Effect of a Co-Located Bridging Recovery Initiative on Hospital Length of Stay Among Patients With Opioid Use Disorder: The BRIDGE Randomized Clinical Trial.

Importance: Co-located bridge clinics aim to facilitate a timely transition to outpatient care for inpatients with opioid use disorder (OUD); however, their effect on hospital length of stay (LOS) and postdischarge outcomes remains unclear. Objective: To evaluate the effect of a co-located bridge clinic on hospital LOS among inpatients with OUD. Design, Setting, and Participants: This parallel-group randomized clinical trial recruited 335 adult inpatients with OUD seen by an addiction consultation service and without an existing outpatient clinician to provide medication for OUD (MOUD) between November 25, 2019, and September 28, 2021, at a tertiary care hospital affiliated with a large academic medical center and its bridge clinic. Intervention: The bridge clinic included enhanced case management before and after hospital discharge, MOUD prescription, and referral to a co-located bridge clinic. Usual care included MOUD prescription and referrals to community health care professionals who provided MOUD. Main Outcomes and Measures: The primary outcome was the index admission LOS. Secondary outcomes, assessed at 16 weeks, were linkage to health care professionals who provided MOUD, MOUD refills, same-center emergency department (ED) and hospital use, recurrent opioid use, quality of life (measured by the Schwartz Outcome Scale-10), overdose, mortality, and cost. Analysis was performed on an intent-to-treat basis. Results: Of 335 participants recruited (167 randomized to the bridge clinic and 168 to usual care), the median age was 38.0 years (IQR, 31.9-45.7 years), and 194 (57.9%) were male. The median LOS did not differ between arms (adjusted odds ratio [AOR], 0.94 [95% CI, 0.65-1.37]; P = .74). At the 16-week follow-up, participants referred to the bridge clinic had fewer hospital-free days (AOR, 0.54 [95% CI, 0.32-0.92]), more readmissions (AOR, 2.17 [95% CI, 1.25-3.76]), and higher care costs (AOR, 2.25 [95% CI, 1.51-3.35]), with no differences in ED visits (AOR, 1.15 [95% CI, 0.68-1.94]) or deaths (AOR, 0.48 [95% CI, 0.08-2.72]) compared with those receiving usual care. Follow-up calls were completed for 88 participants (26.3%). Participants referred to the bridge clinic were more likely to receive linkage to health care professionals who provided MOUD (AOR, 2.37 [95% CI, 1.32-4.26]) and have more MOUD refills (AOR, 6.17 [95% CI, 3.69-10.30]) and less likely to experience an overdose (AOR, 0.11 [95% CI, 0.03-0.41]). Conclusions and Relevance: This randomized clinical trial found that among inpatients with OUD, bridge clinic referrals did not improve hospital LOS. Referrals may improve outpatient metrics but with higher resource use and expenditure. Bending the cost curve may require broader community and regional partnerships. Trial Registration: ClinicalTrials.gov Identifier: NCT04084392.

Emerging Adults with Diabetes in Safety-Net Care: Self-Management Influences and Patient-Provider Interactions.

Emerging adults with diabetes, particularly in underserved communities, represent a growing but less studied population whose needs may differ from older adults. This study investigated perspectives of underserved emerging adults regarding diabetes self-management influences and provider interactions. Focus groups and interviews with emerging adults in a safety-net health care setting were conducted to identify perspectives regarding self-management influences and patient-provider interactions. Diabetes was perceived as a psychological burden complicated by busy lifestyles and competing responsibilities. Lack of resources, especially financial barriers, also limited self-management. Participants often perceived diabetes visits as standardized encounters providing access to diabetes supplies but desired additional guidance appropriate to their needs and life-stage. Participants valued encouragement and positive ongoing provider relationships for tailored informational and emotional support and support from family and peers. Providers and health care systems adapting to provide or facilitate this support will be better able to optimize diabetes management at and between visits.

Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications.

There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1) in modulating 5-HTP- and psilocybin-induced HTR. Male C57BL/6J mice (11 weeks, ~30 g) were administered 5-HTP, 50-250 mg/kg i.p., 200 mg/kg i.p. after pretreatment with 5-HT/TAAR1 receptor modulators, psilocybin 0.1-25.6 mg/kg i.p. or 4.4 mg/kg i.p., immediately preceded by 5-HT/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose-dependent increase in the frequency of HTR over 20 min with attenuation by the 5-HT2AR antagonist, M100907, and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS-102221, enhanced HTR at lower doses but reduced it at higher doses. The TAAR1 antagonist, EPPTB, reduced 5-HTP- but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR, an inhibitory effect of 5-HT1AR, a bimodal contribution of 5-HT2CR and a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate psychedelic-induced HTR have important potential in the emerging therapeutic use of these compounds.

Diabetes Care Provider Perceptions Regarding Emerging Adults' Diabetes Self-Management Influences and Patient-Provider Visit Interactions Within a Safety-Net Hospital.

The increasing number of emerging adults with diabetes (EAWD) being cared for in adult health care settings requires a better understanding of the needs of EAWD and their interactions with adult health care providers (HCPs). This article describes findings from interviews with endocrinologists and diabetes nurses from a safety-net health care system to investigate HCPs' perspectives regarding influences on EAWD self-management and HCP interactions with EAWD. HCPs frequently perceived lower EAWD engagement in diabetes management, which was complicated by barriers such as the emotional burden of diabetes, busy lives and multiple responsibilities, and limited access to resources; however, HCPs valued the role of information and communication at visits in tailoring care for EAWD. Measures to tailor care should address the psychosocial burden related to the life stage goals and priorities of EAWD, identification of resources for EAWD and HCPs, and further elucidation of effective self-management guidance and communication strategies to support EAWD in safety-net settings.

I know that voice! Mothers' voices influence children's perceptions of emotional intensity.

The ability to interpret others' emotions is a critical skill for children's socioemotional functioning. Although research has emphasized facial emotion expressions, children are also constantly required to interpret vocal emotion expressed at or around them by individuals who are both familiar and unfamiliar to them. The current study examined how speaker familiarity, specific emotions, and the acoustic properties that comprise affective prosody influenced children's interpretations of emotional intensity. Participants were 51 7- and 8-year-olds presented with speech stimuli spoken in happy, angry, sad, and nonemotional prosodies by both each child's mother and another child's mother unfamiliar to the target child. Analyses indicated that children rated their own mothers as more intensely emotional compared with the unfamiliar mothers and that this effect was specific to angry and happy prosodies. Furthermore, the acoustic properties predicted children's emotional intensity ratings in different patterns for each emotion. The results are discussed in terms of the significance of the mother's voice in children's development of emotional understanding.

Hospital admissions for hyperglycemic emergencies in young adults at an inner-city hospital.

AIMS: There is limited information characterizing young adults (18-35 years) (YA) with diabetes, especially those admitted for hyperglycemic emergencies. The study aims were to examine associations of patient-level characteristics with hyperglycemic emergency hospitalization and to identify variations based on diabetes type and glycemic control. METHODS: We conducted retrospective analysis of 273 YA admitted to an inner-city hospital with diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome (HHS). T-tests, Chi-Square tests, and ANOVA identified differences in demographics, diabetes history, clinical indicators, complications/comorbidities, and hospital admission stratified separately by diabetes type (1 vs 2) and admission HbA1c < 9% (75 mmol/mol), ≥9% to 12% (108 mmol/mol), ≥12%). RESULTS: Mean admission HbA1c was 12.4% (112 mmol/ml). HbA1c was ≥9.0% for 90.5%. The main DKA/HHS trigger was medication nonadherence (57.9%), with 35.6% presenting with new-onset type 2 diabetes. Only 3.7% utilized outpatient diabetes clinics, 38.8% were re-hospitalized within the year, and 69% lacked insurance. Diabetes complications (44.7%) and psychiatric co-morbidities (35.5%) were common. Significantly more YA with type 1 diabetes had insurance, whereas YA with type 2 diabetes had higher admission HbA1c. YA with HbA1c ≥12% were more likely to be Black and lack insurance. CONCLUSIONS: YA hospitalized for DKA/HHS in an inner-city hospital tended to have severely uncontrolled diabetes. Many already had comorbidities and diabetes complications, high use of acute care services and low use of diabetes specialty services. YA characteristics varied by diabetes type and HbA1c. Overall, a substantial percentage lacked insurance, potentially impacting healthcare utilization patterns and medication adherence, and leading to DKA/HHS admissions.

