Paraspinous Muscle Flaps in Complex Pediatric Spine Surgeries: A 12-Year Single Institution Experience.

PURPOSE: The benefits of paraspinous flaps in adult complex spine surgery patients are established in the literature; however, their use in pediatric patients has not been well described. This study compares clinical outcomes with and without paraspinous muscle flap closure in pediatric patients who have undergone spine surgery. METHODS: We conducted a retrospective review of all pediatric spine surgeries at the University of California, San Francisco from 2011 to 2022. Patients were divided into 2 cohorts based on whether the plastic surgery service closed or did not close the wound with paraspinous muscle flaps. We matched patients by age, American Society of Anesthesiology classification, prior spinal surgical history, and diagnosis. Surgical outcomes were compared between the 2 cohorts. RESULTS: We identified 226 pediatric patients who underwent at least one spinal surgery, 14 of whom received paraspinous flap closure by plastic surgery. They were matched in a 1:4 ratio with controls (n = 56) that did not have plastic surgery closure. The most common indication for plastic surgery involvement was perceived complexity of disease by the spine surgeon with concern for inadequate healthy tissue coverage (78.6%), followed by infection (21.4%). Postoperative complications were similar between the two groups. The plastic surgery cohort had a higher rate of patients who were underweight (57.1% vs 14.3%, P < 0.01) and had positive preoperative wound cultures (28.6% vs 8.9%, P = 0.05), as well as a higher rate of postoperative antibiotic usage (78.6 vs 17.9%, P < 0.01). There was no difference in recorded postoperative outcomes. CONCLUSIONS: Spine surgeons requested paraspinous flap closure for patients with more complex disease, preoperative infections, history of chemotherapy, or if they were underweight. Patients with paraspinous flap coverage did not have increased postoperative complications despite their elevated risk profile. Our findings suggest that paraspinous muscle flaps should be considered in high-risk pediatric patients who undergo spine surgery.

Using the Comprehensive Complication Index to Rethink the ISGLS Criteria for Post-hepatectomy Liver Failure in an International Cohort of Major Hepatectomies.

OBJECTIVE: To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality. SUMMARY OF BACKGROUND DATA: PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. METHODS: Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. RESULTS: Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality. CONCLUSIONS: In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Evidence-based Guidelines on the Use of Virtual Surgical Education Pertaining to the Domains of Cognition and Curriculum, Psychomotor Skills Training, and Faculty Development and Mentorship.

OBJECTIVE: To identify, categorize, and evaluate the quality of literature, and to provide evidence-based guidelines on virtual surgical education within the cognitive and curricula, psychomotor, and faculty development and mentorship domains. SUMMARY OF BACKGROUND DATA: During the coronavirus disease 2019 pandemic, utilizing virtual learning modalities is expanding rapidly. Although the innovative methods must be considered to bridge the surgical education gap, a framework is needed to avoid expansion of virtual education without proper supporting evidence in some areas. METHODS: The Association for Surgical Education formed an ad-hoc research group to evaluate the quality and methodology of the current literature on virtual education and to build evidence-based guidelines by utilizing the SiGN methodology. We identified patient/problem-intervention-comparison-outcome-style questions, conducted systematic literature reviews using PubMed, EMBASE, and Education Resources information Center databases. Then we formulated evidence-based recommendations, assessed the quality of evidence using Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle-Ottawa Scale for Education, and Kirkpatrick ratings, and conducted Delphi consensus to validate the recommendations. RESULTS: Eleven patient/problem-intervention-comparison-outcome-style questions were designed by the expert committees. After screening 4723 articles by the review committee, 241 articles met inclusion criteria for full article reviews, and 166 studies were included and categorized into 3 domains: cognition and curricula (n = 92), psychomotor, (n = 119), and faculty development and mentorship (n = 119). Sixteen evidence-based recommendations were formulated and validated by an external expert panel. CONCLUSION: The evidence-based guidelines developed using SiGN methodology, provide a set of recommendations for surgical training societies, training programs, and educators on utilizing virtual surgical education and highlights the area of needs for further investigation.

Preventing Rectourethral Fistula Recurrence With Gracilis Flap.

