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Adenoid cystic carcinoma (ACC) of the breast is an exceptionally rare malignancy, accounting for less than 0.1% of all breast cancers. Despite its favorable prognosis, optimal management remains undefined due to its rarity and lack of consensus guidelines. We report a case of recurrent ACC of the breast, illustrating treatment challenges and the need for individualized management. A 64-year-old woman presented with a palpable mass in her left breast; imaging and biopsy confirmed ACC with very poor hormone receptor positivity. She started neoadjuvant chemotherapy but discontinued after 3 cycles due to severe neutropenia and lack of response. She then underwent breast-conserving surgery and radiotherapy. Three years later, she developed a local recurrence. Imaging and biopsy reconfirmed ACC and a subsequent total mastectomy achieved clear margins. Local recurrence of breast ACC can occur despite chemotherapy, surgery, and radiotherapy. Ineffectiveness of chemotherapy and recurrence after breast-conserving surgery suggest mastectomy might offer better local control. Hormone receptor positivity raises considerations for hormonal therapy, not standard for typically triple-negative ACC. The rarity of ACC complicates establishing standard protocols, necessitating personalized treatment plans based on tumor and patient factors. Recurrent breast ACC presents management challenges due to rarity and unpredictable behavior. More aggressive surgery and tailored treatment may improve outcomes. Further research is essential to develop evidence-based guidelines for managing this rare carcinoma., (© 2024 The Authors.)

Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid disorder. Affected patients often remain undiagnosed until the age of 20-30 years, when they have already developed significant neurologic disease that may not be reversible. An elevated plasma cholestanol concentration has been accepted as a diagnostic criterion for CTX for decades., Objective: Full biochemical characterization was performed for three genetically and clinically confirmed atypical CTX cases with normal plasma cholestanol levels., Methods: Clinical assessment and genetic/biochemical testing for patients with CTX was performed by their physician providing routine standard of care., Results: We report three new atypical CTX cases with large extensor tendon xanthomas but normal plasma cholestanol levels. All three cases had marked elevations of bile acid precursors and bile alcohols in plasma and urine that decreased on treatment with chenodeoxycholic acid. We also review eight published cases of atypical CTX with normal/near normal circulating cholestanol levels., Conclusion: The atypical biochemical presentation of these cases provides a diagnostic challenge for CTX, a disorder for which cholestanol has been believed to be a sensitive biomarker. These cases demonstrate measurements of plasma cholestanol alone are insufficient to exclude a diagnosis of CTX. The data presented is consistent with the concept that bile acid precursors and bile alcohols are sensitive biomarkers for atypical CTX with normal cholestanol, and that such testing is indicated, along with CYP27A1 gene analyses, in patients presenting with significant tendon and/or tuberous xanthomas and/or neurologic disease in early adulthood despite normal or near normal cholesterol and cholestanol levels., Competing Interests: Declaration of competing interest Andrea DeBarber is an employee of Oregon Health & Science University, Portland, OR, an academic health center reference laboratory providing laboratory services to healthcare providers throughout the United States focusing on biochemical confirmation of genetic diseases of cholesterol synthesis; Consultant: Leadiant Biosciences, Travere Therapeutics and Mirum Pharma. The OHSU Foundation and OSHU Departments have received gifts from Travere Therapeutics. These gifts, which have not been made specifically in connection with this research, have been reviewed by the OHSU integrity office. Serves as a volunteer Medical and Scientific Advisory Board member for the CTX Alliance and the United Leukodystrophy Foundation. Ernst J. Schaefer is an employee of Boston Heart Diagnostics, Framingham, MA, a reference laboratory providing laboratory services to healthcare providers throughout the United States focusing on cardiovascular disease prevention. Jenny Do; no disclosures. Joseph W. Ray; no disclosures. Austin Larson; Advisory activities for Illumina, Tisento, UCB. Institutional grants; Travere, Astellas, Neuren, Entrada and Stealth. Samantha Redder; no disclosures. Maya Fowler; no disclosures. P Barton Duell is an employee of Oregon Health & Science University, Portland, OR, an academic health center reference laboratory providing laboratory services to healthcare providers throughout the United States focusing on biochemical confirmation of genetic diseases of cholesterol synthesis; Advisory activities: Akcea/Ionis, Esperion, Regeneron, Kaneka, Novo Nordisk. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere. Also serves as a volunteer Medical and Scientific Advisory Board member for the CTX Alliance., (Copyright © 2024. Published by Elsevier Inc.)

Authors of previous studies of patients with acute hamstring strains have reported injury to the biceps femoris and semitendinosus (ST) in 50% to 100% and 0% to 30%, respectively. This retrospective case series of hamstring injuries in National Collegiate Athletic Association Division I collegiate athletes exhibited an injury pattern on ultrasound imaging that differed from what would be expected based on prior literature. We examined ultrasound images of 38 athletes with acute hamstring strains for injury location (proximal muscle, proximal myotendinous junction, midportion of muscle, distal muscle) and affected muscles (biceps femoris, ST, or semimembranosus). Twenty-six athletes (68.4%) injured the ST, and 9 athletes (23.7%) injured the biceps femoris long head. Most athletes (23, 60.5%) injured the proximal portion of the muscle or myotendinous junction. Though this study had many limitations, we demonstrated more frequent involvement of the ST and less frequent involvement of the biceps femoris than reported in the literature., (© by the National Athletic Trainers’ Association, Inc.)