Child language and parenting antecedents and externalizing outcomes of emotion regulation pathways across early childhood: A person-centered approach.

Decreases in children's anger reactivity because of the onset of their autonomous use of strategies characterizes the prevailing model of the development of emotion regulation in early childhood (Kopp, 1989). There is, however, limited evidence of the varied pathways that mark this development and their proposed antecedents and consequences. This study used a person-centered approach to identify such pathways, antecedents, and outcomes. A sample of 120 children from economically strained rural and semirural households were observed while waiting to open a gift at ages 24, 36, and 48 months. Multitrajectory modeling of children's anger expressions and strategy use yielded three subgroups. As they aged, typically developing children's strategy use (calm bids and focused distraction) increased while anger expressions decreased. Later developing children, though initially elevated in anger expression and low in strategy use, demonstrated marked growth across indicators and did not differ from typically developing children at 48 months. At-risk children, despite developing calm bidding skills, did not display longitudinal self-distraction increases or anger expression declines. Some predicted antecedents (12-24 month child language skills and language-capitalizing parenting practices) and outcomes (age 5 years externalizing behavior) differentiated pathways. Findings illustrate how indicator-specific departures from typical pathways signal risk for behavior problems and point to pathway-specific intervention opportunities.

Feasibility of a Low-Cost, Interactive Gaming System to Assess Balance in Older Women.

The use of low-cost interactive game technology for balance rehabilitation has become more popular recently, with generally good outcomes. Very little research has been undertaken to determine whether this technology is appropriate for balance assessment. The Wii balance board has good reliability and is comparable to a research-grade force plate; however, recent studies examining the relationship between Wii Fit games and measures of balance and mobility demonstrate conflicting findings. This study found that the Wii Fit was feasible for community-dwelling older women to safely use the balance board and quickly learn the Wii Fit games. The Ski Slalom game scores were strongly correlated with several balance and mobility measures, whereas Table Tilt game scores were not. Based on these findings, the Ski Slalom game may have utility in the evaluation of balance problems in community-dwelling older adults.

Time to clinical stability among children hospitalized with pneumonia.

We evaluated the performance of time to clinical stability (TCS), a longitudinal outcome measure using 4 physiologic parameters (temperature, heart rate, respiratory rate, and use of supplemental oxygen), among children enrolled in a prospective study of pneumonia hospitalizations. We calculated the time from admission to normalization for each of the 4 parameters individually along with various combinations of these parameters (≥2 parameters). We assessed for agreement between the combined TCS measures and both hospital length of stay and an ordinal severity scale (nonsevere, severe, and very severe). Overall, 323 (96.7%) of 334 included children had ≥1 parameter abnormal on admission; 70 (21%) children had ≥1 parameter abnormal at discharge. For the 4 combined measures, median TCS decreased with increasing age. Increasing TCS was associated with both longer length of stay and increasing disease severity. The simplest combined measure incorporating only respiratory rate and need for supplemental oxygen performed similarly to more complex measures including additional parameters. Our study demonstrates that longitudinal TCS measures may be useful in children with pneumonia, both in clinical settings to assess recovery and readiness for discharge, and as an outcome measure in research and quality assessments. Additional study is needed to further validate our findings.

Factors associated with growth and blood pressure patterns in children with sickle cell anemia: Silent Cerebral Infarct Multi-Center Clinical Trial cohort.

Individuals with sickle cell anemia (SCA) exhibit delayed growth trajectories and lower blood pressure (BP) measurements than individuals without SCA. We evaluated factors associated with height, weight, and BP and established reference growth curves and BP tables using data from the Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial (NCT00072761). Quantile regression models were used to determine the percentiles of growth and BP measurements. Multivariable quantile regression was used to test associations of baseline variables with height, weight, and BP measurements. Height and weight measurements were collected from a total of 949 participants with median age of 10.5 years [Interquartile range (IQR) 8.2-12.9] and median follow-up time of 3.2 years (IQR 1.8-4.7, range 0-12.9). Serial BP measurements were collected from a total of 944 and 943 participants, respectively, with median age of 10.6 years (IQR = 8.3-12.9 years), and median follow-up time of 3.3 years (IQR = 1.7-4.8). Multivariable quantile regression analysis revealed that higher hemoglobin measurements at baseline were associated with greater height (P < 0.001), weight (P = 0.000), systolic BP (P < 0.001), and diastolic BP (P = 0.003) measurements. We now provide new reference values for height, weight, and BP measurements that are now readily available for medical management.

Nocturnal enuresis in sickle cell disease.

Nocturnal enuresis is a prevalent and challenging problem in children and young adults with sickle cell disease (SCD). Limited progress has been made in elucidating etiology and pathophysiology of nocturnal enuresis in individuals with SCD. Among adults with SCD ages 18-20 years, approximately 9% report nocturnal enuresis. Nocturnal enuresis contributes to decreased health related quality of life in people with SCD, resulting in low self-esteem and sometimes social isolation. Postulated non-mutually exclusive causes of nocturnal enuresis in individuals with SCD include hyposthenuria leading to nocturnal polyuria, decreased bladder capacity or nocturnal bladder overactivity, increased arousal thresholds, and sleep disordered breathing. No evidence-based therapy for nocturnal enuresis in SCD exists. This review is focused on describing the natural history, postulated causes and a rational approach to the evaluation and management of nocturnal enuresis in children and adults with SCD.

High-throughput genetic identification of functionally important regions of the yeast DEAD-box protein Mss116p.

The Saccharomyces cerevisiae DEAD-box protein Mss116p is a general RNA chaperone that functions in splicing mitochondrial group I and group II introns. Recent X-ray crystal structures of Mss116p in complex with ATP analogs and single-stranded RNA show that the helicase core induces a bend in the bound RNA, as in other DEAD-box proteins, while a C-terminal extension (CTE) induces a second bend, resulting in RNA crimping. Here, we illuminate these structures by using high-throughput genetic selections, unigenic evolution, and analyses of in vivo splicing activity to comprehensively identify functionally important regions and permissible amino acid substitutions throughout Mss116p. The functionally important regions include those containing conserved sequence motifs involved in ATP and RNA binding or interdomain interactions, as well as previously unidentified regions, including surface loops that may function in protein-protein interactions. The genetic selections recapitulate major features of the conserved helicase motifs seen in other DEAD-box proteins but also show surprising variations, including multiple novel variants of motif III (SAT). Patterns of amino acid substitutions indicate that the RNA bend induced by the helicase core depends on ionic and hydrogen-bonding interactions with the bound RNA; identify a subset of critically interacting residues; and indicate that the bend induced by the CTE results primarily from a steric block. Finally, we identified two conserved regions-one the previously noted post II region in the helicase core and the other in the CTE-that may help displace or sequester the opposite RNA strand during RNA unwinding.

ATP-dependent roles of the DEAD-box protein Mss116p in group II intron splicing in vitro and in vivo.

The yeast DEAD-box protein Mss116p functions as a general RNA chaperone in splicing mitochondrial group I and group II introns. For most of its functions, Mss116p is thought to use ATP-dependent RNA unwinding to facilitate RNA structural transitions, but it has been suggested to assist in the folding of one group II intron (aI5γ) primarily by stabilizing a folding intermediate. Here we compare three aI5γ constructs: one with long exons, one with short exons, and a ribozyme construct lacking exons. The long exons result in slower splicing, suggesting that they misfold and/or stabilize nonnative intronic structures. Nevertheless, Mss116p acceleration of all three constructs depends on ATP and is inhibited by mutations that compromise RNA unwinding, suggesting similar mechanisms. Results of splicing assays and a new two-stage assay that separates ribozyme folding and catalysis indicate that maximal folding of all three constructs by Mss116p requires ATP-dependent RNA unwinding. ATP-independent activation is appreciable for only a subpopulation of the minimal ribozyme construct and not for constructs containing exons. As expected for a general RNA chaperone, Mss116p can also disrupt the native ribozyme, which can refold after Mss116p removal. Finally, using yeast strains with mitochondrial DNA containing only the single intron aI5γ, we show that Mss116p mutants promote splicing in vivo to degrees that correlate with their residual ATP-dependent RNA-unwinding activities. Together, our results indicate that, although DEAD-box proteins play multiple roles in RNA folding, the physiological function of Mss116p in aI5γ splicing includes a requirement for ATP-dependent local unfolding, allowing the conversion of nonfunctional RNA structure into functional RNA structure.

Mne1 is a novel component of the mitochondrial splicing apparatus responsible for processing of a COX1 group I intron in yeast.

Saccharomyces cerevisiae cells lacking Mne1 are deficient in intron splicing in the gene encoding the Cox1 subunit of cytochrome oxidase but contain wild-type levels of the bc(1) complex. Thus, Mne1 has no role in splicing of COB introns or expression of the COB gene. Northern experiments suggest that splicing of the COX1 aI5ß intron is dependent on Mne1 in addition to the previously known Mrs1, Mss116, Pet54, and Suv3 factors. Processing of the aI5ß intron is similarly impaired in mne1Δ and mrs1Δ cells and overexpression of Mrs1 partially restores the respiratory function of mne1Δ cells. Mrs1 is known to function in the initial transesterification reaction of splicing. Mne1 is a mitochondrial matrix protein loosely associated with the inner membrane and is found in a high mass ribonucleoprotein complex specifically associated with the COX1 mRNA even within an intronless strain. Mne1 does not appear to have a secondary function in COX1 processing or translation, because disruption of MNE1 in cells containing intronless mtDNA does not lead to a respiratory growth defect. Thus, the primary defect in mne1Δ cells is splicing of the aI5ß intron in COX1.

Convergent evolution of coenzyme M biosynthesis in the Methanosarcinales: cysteate synthase evolved from an ancestral threonine synthase.

The euryarchaeon Methanosarcina acetivorans has no homologues of the first three enzymes that produce the essential methanogenic coenzyme M (2-mercaptoethanesulfonate) in Methanocaldococcus jannaschii. A single M. acetivorans gene was heterologously expressed to produce a functional sulfopyruvate decarboxylase protein, the fourth canonical enzyme in this biosynthetic pathway. An adjacent gene, at locus MA3297, encodes one of the organism's two threonine synthase homologues. When both paralogues from this organism were expressed in an Escherichia coli threonine synthase mutant, the MA1610 gene complemented the thrC mutation, whereas the MA3297 gene did not. Both PLP (pyridoxal 5'-phosphate)-dependent proteins were heterologously expressed and purified, but only the MA1610 protein catalysed the canonical threonine synthase reaction. The MA3297 protein specifically catalysed a new beta-replacement reaction that converted L-phosphoserine and sulfite into L-cysteate and inorganic phosphate. This oxygen-independent mode of sulfonate biosynthesis exploits the facile nucleophilic addition of sulfite to an alpha,beta-unsaturated intermediate (PLP-bound dehydroalanine). An amino acid sequence comparison indicates that cysteate synthase evolved from an ancestral threonine synthase through gene duplication, and the remodelling of active site loop regions by amino acid insertion and substitutions. The cysteate product can be converted into sulfopyruvate by an aspartate aminotransferase enzyme, establishing a new convergent pathway for coenzyme M biosynthesis that appears to function in members of the orders Methanosarcinales and Methanomicrobiales. These differences in coenzyme M biosynthesis afford the opportunity to develop methanogen inhibitors that discriminate between the classes of methanogenic archaea.

