The effect of climate change on avian offspring production: A global meta-analysis.

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to reproductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young.

Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis.

BACKGROUND: The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS: In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS: A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS: Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

Adjuvanted Vaccine Induces Functional Antibodies against Pseudomonas aeruginosa Filamentous Bacteriophages.

Pseudomonas aeruginosa (Pa), a WHO priority 1 pathogen, resulted in approximately 559,000 deaths globally in 2019. Pa has a multitude of host-immune evasion strategies that enhance Pa virulence. Most clinical isolates of Pa are infected by a phage called Pf that has the ability to misdirect the host-immune response and provide structural integrity to biofilms. Previous studies demonstrate that vaccination against the coat protein (CoaB) of Pf4 virions can assist in the clearance of Pa from the dorsal wound model in mice. Here, a consensus peptide was derived from CoaB and conjugated to cross-reacting material 197 (CRM197). This conjugate was adjuvanted with a novel synthetic Toll-like receptor agonist (TLR) 4 agonist, INI-2002, and used to vaccinate mice. Mice vaccinated with CoaB-CRM conjugate and INI-2002 developed high anti-CoaB peptide-specific IgG antibody titers. Direct binding of the peptide-specific antibodies to whole-phage virus particles was demonstrated by ELISA. Furthermore, a functional assay demonstrated that antibodies generated from vaccinated mice disrupted the replicative cycle of Pf phages. The use of an adjuvanted phage vaccine targeting Pa is an innovative vaccine strategy with the potential to become a new tool targeting multi-drug-resistant Pa infections in high-risk populations.

Induced and sustained hypernatremia for the prevention and treatment of cerebral edema following brain injury.

Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.

Hypofractionated postoperative stereotactic radiotherapy for large resected brain metastases.

PURPOSE: The aim of the present retrospective study was to report outcomes after hypofractionated stereotactic radiotherapy (HSRT) for resected brain metastases (BM). PATIENTS AND METHODS: We reviewed results of patients with resected BM treated with postoperative HSRT (3×7.7Gy to the prescription isodose 70%) between May 2013 and June 2020. Local control (LC), distant brain control (DBC), overall survival (OS), leptomeningeal disease relapse (LMDR), and radiation necrosis (RN) occurrence were reported. RESULTS: Twenty-two patients with 23 brain cavities were included. Karnofsky Performance status (KPS) was≥70 in 77.3%. Median preoperative diameter was 37mm [21.0-75.0] and median planning target volume (PTV) was 23 cm3 [9.9-61.6]. Median time from surgery to SRT was 69 days [7-101] and 48% of patients had a local relapse on pre-SRT imaging. Median follow-up was 17.5 months [1.6-95.9]. One and two-year LC rates were 60.9 and 52.2% respectively. One and 2-year DBC rates were 45.5 and 40.9%. Median OS was 16.5 months. Four patients (18.2%) presented LMDR during follow-up. RN occurred in 6 patients (27.2%). Three factors were associated with OS: ECOG-PS (P=0.009), KPS (P=0.04), cystic or solid nature of the metastasis before surgery (P=0.037). Several factors were related to RN occurrence: PTV diameter and volume, Normal brain V21, V21 and V24 isodoses volumes. CONCLUSION: HSRT is the most widely used scheme for larger brain cavities after surgery. The optimal dose and scheme remain to be defined as well as the optimal delay between postoperative SRT and surgery. Dose escalation may be necessary, especially in case of subtotal resection.

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases.

PURPOSE: Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery. PATIENTS AND METHODS: From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3. RESULTS: The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05). CONCLUSION: A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.

Applying objective metrics to neurosurgical skill development with simulation and spaced repetition learning.

