods are recommended by the National Cholesterol Education Program as the first line of prevention and treatment for hypercholesterolemia and other risk factors. Research shows that CHD morbidity and mortality and major risk factors may be modifiable by behavioral intervention. Specifically, the Transcendental Meditation technique, an effective antidote to stress, reduces levels of major CHD risk factors including hypercholesterolemia, as well as blood pressure and smoking. Using an effective stress reduction approach for prevention and treatment of CHD and its risk factors in African Americans may prove to be a valuable asset for this underserved population.

Heterophilic binding of L1 on unmyelinated sensory axons mediates Schwann cell adhesion and is required for axonal survival.

This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.

Combinatorial peptide on-resin analysis: optimization of static nanoelectrospray ionization technique for sequence determination.

The optimizations of static nanoelectrospray parameters to determine peptide or mimetic sequences released from resin were explored. Several different manufacturers of probe tips were utilized and a method was developed for the direct analysis of bead-bound peptides by nanoelectrospray. The method involved minimum sample handling to assure maximum recovery from individual beads. Parameters that were explored included an inside and outside wash of the probe tip, the distance from the probe housing to the probe tip, source temperature, drying gas flow, individual tips and presence of beads. The same soluble synthetic peptide was used in all comparisons, which had a molecular weight of 717 amu. The discovery of the sequence of a bead-bound peptide was achieved. The parameters that were found to effect signal were outside wash, presence of bead and distance. There was the need for pneumatic assist to initiate electrospray on some occasions, although this generally resulted in unsatisfactory performance.