Heart Attacks, Bloody Noses, and Other "Emotional Problems": Cultural and Conceptual Issues With the Spanish Translation of Self-Report Emotional Health Items.

This article examines how respondents understood items in the Spanish versions of the Short-Form 36 (SF-36v2). Cognitive interviews of the SF-36 were conducted in 2 phases with 46 Spanish speakers living in the United States. Roughly one-third (17/46) of respondents had difficulty understanding the Role Emotional items upon their initial reading, and almost half (21/46) provided examples that were inconsistent with the intended meaning of the items. The findings of this study underscore the importance of conducting cognitive testing to ensure conceptual equivalence of any instrument regardless of how well validated it appears to be.

Community climate resilience in Cambodia.

Building resilience is a critical response to climate change. Developing countries are the most vulnerable to climate change, yet planning rarely considers how broader community development interventions can enhance resilience and support development. One solution is resilience assessment. However, few assessment frameworks exist that are sufficiently simple to empower communities to build resilience and take ownership of adaptation efforts. This article provides an example of a 27-question framework applied with two Cambodian communes (communities) to assess and understand trends in resilience over time. It is structured around community development outcomes of economic development, environmental quality, infrastructure that matches demands, community self-reliance and capacity to adapt to climate change; it also assesses how inputs and planning contribute to these outcomes. Longitudinal analyses reveal improvements over time driven primarily by commodity values. However, the sustainability of some of these improvements is questionable given volatile commodity markets and land degradation. Oversensitivity in the assessment is acknowledged as awareness increases over time, which can be conflated with poor performance. Maladaptive pathways may be unavoidable without building resilience by attending to broader community development issues, e.g. psychological wellbeing and education on alternative livelihoods. This article makes a significant contribution to community resilience by providing a simple resilience assessment framework that has demonstrably empowered communes to adapt to change. It is novel in the use of assessment design and process principles that build reflection on the drivers of resilience and development. Critical issues remain in the power dynamics of aid dependence, weakening of family bonds and patron-client relationships that affect resilience building in Cambodia.

Knowledge, Attitude, and Practices Related to COVID-19 among Healthcare Personnel in a Tertiary Care Hospital in Nepal: A Cross-sectional Survey.

Background COVID-19 is significantly affecting the healthcare system globally. As a result, healthcare workers need to be updated on the best practices for the proper management of the disease. Objective The purpose of this study was to assess the knowledge, attitude, and practices (KAP) related to COVID-19 among healthcare personnel. Method This was a cross-sectional study conducted among medical personnel at Dhulikhel Hospital Kathmandu University Hospital using a semi-structured questionnaire on KAP related to COVID-19 from May 8th to June 8th, 2020. We analyzed survey data by using descriptive statistics. Spearman rank correlation, chi-square test and binary logistic analysis were used to examine the association between sociodemographic characteristics with KAP related to COVID-19. Result Among 220 participants, the majority were nurses (60%) followed by doctors (27.7%), paramedics (10%) and technicians (2.3%). The results showed that 68.6% of healthcare personnel had a good knowledge with appropriate practices (98.5%) and negative attitude (59.3%). In the multivariate binary logistic analysis, the healthcare workers with the clinical experience level of one to five years (OR:.42, 95% CI:.19- .96) and more than 5 years (OR: .16, 95% CI: .04-.63) were significantly associated with negative attitude. The confidence score for managing COVID-19 (OR:1.16, 95% CI:1.02-1.34) was significantly associated with an optimistic attitude. Conclusion Healthcare workers are knowledgeable about COVID-19 and proactively practising to minimize the spread of infection but lack optimistic attitudes. Hence, the constantly updated educational programmes related to COVID-19 for targeted groups will contribute to improving healthcare workers' attitude and practices.

Reasons for Summoning Ambulance Services in the Hilly Region of Nepal.