OBJECTIVE: Surgical skills laboratories augment educational training by deepening one's understanding of anatomy and allowing the safe practice of technical skills. Novel, high-fidelity, cadaver-free simulators provide an opportunity to increase access to skills laboratory training. The neurosurgical field has historically evaluated skill by subjective assessment or outcome measures, as opposed to process measures with objective, quantitative indicators of technical skill and progression. The authors conducted a pilot training module with spaced repetition learning concepts to evaluate its feasibility and impact on proficiency. METHODS: The 6-week module used a simulator of a pterional approach representing skull, dura mater, cranial nerves, and arteries (UpSurgeOn S.r.l.). Neurosurgery residents at an academic tertiary hospital completed a video-recorded baseline examination, performing supraorbital and pterional craniotomies, dural opening, suturing, and anatomical identification under a microscope. Participation in the full 6-week module was voluntary, which precluded randomizing by class year. The intervention group participated in four additional faculty-guided trainings. In the 6th week, all residents (intervention and control) repeated the initial examination with video recording. Videos were evaluated by three neurosurgical attendings who were not affiliated with the institution and who were blinded to participant grouping and year. Scores were assigned via Global Rating Scales (GRSs) and Task-based Specific Checklists (TSCs) previously built for craniotomy (cGRS, cTSC) and microsurgical exploration (mGRS, mTSC). RESULTS: Fifteen residents participated (8 intervention, 7 control). The intervention group included a greater number of junior residents (postgraduate years 1-3; 7/8) compared to the control group (1/7). External evaluators had internal consistency within 0.5% (kappa probability > Z of 0.00001). The total average time improved by 5:42 minutes (p < 0.003; intervention, 6:05, p = 0.07; control, 5:15, p = 0.001). The intervention group began with lower scores in all categories and surpassed the comparison group in cGRS (10.93 to 13.6/16) and cTSC (4.0 to 7.4/10). Percent improvements for the intervention group were cGRS 25% (p = 0.02), cTSC 84% (p = 0.002), mGRS 18% (p = 0.003), and mTSC 52% (p = 0.037). For controls, improvements were cGRS 4% (p = 0.19), cTSC 0.0% (p > 0.99), mGRS 6% (p = 0.07), and mTSC 31% (p = 0.029). CONCLUSIONS: Participants who underwent a 6-week simulation course showed significant objective improvement in technical indicators, particularly individuals who were early in their training. Small, nonrandomized grouping limits generalizability regarding degree of impact; however, introducing objective performance metrics during spaced repetition simulation would undoubtedly improve training. A larger multiinstitutional randomized controlled study will help elucidate the value of this educational method.

The use of intra-operative blood gas analysis in the investigation of suspected iatrogenic vascular injury.

BACKGROUND: Iatrogenic injury to the vertebral artery during posterior cervical fusion is a rare and potentially disastrous complication. Differentiating arterial from brisk venous bleeding would be ideal to assist in the intra-operative management. Definitive angiography is typically not feasible during most routine spine surgery. CASE DESCRIPTION: We describe the case of a patient undergoing an occipitocervical fusion, where brisk bleeding was encountered during dissection of the CB lateral mass. While the dissection was thought to be superficial to critical structures, the nature of the hemorrhage could not be definitely determined by visual inspection by two senior surgeons. The hemorrhage did not readily cease with standard maneuvers such as, the application of various hemostatic agents. Simultaneous blood gas analysis was performed on samples obtained from the patient's radial artery and from the hemorrhage in the operative bed. Comparative analysis concluded that the bleeding encountered in the surgical field was venous in nature. CONCLUSION: Blood gas analysis can be a useful adjunct in determining the nature of hemorrhage from vascular structures in spine surgery when visual inspection is indeterminate.

Infection following operations on the central nervous system: deconstructing the myth of the sterile field.

Neurosurgical patients are at a high risk for infectious sequelae following operations. For neurosurgery in particular, the risk of surgical site infection has a unique implication given the proximity of the CSF and the CNS. Patient factors contribute to some degree; for example, cancer and trauma are often associated with impaired nutritional status, known risk factors for infection. Additionally, care-based factors for infection must also be considered, such as the length of surgery, the administration of steroids, and tissue devascularization (such as a craniotomy bone flap). When postoperative infection does occur, attention is commonly focused on potential lapses in surgical "sterility." Evidence suggests that the surgical field is not free of microorganisms. The authors propose a paradigm shift in the nomenclature of the surgical field from "sterile" to "clean." Continued efforts aimed at optimizing immune capacity and host defenses to combat potential infection are warranted.

A review of lumbar spinal instrumentation: evidence and controversy.

Disability secondary to disorders of the spine is a significant problem worldwide. In the USA, there has been a recent surge in the costs associated with caring for spinal pathology; from 1997 to 2005, there was a growth of 65% in healthcare expenditures on spinal disease, totalling $86 billion in 2005. Increasingly, there has been media and public scrutiny over the rapid rise in the volume of procedures with spinal instrumentation; some have suggested that this rise has been fuelled by non-medical drivers such as the financial incentives involved with the use of instrumentation; others suggest that innovation in spine technology and devices has led to improved options for the treatment of spine pathology.In this context, we conducted a review of the literature to assess the use of instrumentation in lumbar procedures and its relationship to successful fusion and patient outcome. Our review suggests that there is data supporting the thesis that lumbar instrumentation improves rates of fusion. However, there is no consistent correlation between increased rates of fusion and improved patient outcomes.

Incidental vertebral lesions.

Incidental vertebral lesions on imaging of the spine are commonly encountered in clinical practice. Contributing factors include the aging population, the increasing prevalence of back pain, and increased usage of MR imaging. Additionally, refinements in CT and MR imaging have increased the number of demonstrable lesions. The management of incidental findings varies among practitioners and commonly depends more on practice style than on data or guidelines. In this article we review incidental findings within the vertebral column and review management of these lesions, based on available Class III data.

