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2.
J Neurol Neurosurg Psychiatry ; 95(2): 103-113, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38041679

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed. RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS. CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.


Subject(s)
Amyotrophic Lateral Sclerosis , Hereditary Sensory and Autonomic Neuropathies , Neurodegenerative Diseases , Child , Humans , Amyotrophic Lateral Sclerosis/genetics , Sphingolipids , Serine C-Palmitoyltransferase/genetics , Serine C-Palmitoyltransferase/metabolism , Hereditary Sensory and Autonomic Neuropathies/genetics , Serine
3.
Article in English | MEDLINE | ID: mdl-37796429

ABSTRACT

This critical scoping review examined a decade of mental health and wellbeing outcome research inclusive of subsamples of multiracial participants (or persons identifying with two or more different racial groups) in order to draw initial conclusions about the contemporary state of multiracial mental health. Mental health disparities research inclusive of multiracial subsamples appears to be trending upward. Studies that used subsample analyses offer initial evidence that multiracial persons are at greater risk to experience worsened mental health in comparison to white monoracial peers, and that this disparity is compounded for multiracial persons from gender and/or sexual minoritized groups. This review uncovered numerous theoretical and methodological inconsistencies that constrained existing research from advancing more meaningful understandings of how white supremacy and systemic mono/racism differently impact the mental health and wellbeing of multiracial persons in the USA. Implications for future mental health disparities research inclusive of multiracial subsamples are presented.

4.
J Pers Med ; 13(7)2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37511639

ABSTRACT

BACKGROUND: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents' experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. METHODS: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child's sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. RESULTS: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child's future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent-infant bonding, and reported variable impact on their feelings of guilt. CONCLUSION: Parents reported that GS during the neonatal period was useful because it provided a "backbone" for their child's care. Parents did not consistently endorse negative impacts like interference with parent-infant bonding.

5.
Clin Infect Dis ; 77(4): 629-637, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37083882

ABSTRACT

BACKGROUND: Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review. RESULTS: Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure. CONCLUSIONS: Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions.


Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , Female , Male , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria , Lung/microbiology , Lung Diseases/epidemiology , Lung Diseases/microbiology , Oregon/epidemiology
6.
Clin Infect Dis ; 76(1): 89-95, 2023 01 06.
Article in English | MEDLINE | ID: mdl-35797187

ABSTRACT

BACKGROUND: Frozen foods have rarely been linked to Listeria monocytogenes illness. We describe an outbreak investigation prompted by both hospital clustering of illnesses and product testing. METHODS: We identified outbreak-associated listeriosis cases using whole-genome sequencing (WGS), product testing results, and epidemiologic linkage to cases in the same Kansas hospital. We reviewed hospital medical and dietary records, product invoices, and molecular subtyping results. Federal and state officials tested product and environmental samples for L. monocytogenes. RESULTS: Kansas officials were investigating 5 cases of listeriosis at a single hospital when, simultaneously, unrelated sampling for a study in South Carolina identified L. monocytogenes in Company A ice cream products made in Texas. Isolates from 4 patients and Company A products were closely related by WGS, and the 4 patients with known exposures had consumed milkshakes made with Company A ice cream while hospitalized. Further testing identified L. monocytogenes in ice cream produced in a second Company A production facility in Oklahoma; these isolates were closely related by WGS to those from 5 patients in 3 other states. These 10 illnesses, involving 3 deaths, occurred from 2010 through 2015. Company A ultimately recalled all products. CONCLUSIONS: In this US outbreak of listeriosis linked to a widely distributed brand of ice cream, WGS and product sampling helped link cases spanning 5 years to 2 production facilities, indicating longstanding contamination. Comprehensive sanitation controls and environmental and product testing for L. monocytogenes with regulatory oversight should be implemented for ice cream production.


Subject(s)
Foodborne Diseases , Ice Cream , Listeria monocytogenes , Listeriosis , Humans , United States/epidemiology , Listeria monocytogenes/genetics , Foodborne Diseases/epidemiology , Food Microbiology , Listeriosis/epidemiology , South Carolina , Disease Outbreaks
7.
J Genet Couns ; 31(6): 1404-1420, 2022 12.
Article in English | MEDLINE | ID: mdl-35915971

ABSTRACT

Newborn screening (NBS) for Pompe disease (PD) was added to the Recommended Uniform Screening Panel (RUSP) in the United States in 2015 because there was compelling evidence of health benefits for early diagnosis of Infantile-onset Pompe disease (IOPD). However, one limitation of NBS for PD is its inability to distinguish IOPD and late onset forms of Pompe disease (LOPD). Management of LOPD is challenging because of uncertainty around progression of LOPD and determining the appropriate time for treatment initiation. The aims of this study were to understand the impact of LOPD identified through NBS, by exploring the differences in attitudes, emotions and opinions among parents and identify their needs for follow-up care. Study participants were recruited from states that included PD on their NBS panel. Semi-structured interviews were conducted with parents of nine children who were diagnosed with LOPD after an abnormal NBS result. Predominantly, parents reported a lack of adequate information, guidance, and psychosocial support from the very beginning and through the course of their diagnosis. This caused uncertainty, anxiety, frustration, and fear of the unknown. Parents live in a 'worry or not to worry' phase, balancing between coping methods to avoid over medicalization of their child, but also preparing concrete follow-up plans to be on the lookout for any signs of PD-related symptoms. Understanding parents' experiences allows genetic counselors and NBS programs to proactively design care plan for parents during this difficult period.


Subject(s)
Glycogen Storage Disease Type II , Infant, Newborn , Child , Humans , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/genetics , Glycogen Storage Disease Type II/therapy , Neonatal Screening/methods , Aftercare , Parents/psychology , Delayed Diagnosis
8.
Front Pediatr ; 10: 857106, 2022.
Article in English | MEDLINE | ID: mdl-35463892

ABSTRACT

Introduction: The assessment of fluid responsiveness is important in the management of shock but conventional methods of assessing fluid responsiveness are often inaccurate. Our study aims to evaluate changes in objective hemodynamic parameters as measured using electrical cardiometry (ICON® monitor) following the fluid bolus in children presenting with shock and to evaluate whether any specific hemodynamic parameter can best predict fluid responsiveness among children with shock. Materials and Methods: We conducted a prospective observational study in children presenting with shock to our emergency department between June 2020 and March 2021. We collected the parameters such as heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and hemodynamic data such as cardiac output CO), cardiac index (CI), index of contractility (ICON), stroke volume (SV), stroke index (SI), corrected flow time (FTC), systolic time ratio (STR), variation of index of contractility (VIC), stroke volume variation (SVV), systemic vascular resistance (SVR), and thoracic fluid content (TFC) using the ICON monitor before and after fluid bolus (FB). We assessed percent change (Δ) and used paired-sample Student's t-test to compare pre- and post-hemodynamic data and Mann-Whitney U-test to compare fluid responders and non-responders. P-Values < 0.05 were considered statistically significant. Results: We recorded 42 fluid interventions in 40 patients during our study period. The median IQR age was 10.56 (4.8, 14.8) years with male/female ratio (1.2:1). There was a significant decrease in ΔRR [-1.61 (-14.8, 0); p = 0.012], ΔDBP [-5.5 (-14.4, 8); p = 0.027], ΔMAP [-2.2 (-11, 2); p = 0.018], ΔSVR [-5.8 (-20, 5.2); p = 0.025], and ΔSTR [-8.39 (-21, 3); p = 0.001] and significant increase in ΔTFC [6.2 (3.5, 11.4); p = 0.01] following FB. We defined fluid responders by an increase in SV by ≥10% after a single FB of 20 ml/kg crystalloid. Receiver operating curve analysis revealed that among all the parameters, 15% change in ICON had an excellent AUC (0.85) for the fluid responsiveness. Conclusion: Our study showed significant changes in objective hemodynamic parameters, such as SVR, STR, and TFC following FB in children presenting with shock. A 15% change in ICON had an excellent predictive performance for the fluid responsiveness among our cohort of pediatric shock.

9.
Ann Intern Med ; 175(4): 513-522, 2022 04.
Article in English | MEDLINE | ID: mdl-35038274

ABSTRACT

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Ad26COVS1/adverse effects , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , Female , Humans , Male , Middle Aged , RNA, Messenger , Syndrome , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Thrombosis/chemically induced , Thrombosis/etiology , United States/epidemiology , Vaccination/adverse effects , Vaccines/adverse effects , Young Adult
10.
Am J Community Psychol ; 69(3-4): 484-502, 2022 06.
Article in English | MEDLINE | ID: mdl-34723397

ABSTRACT

Across two studies, we examined whether racially diverse contexts in combination with creating a third (multiracial) space played a protective role in the association between perceived monoracism and psychological adjustment for multiracial adults. Study 1 participants (N = 263; 77.8% female, Mage = 32.16 years) were recruited from national multiracial organizations and completed an online cross-sectional survey in 2009. Study 2 participants (N = 1478; 56.2% female, Mage = 48.89 years) were recruited by the Pew Research Center and completed a nationally representative survey in 2015. Results indicated significant three-way interaction effects on psychological adjustment, with differential effects depending on the types of perceived monoracism. Specifically, when subjective racial diversity was high, creating a third space buffered against the deleterious effects of multiracial discrimination on distress, negative affect, and life satisfaction; while it exacerbated the link between perceived racial ambiguity and negative affect. This study provides empirical evidence for the importance of using an ecological framework when examining multiracial identity and experiences. Results also highlight the need to move beyond conceptualizing and measuring multiracial experiences as dichotomous risks or resiliencies. Rather, we should aim to understand multiracial experiences as either promoting or inhibiting across contexts, time, and individual characteristics.


Subject(s)
Emotional Adjustment , Social Identification , Adaptation, Psychological , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Racial Groups
11.
J Fam Psychol ; 36(2): 179-190, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34516156

ABSTRACT

This qualitative interview study investigated the types of parental racial-ethnic socialization messages received by Multiracial American youth over the course of their development. The Multiracial population in America is the largest demographic group among individuals under the age of 18 (Saulny, 2011), but there is a dearth of research about the development of this rapidly growing population. Multiracial youth are members of multiple racial-ethnic groups. Thus, racial-ethnic socialization is particularly complex for Multiracial families because parents typically have different racial backgrounds and experiences compared to their children. Interviews were conducted with 20 Multiracial emerging adult college students (Mage = 20.55; 10 male, 10 female) of diverse racial backgrounds to identify the types of parental racial-ethnic socialization messages they received growing up. Using thematic analysis (Braun & Clarke, 2006), nine themes of racial-ethnic socialization content emerged: Cultural socialization, racial identity socialization, preparation for bias socialization, colorblind socialization, race-conscious socialization, diversity appreciation socialization, negative socialization, exposure to diversity socialization, and silent socialization. This research advances the literature by (a) identifying domains of racial-ethnic socialization messages for Multiracial American families, (b) examining a diverse sample of male and female Multiracial youth, (c) differentiating monoracial versus Multiracial socialization messages, and (d) distinguishing the unique connotations of egalitarian socialization messages (e.g., colorblind, race-conscious, diversity appreciation). The findings have important implications for understanding the development of Multiracial American individuals and families. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Ethnicity , Socialization , Adolescent , Adult , Child , Female , Humans , Male , Parents , Racial Groups , Social Identification , United States , Young Adult
12.
J Fam Psychol ; 36(1): 13-22, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34060893

ABSTRACT

Multiracial children are the largest demographic group in the United States among individuals under the age of 18 (Pew Research Center, 2015), but their developmental processes are understudied. Parents and caregivers play an important role in preparing youth to navigate racialized society by teaching them to understand what it means to be a member of a racial-ethnic group (Hughes et al., 2006). However, this process is more complex in multiracial families, where youth belong to multiple racial-ethnic groups. Thus, the purpose of the present study was to develop and validate the first measure of racial-ethnic socialization for Multiracial youth, the Multiracial Youth Socialization (MY-Soc) Scale, to assess the unique messages that are communicated in multiracial families regarding topics of race, ethnicity, and culture. Using a sample of 901 Multiracial emerging adults (mage = 22.43), we separately captured the socialization practices of two of the youths' primary caregivers from the youths' perspective. Exploratory and confirmatory factor analyses supported a 62-item scale measuring eight types of socialization: Navigating Multiple Heritages Socialization, Multiracial Identity Socialization, Preparation for Monoracism Socialization, Negative Socialization, Colorblind Socialization, Diversity Appreciation Socialization, Race-Conscious Socialization, and Silent Socialization. The MY-Soc Scale was also supported by validity and reliability tests. This study contributes an important tool for scholars and practitioners to learn which racial-ethnic socialization messages are promotive for Multiracial youth development in different contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Social Identification , Socialization , Adolescent , Adult , Child , Ethnicity , Humans , Racial Groups , Reproducibility of Results , United States , Young Adult
13.
Genet Med ; 24(4): 851-861, 2022 04.
Article in English | MEDLINE | ID: mdl-34930662

ABSTRACT

PURPOSE: SouthSeq is a translational research study that undertook genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern United States, which are historically underrepresented in genomic medicine research. METHODS: GS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. RESULTS: Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants, and 14% of infants harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing, suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. CONCLUSION: We describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results show the utility of GS because it provides early-in-life detection of clinically relevant genetic variations not detected by current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.


Subject(s)
Diagnostic Tests, Routine , Genetic Testing , Base Sequence , Chromosome Mapping , Genetic Testing/methods , Genomics , Humans
14.
Int J Neonatal Screen ; 7(3)2021 Jul 23.
Article in English | MEDLINE | ID: mdl-34449521

ABSTRACT

Homocystinuria, caused by cystathionine ß-synthase deficiency, is a rare inherited disorder involving metabolism of methionine. Impaired synthesis of cystathionine leads to accumulation of homocysteine that affects several organ systems leading to abnormalities in the skeletal, cardiovascular, ophthalmic and central nervous systems. We report a 14-month-old and a 7-year-old boy who presented with neurologic dysfunction and were found to have cerebral venous sinus thromboses on brain magnetic resonance imaging (MRI)/magnetic resonance venogram (MRV) and metabolic and hypercoagulable work-up were consistent with classic homocystinuria. The 14-month-old boy had normal newborn screening. The 7-year-old boy initially had an abnormal newborn screen for homocystinuria but second tier test that consisted of total homocysteine was normal, so his newborn screen was reported as normal. With the advent of expanded newborn screening many treatable metabolic disorders are detected before affected infants and children become symptomatic. Methionine is the primary target in newborn screening for homocystinuria and total homocysteine is a secondary target. Screening is usually performed after 24-48 h of life in most states in the US and some states perform a second screen as a policy on all tested newborns or based on when the initial newborn screen was performed. This is done in hopes of detecting infants who may have been missed on their first screen. In the United Kingdom, NBS using dried blood spot is performed at 5 to 8 days after birth. It is universally known that methionine is a poor target and newborn screening laboratories have used different cutoffs for a positive screen. Reducing the methionine cutoff increases the sensitivity but not necessarily the specificity of the test and increasing the cutoff will miss babies who may have HCU whose levels may not be high enough to be detected at their age of ascertainment. It is not clear whether adjusting methionine level to decrease the false negative rates combined with total homocysteine as a second-tier test can be used effectively and feasibly to detect newborns with HCU. Between December 2005 and December 2020, 827,083 newborns were screened in Kentucky by MS/MS. Kentucky NBS program uses the postanalytical tools offered by the Collaborative Laboratory Integrated Reports (CLIR) project which considers gestational age and birthweight. One case of classical homocystinuria was detected and two were missed on first and second tier tests respectively. The newborn that had confirmed classical homocystinuria was one of twenty-three newborns that were referred for second tier test because of elevated methionine (cutoff is >60 µmol/L) and/or Met/Phe ratio (cutoff is >1.0); all 23 dried blood spots had elevated total homocysteine. One of the subjects of this case report had a normal methionine on initial screen and the other had a normal second-tier total homocysteine level. The performance of methionine and total homocysteine as screening analytes for homocystinuria suggest that it may be time for newborn screening programs to consider adopting next generation sequencing (NGS) platforms as alternate modality of metabolic newborn screening. Because of cost considerations, newborn screening programs may not want to adopt NGS, but the downstream healthcare cost incurred due to missed cases and the associated morbidity of affected persons far exceed costs to newborn screen programs. Since NGS is becoming more widely available and inexpensive, it may be feasible to change testing algorithms to use Newborn Metabolic NGS as the primary mode of testing on dry blood specimens with confirmation with biochemical testing. Some commercial laboratories have Newborn Screening Metabolic gene panel that includes all metabolic disorders on the most comprehensive newborn screening panel in addition to many other conditions that are not on the panel. A more targeted NGS panel can be designed that may not cost much and eventually help avoid the pitfalls associated with delayed diagnosis and cost of screening.

15.
Mol Genet Metab Rep ; 27: 100735, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33732618

ABSTRACT

Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. Here, we report 14 arginase deficiency cases, including two patients with positive NBS for hyperargininemia in whom the diagnosis of arginase deficiency was delayed owing to normal or near normal plasma arginine levels on follow-up testing. To improve the detection capability for arginase deficiency, we evaluated plasma Arg/Orn ratio as a secondary diagnostic marker in positive NBS cases for hyperargininemia. We found that plasma Arg/Orn ratio combined with plasma arginine was a better marker than plasma arginine alone to differentiate patients with arginase deficiency from unaffected newborns. In fact, elevated plasma arginine in combination with an Arg/Orn ratio of ≥1.4 identified all 14 arginase deficiency cases. In addition, we examined the impact of age on plasma arginine and ornithine levels. Plasma arginine increased 0.94 µmol/L/day while ornithine was essentially unchanged in the first 31 days of life, which resulted in a similar increasing trend for the Arg/Orn ratio (0.01/day). This study demonstrated that plasma Arg/Orn ratio as a secondary diagnostic marker improved the detection capability for arginase deficiency in newborns with hyperargininemia, which will allow timely detection of arginase deficiency and hence initiation of treatment before developing symptoms.

16.
Clin Case Rep ; 8(8): 1392-1398, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32884761

ABSTRACT

Class II division 1 malocclusions are common, and first permanent molars are frequently compromised teeth. Removal of compromised maxillary first permanent molars with planned orthodontic treatment can result in favorable treatment outcomes.

17.
Clin Infect Dis ; 70(6): 1021-1028, 2020 03 03.
Article in English | MEDLINE | ID: mdl-31245810

ABSTRACT

BACKGROUND: Public health and infection control prevention and surveillance efforts in the United States have primarily focused on methicillin-resistant Staphylococcus aureus (MRSA). We describe the public health importance of methicillin-susceptible S. aureus (MSSA) in selected communities. METHODS: We analyzed Emerging Infections Program surveillance data for invasive S. aureus (SA) infections (isolated from a normally sterile body site) in 8 counties in 5 states during 2016. Cases were considered healthcare-associated if culture was obtained >3 days after hospital admission; if associated with dialysis, hospitalization, surgery, or long-term care facility (LTCF) residence within 1 year prior; or if a central venous catheter was present ≤2 days prior. Incidence per 100 000 census population was calculated, and a multivariate logistic regression model with random intercepts was used to compare MSSA risk factors with those of MRSA. RESULTS: Invasive MSSA incidence (31.3/100 000) was 1.8 times higher than MRSA (17.5/100 000). Persons with MSSA were more likely than those with MRSA to have no underlying medical conditions (adjusted odds ratio [aOR], 2.06; 95% confidence interval [CI], 1.26-3.39) and less likely to have prior hospitalization (aOR, 0.70; 95% CI, 0.60-0.82) or LTCF residence (aOR, 0.37; 95% CI, 0.29-0.47). MSSA accounted for 59.7% of healthcare-associated cases and 60.1% of deaths. CONCLUSIONS: Although MRSA tended to be more closely associated with healthcare exposures, invasive MSSA is a substantial public health problem in the areas studied. Public health and infection control prevention efforts should consider MSSA prevention in addition to MRSA.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Methicillin , Public Health , Renal Dialysis , Staphylococcal Infections/epidemiology , Staphylococcus aureus , United States/epidemiology
18.
Pain ; 160(12): 2766-2775, 2019 12.
Article in English | MEDLINE | ID: mdl-31408049

ABSTRACT

Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system mainly characterized by impaired nociception and autonomic dysfunction. We previously identified heme metabolism as a novel pathway contributing to sensory neurons maintenance and nociception. Indeed, we reported mutations in the feline leukemia virus subgroup C receptor 1 (FLVCR1) gene in individuals affected by HSAN. FLVCR1 gene encodes for 2 heme export proteins, FLVCR1a (plasma membrane) and FLVCR1b (mitochondria), crucially involved in the regulation of cellular heme homeostasis. Here, we report on 2 additional patients carrying novel biallelic mutations in FLVCR1 translation initiation codon (c.2T>C; p.(Met1Thr) and c.3G>T; p.(Met1Ile)). We overexpressed the c.2T>C; p.(Met1Thr) mutant in human cell lines and we describe its impact on protein structure and function in comparison with other HSAN-related mutations. We found that the mutation interferes with translation in 2 different ways: by lowering levels of translation of wild-type protein and by inducing translation initiation from a downstream in-frame ATG, leading to the production of an N-terminal truncated protein that is retained in the endoplasmic reticulum. The impact of different kinds of mutations on FLVCR1a localization and structure was also described. The identification of novel FLVCR1 mutations in HSAN reinforces the crucial role of heme in sensory neuron maintenance and pain perception. Moreover, our in vitro findings demonstrate that heme export is not completely lost in HSAN patients, thus suggesting the possibility to improve FLVCR1 expression/activity for therapeutic purposes.


Subject(s)
Heme/metabolism , Hereditary Sensory and Autonomic Neuropathies/genetics , Membrane Transport Proteins/genetics , Receptors, Virus/genetics , DNA Mutational Analysis , Female , HeLa Cells , Humans , Infant , Infant, Newborn , Male , Mutation
19.
Emerg Infect Dis ; 25(8): 1461-1468, 2019 08.
Article in English | MEDLINE | ID: mdl-31310227

ABSTRACT

We investigated an outbreak of listeriosis detected by whole-genome multilocus sequence typing and associated with packaged leafy green salads. Nineteen cases were identified in the United States during July 5, 2015-January 31, 2016; isolates from case-patients were closely related (median difference 3 alleles, range 0-16 alleles). Of 16 case-patients interviewed, all reported salad consumption. Of 9 case-patients who recalled brand information, all reported brands processed at a common US facility. The Public Health Agency of Canada simultaneously investigated 14 cases of listeriosis associated with this outbreak. Isolates from the processing facility, packaged leafy green salads, and 9 case-patients from Canada were closely related to US clinical isolates (median difference 3 alleles, range 0-16 alleles). This investigation led to a recall of packaged leafy green salads made at the processing facility. Additional research is needed to identify best practices and effective policies to reduce the likelihood of Listeria monocytogenes contamination of fresh produce.


Subject(s)
Disease Outbreaks , Food Microbiology , Foodborne Diseases/epidemiology , Foodborne Diseases/microbiology , Listeria , Listeriosis/epidemiology , Listeriosis/microbiology , Salads/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Canada/epidemiology , Child , Child, Preschool , Disease Notification , Female , Genome, Bacterial , Geography, Medical , Humans , Listeria/classification , Listeria/genetics , Listeria/isolation & purification , Listeriosis/transmission , Male , Middle Aged , Multilocus Sequence Typing , Pregnancy , Public Health Surveillance , Seasons , United States/epidemiology , Young Adult
20.
MMWR Morb Mortal Wkly Rep ; 68(26): 583-586, 2019 Jul 05.
Article in English | MEDLINE | ID: mdl-31269011

ABSTRACT

During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.* Unpublished surveillance data also indicate that an increasing proportion of all Candida spp. bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs. In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1). To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York. The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder. Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3). In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment. The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin. Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment. Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5).


Subject(s)
Bacterial Infections/epidemiology , Mycoses/epidemiology , Population Surveillance , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/epidemiology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , New York/epidemiology , Young Adult
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