Background Nepal lacks a unified and countrywide emergency medical services system as other developing countries. However, the emergence of ambulance service initiatives in the past decade shows a promising future for pre-hospital care. Nepal Ambulance Service (Est. 2011) and Dhulikhel Emergency Medical Services (Est. 2013) are the existing emergency medical services initiatives in Nepal. Objective To describe the reason for summoning ambulance services and demographics of the patients who were transported by Dhulikhel Emergency Medical Services at Dhulikhel hospital, hilly region of Nepal. Method One thousand three hundred and ninety three patient records at Dhulikhel hospital transported by Dhulikhel Emergency Medical Services during the five-year period (2013 - 2018) were included in the study. Chief complaints and demographic data were collected and categorized into overarching systemic categories. Result Among 1393 patients, majority were female (60.4%) and the most common age group was 20-29 years. The most common reason for calling ambulances was gastrointestinal problem (22.6%). Similarly, respiratory (17%), obstetric and gynecological (15.2%), trauma (12.7%) and neurological (9.6%) problems were other common reasons. The number of respiratory problem was increased during the winter season. The overall percentage of patients arriving at hospital with trauma problems was increased steadily, but it was not statistically significant. Conclusion Gastrointestinal problem was the most common reason, followed by respiratory and obstetric and gynecological problems for summoning ambulances services in the hilly regions of Nepal. The incidence of respiratory problem significantly increased during the winter season.

Undocumented status as a social determinant of occupational safety and health: The workers' perspective.

BACKGROUND: Undocumented immigration to the United States has grown dramatically over the past 25 years. This study explores undocumented status as a social determinant of occupational health by examining its perceived consequences on workplace safety of Latino immigrants. METHODS: Guided by the Theory of Work Adjustment, qualitative analysis was conducted on transcripts from focus groups and individual interviews conducted with a convenience sample of Latino immigrant workers. RESULTS: Participants reported that unauthorized status negatively impacted their safety at work and resulted in a degree of alienation that exceeded the specific proscriptions of the law. Participants overwhelming used a strategy of disengagement to cope with the challenges they face as undocumented immigrants. CONCLUSION: This study describes the complex web of consequences resulting from undocumented status and its impact on occupational health. This study presents a framework connecting the daily work experiences of immigrants, the coping strategy of disengagement, and efforts to minimize the impact of structural violence.

Patterns of relating between physicians and medical assistants in small family medicine offices.

PURPOSE: The clinician-colleague relationship is a cornerstone of relationship-centered care (RCC); in small family medicine offices, the clinician-medical assistant (MA) relationship is especially important. We sought to better understand the relationship between MA roles and the clinician-MA relationship within the RCC framework. METHODS: We conducted an ethnographic study of 5 small family medicine offices (having <5 clinicians) in the Cincinnati Area Research and Improvement Group (CARInG) Network using interviews, surveys, and observations. We interviewed 19 MAs and supervisors and 11 clinicians (9 family physicians and 2 nurse practitioners) and observed 15 MAs in practice. Qualitative analysis used the editing style. RESULTS: MAs' roles in small family medicine offices were determined by MA career motivations and clinician-MA relationships. MA career motivations comprised interest in health care, easy training/workload, and customer service orientation. Clinician-MA relationships were influenced by how MAs and clinicians respond to their perceptions of MA clinical competence (illustrated predominantly by comparing MAs with nurses) and organizational structure. We propose a model, trust and verify, to describe the structure of the clinician-MA relationship. This model is informed by clinicians' roles in hiring and managing MAs and the social familiarity of MAs and clinicians. Within the RCC framework, these findings can be seen as previously undefined constraints and freedoms in what is known as the Complex Responsive Process of Relating between clinicians and MAs. CONCLUSIONS: Improved understanding of clinician-MA relationships will allow a better appreciation of how clinicians and MAs function in family medicine teams. Our findings may assist small offices undergoing practice transformation and guide future research to improve the education, training, and use of MAs in the family medicine setting.

Faith-based HIV prevention and counseling programs: findings from the Cincinnati census of religious congregations.

Congregations are well positioned to address HIV in their communities, but their response to HIV has been mixed. An emerging literature describes HIV programming in urban, predominantly black congregations, but population-based data remain limited. This study examined the levels of HIV prevention and counseling programs and associated factors (e.g., religious, organizational) by using data from a phone census of congregations in the Greater Cincinnati area (N = 447). Over 10 % of congregations (36 % of Black Protestant and 5-18 % of other types of congregations) offered HIV education/prevention alone or in combination with counseling or with counseling and testing. Path analysis results showed notable significant (p < 0.05) total effects of theology-polity on HIV prevention/counseling programs, but these effects were fully mediated by other factors, including other community work and racial composition. The levels of HIV programming in this study were high by national standards, but further outreach is needed in high-risk African American communities.

Disclosure and self-report of emotional, social, and physical health in children and adolescents with chronic pain--a qualitative study of PROMIS pediatric measures.

OBJECTIVES: To examine the content validity of the Patient-Reported Outcomes Measurement Information System pediatric measures, including the pain interference scale, among children and adolescents (aged 8-18 years) who experience chronic pain. To describe children's understandings of the health domain constructs and elucidate verbal and conceptual aspects of self-reported pain-related functioning, which shape disclosure and reporting. METHODS: 34 children and youth with diagnoses of juvenile idiopathic arthritis or noninflammatory chronic pain completed semistructured and cognitive interviews exploring the meaning, experience, and expression of up to 4 of the Patient-Reported Outcomes Measurement Information System pediatric domains: anger, anxiety, depressive symptoms, fatigue, pain interference, and peer relationships. Team-based thematic and content analyses were conducted. RESULTS: Clear verbal and social-cognitive differences were observed in representations and accounts of the domain-experiences across age-groups, but we noted little, if any, evidence of problems with content validity. CONCLUSIONS: Findings suggest the importance of a rigorous developmental approach for understanding the verbal and cognitive dimensions of pediatric self-reports and patient-reported outcomes.

Improving technical information use: what can be learnt from a manager's perspective?

Conservation practice reportedly suffers from low use of technical information. Understanding of factors that affect the influence of technical information on management decision-making is limited. We sought to identify leverage points for improved technical information dissemination in the New South Wales Parks and Wildlife Service, Australia, given the significant recent investments in monitoring and evaluation that had been made. We did so by exploring the inter-relationships between factors affecting the influence of different information types on management decisions. Results indicate that managers have a high inclination toward adaptive behavior, given they operate in an information poor environment. The most influential types of information were those that enabled interaction between information provider and recipient (e.g., staff experience and expertise). An analysis of the concordance in individuals' responses for different information types showed that neither accessibility nor organizational expectation of use was aligned with influence on decision-making. Alignment of responses also varied by work area. Raising expectations of information use or increasing access to particular types of information is therefore unlikely to result in an increase in influence on management decision-making. Rather than focussing on matching accessibility and expected use of particular information types, our results indicate that technical information uptake is best supported through existing peer networks tailored to specific work areas.

Seropositivity to Campylobacter and association with abortion and lamb mortality in maiden ewes from Western Australia, South Australia and Victoria.

This case-control study investigated associations between Campylobacter fetus or Campylobacter jejuni titre and reproductive outcomes in 22 flocks of Merino and non-Merino maiden ewes aged 1-2 years old. Campylobacter titres were also determined for multiparous ewes aged 3 years or older on the same farms. C. fetus 'positivity' (titre ≥1:80) was detected for 12% (57/462; 95% confidence interval [95% CI] 9.6 to 15.6) of maiden ewes and 31% (65/210; 95% CI 25.0 to 37.4) of mature ewes. The odds for failing to rear a lamb in C. fetus-'exposed' maiden ewes (titre ≥1:10) was 2.01 times that of seronegative ewes (95% CI 1.09 to 3.77; P = 0.027), but there was no association between C. fetus-'positivity' (titre ≥1:80) and failure to rise (OR 1.69; 95% CI 0.77 to 3.76; P = 0.191). C. fetus abortions were confirmed with microbial culture in one maiden ewe flock. In this flock, C. fetus titres fluctuated and often waned by lamb marking, highlighting the value of necropsies during abortion investigations. C. jejuni-'positivity' (titre ≥1:80) was detected for 44% (204/462; 95% CI 39.7 to 48.7) maiden ewes, but odds of failing to rear were decreased for C. jejuni-'positive' ewes (OR 0.52; 95% CI 0.32 to 0.83; P = 0.007). The association between Campylobacter serology and the reproductive outcome was inconsistent in these flocks. Serology should be considered in the context of other risk factors and used in conjunction with other strategies to investigate the impact of Campylobacter exposure on ewe reproductive performance such as monitoring for abortions and lamb necropsies to determine aetiological diagnosis, and vaccination trials.

Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.

The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generate spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes. We identify a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we report a prognostic role of a proliferative tumor-cell subpopulation, which associates with enhanced spatial tumor-immune interactions by CD8+ and CD4 + T-cells in the BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the potential to improve immunotherapeutic strategies and patient stratification in HGSC.

Clinical work intensity among physician specialties: how might we assess it? What do we find?

BACKGROUND: The level of work intensity associated with patient encounters has implications for quality of care, patient safety, practice management, and reimbursement. The utility of available instruments for clinical work intensity assessment is unknown. OBJECTIVE: We assessed, in the clinical setting, the performance of existing measures of work intensity that are valid for nonclinical contexts. RESEARCH DESIGN: A cross-sectional, multimeasure design involving work intensity assessments for the last patient encounter and for an entire half-day clinic session. SUBJECTS: A convenience sample of 14 providers from the following 4 specialties: family medicine, general internal medicine, neurology, and surgery. MEASURES: Perceived clinical work intensity was measured by the following 3 instruments: National Aeronautic and Space Administration-Task Load Index, Subjective Workload Assessment Technique, and Multiple Resources Questionnaire; stress was measured by the Dundee Stress State Questionnaire. Convergent validity was assessed by correlation among the instruments. RESULTS: For the last patient encounter, there was a moderate to high correlation between the work intensity instruments' scores (Pearson's r ranged from 0.41 to 0.73) and low to moderate correlation with the distress subscale of the Dundee Stress State Questionnaire (Pearson's r ranged from -0.11 to 0.46), reflecting their stress dimension. Provider personality was associated with reported levels of work intensity and stress. Similar results were obtained when the entire clinic session was the unit of reference. CONCLUSION: Existing measures of work intensity and stress appear to be valid for use in the clinical setting to generate evidence on perceived intensity and stress experienced by providers in the performance of medical services.

Temporal and subjective work demands in office-based patient care: an exploration of the dimensions of physician work intensity.

BACKGROUND: Physician work intensity (WI) during office-based patient care affects quality of care and patient safety as well as physician job-satisfaction and reimbursement. Existing, brief work intensity measures have been used in physician studies, but their validity in clinical settings has not been established. OBJECTIVES: Document and describe subjective and temporal WI dimensions for physicians in office-based clinical settings. Examine these in relation to the measurement procedures and dimensions of the SWAT and NASA-TLX intensity measures. DESIGN: A focused ethnographic study using interviews and direct observations. PARTICIPANTS: Five family physicians, 5 general internists, 5 neurologists, and 4 surgeons. METHODS: Through interviews, each physician was asked to describe low and high intensity work responsibilities, patients, and events. To document time and task allotments, physicians were observed during a routine workday. Notes and transcripts were analyzed using the editing method in which categories are obtained from the data. RESULTS: WI factors identified by physicians matched dimensions assessed by standard, generic instruments of work intensity. Physicians also reported WI factors outside of the direct patient encounter. Across specialties, physician time spent in direct contact with patients averaged 61% for office-based services. CONCLUSIONS: Brief work intensity measures such as the SWAT and NASA-TLX can be used to assess WI in the office-based clinical setting. However, because these measures define the physician work "task" in terms of effort in the presence of the patient (ie, intraservice time), substantial physician effort dedicated to pre- and postservice activities is not captured.

Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor.

PURPOSE: The aim of this study was to evaluate the effects of unilateral and bilateral ventralis intermedius (Vim) deep brain stimulation (DBS) on mood and motor function. METHODS: Thirty-one consecutive medication refractory patients with essential tremor who underwent unilateral or bilateral Vim DBS at University of Florida and returned for at least 6 -month follow-up completed the Visual Analog Mood (VAMS), the Beck Depression Inventory (BDI), and the Tremor Rating Scale (TRS) before and after surgery. We excluded all patients who were implanted at other institutions. RESULTS: The tense subscale of the VAMS improved significantly in both the unilateral and bilateral DBS groups (P < 0.001). On the VAMS afraid subscale, only the bilateral group trended toward improvement (P = 0.075). There were no significant changes for either group for the happy, confused, sad, angry, energetic or tired VAMS scores. TRS subscale scores all improved after unilateral and bilateral Vim DBS surgery (P < 0.001). CONCLUSIONS: Feelings of tenseness, tremor severity and ADLs improved following unilateral or bilateral Vim DBS for ET.

Translating questionnaire items for a multi-lingual worker population: the iterative process of translation and cognitive interviews with English-, Spanish-, and Chinese-speaking workers.

BACKGROUND: The increasing ethnic diversity of the US workforce has created a need for research tools that can be used with multi-lingual worker populations. Developing multi-language questionnaire items is a complex process; however, very little has been documented in the literature. METHODS: Commonly used English items from the Job Content Questionnaire and Quality of Work Life Questionnaire were translated by two interdisciplinary bilingual teams and cognitively tested in interviews with English-, Spanish-, and Chinese-speaking workers. RESULTS: Common problems across languages mainly concerned response format. Language-specific problems required more conceptual than literal translations. Some items were better understood by non-English speakers than by English speakers. De-centering (i.e., modifying the English original to correspond with translation) produced better understanding for one item. CONCLUSIONS: Translating questionnaire items and achieving equivalence across languages require various kinds of expertise. Backward translation itself is not sufficient. More research efforts should be concentrated on qualitative approaches to developing useful research tools.

Core neuropsychological characteristics of children and adolescents with 22q11.2 deletion.

BACKGROUND: The 22q11.2 deletion syndrome (22qDS) confers high risk for intellectual disability and neuropsychological/academic impairment, although a minority of patients show average intelligence. Intellectual heterogeneity and the high prevalence of psychiatric diagnoses in earlier studies may have obscured the prototypical neuropsychological profile in 22qDS. METHODS: We examined intelligence, memory, reading and mathematical processes in 31 children/adolescents with 22qDS, selected for educational underachievement and an absence of psychiatric diagnoses, using standardised, psychometrically matched instruments that specify how typical a score is for a given intelligence quotient (IQ). RESULTS: Corroborating earlier findings, verbal IQ was significantly superior to performance IQ; verbal memory and basic reading were relative strengths; and visual/spatial memory was a relative weakness. All four findings transcended performance characteristics that are typical of low-IQ individuals. Rote learning yielded the highest score; reading comprehension, numerical operations and mathematical reasoning were among the lowest-performed academic domains. Albeit in the expected direction, performance in the respective components could not be clearly differentiated from what is IQ-appropriate. CONCLUSIONS: A superiority of verbal intelligence over non-verbal intelligence, relative strengths in verbal memory and basic reading, and a relative weakness in visual/spatial memory are likely to be core characteristics of children/adolescents with 22qDS, transcending performance features that are typical of individuals with low IQ.

Conditions that influence a primary care clinician's decision to refer patients for depression care.