Walled-off pancreatic necrosis (WOPN) is a local complication of acute necrotizing pancreatitis frequently requiring intervention. Treatment is typically through the coordinated efforts of a multidisciplinary team. Current management guidelines recommend a step-up approach beginning with minimally invasive techniques (percutaneous or transmural endoscopic drainage) followed by escalation to more invasive procedures if needed. Although the step-up approach is an evidence-based treatment paradigm for management of pancreatic fluid collections, it lacks guidance regarding optimal invasive technique selection based on the anatomic characteristics of pancreatic fluid collections. Similarly, existing cross-sectional imaging-based classification systems of pancreatic fluid collections have been used to predict disease severity and prognosis; however, none of these systems are designed to guide intervention. We propose a novel classification system which incorporates anatomic characteristics of pancreatic fluid collections (location and presence of disconnected pancreatic duct) to guide intervention selection and clinical decision making. We believe adoption of this simple classification system will help streamline treatment algorithms and facilitate cross-study comparisons for pancreatic fluid collections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Isolated first rib stress fractures in athletes are thought to be rare. In this case series, 3 National Collegiate Athletic Association Division I athletes developed isolated first rib stress fractures over the span of 1 year, indicating that these injuries may occur more often than previously understood. These fractures can be easily missed because of the low incidence, lack of clinical suspicion, and vague presentation. Further, radiographs can fail to reveal such fractures. To our knowledge, this is the largest case series of athletes with first rib stress fractures presenting with vague rhomboid interscapular pain. We also demonstrated that ultrasound successfully visualized these injuries; in the hands of an ultrasonographer or clinical provider trained in musculoskeletal ultrasound, this technique offers an advantageous point-of-care screening imaging modality., (© by the National Athletic Trainers’ Association, Inc.)

Abstract: Infectious mononucleosis (IM) is a common illness in children and young adults caused primarily by the Epstein-Barr Virus (EBV). Transmission occurs primarily through sharing oral secretions, thus IM is known as the "kissing disease." Common clinical manifestations include fever, pharyngitis, posterior cervical lymphadenopathy, and splenomegaly. Atypical lymphocytosis and transaminase elevations are common, and the diagnosis of IM is confirmed with laboratory findings of a positive heterophile antibody ("Monospot"), polymerase chain reaction, or antibodies specific to EBV. Individuals with acute IM may be quite symptomatic and not feel well enough to participate in sports. Splenic enlargement is common, with rupture a relatively rare occurrence, typically occurring within a month of symptom onset, but this risk complicates sports participation, and is often the reason for restricting activity. The management of IM is primarily supportive, with no role for antivirals or corticosteroids. The variability of clinical presentation and the risk of splenic rupture in patients with IM present clinicians with challenging return to play/return to sport (RTS) decisions. This position statement updates the Evidence-Based Subject Review on Mononucleosis by the American Medical Society for Sports Medicine published in 2008 and reviews the epidemiology, clinical manifestations, laboratory assessment, and management including RTS for the athlete with IM. This statement also addresses complications, imaging, special considerations, diversity and equity considerations, and areas for future clinical research. Understanding the evidence regarding IM and sport is essential when communicating with athletes and their families and incorporating shared decision-making in the RTS decision., Competing Interests: Dr. Putukian is a consultant and Chief Medical Officer for Major League Soccer, serves as senior advisor for the NFL Head, Neck & Spine Committee, and as a team physician for US Soccer. She has written a chapter for UpToDate, and serves on several other committees and as a research advisor but has no conflicts of interest to report. The Publications Committee of AMSSM contacted the lead author (MP) of the original Evidence-Based Subject Review on Mononucleosis and the Athlete10 with the request to chair and update the 2008 Position paper to a Society Position Stand; a co-author on the 2008 paper (CAM) was chosen as co-chair. A call for nominations that included the AMSSM membership at large, the AMSSM Diversity Special Interest Group and the AMSSM Women in Leadership Group was performed, and the Chair and Co-chair selected the writing group that included one or more representatives from each group, an outside consultant who provided expertise in imaging, and the services of an outside librarian. The lead author created a Project Plan that included the proposed outline and writing group which was approved by the AMSSM Board of Directors. One of the selected writing group members decided to withdraw from participating based on time commitments. All final authors have disclosed financial and other relevant conflicts of interest, if any, related to the research and written presentation of their work., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 infants with non-syndromic A/M, of whom 38% (N = 492) were diagnosed with co-occurring major defects. Top combinations included: hydrocephalus, ventricular septal defect, and spinal anomalies (OER 58.4); microphthalmia and anomalies of the aorta (OER 55.4); and cleft lip with or without cleft palate and rib or sternum anomalies (OER 32.8). Some combinations observed in our study may represent undiagnosed/atypical presentations of known A/M associations or syndromes, or novel syndromes yet to be described in the literature. Careful evaluation of infants with multiple birth defects including A/M is warranted to identify individuals with potential genetic or chromosomal syndromes., (© 2022 Wiley Periodicals LLC.)

Objectives: The current lack of agreement regarding standardized terminology in musculoskeletal and sports ultrasound presents challenges in education, clinical practice, and research. This consensus was developed to provide a reference to improve clarity and consistency in communication., Methods: A multidisciplinary expert panel was convened consisting of 18 members representing multiple specialty societies identified as key stakeholders in musculoskeletal and sports ultrasound. A Delphi process was used to reach consensus which was defined as group level agreement >80%., Results: Content was organized into seven general topics including: 1) General Definitions, 2) Equipment and Transducer Manipulation, 3) Anatomic and Descriptive Terminology, 4) Pathology, 5) Procedural Terminology, 6) Image Labeling, and 7) Documentation. Terms and definitions which reached consensus agreement are presented herein., Conclusions: The historic use of multiple similar terms in the absence of precise definitions has led to confusion when conveying information between colleagues, patients, and third-party payers. This multidisciplinary expert consensus addresses multiple areas of variability in diagnostic ultrasound imaging and ultrasound-guided procedures related to musculoskeletal and sports medicine., (© 2022 American Institute of Ultrasound in Medicine.)

Objective: To investigate 2- to 5-way patterns of defects co-occurring with orofacial clefts using data from a population-based registry., Design: We used data from the Texas Birth Defects Registry for deliveries between 1999 and 2014 to Texas residents, including 1884 cases with cleft palate (CP) and 5289 cases with cleft lip with or without cleft palate (CL±P) without a known syndrome. We identified patterns of defects co-occurring with CP and with CL±P observed more frequently than would be expected if these defects occurred independently. We calculated adjusted observed-to-expected ( O / E ) ratios to account for the known tendency of birth defects to cluster nonspecifically., Results: Among infants without a syndrome, 23% with CP and 21% with CL±P had at least 1 additional congenital anomaly. Several combinations of defects were observed much more often than expected. For example, the combination of CL±P, congenital hydrocephaly, anophthalmia, and other nose anomalies had an O / E ratio of 605. For both CP and CL±P, co-occurrence patterns with the highest O / E ratios involved craniofacial and brain abnormalities, and many included the skeletal, cardiovascular, and renal systems., Conclusions: The patterns of defects we observed co-occurring with clefts more often than expected may help improve our understanding of the relationships between multiple defects. Further work to better understand some of the top defect combinations could reveal new phenotypic subgroups and increase our knowledge of the developmental mechanisms that underlie the respective defects.

Background: The population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood., Methods: We analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects., Results: Among 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of defects with the highest O/E ratio (193.8) encompassed the diaphragm, spine, spleen, and heart defects. Fourteen patterns involved heart and spine defects with or without rib defects. Ten additional patterns primarily involved two hallmark components of VACTERL association (specifically, vertebral defects, anal atresia, cardiac defects, renal, or limb defects, but not tracheoesophageal fistula)., Conclusions: Our analyses provide a description of the birth defect co-occurrence patterns in a multi-ethnic, population-based sample, and revealed several patterns of interest. This work complements prior work that has suggested etiologic connections between select defects (e.g., diaphragmatic hernia and heart and spleen anomalies; heart and spine defects)., Impact: In this large-scale, population-based study of birth defect co-occurrence patterns, we found several birth defect combinations of potential interest that warrant further investigation: congenital diaphragmatic hernia, heart, spine, and spleen defects and scimitar syndrome with vertebral defects. The majority of patterns of co-occurring defects observed more frequently than expected involved multiple defects within the same system and combinations suggestive of known associations. Nearly all of the top patterns (beyond the same system and those suggestive of known associations) involved organ systems that are components of the VACTERL association, with heart, spine, and rib defect patterns being the most common., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Sports ultrasound is commonly used by sports medicine physicians to enhance diagnostic and procedural accuracy. This expert consensus statement serves as an update to the 2015 American Medical Society for Sports Medicine recommended sports ultrasound curriculum for sports medicine fellowships. Although written in the context of the American sports medicine fellowship training model, we present a stepwise progression in both diagnostic and interventional sports ultrasound that may be applicable to the broader sports medicine community. The curriculum is divided into 12 units with each unit including didactic instructional sessions, practical hands-on instruction, independent scanning practice sessions and mentored clinical experience. To assist with prioritisation of learning, we have organised relevant pathology and procedures as essential , desirable and optional The expanded content can serve as an outline for continuing education postfellowship or for any physician to further advance their sports ultrasound knowledge and skill. We also provide updated scanning protocols, sample milestones and a sample objective structured clinical examination to aid fellowships with implementation of the curriculum and ongoing assessment of fellow progress., Competing Interests: Competing interests: MMH reports personal fees from Tenex Health, personal fees from Sonex Health, other from UpToDate, Inc, outside the submitted work. JTF reports other from DEMOS Publishing, other from up to date, personal fees from COVR Medical, personal fees from Sanofi, personal fees from Aim Specialty Health, outside the submitted work. KM reports personal fees from McGraw Hill, personal fees from Elsevier, other from Tenex, outside the submitted work. JS reports other from Sonex Health, other from Tenex Health, outside the submitted work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate., Methods: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases., Results: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects., Conclusion: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.

Objective: To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers., Methods: Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings., Results: Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important., Conclusion: This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice., Competing Interests: DA reports grants from BioMarin outside the submitted work. HCA and KC received payments from BioMarin to participate in the advisory board meeting related to the submitted work. HB reports personal fees from BioMarin related to the submitted work and personal fees from BioMarin, Cambrooke, Horizon, Nutricia, Ultragenyx, and Vitaflo outside the submitted work. CE received payments from BioMarin to participate in the advisory board meeting related to the submitted work, and payments from BioMarin outside the submitted work. ML received personal fees to participate in the advisory board meeting related to the submitted work; payments from BioMarin outside the submitted work; and is an investigator in clinical trials sponsored by BioMarin. JL and KW are employees of BioMarin. KL received payments from BioMarin for participating in the advisory board meeting related to the submitted work; she is currently an employee of BioMarin. MM reports personal fees and non-financial support from BioMarin related to the submitted work and personal fees from Applied Therapeutics, Cycle Pharmaceuticals and Rhythm Pharmaceuticals, personal fees and non-financial support from Aeglea Biotherapeutics and Horizon Therapeutics, and grants from Censa Pharmaceuticals outside the submitted work. JWR received payments and travel support from BioMarin for participating in the advisory board meeting related to the submitted work. HS received payments and travel support from BioMarin related to the submitted work, was involved as an investigator in clinical trials for BioMarin, and received payments from BioMarin, Vitaflo, MetEd and Symbiotics outside the submitted work. SS received consulting fees, speaker fees, and travel support from BioMarin and was involved as an investigator in clinical trials for BioMarin. DS received personal fees from BioMarin related to the submitted work and personal fees from BioMarin, Cambrooke, Horizon, Nutricia, Ultragenyx, Cycle Pharmaceuticals and Vitaflo outside the submitted work. JT-A received personal fees for participating in the advisory board related to the submitted work and personal fees from BioMarin outside the submitted work. JT was involved as an investigator in clinical trials for BioMarin and was a member of the Phase III advisory board. EV received personal fees for participating in the advisory board related to the submitted work and personal fees from BioMarin outside the submitted work. LBW received personal fees from BioMarin for participating in the advisory board and virtual platform meeting related to the submitted work, and personal fees from BioMarin and Nutricia outside the submitted work., (© 2021 The Authors.)

Abstract: Sports ultrasound is commonly used by sports medicine physicians to enhance diagnostic and procedural accuracy. This expert consensus statement serves as an update to the 2015 American Medical Society for Sports Medicine recommended sports ultrasound curriculum for sports medicine fellowships. Although written in the context of the American sports medicine fellowship training model, we present a stepwise progression in both diagnostic and interventional sports ultrasound that may be applicable to the broader sports medicine community. The curriculum is divided into 12 units with each unit including didactic instructional sessions, practical hands-on instruction, independent scanning practice sessions, and mentored clinical experience. To assist with prioritization of learning, we have organized relevant pathology and procedures as essential, desirable, and optional. The expanded content can serve as an outline for continuing education postfellowship or for any physician to further advance their sports ultrasound knowledge and skill. We also provide updated scanning protocols, sample milestones, and a sample objective structured clinical examination (OSCE) to aid fellowships with implementation of the curriculum and ongoing assessment of fellow progress., Competing Interests: M. M. Hall reports personal fees from Tenex Health, personal fees from Sonex Health, and other from UpToDate, Inc, outside the submitted work. J. T. Finnoff reports other from DEMOS Publishing, other from UpToDate, personal fees from COVR Medical, personal fees from Sanofi, and personal fees from Aim Specialty Health, outside the submitted work. K. R. Mautner reports personal fees from McGraw Hill, personal fees from Elsevier, and other from Tenex, outside the submitted work. J. Smith reports other from Sonex Health and other from Tenex Health, outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Few population-based studies have analyzed patterns of co-occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co-occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999-2014. We calculated the observed-to-expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non-specifically. To address potential ascertainment differences among live births and non-live births, we repeated analyses specifically among live births. The combination of defects with the largest observed-to-expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed-to-expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition., (© 2021 Wiley Periodicals LLC.)

Introduction: Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally., Objective: This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects., Study Design: We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA)., Results: Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias., Discussion: Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified., Conclusion: In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices., Competing Interests: Conflict of interest None., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Patients with chromosome 22q11.2 deletion syndromes classically present with variable cardiac defects, parathyroid and thyroid gland hypoplasia, immunodeficiency and velopharyngeal insufficiency, developmental delay, intellectual disability, cognitive impairment, and psychiatric disorders. New technologies including chromosome microarray have identified smaller deletions in the 22q11.2 region. An increasing number of studies have reported patients presenting with various features harboring smaller 22q11.2 deletions, suggesting a need to better elucidate 22q11.2 deletions and their phenotypic contributions so that clinicians may better guide prognosis for families. We identified 16 pediatric patients at our institution harboring various 22q11.2 deletions detected by chromosomal microarray and report their clinical presentations. Findings include various neurodevelopmental delays with the most common one being attention deficit hyperactivity disorder (ADHD), one reported case of infant lethality, four cases of preterm birth, one case with dual diagnoses of 22q11.2 microdeletion and Down syndrome. We examined potential genotypic contributions of the deleted regions., Competing Interests: Conflict of interest All authors declare no conflict of interest in this paper.

The utility of ultrasound in sports medicine is improving the sports medicine physician's ability to rapidly diagnose and treat a multitude of sports related pathologies. In this article, we clearly outline the current status of the evidence in support of using sports ultrasound in the setting of acute ocular injury, evaluation of elevated intracranial pressures, deep venous thrombosis, and soft tissue complaints.

Chromosome 16p11.2 is one of the susceptible sites for recurrent copy number variations (CNVs) due to flanking near-identical segmental duplications. Five segmental duplications, named breakpoints 1 to 5 (BP1-BP5), have been defined as recombination hotspots within 16p11.2. Common CNVs on 16p11.2 include a proximal ~593 kb between BP4 and BP5, and a distal ~220 kb between BP2 and BP3. We performed a search for patients carrying 16p11.2 CNVs, as detected using chromosome microarray (CMA), in the Molecular Diagnostic Laboratory at the University of Texas Medical Branch (UTMB), in Galveston. From March 2013 through April 2018, a total of 1200 CMA results were generated for germline testing, and 14 patients tested positive for 16p11.2 CNVs, of whom 7 had proximal deletion, 2 had distal deletion, 4 had proximal duplication, and 1 had distal duplication. Herein, we provide detailed phenotype data for these patients. Our study results show that developmental delay, abnormal body weight, behavioral problems, and hypotonia are common phenotypes associated with 16p11.2 CNVs., (© American Society for Clinical Pathology 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gastroschisis and omphalocele are the two most common abdominal wall birth defects, and epidemiologic characteristics and frequency of occurrence as part of a syndromic condition suggest distinct etiologies between the two defects. We assessed complex patterns of defect co-occurrence with these defects separately using the Texas Birth Defects Registry. We used co-occurring defect analysis (CODA) to compute adjusted observed-to-expected (O/E) ratios for all observed birth defect patterns. There were 2,998 non-syndromic (i.e., no documented syndrome diagnosis identified) cases with gastroschisis and 789 (26%) of these had additional co-occurring defects. There were 720 non-syndromic cases with omphalocele, and 404 (56%) had additional co-occurring defects. Among the top 30 adjusted O/E ratios for gastroschisis, most of the co-occurring defects were related to the gastrointestinal system, though cardiovascular and kidney anomalies were also present. Several of the top 30 combinations co-occurring with omphalocele appeared suggestive of OEIS (omphalocele, exstrophy of cloaca, imperforate anus, spinal defects) complex. After the exclusion of additional cases with features suggestive of OEIS in a post-hoc sensitivity analysis, the top combinations involving defects associated with OEIS (e.g., spina bifida) were no longer present. The remaining top combinations involving omphalocele included cardiovascular, gastrointestinal, and urogenital defects. In summary, we identified complex patterns of defects that co-occurred more frequently than expected with gastroschisis and omphalocele using a novel software platform. Better understanding differences in the patterns between gastroschisis and omphalocele could lead to additional etiologic insights., (© 2020 Wiley Periodicals LLC.)

Objectives: To provide a descriptive analysis for species identification of culture and Gram stain results from ultrasound transducers and multiuse ultrasound transmission gel bottle tips in active clinical use and to compare bacterial cultures from ultrasound transducers before and after aseptic cleansing., Methods: A prospective blinded descriptive analytic study of 18 distinct clinical care sites within a single primary clinical institution was conducted. Before and after a disinfectant towel cleanse, transducers were pressed against tryptic soy agar contact plates. Plates were deidentified and submitted for blind incubation, Gram staining, and species identification with microsequencing. Results were classified as clinically relevant (CR) or non-clinically relevant. In total, 188 samples were analyzed: 80 from ultrasound transducers before and cleansing, 13 from multiuse gel bottle tips before and after cleansing, and 2 precleansing samples from the data collector's pen and badge., Results: Fifty-nine precleansing samples (73.8%) grew cultures with CR bacteria, and 21 samples (26.3%) did not. Staphylococcus simulans represented 31.0% of all positive culture samples. Thirteen postcleansing samples (16.3%) grew cultures with CR bacteria, equating to a 78.0% reduction of CR bacterial growth (likelihood ratio, 57.10; P < .001)., Conclusions: Ultrasound transducers have a notable CR bacterial burden and may serve as potential infective vectors. Aseptic cleansing effectively eliminates most of the bacterial load from ultrasound transducers, but some bacteria persist, presenting a risk of nosocomial infection with ultrasound-guided interventions. These findings support American Institute of Ultrasound in Medicine 2018 guidelines intended to ensure an appropriate level of transducer preparation based on the examination type while emphasizing rational infection control measures to minimize the risk of potential patient harm., (© 2020 by the American Institute of Ultrasound in Medicine.)

Background: Few studies have systematically evaluated birth defect co-occurrence patterns, perhaps, in part, due to the lack of software designed to implement large-scale, complex analytic methods., Methods: We created an R-based platform, "co-occurring defect analysis" (CODA), designed to implement analyses of birth defect co-occurrence patterns in birth defect registries. CODA uses an established algorithm for calculating the observed-to-expected ratio of a given birth defect combination, accounting for the known tendency of birth defects to co-occur nonspecifically. To demonstrate CODA's feasibility, we evaluated the computational time needed to assess 2- to 5-way combinations of major birth defects in the Texas Birth Defects Registry (TBDR) (1999-2014). We report on two examples of pairwise patterns, defects co-occurring with trisomy 21 or with non-syndromic spina bifida, to demonstrate proof-of-concept., Results: We evaluated combinations of 175 major birth defects among 206,784 infants in the TBDR. CODA performed efficiently in the data set, analyzing 1.5 million 5-way combinations in 18 hr. As anticipated, we identified large observed-to-expected ratios for the birth defects that co-occur with trisomy 21 or spina bifida., Conclusions: CODA is available for application to birth defect data sets and can be used to better understand co-occurrence patterns. Co-occurrence patterns elucidated by using CODA may be helpful for identifying new birth defect associations and may provide etiological insights regarding potentially shared pathogenic mechanisms. CODA may also have wider applications, such as assessing patterns of additional types of co-occurrence patterns in other large data sets (e.g., medical records)., (© 2019 Wiley Periodicals, Inc.)

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype-phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients., (© 2019 Wiley Periodicals, Inc.)

The androgenic gland (AG) is a male-specific endocrine organ that controls the primary and secondary sexual characteristics in male crustaceans. More evidence indicates that the insulin-like androgenic gland hormone gene ( IAG ) is the key male sexual differentiation factor, particularly the application of RNA interference (RNAi) technology on IAG . In this study, the full-length cDNA of IAG (termed PcIAG ) was isolated from the red swamp crayfish, Procambarus clarkii . Tissue distribution analysis showed that in addition to its expression in the AG of male P. clarkii , PcIAG was widely expressed in female tissues and other male tissues. The PcIAG protein was detected in the reproductive and nervous systems of adult male P. clarkii . Additionally, RNAi results showed that the PcIAG expression could be silenced efficiently, and the male sperm maturation and release possibly present a transient adverse interference at lower doses (0.1 μg/g and 1 μg/g) of PcIAG-dsRNA ( PcIAG double-stranded RNA). Dramatically, the expression level of PcIAG increased sharply shortly after the injection of higher doses (5 μg/g and 10 μg/g) of PcIAG-dsRNA, which might accelerate the maturation and release of sperm. Moreover, the expression of PcSxl ( P. clarkii Sex-lethal ) was detected by Quantitative Real-Time PCR (qPCR) after the injection of PcIAG-dsRNA to explore whether the PcIAG gene regulates the PcSxl gene, and we found that the PcIAG did not directly regulate PcSxl in P. clarkii . The study could help accelerate the progress of PcIAG functional research and provide a useful reference for the single-sex selective breeding of P. clarkii .

Cornelia de Lange syndrome (CdLS) is an autosomal dominant genetic disorder caused by pathogenic variants in NIPBL, RAD21, SMC3, HDAC8, or SMC1A; all of which code for proteins that are components of, or interact with, the cohesin complex. Despite the identification of multiple genes associated with CdLS, over 25% of individuals strongly suspected to have CdLS have negative genetic testing, indicating that there are additional genes associated with the condition. HDAC2 codes for histone deacetylase 2 (HDAC2) and, like HDAC8, is a Class 1 histone deacetylase. We present a patient with a novel de novo variant in HDAC2 with many clinical features consistent with CdLS including severe developmental delay, limb abnormalities, congenital heart defect, cryptorchidism and hypoplastic genitalia, growth retardation, and characteristic craniofacial features. Although variants in HDAC2 are not currently associated with human disease, the variant identified in this patient is within a highly conserved amino acid residue and has not been observed in healthy populations. This information, along with the patient's clinical presentation and the functional similarity between the HDAC2 and HDAC8 proteins, suggests that HDAC2 should be further investigated as a candidate gene for CdLS or a CdLS-like syndrome., (© 2019 Wiley Periodicals, Inc.)

Hepatic metabolism and elimination of endobiotics (for example, steroids, bile acids) and xenobiotics (for example, drugs, toxins) is essential for health. While the enzymatic (termed phase I-II) and transport machinery (termed phase III) controlling endobiotic and xenobiotic metabolism (EXM) is known, understanding of molecular nodal points that coordinate EXM function in physiology and disease remains incomplete. Here we show that the transcription factor Kruppel-like factor 15 (KLF15) regulates all three phases of the EXM system by direct and indirect pathways. Unbiased transcriptomic analyses coupled with validation studies in cells, human tissues, and animals, support direct transcriptional control of the EXM machinery by KLF15. Liver-specific deficiency of KLF15 (Li-KO) results in altered expression of numerous phase I-III targets, and renders animals resistant to the pathologic effects of bile acid and acetaminophen toxicity. Furthermore, Li-KO mice demonstrate enhanced degradation and elimination of endogenous steroid hormones, such as testosterone and glucocorticoid, resulting in reduced male fertility and blood glucose levels, respectively. Viral reconstitution of hepatic KLF15 expression in Li-KO mice reverses these phenotypes. Our observations identify a previously unappreciated transcriptional pathway regulating metabolism and elimination of endobiotics and xenobiotics.

SATB2-associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted to case reports and small series without in-depth phenotypic characterization or genotype-phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and genotypic characterization of SAS to date, including prevalence of each clinical feature, neurodevelopmental milestones, and when available, patient management. We confirm that the most distinctive features are neurodevelopmental delay with invariably severely limited speech, abnormalities of the palate (cleft or high-arched), dental anomalies (crowding, macrodontia, abnormal shape), and behavioral issues with or without bone or brain anomalies. This comprehensive clinical characterization will help clinicians with the diagnosis, counseling and management of SAS and help provide families with anticipatory guidance., (© 2018 Wiley Periodicals, Inc.)

Intestinal resection is a common therapeutic approach for human diseases such as obesity, inflammatory bowel disease, Crohn's disease, and colon cancer that often results in severe short bowel syndrome-like adverse effects including bile acid diarrhea, dehydration, electrolyte disturbances, and nutrient malabsorption. Here we introduce a murine ileal resection model, termed ileectomy, to evaluate tissue communication and the maintenance of systemic homeostasis. After ileal resection, circulating blood is permanently devoid of the ileum-specific endocrine hormone fibroblast growth factor 15 (FGF15), which releases its endocrinal inhibition of bile acid synthesis in the liver. In combination with the increased production and abolished reabsorption of bile acids after removing the ileum, mice that underwent surgery suffer from bile salt overaccumulation in the intestine and associated diarrhea, morbidity, and mortality. Novel usage of the surgery model introduced in this study may provide mechanistic and functional insights into ileal control of systemic metabolic regulation in physiology and disease.

Purpose: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients' phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype., Methods: Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant., Results: All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990-1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf-Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints., Conclusion: This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.Genet Med 19 1, 45-52.

Objective: To characterize the visual phenotype caused by mutations in the BTB-Kelch protein, KLHL7, responsible for the RP42 form of autosomal dominant retinitis pigmentosa (RP)., Methods: Comprehensive ophthalmic testing included visual acuity, static visual field, kinetic visual field, dark adaptometry, full-field electroretinography, spectral-domain optical coherence tomography, and fundus photography. Longitudinal visual function data (range, 15-27 years) were available for some of the affected individuals., Results: We report a phenotypic assessment of 3 unrelated families, each harboring different KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). The fundi showed classic signs of RP. Best-corrected visual acuity was 20/50 or better in at least one eye up to age 65 years. Static and kinetic visual fields showed concentric constriction to central 10° to 20° by age 65 years; 2 patients with Goldmann perimetry exhibited bilateral visual field retention in the far periphery. Both rod and cone full-field electroretinographic amplitudes were substantially lower than normal, with a decline rate of 3% per year in cone 31-Hz flicker response. Rod and cone activation and inactivation variables were abnormal. Spectral-domain optical coherence tomography indicated retention of foveal inner segment-outer segment junction through age 65 years., Conclusions: Mutations in KLHL7 are associated with a late-onset form of autosomal dominant retinal degeneration that preferentially affects the rod photoreceptors. Full-field electroretinographic findings, including recovery kinetics, are consistent with those observed in other forms of autosomal dominant RP., Clinical Relevance: The phenotypes are similar among patients with 3 types of KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). Strong retention of foveal function and bilateral concentric constriction of visual fields with far periphery sparing may guide mutation screening in autosomal dominant RP.

Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G-->A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.

Mutations in the presenilin-1 (PS-1) gene account for a significant fraction of familial Alzheimer's disease. The biological function of PS-1 is not well understood. We report here that the proliferation-associated gene (PAG) product, a protein of the thioredoxin peroxidase family, interacts with PS-1. Microinjection of a plasmid expressing PAG into superior cervical ganglion (SCG) sympathetic neurons in primary cultures led to apoptosis. Microinjection of plasmids expressing wild-type PS-1 or a PS-1 mutant with a deletion of exon 10 (PS1dE10) by themselves had no effect on the survival of primary SCG neurons. However, co-injection of wild-type PS-1 with PAG prevented neuronal death, whereas co-injection with the mutant PS-1 did not affect PAG-induced apoptosis. Furthermore, overexpression of PAG accelerated SCG neuronal death induced by nerve growth factor deprivation. This sensitizing effect was also blocked by wild-type PS-1, but not by PS1dE10. These results establish an assay for studying the function of PS-1 in primary neurons, reveal the neurotoxicity of a thioredoxin peroxidase, demonstrate a neuroprotective activity of the wild-type PS-1, and suggest possible involvement of defective neuroprotection by PS-1 mutants in neurodegeneration., ((c)2002 Elsevier Science (USA).)

This study examined the relationship between smoking status and weight change from baseline to Year 7 in a large biracial cohort, the Coronary Artery Risk Development in Young Adults study. Unadjusted for covariates, only male smokers weighed less than nonsmokers, with no effect among women. Adjusted for covariates, male and female smokers weighed less than nonsmokers at baseline, adjusted for age, total energy intake, alcohol intake, and physical fitness. Over the 7-year follow-up, all smoking status groups gained weight, including continuous smokers and initiators. Weight gain was greatest among those who quit smoking. Weight gain attributable to smoking cessation was 4.2 kg for Whites and 6.6 kg for Blacks. Smoking had a small weight-attenuating effect on Blacks. No such effects, however, were observed among Whites. These results suggest, at least in younger smokers, that smoking has minimal impact on body weight.

Estimates of postcessation weight gain vary widely. This study determined the magnitude of weight gain in a cohort using both point prevalence and continuous abstinence criteria for cessation. Participants were 196 volunteers who participated in a smoking cessation program and who either continuously smoked (n = 118), were continuously abstinent (n = 51), or who were point prevalent abstinent (n = 27) (i.e., quit at the 1-year follow-up visit but not at others). Continuously abstinent participants gained over 13 lbs. (5.90 kg) at 1 year, significantly more than continuously smoking (M = 2.4 lb.) and point prevalent abstinent participants (M = 6.7 lbs., or 3.04 kg). Individual growth curve analysis confirmed that weight gain and the rate of weight gain (pounds per month) were greater among continuously smoking participants and that these effects were independent of gender, baseline weight, smoking and dieting history, age, and education. Results suggest that studies using point prevalence abstinence to estimate postcessation weight gain may be underestimating postcessation weight gain.

The computation of effect sizes is a key feature of meta-analysis. In treatment outcome meta-analyses, the standardized mean difference statistic on posttest scores (d) is usually the effect size statistic used. However, when primary studies do not report the statistics needed to compute d, many methods for estimating d from other data have been developed. Little is known about the accuracy of these estimates, yet meta-analysts frequently use them on the assumption that they are estimating the same population parameter as d. This study investigates that assumption empirically. On a sample of 140 psychosocial treatment or prevention studies from a variety of areas, the present study shows that these estimates yield results that are often not equivalent to d in either mean or variance. The frequent mixing of d and other estimates of d in past meta-analyses, therefore, may have led to biased effect size estimates and inaccurate significance tests.

This study determined evidence for digit preference in self-reports of smoking in the Second National Health and Nutrition Examination Survey (NHANES II). Subjects were 4275 adult smokers. Self-reports of smoking showed a marked degree of digit preference, with the vast majority of smokers reporting in multiples of 10 cigarettes per day. When number per day was compared to an objective measure of smoking exposure (carboxyhemoglobin; n = 2070) the distribution was found to be significantly assymetrical. Analysis of the distribution of COHb and various levels of number per day indicates that the differences in distribution are not due to variability in COHb. Heavier smokers, Caucasians, and those with less education were more likely to report a digit preference than lighter smokers. African-Americans, and those with more education. Results suggest that self-reports of number of cigarettes per day may be biased towards round numbers (particularly 20 cigarettes per day). Implications for assessment of smoking behavior are discussed.

The present study sought to identify the presence and degree of apparent underreporting of dietary intake in 11,663 participants in the Second National Health and Nutrition Examination Survey (NHANES II). Self-reported dietary intake was compared with estimated basal metabolic rate. Underreporting was based on cutoff limits that identified plausible levels of energy expenditure for adult individuals. Results indicated that up to 31% of adults in this sample may have underreported dietary intake. Those individuals at greatest risk of underreporting were less well educated and heavier. The Sex x Race interaction indicated that for both ethnic categories, women were more likely to underreport than men, but the difference between men and women was greater among Caucasian participants. It is concluded that such factors as reduced energy needs, deliberate falsification, and measurement error inherent in dietary assessment contribute to apparent underreporting, and this occurs in a large percentage of dietary data.

The aim of this work was to assess the accuracy of physicians' subjective assessments of obesity status. The subjects were participants in The Second National Health and Nutrition Examination (NHANES II) Survey. The physicians' subjective judgments of obesity were compared to BMI, an objective measure of actual body mass. Subjects with a body mass index (BMI = weight in kg/(height in cm/100)2) less than or equal to 27.5 were classified as normal weight and those with a BMI greater than or equal to 30.4 were considered to be obese. Physicians were accurate in their diagnosis of the normal weight group with only 4.03% being misdiagnosed as obese. However, 12.6% of the obese group was misdiagnosed as normal weight. The odds of an incorrect normal weight diagnosis increased with age. Similarly, as the fat distribution ratio increased, i.e., a more central pattern, the odds of being actually obese but incorrectly diagnosed as normal weight increased. Men were more likely than women to be incorrectly diagnosed as normal weight. Non-Caucasian normal weight persons appear to have been diagnosed more stringently than Caucasians as they were more likely to be misdiagnosed as obese regardless of their gender. There appear to be several variables affecting the physicians' subjective assessment of obesity status in this data set.

Recent studies have shown that smokers' intake of caffeine is higher than nonsmokers. This investigation evaluated the relationships between smoking status and self-reported caffeine intake from both coffee and tea. Subjects were adults who participated in the Second National Health and Nutrition Examination Survey (NHANES II). Results indicated that subjects who ingested caffeine from tea were more likely to be female, less educated, younger, non-Caucasian, and lighter drinkers. In contrast, those who ingested caffeine from coffee were more likely to be older, Caucasian, heavier drinkers, and have higher incomes. Smokers were not more likely to drink caffeinated tea. In contrast, smokers were much more likely to drink caffeinated coffee, and a dose-response relationship between caffeine from coffee and smoking intake was observed. These results clarify the relationship between smoking and caffeine intake. Implications for intervention efforts are discussed.