Transcriptional regulation of the Escherichia coli gene rraB, encoding a protein inhibitor of RNase E.

The Escherichia coli RNA degradosome is a protein complex that plays a critical role in the turnover of numerous RNAs. The key component of the degradosome complex is the endoribonuclease RNase E, a multidomain protein composed of an N-terminal catalytic region and a C-terminal region that organizes the other protein components of the degradosome. Previously, the RNase E inhibitors RraA and RraB were identified genetically and shown to bind to the C-terminal region of RNase E, thus affecting both the protein composition of the degradosome and the endonucleolytic activity of RNase E. In the present work, we investigated the transcriptional regulation of rraB. rraB was shown to be transcribed constitutively from its own promoter, PrraB. Transposon mutagenesis and screening for increased beta-galactosidase activity from a chromosomal PrraB-lacZ transcriptional fusion resulted in the isolation of a transposon insertion in glmS, encoding the essential enzyme glucosamine-6-phosphate synthase that catalyzes the first committed step of the uridine 5'-diphospho-N-acetyl-glucosamine (UDP-GlcNAc) pathway, which provides intermediates for peptidoglycan biogenesis. The glmS852::Tn5 allele resulted in an approximately 50% lower intracellular concentration of UDP-GlcNAc and conferred a fivefold increase in the level of rraB mRNA. This allele also mediated a twofold increase in beta-galactosidase activity from a chromosomal fusion of the 5' untranslated region of the rne gene to lacZ, suggesting that a reduction in cellular concentration of UDP-GlcNAc and the resulting increased expression of RraB might modulate the action of RNase E.

Nursing staff perceptions of methicillin-resistant Staphylococcus aureus and infection control in a long-term care facility.

OBJECTIVES: To assess perceptions of nursing staff regarding methicillin-resistant Staphylococcus aureus (MRSA), infection control (IC) and prevention strategies, barriers to IC, and IC resources. DESIGN: Cross-sectional mixed methods study. SETTING: Atlanta Veterans Affairs (VA) long-term care facility (LTCF). PARTICIPANTS: Forty-two direct-care nursing staff employed at the LTCF during August 2006. MEASUREMENTS: Health Belief Model (HBM) guided the development of 6 focus group discussions combined with a quantitative form assessing 5 IC practices, risk perceptions, and sources of IC information. RESULTS: Only 59% of participants perceived that MRSA posed a risk to patients. Consistency of self-reported IC practices varied by specific behavior. Lack of supplies (26%) and lack of information/communication (24%) were reported as primary barriers to IC. All participants perceived patient behavior as a barrier, and all were interested in additional education about MRSA and IC. Comparing nurses with nursing assistants (NAs), nurses more frequently reported the IC professional as the most trusted information source (60% versus 0%, P < .005); NAs were more likely to trust the charge nurse (77% versus 4%, P < .001). CONCLUSION: These results suggest that the perceptions regarding the real threat of MRSA and infection transmission that would drive IC prevention behaviors in this high-risk population vary among nursing staff, as do nursing staff IC practices. This study provides insight into the complex educational and other strategies needed to implement multilevel, multidimensional IC in LTCFs.

Combinatorial microRNA target predictions.

MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript. Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.

Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease.