Ultraviolet Radiation-Induced Impairment of the Early Initiating and the Late Effector Phases of Contact Hypersensitivity to Picrylcholoride: Regulation by Different Mechanisms

Two types of antigen-specific T cells are needed for the elicitation of contact hypersensitivity reactions. They act in an obligate sequence to mediate the early initiating and late effector phases of contact hypersensitivity, which are accompanied by skin-swelling responses at 2 and 24h after challenge, respectively. The magnitude of the late ear swelling depends on that of the early swelling.We studied the influence of ultraviolet radiation on both phases of contact hypersensitivity to picrylchloride. Mice were exposed to subedemal doses of ultraviolet radiation on the shaved backs for four consecutive days. Four days later mice were sensitized on non-irradiated skin. Four days after sensitization mice were challenged on the ears, and swelling was measured 2, 4, and 24h after challenge. The early and late phases of contact hypersensitivity were largely suppressed in ultraviolet-irradiated, actively sensitized mice. Transfer of immune lymphoid cells from donor mice that were sensitized 4 d earlier induced early and late components of contact hypersensitivity in naive recipients after challenge. Transfer of immune lymphoid cells from donors that were sensitized 1 d earlier only induced the early component of contact hypersensitivity. Ultraviolet irradiation of donor mice significantly reduced the capacity of the immune lymphoid cells to induce contact hypersensitivity. We show that lymphoid cells responsible for the early and late components of contact hypersensitivity are both affected

Cells with UV-Specific DNA Damage Are Present in Murine Lymph Nodes After In Vivo UV Irradiation

Ultraviolet radiation is absorbed in the skin, especially in the epidermis. After ultraviolet irradiation the number of major histocompatibility complex class II+, adenosine triphosphatase+ Langerhans cells and Thy-1+ dendritic epidermal cells in the epidermis decreases. Whether this decrease is due to migration of these cells or to loss of membrane markers is not clear. To address this question we have used the monoclonal antibody H3 directed against cyclobutyl thymine dimers – a form of DNA damage that is specifically induced by ultraviolet radiation – to investigate whether H3+ cells are present in the draining lymph nodes of the skin after ultraviolet irradiation of hairless, inbred mice (HRA/Skh). After a single dose of ultraviolet radiation (Westinghouse FS40, 1.5 kJ/m2), H3+ cells were present in the paracortex of the draining lymph nodes. No positive cells were found in t:he blood of irradiated mice. These results suggest that the H3+ cell in the lymph nodes originate from the skin. The number H3+ cells in the draining lymph nodes increased the first 24 h after irradiation and then stabilized. Immunohistochemical double staining revealed that all H3+ cells were major histocompatibility complex II+, and that only a fraction of the cells were NLDC-145 positive. No Vγ3-cell receptor bearing cells could be found in the lymph nodes after UV irradiation of the skin

Analyzing Patterns in NewSTEPs Site Review Recommendations: Practical Applications for Newborn Screening Programs

The Newborn Screening Technical assistance and Evaluation Program (NewSTEPs) conducts non-regulatory site reviews of state newborn screening programs in the US with the goal of providing comprehensive reports and recommendations to support quality improvements within the system. A detailed coding and qualitative analysis of data extracted from reports of seven programs visited between 2012 and 2017, of thirteen pre-site visit surveys completed by state newborn screening programs, and of information from interviews conducted with three site review experts revealed four common themes that exist across states within the national newborn screening system. These themes include opportunities to implement improvements in: (1) communications inside and outside of the state newborn screening program, (2) education, (3) information technology, and (4) operations. The cross-cutting recommendations provided by NewSTEPs within the comprehensive site review reports may prove valuable for all state programs to consider and to incorporate as quality improvement measures in the absence of a full site review. The analysis of the site review process and recommendations identified important opportunities for improvement, many of which were previously unknown to be common across programs, and also provided affirmation of known challenges

Implementing Statewide Newborn Screening for New Disorders: U.S. Program Experiences

Data were collected from 39 newborn screening (NBS) programs to provide insight into the time and factors required for implementing statewide screening for Pompe, Mucopolysaccharidosis type I (MPS I), adrenoleukodystrophy (ALD), and Spinal Muscular Atrophy (SMA). Newborn screening program readiness to screen statewide for a condition was assessed using four phases: (1) approval to screen; (2) laboratory, follow-up, and information technology capabilities; (3) education; and (4) implementation of statewide newborn screening. Seventeen states (43.6%) reached statewide implementation for at least one new disorder. Those states reported that it took 28 months to implement statewide screening for Pompe and MPS I, 30.5 months for ALD, and 20 months for SMA. Using survival curve analysis to account for states still in progress, the estimated median time to statewide screening increased to 75 months for Pompe and 66 months for MPS I. When looking at how long each readiness component took to complete, laboratory readiness was one of the lengthier processes, taking about 39 months. Collaboration with other NBS programs and hiring were the most frequently mentioned facilitators to implementing newborn screening. Staffing or inability to hire both laboratory and follow-up staff was the most frequently mentioned barrier

NewSTEPs: The Establishment of a National Newborn Screening Technical Assistance Resource Center

As newborn screening (NBS) programs in the US implement expanded screening panels, utilize emerging technologies and identify areas for improvement, the need to establish and maintain a community engagement based national technical assistance center becomes apparent. The Newborn Screening Technical assistance and Evaluation Program (NewSTEPs)—a program of the Association of Public Health Laboratories (APHL) in partnership with the Colorado School of Public Health (ColoradoSPH), offers expertise in newborn screening program development, member connection, data analysis, and program evaluation. NewSTEPs provides a secure online data repository designed to collect comprehensive data on newborn screening programs in three strata: state profiles (description of each state program including program hours, fees, and disorders screened), quality indicators (metrics of program performance encompassing screening accuracy and timeliness) and NBS public health surveillance case definitions. NewSTEPs was created in 2012 under a cooperative agreement with the United States Department of Health and Human Services (HHS), Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB). Successful activities of NewSTEPs have resulted in the establishment of a technical assistance resource center and the organization of a network of newborn screening experts. In addition, NewSTEPs coordinates efforts with other federally funded programs in order to maximize resources and to ensure a unified approach to data collection and information sharing

Newborn screening timeliness quality improvement initiative: Impact of national recommendations and data repository.

BackgroundNewborn screening (NBS) aims to achieve early identification and treatment of affected infants prior to onset of symptoms. The timely completion of each step (i.e., specimen collection, transport, testing, result reporting), is critical for early diagnosis. Goals developed by the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for NBS timeliness were adopted (time-critical results reported by five days of life, and non-time-critical results reported by day seven), and implemented into a multi-year quality improvement initiative (NewSTEPS 360) aimed to decrease the time to result reporting and intervention.MethodsThe NBS system from specimen collection through reporting of results was assessed (bloodspot specimen collection, specimen shipping, sample testing, and result reporting). Annual data from 25 participating NBS programs were analyzed; the medians (and interquartile range, IQR) of state-specific percent of specimens that met the goal are presented.ResultsThe percent of specimens collected before 48 hours of life increased from 95% (88-97%) in 2016 to 97% (IQR 92-98%) in 2018 for the 25 states, with 20 (80%) of programs collecting more than 90% of the specimens within 48 hours of birth. Approximately 41% (IQR 29-57%) of specimens were transported within one day of collection. Time-critical result reporting in the first five days of life improved from 49% (IQR 26-74%) in 2016 to 64% (42%-71%) in 2018, and for non-time critical results from 64% (IQR 58%-78%) in 2016 to 81% (IQR 68-91%) in 2018. Laboratories open seven days a week in 2018 reported 95% of time-critical results within five days, compared to those open six days (62%), and five days (45%).ConclusionNBS programs that participated in NewSTEPs 360 made great strides in improving timeliness; however, ongoing quality improvement efforts are needed in order to ensure all infants receive a timely diagnosis

Newborn Screening for Cystic Fibrosis: A Qualitative Study of Successes and Challenges from Universal Screening in the United States

Cystic fibrosis (CF) newborn screening (NBS) was universally adopted in 2009 in the United States. Variations in NBS practices between states may impact the timing of diagnosis and intervention. Quantitative metrics can provide insight into NBS programs (NBSP), but the nuances cannot be elucidated without additional feedback from programs. This study was designed to determine facilitators and barriers to timely diagnosis and intervention following NBS for CF. The median age at the first CF event for infants with CF within each state was used to define early and late states (n = 15 per group); multiple CF centers were invited in states with more than two CF centers. Thirty states were eligible, and 61 NBSP and CF centers were invited to participate in structured interviews to determine facilitators and barriers. Once saturation of themes was reached, no other interviews were conducted. Forty-five interviews were conducted (n = 16 early CF center, n = 12 late CF center, n = 11 early NBSP, and n = 6 late NBSP). Most interviewees reported good communication between CF centers and NBSP. Communication between primary care providers (PCPs) and families was identified as a challenge, leading to delays in referral and subsequent diagnosis. The misperception of low clinical risk in infants from racial and ethnic minority groups was a barrier to early diagnostic evaluation for all groups. NBSP and CF centers have strong relationships. Early diagnosis may be facilitated through more engagement with PCPs. Quality improvement initiatives should focus on continuing strong partnerships between CF centers and NBS programs, improving education, communication strategies, and partnerships with PCPs, and improving CF NBS timeliness and accuracy