Diagnostic pitfalls in spine surgery: masqueraders of surgical spine disease.

Disorders of the spine are common in clinical medicine, and spine surgery is being performed with increasing frequency in the US. Although many patients with an established diagnosis of a true surgically treatable lesion are referred to a neurosurgeon, the evaluation of patients with spinal disorders can be complex and fraught with diagnostic pitfalls. While "common conditions are common," astute clinical acumen and vigilance are necessary to identify lesions that masquerade as surgically treatable spine disease that can lead to erroneous diagnosis and treatment. In this review, the authors discuss musculoskeletal, peripheral nerve, metabolic, infectious, inflammatory, and vascular conditions that mimic the syndromes produced by surgical lesions. It is possible that nonsurgical and surgical conditions coexist at times, complicating treatment plans and natural histories. Awareness of these diagnoses can help reduce diagnostic error, thereby avoiding the morbidity and expense associated with an unnecessary operation.

Familial Chiari malformation: case series.

Chiari malformations (Types I-IV) are abnormalities of the posterior fossa that affect the cerebellum, brainstem, and the spinal cord with prevalence rates of 0.1%-0.5%. Case reports of familial aggregation of Chiari malformation, twin studies, cosegregation of Chiari malformation with known genetic conditions, and recent gene and genome-wide association studies provide strong evidence of the genetic underpinnings of familial Chiari malformation. The authors report on a series of 3 family pairs with Chiari malformation Type I: 2 mother-daughter pairs and 1 father-daughter pair. The specific genetic causes of familial Chiari malformation have yet to be fully elucidated. The authors review the literature and discuss several candidate genes. Recent advances in the understanding of the genetic influences and pathogenesis of familial Chiari malformation are expected to improve management of affected patients and monitoring of at-risk family members.

Radiotherapy of non-tumoral refractory neurological pathologies.

Intracranial radiotherapy has been improved, primarily because of the development of stereotactic approaches. While intracranial stereotactic body radiotherapy is mainly indicated for treatment of benign or malignant tumors, this procedure is also effective in the management of other neurological pathologies; it is delivered using GammaKnife® and linear accelerators. Thus, brain arteriovenous malformations in patients who are likely to experience permanent neurological sequelae can be managed by single session intracranial stereotactic body radiotherapy, or radiosurgery, in specific situations, with an advantageous benefit/risk ratio. Radiosurgery can be recommended for patients with disabling symptoms, which are poorly controlled by medication, such as trigeminal neuralgia, and tremors, whether they are essential or secondary to Parkinson's disease. This literature review aims at defining the place of intracranial stereotactic body radiotherapy in the management of patients suffering from non-tumoral refractory neurological pathologies. It is clear that the multidisciplinary collaboration of experienced teams from Neurosurgery, Neurology, Neuroradiology, Radiation Oncology and Medical Physics is needed for the procedures using high precision radiotherapy techniques, which deliver high doses to locations near functional brain areas.

Multidisciplinary approaches to complication reduction in complex spine surgery: a systematic review.

BACKGROUND CONTEXT: Complex spine surgery carries a high complication rate that can produce suboptimal outcomes for patients undergoing these extensive operations. However, multidisciplinary pathways introduced at multiple institutions have demonstrated a promising potential toward reducing the burden of complications in patients being treated for spinal deformities. To date, there has been no effort to systematically collate the multidisciplinary approaches in use at various institutions. PURPOSE: The present study aims to determine effective multidisciplinary strategies for reducing the complication rate in complex spine surgery by analyzing existing institutional multidisciplinary approaches and delineating common themes across multiple practice settings. STUDY DESIGN: Systematic review. METHODS: We followed guidelines established under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The studies reported on data from PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Cochrane. We included articles that described either approaches to, or results from, the implementation of multidisciplinary paradigms during the preoperative, perioperative, and postoperative phases of care for patients undergoing complex spine surgery. We excluded studies that only targeted one complication unless such an approach was in coordination with more extensive multidisciplinary planning at the same institution. RESULTS: A total of 406 unique articles were identified. Following an initial determination based on title and abstract, 22 articles met criteria for full-text review, and 10 met the inclusion criteria to be included in the review. Key aspects of multidisciplinary approaches to complex spine surgery included extensive preoperative workup and interdisciplinary conferencing, intraoperative communication and monitoring, and postoperative floor management and discharge planning. These strategies produced decreases in surgical duration and complication rates. CONCLUSIONS: This study represents the first to systematically analyze multidisciplinary approaches to reduce complications in complex spine surgery. This review provides a roadmap toward reducing the elevated complication rate for patients undergoing complex spine surgery.

Development of a Breast Cancer Treatment Program in Port-au-Prince, Haiti: Experiences From the Field.

PURPOSE: The nonprofit Project Medishare launched a breast cancer treatment program in Port-au-Prince in July 2013 to address the demand for breast cancer care in Haiti. We outline the development of the program, highlight specific challenges, and discuss key considerations for others working in global oncology. METHODS: We reflected on our experiences in the key areas of developing partnerships, building laboratory capacity, conducting medical training, using treatment algorithms, and ensuring access to safe, low-cost chemotherapy drugs. We also critically reviewed our costs and quality measures. RESULTS: The program has treated a total of 139 patients with breast cancer with strong adherence to treatment regimens in 85% of patients. In 273 chemotherapy administrations, no serious exposure or adverse safety events were reported by staff. The mortality rate for 94 patients for whom we have complete data was 24% with a median survival time of 53 months. Our outcome data were likely influenced by stage at presentation, with more than half of patients presenting more than 12 months after first noticing a tumor. Future efforts will therefore focus on continuing to improve the level of care, while working with local partners to spread awareness, increase screening, and get more women into care earlier in the course of their disease. CONCLUSION: Our experiences may inform others working to implement protocol-based cancer treatment programs in resource-poor settings and can provide valuable lessons learned for future global oncology efforts.

A phase I/II study of herpes simplex virus type 1 thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma.

Despite extensive surgery for glioblastoma, residual tumor cells always lead to relapse. Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which specifically sensitizes dividing cells to ganciclovir (GCV) toxicity, may help eradicate such cells. During glioblastoma surgery, HSV-1 TK retroviral vector-producing cells (M11) were injected into the surgical cavity margins after tumor debulking. After a 7-day transduction period, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival. Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV. Quality of life was not negatively influenced by this treatment. Overall median survival was 206 days, with 25% of the patients surviving longer than 12 months. At 4 months after treatment, 4 of 12 patients had no recurrence; their median overall survival was 528 days, compared with 194 days for patients with recurrence (p=0.03 by the log rank test). One patient is still free of detectable recurrence, steroid free and independent, 2.8 years after treatment. Thus, brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses. These results warrant further development of this therapeutic strategy in brain tumor, including recurrent glioblastoma.

Identification by cDNA microarray technology of genes modulated by artificial ultraviolet radiation in normal human melanocytes: relation to melanocarcinogenesis.

Target genes of ultraviolet stress response in cutaneous melanocytes, potentially associated with solar-induced melanocarcinogenesis, were characterized by cDNA microarray technology. In cultured normal human melanocytes, 198 genes out of approximately 9000 arrayed were found modulated > or = 1.9 times following artificial ultraviolet minus sign mainly ultraviolet-B minus sign irradiation (100 mJ per cm(2)). Among them, 159 corresponded to known sequences, the encoded proteins being mostly involved in DNA or RNA binding/synthesis/modification, or ribosomal proteins. The others were transcription factors, receptors, tumor suppressors, and (proto)oncogenes. Members of these families have already been linked to melanoma. In addition, some of the modulated genes were borne by chromosomes harboring candidate melanoma loci. Comparisons with genes modified in melanoma samples reported in previous studies with similar microarray platform showed that 59% of the known genes sensitive to ultraviolet were modulated in the same way. Furthermore, 39 expressed sequence tags were modulated, and preliminary experiments showed that two expressed sequence tags displayed differential expressions both in melanoma cell lines and in melanoma tumors. These results provide a basis for further studies on the role of modulated genes in ultraviolet-induced melanoma. Because some of these genes are potential markers of the disease, they might help for developing new molecular-based strategies for risk prediction in patients.

Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human melanocytes and melanoma cells.

Pancreatitis associated protein I is a secretory stress protein first characterized in pancreas during pancreatitis but also expressed in several tissues including hepatic, gastric, and colon cancer. Its concentration in serum can be significant. The relationship of pancreatitis associated protein I to skin cancers was investigated in normal melanocytes, melanoma tumors, and melanoma cell lines. None of them expressed pancreatitis associated protein I, even after stress induction. Adenovirus-mediated pancreatitis associated protein I expression, however, reduced cell adhesion to laminin-1 and fibronectin with a loss of integrin participation. Pancreatitis associated protein I expression stimulated haptotactic and directed migrations of some melanoma cells, but only directed migration was activated in normal melanocytes. Importantly, directed migration and spreading on fibronectin of the responsive melanoma cells were also enhanced when purified rat pancreatitis associated protein I was added to the culture medium of noninfected cells. This indicates that effects in infected cells were elicited by pancreatitis associated protein I after its secretion. Exogenous pancreatitis associated protein I can therefore modify the adhesion and motility of normal and transformed melanocytes, suggesting a potential interaction with melanoma invasivity.