Amish Population Research Articles

Longitudinal assessment of cognitive decline in the Amish

AbstractBackgroundThe Modified Mini‐Mental State (3MS) is a widely used measure of global cognition. The Old Order Amish are both genetically and environmentally homogeneous, with similar years of formal education across the population. Here, we investigated the longitudinal course of cognitive function as measured by the distribution of 3MS in the Mid‐Western Amish.MethodAfter extensive QC, the 919 subjects with both baseline 3MS and AD status were analyzed. The change from 1st to 2nd measurement was used as the main longitudinal trait of interest. Mean decline differences in 4 baseline age groups (<70, 70‐80, 80‐90, >=90) were assessed. The differences in the average longitudinal decline of 3MS between AD cases and controls was assessed using Kolmogorov‐Smirnov tests and ANCOVA adjusted for age at exam and sibship.ResultThe overall baseline mean 3MS score was 89.52 [42, 100] at the mean age of exam 75.52 [60, 99]. The overall annual rate of decline was ‐0.3 [‐5, 5] from 1st to 2nd measurement (n=242) and ‐0.6 [‐2.1, 1.3] from 2nd to 3rd measurement (n = 23). The annual rate of decline was ‐0.96 [‐4, 1.7] in AD cases (n=18), ‐0.01 [‐5, 5] in AD controls (n=180) and ‐1.08 [‐5, 0.7] in an ‘Unclear’ group (n = 44). The most rapid annual decline of the 3MS was in age 80 to 90 group and the decline rate was significant (p‐value=0.004) compared to the lowest age group (<70) overall and in AD cases. In the Unclear group, the rate of decline was greatest in age 70 to 80. However, in the control group, cognition improved, with a 1.29 [‐1, 5] annual increase in age 80 to 90. The age and sibship adjusted differences in decline were significant (p‐value<2e‐10) between AD cases vs. controls as well as between Unclear vs. controls.ConclusionWe explored the changes of 3MS scores over time and demonstrated different patterns of decline by age and AD status in the Amish. Our study is the first in this homogeneous Amish population, providing a better understanding and insight into the cognitive decline examining the change in 3MS over time.

The Amish health culture and culturally sensitive health services: An exhaustive narrative review.

As the Amish population is growing, researcher and practitioner interest in the Amish health culture is also growing. This is largely due to demand from practitioners for population-specific cultural guidance. Once a small area of study, health-themed publications in Amish studies (n=246) now account for approximately one-fourth of all peer-reviewed publications, and a sizeable percentage address the health culture, i.e. Amish beliefs, practices, attitudes, decision-making processes, financing, and values. In this article, we provide a first-ever exhaustive narrative review of the Amish health culture literature (addressing Amish health conditions elsewhere). Specifically, we address Amish use of modern medicine, complementary & alternative medicine, cultural norms for birthing and intercourse, support and care for the sick and aged, health knowledge, payment for services, barriers to service access, service provider effectiveness, health programming, and ethical conflicts. Our goal is to organize the literature, synthesize findings, identify orienting perspectives, and clarify research questions and directions. Following our synthesis, we reflect on the current state of Amish health culture research, drawing particular attention to strengths and limitations of the oft-used cultural competency paradigm, and recommending more rigorous social scientific theorization of the Amish health culture.

Orthopaedic manifestations of glutaric acidemia Type 1.

PurposeGlutaric acidemia type 1 (GA1), a rare hereditary metabolic disease caused by biallelic mutations of GCDH, can result in acute or insidious striatal degeneration within the first few years of life. We reviewed the orthopaedic sequelae and management of 114 neurologically injured patients with a confirmed molecular diagnosis of GA1.MethodsWe performed a retrospective chart review spanning 28 years identifying 114 GA1 patients, most from the Old Order Amish population of Lancaster County, Pennsylvania, who were homozygous for a pathogenic founder variant of GCDH (c.1262C>T). We collected demographics, medical comorbidities, muscle tone patterns, Gross Motor Function Classification System level, gastrostomy tube status, seizure history, inpatient events, orthopaedic diagnoses and operative characteristics.ResultsOver an average follow-up of 4.7 ± 3.4 years, 24 (21%) of 114 patients had musculoskeletal problems requiring orthopaedic consultation. Scoliosis (n = 14), hip dislocation (n = 8/15 hips), hip subluxation (n = 2/three hips), and windswept hip deformity (n = 2) in the spine and hip joint were most common. In total, 35 orthopaedic surgeries were performed in 17 (71%) patients. The most common primary operations were one-stage procedures with proximal femoral varus derotation osteotomy and/or pelvic osteotomy (n = 8/14 hips) for subluxation or dislocation. In all, 11 patients had posterior spinal fusion for severe scoliosis. With the recommended metabolic management, there were no disease-specific complications in this cohort.ConclusionsChildren with GA1 who have static striatal lesions are at risk for musculoskeletal complications, especially scoliosis and hip dislocation, and appropriate operative management requires consultation with a metabolic specialist with specific considerations for fluid management and nutrition.Level of EvidenceIV

S2468 Crigler-Najjar Syndrome Type 2 in an Adult Amish Male: A Rare Case Report of Unexplained Jaundice

INTRODUCTION: Crigler-Najjar type 2 syndrome is a rare genetic disorder caused by reduced enzyme activity of glucuronyl transferase, resulting in abnormally elevated levels of unconjugated bilirubin in blood. There are an estimated 100 known cases worldwide. We present a case of Crigler-Najjar type 2 (Arias syndrome) in an adult Amish male with new unexplained jaundice. CASE DESCRIPTION/METHODS: A 28 year old male with no medical history presented with 5 days of intermittent, right upper quadrant discomfort and jaundice. He denied any associated nausea, emesis or diarrhea. The night prior to symptom onset, he consumed several alcoholic beverages along with an unknown amount of acetaminophen. Initial laboratory work-up showed AST 10 unit/L, ALT 25 unit/L, total bilirubin 5.4 mg/dL and lipase 79 unit/L. Acetaminophen level was undetectable. Abdominal ultrasound demonstrated a heterogeneous liver measuring 15.26 cm, cholelithiasis and common bile duct of 3 mm in diameter. Endoscopic ultrasound revealed similar findings. Repeat liver testing showed uptrending total bilirubin of 8.4 mg/dL with indirect predominance (8.0 mg/dL).Viral hepatitis panel was negative. His abdominal pain resolved with simultaneous improvement of bilirubin levels without intervention. Genetic testing for UGT1A1*28 was sent and he was discharged in stable condition. Outpatient follow up revealed a single copy of the UGT1A1*28 allele, confirming Crigler-Najjar type 2. DISCUSSION: Different mutations to the coding sequence of the enzyme uridine diphosphate-glucoronyl transferase (UGT1A1) result in a spectrum of diseases known as Crigler-Najjar type 1 (CN1) and Crigler-Najjar type 2 (CN2). CN1 is diagnosed in infancy and results from absent or low levels of UGT1A1 due to abnormal protein production. CN2 typically presents later in life from point mutations that result in a single amino-acid substitution, rendering decreased enzymatic activity. Under physiologic stress, patients can develop unconjugated hyperbilirubinemia. Treatment of CN2 usually involves CYP450 induction with phenobarbital, which can also help differentiate between these 2 syndromes. While only about 100 cases of CN2 are known, studies have reported nearly 20% of these within the Pennsylvania Amish population. After thorough review of our patient’s family history, patrilineal descent of this population was discovered. Therefore, while a diagnostic challenge, specific family history can improve pretest probability for genetic testing of UGT1A1*28.

Ethical considerations for treating the old order Amish

ABSTRACT The Old Order Amish are the fastest growing religious subpopulation in the United States. The Amish population, most recently estimated at 340,000, is expected to double in size during the next 20 years. While still relatively few in number, their growing population and increasing interaction with American society will likely result in more Amish individuals seeking mental health treatment. Despite the call for culturally competent mental health professionals, this population has been underrepresented in the psychotherapy literature. To the best of the author’s knowledge, this article is the first known attempt to review the ethical considerations that may arise when working with members of the Old Order Amish. This article uses the American Psychological Association’s Ethical Principles of Psychologists and Code of Conduct to frame the discussion of ethical mental health treatment with Amish individuals.