BACKGROUND: Rectourethral fistula (RUF) is an uncommon serious condition with various etiologies including neoplasm, radiation therapy, and surgery. Treatment for RUF remains problematic with a high recurrence rate. Although studies have suggested the recurrence rate of RUF is lower after surgical repair using a gracilis flap, outcomes have varied and the studies were small and inadequately controlled. Here, we compare outcomes of RUF repair with and without gracilis flap to evaluate its efficacy in preventing fistula recurrence and identify risk factors for recurrence. METHODS: We retrospectively reviewed patients who had undergone surgical repair for RUF between 2007 and 2018 at our institution and had at least 30 days of follow-up. Patient demographics, comorbidities, and surgical outcomes were recorded and compared for patients who had gracilis flap repair and those who did not (controls). Single variable logistic regression analysis was used to identify risk factors for recurrence. RESULTS: The gracilis group (n = 24) and control group (n = 12) had similar demographics and comorbidities. Fistula recurrence was far less frequent in the gracilis group (8% vs 50%, P = 0.009). There were no significant differences in other outcomes including length of hospitalization and surgical complications. When recurrent RUF was treated with a muscle flap (gracilis or inferior gluteus), 83% of the group had no additional fistula recurrence. In the control group, history of radiation ( P = 0.04) and urinary incontinence ( P = 0.015) were associated with fistula recurrence. CONCLUSIONS: We recommend using a gracilis flap for RUF repair given its association with lower recurrence without increased surgical complications.

A radial axis defined by semaphorin-to-neuropilin signaling controls pancreatic islet morphogenesis.

The islets of Langerhans are endocrine organs characteristically dispersed throughout the pancreas. During development, endocrine progenitors delaminate, migrate radially and cluster to form islets. Despite the distinctive distribution of islets, spatially localized signals that control islet morphogenesis have not been discovered. Here, we identify a radial signaling axis that instructs developing islet cells to disperse throughout the pancreas. A screen of pancreatic extracellular signals identified factors that stimulated islet cell development. These included semaphorin 3a, a guidance cue in neural development without known functions in the pancreas. In the fetal pancreas, peripheral mesenchymal cells expressed Sema3a, while central nascent islet cells produced the semaphorin receptor neuropilin 2 (Nrp2). Nrp2 mutant islet cells developed in proper numbers, but had defects in migration and were unresponsive to purified Sema3a. Mutant Nrp2 islets aggregated centrally and failed to disperse radially. Thus, Sema3a-Nrp2 signaling along an unrecognized pancreatic developmental axis constitutes a chemoattractant system essential for generating the hallmark morphogenetic properties of pancreatic islets. Unexpectedly, Sema3a- and Nrp2-mediated control of islet morphogenesis is strikingly homologous to mechanisms that regulate radial neuronal migration and cortical lamination in the developing mammalian brain.

Developing Gender-Affirming Surgery Curricula for Plastic Surgery Residency and Fellowship via Delphi Consensus.

BACKGROUND: Gender-affirming surgery (GAS) is a rapidly growing field within plastic surgery, and residents and fellows must receive appropriate training. However, there are no standardized surgical training curricula. The objective of this study was to identify core curricula within the field of GAS. METHODS: Four GAS surgeons from different academic institutions identified initial curricular statements within six categories: (1) comprehensive GAS care, (2) gender-affirming facial surgery, (3) masculinizing chest surgery, (4) feminizing breast augmentation, (5) masculinizing genital GAS, and (6) feminizing genital GAS. Expert panelists consisting of plastic surgery residency program directors and GAS surgeons were recruited for three rounds of the Delphi-consensus process. The panelists decided whether each curriculum statement was appropriate for residency, fellowship, or neither. A statement was included in the final curriculum when Cronbach α value was greater than or equal to 0.8, meaning that 80% or more of the panel agreed on inclusion. RESULTS: A total of 34 panelists (14 plastic surgery residency program directors and 20 GAS surgeons representing 28 US institutions) participated. The response rate was 85% for the first round, 94% for the second, and 100% for the third. Out of 124 initial curriculum statements, 84 reached consensus for the final GAS curricula, 51 for residency, and 31 for fellowship. CONCLUSIONS: A national consensus on core GAS curriculum for plastic surgery residency and GAS fellowship was achieved by a modified Delphi method. Implementation of this curriculum will ensure that trainees in plastic surgery are adequately prepared in the field of GAS.

Trends in the Management of Pediatric Trigger Thumb in the United States.

BACKGROUND: Recent literature suggests that initial observation of pediatric trigger thumb without early surgical interventions can lead to spontaneous resolution. We sought to analyze current trends in the management of pediatric trigger thumb and compare real-world data with what the literature supports. METHODS: We conducted a retrospective study of data collected using the PearlDiver database between 2015 and 2018. Patients who were aged younger than 10 years with a diagnosis of trigger thumb were identified using International Classification of Diseases codes. Current Procedural Terminology codes were used to identify patients who had an operation for trigger thumb. Patient demographics, comorbidities, utilization of hand therapy, and treatment cost were also collected. RESULT: Of the 997 patients included in the study, 69% were diagnosed with trigger thumb between the age of 2 and 5 years. In all, 492 patients (49%) had surgery for trigger thumb: 65% of patients had surgery within 1 year of diagnosis, and 76% patients had surgery before the age of 5 years. This treatment pattern was similar across multiple regions of the United States, and there were no significant predictors for surgery. The average cost of treating patients without surgery was $593/patient, whereas that for patients with surgery was $1363/patient. CONCLUSIONS: Nationwide data show that pediatric trigger thumb may be managed surgically at higher frequencies and in patients at younger ages than supported by the existing literature. Possible overtreatment is not only detrimental to patients but also burdens the health care system with unnecessary cost.

Virtual Interviews: Assessing How Expectations Meet Reality.

OBJECTIVE: This study aimed to determine the post-matriculation perceptions of interns and faculty who participated in the 2020-2021 virtual interview process and how their expectations of the program and the applicants, respectively, aligned with reality. DESIGN, SETTING, AND PARTICIPANTS: Published surveys on virtual interviewing were reviewed and modified to design two surveys, for interns and for faculty who interviewed. Interns and faculty members from the Departments of Surgery and Medicine at one institution who participated in the 2020-2021 virtual interview process completed the surveys four to six months after the start of the academic year. Following survey completion, surgical interns from the same application cycle participated in one in-person focus group nine months after the start of the academic year to clarify points raised in the surveys. RESULTS: Forty-six interns and faculty members responded to the survey (subgroup response rates ranging from 13-30%) and ten interns participated in the focus group (participation rate 100%). Most faculty and intern participants found that expectations formed during virtual interviews were accurate. However, our respondents noted limitations to virtual interviews that reduced their usefulness, including challenges with unnatural social interactions, understanding city fit, and getting a sense of resident and program culture. Participants provided possible solutions to address these challenges. CONCLUSIONS: Overall, this mixed-methods study at a single institution found that perceptions from virtual interviews were generally accurate but with some limitations. We describe several opportunities to improve the virtual interview process and optimize the application experience.

Treatment Options for Dupuytren's Disease: Tips and Tricks.

Dupuytren's disease (DD) is a common fibroproliferative condition of the hand. METHODS: Management of DD includes observation, non-operative management, and operative management. Operative treatments include percutaneous needle fasciotomy (PNF), open fasciotomy (OF), Clostridium collagenase histolyticum (CCH) injections, limited fasciectomy (LF) and dermofasciectomy (DF). The various methods of DD treatment are reviewed. RESULTS: We summarize the highlights of each treatment option as well as the strengths and weaknesses. PNF has an immediate improvement, but a higher recurrence rate, potential problematic skin tears, and rare tendon or nerve complications. Limited fasciectomy removes the thickened, diseased tissue but has a more prolonged recovery and has a higher rate of significant complications. Dermofasciectomy has the highest complication rate, and the lowest recurrence. Also, secondary fasciectomy after a previous dermofasciectomy has an unexpected amputation rate as high as 8%. Collagenase injections require two visits, have an increased number of minor side effects such as skin tears, and have rare but significant side effects such as tendon rupture. CONCLUSIONS: This article gives an overview of different treatment options for DD and each of their strengths and weaknesses and provides procedural tips.

Needle Aponeurotomy for Stage IV Dupuytren Contracture: A Wide-Awake First Step Approach in 204 Consecutive Rays.

SUMMARY: Severe forms of Dupuytren disease are difficult to treat. Surgical fasciectomy is often the first choice, despite its high complication rate. At times, amputation is recommended. The authors evaluated the efficacy of minimally invasive needle fasciotomy (needle aponeurotomy) as the first and only treatment for severe (stage IV) Dupuytren contracture using a retrospective chart review of a single surgeon's consecutive experience over 8 years. A total of 204 rays from 165 patients with severe Dupuytren disease with total passive extension digit contracture of 135 degrees or greater were included in the study. Mean follow-up was 22.3 months. Standard goniometric measurements of finger joint contractures were taken before needle aponeurotomy and at follow-up visits. Total passive extension digit and flexion contracture improved significantly at each finger joint. Before the procedure, median flexion contractures were as follows: at the metacarpophalangeal joint, -70 degrees (interquartile range, -80 to -55); at the proximal interphalangeal joint, -75 degrees (interquartile range, -85 to -65); and at the distal interphalangeal joint, -5 degrees (interquartile range, -20 to 0); median total passive extension of digit was -145 degrees (interquartile range, -160 to -135). Flexion contractures after the procedure improved with 74 percent gain at the metacarpophalangeal joint, 32 percent gain at the proximal interphalangeal joint, and 46 percent gain at the distal interphalangeal joint, with 55 percent gain of total passive digit extension overall ( p < 0.001). The study shows that needle aponeurotomy led to significant improvements in joint contractures at all finger joints with minimal adverse effects. Needle aponeurotomy is an effective and safe first-line treatment for severe Dupuytren disease as the sole treatment or as a preliminary step for more invasive procedures if needed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Evaluating the Quality and Reliability of Gender-affirming Surgery Videos on YouTube and TikTok.

Background: Social media platforms have changed the way medical information is disseminated. Transgender patients may utilize social media to learn about gender-affirming surgery (GAS). Although videos on social media are readily accessible, their content is not verified or peer-reviewed. Therefore, this study aimed to evaluate the quality and reliability of YouTube and TikTok videos related to GAS. Methods: YouTube and TikTok were queried for gender-affirming top surgery, metoidioplasty, phalloplasty, breast augmentation, and vaginoplasty. Quality of video content was analyzed by the DISCERN scale. Quality scores were compared among the type of GAS, account user, and content category. Results: There were 275 YouTube videos and 55 TikTok videos. Most videos focused on masculinizing top surgery (P < 0.001). Overall, videos on masculinizing GAS had higher quality and reliability than videos on feminizing GAS (P < 0.001). Chest surgery videos were of higher quality than those on genital surgery (P ≤ 0.001). Videos on masculinizing top surgery had the highest quality, whereas vaginoplasty had the lowest quality and reliability (P < 0.001). Videos produced by health care professionals and academic institutions had the greatest quality and reliability, respectively (P < 0.0001), whereas videos produced by patients were the least reliable (P < 0.0001). Conclusions: Videos on GAS ranged from poor to good quality and reliability. Health care professionals, especially plastic surgeons, should create high-quality videos on social media to educate transgender patients. There should also be greater efforts in disseminating existing high-quality videos on social media. Resources posted on social media platforms can reach a wide audience through accessible means.

Resident Readiness for Senior Level Decision Making: Identifying the Domains for Formative Assessment and Feedback.

OBJECTIVE: To establish expert consensus regarding the domains and topics for senior surgery residents (PGY-4) to make critical decisions and assume senior-level responsibilities, and to develop the formative American College of Surgeons Senior Resident Readiness Assessment (ACS SRRA) Program. DESIGN: The American College of Surgeons (ACS) education leadership team conducted a focus group with surgical experts to identify the content for an assessment tool to evaluate senior residents' readiness for their increased levels of responsibility. After the focus group, national experts were recruited to develop consensus on the topics through three rounds of surveys using Delphi methodology. The Delphi participants rated topics using Likert-type scales and their comments were incorporated into subsequent rounds. Consensus was defined as ≥ 80% agreement with internal-consistency reliability (Cronbach's alpha) ≥ 0.8. In a stepwise fashion, topics that did not achieve consensus for inclusion were removed from subsequent survey rounds. SETTING: The surveys were administered via an online questionnaire. PARTICIPANTS: Twelve program directors and assistant program directors made up the focus group. The 39 Delphi participants represented seven different surgical subspecialties and were from diverse practice settings. The median length of experience in general surgery resident education was 20 years (IQR 14.3-30.0) with 64% of the experts being either current or past general surgery residency program directors. RESULTS: The response rate was 100% and Cronbach's alpha was ≥ 0.9 for each round. The Delphi participants contributed a large number of comments. Of the 201 topics that were evaluated initially, 120 topics in 25 core clinical areas were included to create the final domains of ACS SRRA. CONCLUSIONS: National consensus on the domain of the ACS SRRA has been achieved via the modified Delphi method among expert surgeon educators. ACS SRRA will identify clinical topics and areas in which each senior resident needs improvement and provide data to residents and residency programs to develop individualized learning plans. This would help in preparing the senior residents to assume their responsibilities and support their readiness for future fellowship training or surgical practice.

Designing successful virtual residency interviews: a survey-based needs assessment of applicants across medical specialties.

Background: Residency selection in the United States relied on in-person interviews for many decades. The COVID-19 pandemic and recommendations from the Coalition for Physician Accountability (COPA) required programs to implement virtual interviews for the 2020-2021 residency selection cycle. Although virtual interviews may become the norm in the future, there is scant data at the institutional level to inform how to best approach this process. Objective: To describe the perceptions of applicants to several residency programs at one institution on the importance of virtual recruitment features and assess the impact on their overall ranking decisions. Methods: Applicants who interviewed for 12 medical and surgical residency programs during the 2020-2021 cycle at the University of California San Francisco were invited to participate in an anonymous survey in March 2021, after all interviews were completed. A survey consisting of 26 questions was administered to applicants on features that are important during interviews and the impact on their ranking decisions scored on a 5-point Likert scale. Results: Of the 1422 participating applicants, 303 (21%) completed the survey. The most important feature for applicants during the interview day was getting a feel of the program (92%). Conversations with residents (91%) and faculty (79%) were also highly rated. Respondents reported morale and happiness of residents (71%) as an extremely important factor in their overall ranking decision. Conclusion: Programs should consider prioritizing features that aid in alignment with getting to know residents and faculty and provide a sense of morale over emphasis on the institutional and location features. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-022-00004-5.

poky/chuk/ikk1 is required for differentiation of the zebrafish embryonic epidermis.

An epidermis surrounds all vertebrates, forming a water barrier between the external environment and the internal space of the organism. In the zebrafish, the embryonic epidermis consists of an outer enveloping layer (EVL) and an inner basal layer that have distinct embryonic origins. Differentiation of the EVL requires the maternal effect gene poky/ikk1 in EVL cells prior to establishment of the basal layer. This requirement is transient and maternal Ikk1 is sufficient to allow establishment of the EVL and formation of normal skin in adults. Similar to the requirement for Ikk1 in mouse epidermis, EVL cells in poky mutants fail to exit the cell cycle or express specific markers of differentiation. In spite of the similarity in phenotype, the molecular requirement for Ikk1 is different between mouse and zebrafish. Unlike the mouse, EVL differentiation requires functioning Poky/Ikk1 kinase activity but does not require the HLH domain. Previous work suggested that the EVL was a transient embryonic structure, and that maturation of the epidermis required replacement of the EVL with cells from the basal layer. We show here that the EVL is not lost during embryogenesis but persists to larval stages. Our results show that while the requirement for poky/ikk1 is conserved, the differences in molecular activity indicate that diversification of an epithelial differentiation program has allowed at least two developmental modes of establishing a multilayered epidermis in vertebrates.

Early Recurrent Carpal Tunnel Syndrome in Patients with Mucopolysaccharidoses.

Early-onset carpal tunnel syndrome (CTS) is a well-known manifestation of mucopolysaccharidoses (MPS) due to excessive deposition of glycosaminoglycans in soft tissues. Standard treatment has been carpal tunnel release surgery, with the conventional technique of dividing the transverse carpal ligament. With advancement of treatments for MPS, these patients now have a longer life expectancy and are presenting with recurrent CTS. Management of recurrent CTS in these patients is not well studied. Here, we report 2 cases of recurrent CTS in MPS patients after a carpal tunnel release operation. We describe the findings on repeat operations and propose a unique technique for treating CTS in MPS patients to minimize recurrence during the initial CTS surgery. Our method involves resection of a portion of the transverse carpal ligament and use of a hypothenar fat pad flap over the median nerve.

Unifying the Hepatopancreatobiliary Surgery Fellowship Curriculum via Delphi Consensus.

BACKGROUND: Hepatopancreatobiliary (HPB) Fellowship training in the Americas consists of 3 distinctive routes with variable curricula: Surgical Oncology Fellowship via the Society of Surgical Oncology (SSO), Abdominal Transplant Surgery Fellowship via the American Society of Transplant Surgeons (ASTS), and HPB Fellowship via the Americas Hepato-Pancreato-Biliary Association (AHPBA). Our objective was to establish a pan-American consensus among HPB surgeons, surgical oncologists, abdominal transplant surgeons, and general surgery residency program directors (GSPDs) on a core knowledge curriculum for HPB fellowship, and to identify topics appropriate for general surgery residency and subspecialty beyond HPB fellowship. STUDY DESIGN: A 3-round modified Delphi process was used. Baseline statements were developed by the Education and Training Committee of the AHPBA, in collaboration with representatives of the SSO, ASTS, and GSPDs. The expert panel, consisting of members of the 3 societies together with GSPDs, rated the statements on a 5-point Likert scale and suggested editing or adding new statements. A statement was included in the final curriculum when Cronbach's alpha value was ≥ 0.8 and ≥ 80% of the panel agreed on inclusion. RESULTS: The response rate was 100% for the first round, and 98% for the second and third rounds. Eighty-nine of 138 proposed statements were included in the final HPB fellowship curriculum. Curricula for general surgery residency and subspecialty beyond HPB fellowship included 50 and 29 statements, respectively. CONCLUSIONS: A multinational consensus on core knowledge for an HPB fellowship curriculum was achieved via the modified Delphi method. This core curriculum may be used to standardize HPB fellowship training across different pathways in the Americas.

Research Resource: Genetic Labeling of Human Islet Alpha Cells.

The 2 most abundant human pancreatic islet cell types are insulin-producing ß-cells and glucagon-producing α-cells. Defined cis-regulatory elements from rodent Insulin genes have permitted genetic labeling of human islet ß-cells, enabling lineage tracing and generation of human ß-cell lines, but analogous elements for genetically labeling human α-cells with high specificity do not yet exist. To identify genetic elements that specifically direct reporter expression to human α-cells, we investigated noncoding sequences adjacent to the human GLUCAGON and ARX genes, which are expressed in islet α-cells. Elements with high evolutionary conservation were cloned into lentiviral vectors to direct fluorescent reporter expression in primary human islets. Based on the specificity of reporter expression for α- and ß-cells, we found that rat glucagon promoter was not specific for human α-cells but that addition of human GLUCAGON untranslated region sequences substantially enhanced specificity of labeling in both cultured and transplanted islets to a degree not previously reported, to our knowledge. Specific transgene expression from these cis-regulatory sequences in human α-cells should enable targeted genetic modification and lineage tracing.

Role for α6 nicotinic receptors in l-dopa-induced dyskinesias in parkinsonian mice.

L-Dopa-induced dyskinesias are a serious side effect that develops in most Parkinson's disease patients on dopamine replacement therapy. Few treatment options are available to manage dyskinesias; however,recent studies show that nicotine reduces these abnormal involuntary movements (AIMs) in parkinsonian animals by acting at nicotinic acetylcholine receptors (nAChRs). Identification of the nAChR subtypes that mediate this reduction in AIMs is important as it will help in the development of nAChR subtype selective drugs for their treatment. Here we investigate the role of α6ß2* nAChRs, a subtype selectively present in the nigrostriatal pathway, using a6 nAChR subunit null mutant (α6⁻/⁻) mice.Wildtype and α6⁻/⁻ mice were lesioned by unilateral injection of 6-hydroxydopamine (3 mg/ml) into the medial forebrain bundle. They were then given L-dopa (3 mg/kg) plus benserazide (15 mg/kg) 2e3 wk later. L-dopa-induced AIMs developed to a similar extent in α6⁻/⁻ and wildtype mice.However, AIMs in α6⁻/⁻ mice declined to ~50% of that in wildtype mice with continued L-dopa treatment. Nicotine treatment also decreased AIMs by ~50% in wildtype mice, although not in α6⁻/⁻ mice. There were no effects on parkinsonism under any experimental condition. To conclude, the similar declines in L-dopa-induced AIMs in nicotine-treated wildtype mice and in α6⁻/⁻ mice treated with and without nicotine indicate an essential role for α6ß2* nAChRs in the maintenance of L-dopa-induced AIMs.These findings suggest that α6ß2* nAChR drugs have potential for reducing L-dopa-induced dyskinesias in Parkinson's disease.