The objective of this study was to identify conditions that influence primary care clinicians' referral decisions related to depression care. Forty primary care clinicians (15 general internists, 10 nurse practitioners, and 15 family practice physicians) were included in this study. The clinicians participated in semistructured interviews and completed two quantitative instruments (with 33 items on depression treatment decision making and 32 items on provider attitudes toward psychosocial care). Data analysis revealed that several conditions influence a clinician's decision to refer a depressed patient to a mental health specialist: the patient's resources, the clinician's comfort in prescribing antidepressants and counseling patients with depression, and familiarity with a mental health specialist and practice environment. The decision to refer a patient with depression to a mental health specialist is a complex process involving the clinician, patient, and practice-related issues. Understanding these relationships may provide strategies to improve depression care management and lead to the design of depression care quality-improvement interventions that accommodate primary care practice context. The findings from this study suggest a need to increase mental health training opportunities for primary care clinicians to strengthen their skills and comfort level in managing depressed patients and encourage the development of relationships between primary care clinicians and mental health specialists to facilitate timely and accessible mental health care for patients.

Ovine abortion and stillbirth investigations in Australia.

Fetal loss and lamb mortality between mid-pregnancy and weaning are important economic and welfare issues for the Australian sheep industry. The aim of this study was to determine common causes of ovine abortion and stillbirths based on submissions to veterinary laboratories and identify factors that impact the determination of an aetiological diagnosis. Data for 529 investigations on abortion or stillbirth between 2000 and 2018 were retrieved from four state veterinary laboratories in Western Australia, South Australia, Victoria and Tasmania. An aetiological diagnosis was made for 57% of investigations. Investigations that included placental tissue samples were more than twice as likely to have an aetiological diagnosis compared to investigations without placenta (P = 0.017, 95% confidence interval 1.1, 4.5). Of the investigations where an aetiological diagnosis was made, 81% involved infectious abortion, with Campylobacter spp. (32%), Listeria spp. (25%) and Toxoplasma gondii (9%) being the three most common abortigenic pathogens implicated. The remaining 19% of investigations with an aetiological diagnosis included a wide range of infectious and non-infectious diseases. Diagnoses made varied year to year and between states. No evidence of exotic abortigenic pathogens were reported. Veterinary practitioners can improve the probability of an aetiological diagnosis by emphasising to farmers the importance of collecting any aborted material, especially placenta, and appropriate storage of the tissues until they can be submitted to the laboratory. Some diseases that cause abortion in Australian sheep have zoonotic potential, and veterinary practitioners play an important role in educating clients about appropriate hygiene when handling pregnant and lambing ewes or any aborted material.

Brain penetration effects of microelectrodes and DBS leads in STN or GPi.

OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane.

The dystrophin-associated protein (DAP) complex spans the sarcolemmal membrane linking the cytoskeleton to the basement membrane surrounding each myofiber. Defects in the DAP complex have been linked previously to a variety of muscular dystrophies. Other evidence points to a role for the DAP complex in formation of nerve-muscle synapses. We show that myotubes differentiated from dystroglycan-/- embryonic stem cells are responsive to agrin, but produce acetylcholine receptor (AChR) clusters which are two to three times larger in area, about half as dense, and significantly less stable than those on dystroglycan+/+ myotubes. AChRs at neuromuscular junctions are similarly affected in dystroglycan-deficient chimeric mice and there is a coordinate increase in nerve terminal size at these junctions. In culture and in vivo the absence of dystroglycan disrupts the localization to AChR clusters of laminin, perlecan, and acetylcholinesterase (AChE), but not rapsyn or agrin. Treatment of myotubes in culture with laminin induces AChR clusters on dystroglycan+/+, but not -/- myotubes. These results suggest that dystroglycan is essential for the assembly of a synaptic basement membrane, most notably by localizing AChE through its binding to perlecan. In addition, they suggest that dystroglycan functions in the organization and stabilization of AChR clusters, which appear to be mediated through its binding of laminin.