Parkinson’s Disease-Related Motor and Nonmotor Symptoms in the Lancaster Amish

Introduction: Previous research has suggested that the Amish may experience a relatively high prevalence of Parkinson’s disease (PD) and/or parkinsonian motor signs. Methods: In a large sample from the Amish community in Lancaster County, Pennsylvania, age ≥18 years, we assessed the prevalence of self-reported PD diagnosis. For those without self-reported PD diagnosis, we assessed the frequency of PD-related motor symptoms using a 9-item questionnaire that was designed by the PD Epidemiology Research Group. Lastly, we queried study participants for the presence of 2 nonmotor symptoms that have been commonly linked to PD: bowel movement frequency and daytime sleepiness. Results: Among 2,025 subjects who answered the PD questionnaire, 430 were older than 60 years. Of 430 participants ≥60 years, 5 (1.2%) reported a PD diagnosis. Of those without a PD diagnosis, 10.5% reported ≥1 and 1.2% ≥ 4 motor symptoms for the 9-item PD screening questionnaire. Of the 3,789 subjects who answered the question about bowel movement frequency, 0.7% reported ≤3 bowel movements per week. Among 1,710 subjects who answered the question about daytime sleepiness, 8.1% of the participants reported “always” sleepy during the day. Discussion: These data neither support a markedly higher PD prevalence in the older Lancaster Amish nor do they show dramatically higher motor and/or selected nonmotor symptoms than the general population. Future studies that employ more rigorous procedures for case identification and PD-specific preclinical symptoms/tests are needed to determine the potential differences and similarities among different Amish populations and between Amish and non-Amish populations.

700 A Comparison of Pediatric Burn Injuries Based on Cultural Environment

Abstract Introduction The Amish maintain cultural customs that preserve their identity minimizing assimilation into American culture and selectively use technology. Cultural beliefs and environmental situations can predispose the Amish, especially children to burn injuries. As a burn center it is important to examine demographics, incidence and causes of burn injury to bring awareness for prevention efforts. The purpose of this study was to determine if burns in Amish children are associated with greater severity when compared to non-Amish children. Methods A retrospective analysis of the burn registry at a verified burn center collected data on inpatient children < 14 years with an acute burn injury from 2012 through 2018. Children with frostbite and non-accidental burn trauma were excluded. Results Of the 273 children, 16 (5.9%) Amish children were similar to the 257 (94.1%) non-Amish children in age (mean age 4.8y, SD=3.8 vs. 4.0y, SD=3.7), male gender (63% vs. 59%) and percent needing surgery (44% vs. 26%, p=0.14). However, Amish children had a greater median injury severity score (ISS) (9.0, IQR [1, 25] vs. 1.0, [1, 4], p< 0.0001), median TBSA (19.5% [5.2, 52] vs. 4.0 [1.7, 7], p< 0.0001), median length of stay (LOS) (10.5 days [4, 50] vs. 2.0 days [1, 8], p< 0.0001), and median number of surgeries (0.5 [0, 6.5] vs. 0 [0, 1], p< 0.0074). Complications of ARDS (25%), sepsis (25%), compartment syndrome (18.8%), acute renal injury/failure (12.5%) and amputation (18.8%) were more prevalent among Amish children (all p< 0.0033) and non-existent in the non-Amish group. Amish children had a higher incidence of fire/flame burn (43.8% vs. 19.5%) and need for rehabilitation (37.5% vs. 0.8%). Conclusions In this study, Amish children had greater burn area, severity, longer LOS, more surgical interventions and complications than non-Amish children. Applicability of Research to Practice Culturally appropriate prevention efforts and education are needed to enhance existing care and burn or fire awareness with the Amish population.

De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.

Working Together: Women and Men on the Amish Family Farm in 1930s Lancaster County, Pennsylvania

Old Order Amish men did not own gasoline tractors or other large power farm implements to amplify their manhood, and Amish women did not own mechanical household appliances to symbolize their feminine role as housekeepers. Rejecting the notion of mechanized, capital-intensive agriculture in favor of traditional, labor-intensive family farming, the Old Order Amish of Lancaster County, Pennsylvania, practiced a system of labor that necessarily required the crossing of strict gender-role boundaries. Although men primarily identified as farmers and women as homemakers, agricultural success among the Amish necessitated a significant degree of cooperation and mutual labor. In the words of one Old Order Amish wife of the 1930s, “On our farm I did whatever needed to be done.” Employing data from the federal government’s Study of Consumer Purchases, the authors investigate how the traditional gender arrangements of the county’s Amish population enabled them to survive the Great Depression more successfully than other agrarian communities. [Abstract by author.]

Retinal Sensitivity Using Microperimetry in Age-Related Macular Degeneration in an Amish Population.

To evaluate retinal sensitivity (RS) by mesopic and scotopic microperimetry (MP-1S) in an elderly Amish population with age-related macular degeneration (AMD). Mesopic and scotopic microperimetric testing was performed in 148 eyes of 77 elderly Amish subjects (age > 50 years) from Pennsylvania using a retinal function analyzer. Scotopic testing was performed using a 2.0 log unit neutral density filter following 30 minutes of dark adaptation. All subjects underwent complete ophthalmic examinations, including spectral-domain optical coherence tomography, fundus autofluorescence, infrared reflectance imaging, and flash color fundus photography. Certified graders at Doheny Image Reading Center identified subjects with evidence of AMD as defined by the Beckman classification and quantified drusen volume. RS in subjects with and without AMD was compared. Correlations between RS and drusen burden were analyzed. Ten eyes with incomplete MP-1S exams were excluded from the final analysis. Among the 138 eyes from 77 subjects included in the final analysis, 42 eyes from 29 subjects had evidence of early or intermediate AMD. The mean age of subjects with AMD was 69.65 years ± 13.81 years versus 63.04 years ± 12.69 years in those without AMD (P = .06). Mesopic RS was 18.8 dB ± 2.1 dB in subjects with AMD and 19.6 dB ± 1.4 dB in those without AMD (P = .07). Scotopic RS was significantly lower (P = .04) in subjects with AMD (15.9 dB ± 2.9 dB) compared with those without AMD (17.3 dB ± 2.4 dB). There was no relationship between mesopic RS and either drusen area (r = -0.06; P = .32) or drusen volume (r = -0.08; P = .30). There was a trend for an association between scotopic RS and both drusen area (r = -0.39; P = .24) and drusen volume (r = -0.36; P = .30). In an elderly Amish population, eyes with early or intermediate AMD show a greater reduction in scotopic RS than mesopic RS, suggesting that rod function is more severely affected than cone function. Drusen area and volume measurements better correlated with scotopic RS. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e236-e241.].

AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.

Development of a Novel Next-Generation Sequencing Assay for Carrier Screening in Old Order Amish and Mennonite Populations of Pennsylvania

Genetically isolated populations, such as the Old Order Amish and Old Order Mennonite communities, have an increased incidence of specific autosomal recessive disorders caused by the founder effect. In these populations, robust expanded carrier screening and diagnostic testing have the potential to reduce overall medical costs and improve patient outcomes. A novel next-generation sequencing assay was developed using anchored multiplex PCR technology (ArcherDX) for 162 different genetic syndromes caused by 202 pathogenic variants consisting of 150 single-nucleotide changes, 43 small insertion/deletions, and 9 large deletions (>20 nucleotides). To assess the accuracy of the screening panel results, 48 samples were selected on the basis of prior whole exome sequencing results. An additional 15 samples were chosen specifically to validate SMN1 and SMN2 copy number analyses. Collectively, the screening panel detected 273 pathogenic single-nucleotide or small insertion/deletion variants, 35 copy number variations, and 1 chromosomal abnormality (Klinefelter syndrome). Concordance with prior whole exome sequencing was 100%. By using a novel next-generation sequencing workflow, a successful targeted gene variant panel was developed for the Old Order Amish and Old Order Mennonite populations of Lancaster County, Pennsylvania. Population-wide carrier screening may help decrease the morbidity and mortality of these conditions in the high-risk populations.

Comparison of Homozygous for Delta F508 Mutation Nutritional Status, Lung Function Outcomes, Bacterial Growth, Antibiotic Treatments and Therapeutic Outcomes between the Amish and Non-Amish in a Single Pediatric Cystic Fibrosis Centre: A Retrospective Case-Controlled Study

There exists evident differences in the health and the care received of the Amish people in comparison to the general population. Amish patients were 100% homozygous for delta F508 mutation versus 12% in the non-Amish population (P=0.057). The Amish community was prescribed dietary supplements at a rate of 89% versus 50% for non-Amish (P=0.087). BMI > 75th percentile was 51.25% in Amish patients and 61.25% in non-Amish patients (P=0.31). Mean FEV1 value was 83.6% versus 100% while mean FEF 25-75 value was 58% versus 86% for Amish and nonAmish people respectively. There was substantial variance in the number of episodes of the same infection per patient between Amish and non-Amish population (1 IQR 0–1 versus 0 IQR 0–1; p=0.012). The rate of antibiotic prescribing per patient in the Amish group was 7.9 perceptions versus 2.2 prescriptions. The study aims to create the best possible treatment and the highest quality of life for patients with cystic fibrosis. Our manuscript creates a paradigm for future studies on the delta F508 mutation, nutrition supplements, body mass index (BMI), forced expiratory volume in 1 second (FEV1), forced expiratory flow (FEF 25-75), airway microbial organisms and changes in antibiotic treatments in Amish compared to the non-Amish group, as well as developing a platform for an Amish community health program.

Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.

No evidence for airborne transmission of Toxoplasma gondii in a very high prevalence area in Lancaster County.

Background:Toxoplasma gondii (T. gondii) has been associated with acute food-borne illness, chronic low-grade inflammation, neuropsychiatric conditions and reactivation of chronic latent infection in immunocompetent hosts. Primary infection with T. gondii in pregnant women can lead to congenital toxoplasmosis. In addition to well-known oral tissue-cyst or oocyst ingestion, we hypothesized that the very high prevalence of T. gondii in certain populations exposed to agricultural dust could be, in part, a consequence of airborne infection with oocysts.Methods:Wo collected environmental dust samples from an area with a reportedly high T. gondii seroprevalence in the Old Order Amish population, in Lancaster, Pennsylvania. Samples included: a) air filters from air-conditioning units; b) swabs of settled dust; and c) vacuum filters containing airborne field dust. Pools of the swabs and shredded sub-samples of the air filters were fed to pigs, with inoculation into mice of heart tissue from seroconverted pigs. We also investigated the presence of T. gondii DNA using PCR amplification.Results:Only one pig seroconverted. However, bioassay of pig heart tissue further inoculated into mice showed no evidence of T. gondii infection. Consistently, no evidence of T. gondii DNA was revealed in any sample.Conclusions:No evidence of airborne transmission was found in the environmental samples that were examined.

Creating Culturally Competent and Responsive Mental Health Services: A Case Study Among the Amish Population of Geauga County, Ohio.

Providing effective mental health services requires knowledge about and cultural competence across a wide array of beliefs and practices. This study provides an example of a successful project to improve public mental health service delivery in an Amish community. County boards of mental health in a rural area of Northeast Ohio contacted researchers in 1998 to provide assistance in reaching the Amish community because of a concern that mental health services were not being utilized by the Amish population. Following meetings with community leaders, changes were made to improve the relationships of service providers and public funding agencies with the local Amish community, disseminate information about mental health concerns and services, and improve accessibility to mental health services. In 2013, a follow-up analysis of records found a 320% increase in public mental health service utilization by the Amish community within the first five years after these changes were made.

Wholesale produce auctions and regional food systems: The case of Seneca produce auction

AbstractProduce auctions are local aggregation points that facilitate access for small-scale fruit, flower and vegetable farmers to wholesale buyers from a broader geography. Buyers purchase lots from multiple farmers to fulfill wholesale demand and then retail the product to the consumers. Sales are held multiple times per week to create a consistent supply for buyers and a regular market for the farmers. With over 70 produce auctions located in eastern North America, this is a growing trend of intermediated markets. Currently, there are six active produce auctions in New York State, with two more in planning stages. Produce auctions have a positive economic impact on the communities in which they are located, as well as on those who sell and/or buy at the auction. Community values inherent to these populations contribute to the success of produce auctions as an intermediated market. As the auction market channel continues to grow, buyer and consumer education on the benefits of local auctions is important. As these auctions are based in horse-and-buggy communities, extension education needs to be tailored to Amish and Mennonite populations. Auction houses, as well as farmers, will need to stay current with federal food safety regulations and market-based requirements to remain competitive.

Synthesis and Characterization of the R27S Genetic Variant of Insulin-like Peptide 5.

We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analogue that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status, and receptor-based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analogue to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP4), suggesting an alternative basis for the observed effect. In preparation of this synthetically challenging hormone, we have introduced several improvements such as implementation of isoacyl chemistry for high-efficiency preparation of INSL5 B-chain and selective intramolecular A6-11 disulfide formation as a first step in sequential disulfide assembly.

Ellis–Van Creveld syndrome and its anesthetic implications

Ellis–Van-Creveld syndrome (EVC), otherwise known as chondroectodermal or mesoectodermal dysplasia, is an autosomal recessive disorder found in the Amish population of Pennsylvania in the USA, with the incidence of 1:244,000 for the general population. The classical syndrome encompasses a tetrad of clinical manifestations, including di sproportionate dwarfism, postaxial polydactyly, ectodermal dysplasia (mainly affecting the teeth, nails, and hair), and congenital heart disease (CHD). Additional involvement may occur in organs of endodermal origin, such as the pulmonary, renal, gastrointestinal (hepatic and pancreatic), hematologic, and central nervous systems. The perioperative care of a 2-year girl who underwent surgical correction of supernumerary digits is presented here.

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration.