The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting.

Dendritic cells (DCs) form a remarkable cellular network that shapes adaptive immune responses according to peripheral cues. After four decades of research, we now know that DCs arise from a hematopoietic lineage distinct from other leukocytes, establishing the DC system as a unique hematopoietic branch. Recent work has also established that tissue DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. This review discusses major advances in our understanding of the regulation of DC lineage commitment, differentiation, diversification, and function in situ.

Ostrich eggshell beads reveal 50,000-year-old social network in Africa.

Humans evolved in a patchwork of semi-connected populations across Africa1,2; understanding when and how these groups connected is critical to interpreting our present-day biological and cultural diversity. Genetic analyses reveal that eastern and southern African lineages diverged sometime in the Pleistocene epoch, approximately 350-70 thousand years ago (ka)3,4; however, little is known about the exact timing of these interactions, the cultural context of these exchanges or the mechanisms that drove their separation. Here we compare ostrich eggshell bead variations between eastern and southern Africa to explore population dynamics over the past 50,000 years. We found that ostrich eggshell bead technology probably originated in eastern Africa and spread southward approximately 50-33 ka via a regional network. This connection breaks down approximately 33 ka, with populations remaining isolated until herders entered southern Africa after 2 ka. The timing of this disconnection broadly corresponds with the southward shift of the Intertropical Convergence Zone, which caused periodic flooding of the Zambezi River catchment (an area that connects eastern and southern Africa). This suggests that climate exerted some influence in shaping human social contact. Our study implies a later regional divergence than predicted by genetic analyses, identifies an approximately 3,000-kilometre stylistic connection and offers important new insights into the social dimension of ancient interactions.

Earliest known human burial in Africa.

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1-3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1-6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.

The transcriptional landscape of αß T cell differentiation.

The differentiation of αßT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.

Identification of transcriptional regulators in the mouse immune system.

The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage-specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.

Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages.

We assessed gene expression in tissue macrophages from various mouse organs. The diversity in gene expression among different populations of macrophages was considerable. Only a few hundred mRNA transcripts were selectively expressed by macrophages rather than dendritic cells, and many of these were not present in all macrophages. Nonetheless, well-characterized surface markers, including MerTK and FcγR1 (CD64), along with a cluster of previously unidentified transcripts, were distinctly and universally associated with mature tissue macrophages. TCEF3, C/EBP-α, Bach1 and CREG-1 were among the transcriptional regulators predicted to regulate these core macrophage-associated genes. The mRNA encoding other transcription factors, such as Gata6, was associated with single macrophage populations. We further identified how these transcripts and the proteins they encode facilitated distinguishing macrophages from dendritic cells.

Deciphering the transcriptional network of the dendritic cell lineage.

Although much progress has been made in the understanding of the ontogeny and function of dendritic cells (DCs), the transcriptional regulation of the lineage commitment and functional specialization of DCs in vivo remains poorly understood. We made a comprehensive comparative analysis of CD8(+), CD103(+), CD11b(+) and plasmacytoid DC subsets, as well as macrophage DC precursors and common DC precursors, across the entire immune system. Here we characterized candidate transcriptional activators involved in the commitment of myeloid progenitor cells to the DC lineage and predicted regulators of DC functional diversity in tissues. We identified a molecular signature that distinguished tissue DCs from macrophages. We also identified a transcriptional program expressed specifically during the steady-state migration of tissue DCs to the draining lymph nodes that may control tolerance to self tissue antigens.

DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance.

Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.

Diabetes distress in urban Black youth with type 1 diabetes and their caregivers: associations with glycemic control, depression, and health behaviors.

OBJECTIVES: Adolescents with type 1 diabetes (T1D) and their caregivers endorse high diabetes distress (DD). Limited studies have documented the impact of DD on Black youth. The aims of the present study were to (1) describe DD among a sample of Black adolescents with T1D and their caregivers, (2) compare their DD levels with published normative samples, and (3) determine how DD relates to glycemic outcomes, diabetes self-management, parental monitoring of diabetes, and youth depressive symptoms. METHODS: Baseline data from a multicenter clinical trial were used. Participants (N = 155) were recruited from 7 Midwestern pediatric diabetes clinics. Hemoglobin A1c (HbA1c) and measures of DD, parental monitoring of diabetes care, youth depression and diabetes management behaviors were obtained. The sample was split into (1) adolescents (ages 13-14; N = 95) and (2) preadolescents (ages 10-12; N = 60). Analyses utilized Cohen's d effect sizes, Pearson correlations, t-tests, and multiple regression. RESULTS: DD levels in youth and caregivers were high, with 45%-58% exceeding either clinical cutoff scores or validation study sample means. Higher DD in youth and caregivers was associated with higher HbA1c, lower diabetes self-management, and elevated depressive symptoms, but not with parental monitoring of diabetes management. CONCLUSIONS: Screening for DD in Black youth with T1D and caregivers is recommended, as are culturally informed interventions that can reduce distress levels and lead to improved health outcomes. More research is needed on how systemic inequities contribute to higher DD in Black youth and the strategies/policy changes needed to reduce these inequities.

The moderating role of diabetes distress on the effect of a randomized eHealth intervention on glycemic control in Black adolescents with type 1 diabetes.

OBJECTIVE: Due to systemic inequities, Black adolescents with type 1 diabetes are more likely to have suboptimal glycemic control and high rates of diabetes distress, but tailored interventions for this population are lacking. In primary outcomes of a randomized clinical trial, a family-based eHealth intervention improved glycemic control in Black adolescents with type 1 diabetes and elevated depressive symptoms. The present study is a secondary analysis of these clinical trial data examining the moderating effect of diabetes distress on the efficacy of the intervention. METHODS: Using secondary data from a multicenter randomized clinical trial (Clinicaltrials.gov [NCT03168867]), caregiver-adolescent dyads were randomly assigned to either up to three sessions of an eHealth parenting intervention (n = 75) or a standard medical care control group (n = 74). Black adolescents (10 years, 0 months to 14 years, 11 months old) with type 1 diabetes and a caregiver willing to participate were eligible. Adolescents reported their diabetes distress at baseline, and hemoglobin A1c (HbA1c) data were collected at baseline, 6-, 13-, and 18-month follow-up. RESULTS: No between-group contrasts emerged in a linear mixed-effects regression (p's > .09). Within-group contrasts emerged such that adolescents assigned to the intervention who reported high diabetes distress had lower HbA1c at the 18-month follow-up relative to baseline (p = .004); the 18-month decrease in HbA1c was -1.03%. CONCLUSIONS: Black adolescents with type 1 diabetes and high levels of diabetes distress showed significant decreases in HbA1c following a family-based eHealth intervention, suggesting diabetes distress may be a key moderator of intervention efficacy within this population.

Self-management intervention for patients following hospitalization for acute exacerbation of chronic obstructive pulmonary disease (AECOPD): A pilot randomized controlled trial.

The purpose of this study was to evaluate the handoff guidance (HG) self-management intervention for multimorbid chronic obstructive pulmonary disease (COPD) patients following hospitalization for acute exacerbation of COPD (AECOPD) using HG self-management intervention compared to a control group on COPD self-management outcomes (self-care, self-efficacy, health engagement) and assess feasibility, acceptability, and healthcare utilization. A randomized pilot study used a 2-group with repeated measures design. Adults with COPD who had been hospitalized for AECOPD were recruited. After discharge, the HG self-management intervention employed health coaching delivered at: 1-3, 10-12, and 20-22 days after hospital discharge. Follow-up data collected was collected at 1-3, 10-12, 20-22, 30, 60, and 90 days after hospital discharge. A total of 29 subjects participated, with a mean age of 66 (+8.7) years old, the majority were females (n = 18). Intervention participants reported the acceptability of the HG self-management intervention. Participants in both groups continued to report COPD symptoms after discharge, which decreased over time, although not significantly different by group. The use of COPD maintenance, monitoring, and management behaviors was higher in the treatment group, although not significantly different.

Diversity in clinical research: public health and social justice imperatives.

It is well established that demographic representation in clinical research is important for understanding the safety and effectiveness of novel therapeutics and vaccines in diverse patient populations. In recent years, the National Institutes of Health and Food and Drug Administration have issued guidelines and recommendations for the inclusion of women, older adults, and racial and ethnic minorities in research. However, these guidelines fail to provide an adequate explanation of why racial and ethnic representation in clinical research is important. This article aims to both provide the missing arguments for why adequate representation of racial and ethnic minorities in clinical research is essential and to articulate a number of recommendations for improving diversity going forward.Appropriate racial and ethnic representation and fair inclusion help (1) increase the generalisability of clinical trial results, (2) equitably distribute any benefits of clinical research and (3) enable trust in the research enterprise.

Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands.

Cellular and virus-coded long non-coding (lnc) RNAs support multiple roles related to biological and pathological processes. Several lncRNAs sequester their 3' termini to evade cellular degradation machinery, thereby supporting disease progression. An intramolecular triplex involving the lncRNA 3' terminus, the element for nuclear expression (ENE), stabilizes RNA transcripts and promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi's sarcoma-associated herpesvirus (KSHV) polyadenylated nuclear (PAN) lncRNA, represent targets for therapeutic development. Towards identifying novel ligands targeting the PAN ENE triplex, we screened a library of immobilized small molecules and identified several triplex-binding chemotypes, the tightest of which exhibits micromolar binding affinity. Combined biophysical, biochemical, and computational strategies localized ligand binding to a platform created near a dinucleotide bulge at the base of the triplex. Crystal structures of apo (3.3 Å) and ligand-soaked (2.5 Å) ENE triplexes, which include a stabilizing basal duplex, indicate significant local structural rearrangements within this dinucleotide bulge. MD simulations and a modified nucleoside analog interference technique corroborate the role of the bulge and the base of the triplex in ligand binding. Together with recently discovered small molecules that reduce nuclear MALAT1 lncRNA levels by engaging its ENE triplex, our data supports the potential of targeting RNA triplexes with small molecules.

Psychometric Properties of the Patient Activation Measure in Family Caregivers of Patients With Chronic Illnesses.

BACKGROUND: The Patient Activation Measure (PAM) is used clinically and in research to measure an individual's knowledge, skills, and confidence related to their health management engagement. Despite the use of "patient" in the title, the instrument can be used in nonpatient populations. A group at high risk for low activation concerning their own health is family caregivers of patients with chronic illnesses. The psychometric properties of the PAM have not been established in family caregivers. OBJECTIVES: This study aimed to examine the psychometric properties of the PAM 10-item version (PAM-10) in a sample of family caregivers of patients with chronic illnesses. Our focus was on family caregivers' health activation of their own healthcare needs. METHODS: We evaluated the internal consistency reliability of the PAM-10 in a sample of 277 family caregivers. Item-total correlations and interitem correlations were used to assess item homogeneity. Construct validity of the PAM-10 was examined using exploratory factor analysis and testing hypotheses on known relationships. RESULTS: The PAM-10 demonstrated adequate internal consistency. Item-total correlation coefficients and interitem correlation coefficients were acceptable. Construct validity of the instrument was supported. Factor analysis yielded two factors that explained 62.3% of the variance in the model. Lower levels of depressive symptoms were significantly associated with better activation, providing evidence of construct validity. Caregivers with high activation levels were significantly more likely to engage in and adhere to self-care behaviors such as regular exercise, eating a healthy diet, and engaging in stress reduction strategies. DISCUSSION: This study demonstrated that the PAM-10 is a reliable and valid measure for family caregivers of patients with chronic illnesses to measure caregivers' health activation of their own healthcare needs.

Subcutaneous fat necrosis of the newborn: A retrospective study of 32 infants and care algorithm.

OBJECTIVE: To describe the clinical and laboratory outcomes of infants with subcutaneous fat necrosis of the newborn (SCFN) and propose a care algorithm. METHODS: This single-center, retrospective study of infants diagnosed with SCFN at Ann & Robert H. Lurie Children's Hospital of Chicago from 2009 to 2019. RESULTS: Of 32 infants who met inclusion criteria, most were born full-term (84%), born via cesarean section (58%), had normal weight for gestational age (69%), and experienced delivery complications (53%). Twenty-nine infants (91%) had calcium drawn, and all had hypercalcemia. Three infants developed clinical symptoms of hypercalcemia, two required hospital admission, two developed nephrocalcinosis, and one developed acute kidney injury. The majority of infants (62%) had a peak ionized calcium between 1.5 and 1.6 mmol/L. No infants with peak ionized calcium less than 1.5 mmol/L developed complications of hypercalcemia. Most patients were diagnosed with hypercalcemia (86%) and demonstrated peak ionized calcium levels (59%) within the first 28 days of life. No patients developed hypercalcemia after 3 months of age. CONCLUSION: Hypercalcemia occurred in 100% of infants who had laboratory monitoring. We recommend obtaining an initial ionized calcium level when SCFN is suspected, and monitoring for the first 3 months of life if hypercalcemia has not been detected. In patients with asymptomatic hypercalcemia less than 1.5 mmol/L, there appears to be low likelihood of related complications. For symptomatic, markedly elevated (>1.6 mmol/L), or persistently elevated levels (>6 months) we suggest coordinated care with endocrinology or nephrology, consider hospitalization, and urinary system ultrasound.

Interprofessional Education to Address Substance Use among Adults with Persistent Pain: A Pre-Post Program Evaluation.

BACKGROUND: Substance use disorders (SUDs) are highly prevalent among adults with persistent pain. Yet, standard competencies for integrating pain and SUD content are lacking across health science student curricula. Additionally, pharmacotherapies to treat SUDs are underutilized. AIM: To address these gaps, a team of health science faculty created an interprofessional simulation activity using a standardized patient and evaluated learner outcomes related to assessment and treatment of comorbid persistent pain and substance use. METHODS: A total of 304 health science students representing nursing, medicine, pharmacy, and social work programs attended virtual learning sessions. Interprofessional student teams developed a team-based care plan for an adult with musculoskeletal pain who takes prescribed opioids while using alcohol. Pre- and post-activity surveys assessing knowledge and confidence were matched for 198 students. Descriptive statistics summarized survey data with inferential analysis of paired data. RESULTS: The largest significant improvements between pre- and post-activity knowledge were observed in items specific to pharmacotherapy options for alcohol and opioid use disorders. Similar gains were noted in students' confidence regarding pharmacotherapies. No significant differences were noted on pre-post-activity knowledge scores between the three main profession groups (medicine, nursing, and pharmacy). CONCLUSIONS: Students attending this interprofessional simulation demonstrated improved knowledge and confidence, particularly in pharmacotherapies for alcohol and opioid use disorders. Replication of such programs can be used to provide consistent content across health science disciplines to heighten awareness and receptivity to medications available to treat SUDs in people treated for persistent pain. The curriculum is freely available from the corresponding author.

Health Literacy and Perceived Control: Intermediary Factors in the Relationship Between Race and Cardiovascular Disease Risk in Incarcerated Men in the United States.

BACKGROUND: Black race, inadequate health literacy, and poor perceived control are predictors of increased cardiovascular disease (CVD) risk. The purpose of this study was to explore the relationships among race, health literacy, perceived control, and CVD risk while controlling for known risk factors in incarcerated men. METHODS: We included data from 349 incarcerated men to examine race and CVD risk (Framingham Risk Score) using a serial mediation model with health literacy and perceived control using 95% confidence intervals (CIs) from 5000 bootstrap samples. RESULTS: Of the participants (age, 36 ± 10; education, 12 ± 2; body mass index, 28.3 ± 5.0), 64.2% were White and 35.8% were Black. Black incarcerated men were younger (P = .047) with lower levels of health literacy (P < .001). All 3 indirect effects of race on CVD were significant, whereas the direct effect of race was not. Black incarcerated men had higher levels of CVD risk through health literacy (a1b1 = 0.3571; 95% CI, 0.0948-0.7162) and lower levels of CVD risk through perceived control (a2b2 = -0.1855; 95% CI, -0.4388 to -0.0077). Black incarcerated men had higher levels of CVD risk through health literacy influenced by perceived control (a1b2d21 = 0.0627; 95% CI, 0.0028-0.1409), indicating that despite the protective effect of higher levels of perceived control in Black incarcerated men, CVD risk remained higher compared with their White counterparts. CONCLUSION: Future CVD risk reduction interventions in incarcerated men, specifically Black incarcerated men, should include goals of improving health literacy and perceived control as modifiable risk factors.

Recent and lifetime maternal substance use: Rurality and economic distress.

Research on opioid use disorder (OUD) in pregnancy has mainly considered women in urban areas receiving treatment, with less known about women in rural areas. We sought to describe demographics and substance use characteristics of pregnant women with OUD and to compare the women based on urbanicity, in a state (Kentucky) with unfavorable economic conditions in many rural counties; we hypothesized that pregnant women in rural areas would have greater adversity, broadly defined, related to substance use. Using data collected from a larger project between 2017 and 2020, we analyzed characteristics of 93 pregnant women (59 rural and 34 urban) with OUD; we examined data in medical, employment, substance use, legal, family history, relationship, and psychiatric health domains, both overall and within rural (population <50,000) and urban (population ≥50,000) strata. Pregnant women with OUD from rural and urban areas were similar on almost all attributes. Among the few significant differences, 30% from urban areas perceived inadequate prenatal care versus 11% from rural areas (p = 0.024); 21% of urban women used amphetamines/methamphetamines in the month before delivery versus 0% of rural women (p < 0.001); and rural women had longer most recent abstinence from substance use than their urban counterparts (medians 7.0 and 2.8 months, p = 0.049). The few significant differences that were discovered favored rural women. These findings, contrary to our hypothesis, suggest that tailoring interventions may require more than focusing on geography. The participants in this study were pregnant women being treated for OUD, and as such there is patient contribution of data.

'It's been an extraordinary journey': Experience of engagement from the perspectives of people with post-stroke aphasia.

BACKGROUND: Engagement is recognized as an important factor in aphasia treatment response and outcomes, yet gaps remain in our understanding of engagement and practices that promote engagement from the client perspective. AIMS: The purpose of this phenomenological study was to explore how clients with aphasia experience engagement during their inpatient aphasia rehabilitation. METHODS & PROCEDURES: An interpretative phenomenological analysis approach guided the study design and analysis. Data were collected through in-depth interviews with nine clients with aphasia, recruited through purposive sampling, during their inpatient rehabilitation admission. Analysis was completed using a variety of analytic techniques including coding, memoing, triangulation between coders and team discussion. OUTCOMES & RESULTS: The analysis revealed that for clients with aphasia in the acute phrase of recovery, the rehabilitation process resembles travelling on a journey through a foreign land. Successful engagement in the journey was accomplished when one had a therapist who served as a trusted guide and was able to be a friend, invested, adaptable, a co-creator, encouraging and dependable. CONCLUSIONS & IMPLICATIONS: Engagement is a dynamic, multifaceted and person-centred process involving the client, provider and rehabilitation context. Findings from this work have implications for measuring engagement, training student clinicians to be skilled facilitators in engaging their clients and implementing person-centred practices that promote engagement within clinical settings. WHAT THIS PAPER ADDS: What is already known on the subject Engagement is recognized as an important factor in rehabilitation treatment response and outcomes. Prior literature suggests that the therapist plays a critical role in facilitating engagement within the client-provider relationship. Communication impairments associated with aphasia may negatively impact a client's ability to develop interpersonal connections and participate in the rehabilitation process. There is a dearth of research directly exploring the topic of engagement in aphasia rehabilitation, particularly from the perspective of clients with aphasia. Capturing the client perspective can provide novel insights regarding practices to foster and maintain engagement in aphasia rehabilitation. What this paper adds to existing knowledge This interpretative phenomenological study revealed that for individuals with aphasia in the acute phase of recovery, the rehabilitation process resembles travelling on a sudden and foreign journey. Successful engagement in the journey was accomplished when one had a therapist who served as a 'trusted guide' and was able to be a friend, invested, adaptable, a co-creator, encouraging and dependable. Through the client experience, engagement is seen as a dynamic, multifaceted and person-centred process involving the client, provider and rehabilitation context. What are the potential or actual clinical implications of this work? The current study highlights the complexity and nuance of engagement within the rehabilitation context, which has implications for measuring engagement, training student clinicians to be skilled in engaging their clients and implementing person-centred practices that promote engagement within clinical settings. It is necessary to recognize that client and provider interactions (and thus engagement) are embedded in and influenced by the broader healthcare system. With this in mind, a patient-centred approach to engagement in aphasia care delivery cannot be achieved through individual efforts only and may require prioritization and action at the systems level. Future work is needed to explore barriers and facilitators to enacting engagement practices, in order to develop and test strategies to support practice change.

The Arduous Path to Drug Approval for the Management of Prader-Willi Syndrome: A Historical Perspective and Call to Action.

Prader-Willi syndrome (PWS) is a neuroendocrine genetic disorder resulting from the loss of paternally expressed imprinted genes in chromosome 15q11-q13 [...].