When Reality and Research Collide: Guidelines Are Essential for Optimal Nutrition Care in Pediatric Oncology.

Nutritional problems are common in pediatric oncology due to the side effects of the disease and treatment. Nutrition intervention can be challenging, and little is known about the current clinical practice of registered dietitian nutritionists. An online questionnaire emailed to members of the pediatric, oncology nutrition, and clinical manager practice groups of the Academy of Nutrition and Dietetics, consisted of items related to current nutrition practice. Our questionnaire results suggest that the field of pediatric oncology is employed with relatively new dietitians (62% had <5 y of experience). Many registered dietitian nutritionists (60%) are providing care across the cancer care continuum (standard therapy, transplant, and survivorship) versus specializing in a particular area. Approximately half (52%) felt that their center had inadequate staffing, many reporting little in the outpatient setting. Barriers to providing optimal patient care included inadequate staffing, lack of time for research initiatives, and lack of evidence-based guidelines. Future studies should determine follow-up guidelines and appropriate staffing ratios for nutrition care in pediatric oncology. Approaches should be developed to support less experienced dietitians. Collaboration between dietitians at different facilities will likely be key in developing essential evidence-informed guidelines.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.

Phenotypic heterogeneity is a common feature of monogenic neurodevelopmental disorders that can arise from differential severity of missense variants underlying disease, but how distinct alleles impact molecular mechanisms to drive variable disease presentation is not well understood. Here, we investigate missense mutations in the DNA methyltransferase DNMT3A associated with variable overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity in neurodevelopmental disease. We generate a DNMT3A P900L/+ mouse model mimicking a disease mutation with mild-to-moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation. We show that the P900L mutation leads to disease-relevant overgrowth, obesity, and social deficits shared across DNMT3A disorder models, while the R878H mutation causes more extensive epigenomic disruption leading to differential dysregulation of enhancers elements. We identify distinct gene sets disrupted in each mutant which may contribute to mild or severe disease, and detect shared transcriptomic disruption that likely drives common phenotypes across affected individuals. Finally, we demonstrate that core gene dysregulation detected in DNMT3A mutant mice overlaps effects in other developmental disorder models, highlighting the importance of DNMT3A-deposited methylation in neurodevelopment. Together, these findings define central drivers of DNMT3A disorders and illustrate how variable disruption of transcriptional mechanisms can drive the spectrum of phenotypes in neurodevelopmental disease.

Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3aP900L/+ mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation. P900L mutants exhibit core growth and behavioral phenotypes shared across models but show subtle epigenomic changes, while R878H mutants display extensive disruptions. We identify mutation-specific dysregulated genes that may contribute to variable disease severity. Shared transcriptomic disruption identified across mutations overlaps dysregulation observed in other developmental disorder models and likely drives common phenotypes. Together, our findings define central drivers of DNMT3A disorders and illustrate how variable epigenomic disruption contributes to phenotypic heterogeneity in neurodevelopmental disease.

The Effect of COVID-19 Lockdown on PHQ Depression Screening Scores for High School Athletes.

Adolescent behavioral health was in crisis before COVID-19. The shutdown and reopening of in-person learning and extracurricular activities may have worsened this crisis. We examined high school athletes' depression before and during the pandemic. Data were collected as part of a pilot program incorporating Patient Health Questionnaire (PHQ) screenings during high school sports physicals before the COVID-19 lockdown and three timepoints after. Statistical comparisons were made using logistic regression. A total of 927 individual scores were analyzed: 385 from spring 2020; 145 from fall 2020; 163 from fall 2021; and 234 from spring 2022. Fall 2020 students were 3.7 times more likely to have elevated PHQ-2 scores than spring 2020 students (95% CI = 1.8, 7.6). Fall 2021 and spring 2022 scores did not differ significantly from pre-pandemic, although trends of elevated scores persisted (OR = 1.6; 95% CI = 0.7, 3.5, and OR = 1.2; 95% CI = 0.6, 2.4, respectively). A significant difference in PHQ-9 depression severity classification was detected over time (p < 0.01). Elevated PHQ scores were found after the onset of the COVID-19 pandemic. After the initial peak in fall 2020, scores decreased but did not reach pre-pandemic levels.

Treatment considerations for recurrent MRSA bacteremia leading to cholecystitis.

We present an end-stage renal disease patient with acute cholecystitis caused by a recurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Timely antibiotic therapy with vancomycin did not eradicate the patient's infection. In this patient, the minimum inhibitory concentration (MIC) of the organism for vancomycin was at the upper limit of susceptibility. The ability to thoroughly understand and interpret mean inhibitory concentrations is crucial in antibiotic selection. For high-risk patients with Staphylococcus aureus infection with reduced susceptibility to vancomycin as demonstrated by an MIC of 2 mg/L or greater, we suggest further investigation into linezolid as an alternative antibiotic to vancomycin therapy. Compared to vancomycin, linezolid has similar effectiveness in patients with MRSA bacteremia as well as improved penetration, particularly in bile.

The evolving vocabulary of the social sciences: the case of "socialization".

While the term "socialization" stands as a common and clearly understood term regularly used in social science and lay conversations alike, its history is complex. In the 19th century, socialization was introduced to refer to societal activities or projects, and only in the early 20th century did it gain usage as a term describing psychological processes transpiring within the individual. The architecture of the newer meaning harbored ambitions and problems of modern social science, including ideals of interdisciplinary theory and theoretic resolution of the individual/society dualism. Nevertheless, socialization became a central object of social scientific inquiry after World War II. This significant social scientific object was repeatedly altered: initially representing a vision of conforming citizens who were free from certain troubling characteristics depicted in psychoanalysis and well-suited to democracy, it later was engaged to create a vision of autonomous, resilient, and cognitively active actors able to negotiate a complex social world.

Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome.

Germline pathogenic variants in DNMT3A were recently described in patients with overgrowth, obesity, behavioral, and learning difficulties (DNMT3A Overgrowth Syndrome/DOS). Somatic mutations in the DNMT3A gene are also the most common cause of clonal hematopoiesis, and can initiate acute myeloid leukemia (AML). Using whole genome bisulfite sequencing, we studied DNA methylation in peripheral blood cells of 11 DOS patients and found a focal, canonical hypomethylation phenotype, which is most severe with the dominant negative DNMT3AR882H mutation. A germline mouse model expressing the homologous Dnmt3aR878H mutation phenocopies most aspects of the human DOS syndrome, including the methylation phenotype and an increased incidence of spontaneous hematopoietic malignancies, suggesting that all aspects of this syndrome are caused by this mutation.

DNMT3A Haploinsufficiency Results in Behavioral Deficits and Global Epigenomic Dysregulation Shared across Neurodevelopmental Disorders.

Mutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. Here, we define the effects of DNMT3A mutations associated with neurodevelopmental disease. We show that diverse mutations affect different aspects of protein activity but lead to shared deficiencies in neuronal DNA methylation. Heterozygous DNMT3A knockout mice mimicking DNMT3A disruption in disease display growth and behavioral alterations consistent with human phenotypes. Strikingly, in these mice, we detect global disruption of neuron-enriched non-CG DNA methylation, a binding site for the Rett syndrome protein MeCP2. Loss of this methylation leads to enhancer and gene dysregulation that overlaps with models of Rett syndrome and autism. These findings define the effects of DNMT3A haploinsufficiency in the brain and uncover disruption of the non-CG methylation pathway as a convergence point across neurodevelopmental disorders.

National Trends in the Use of Inpatient Hospitalization for Combined Abdominoplasty and Breast Surgery.

BACKGROUND: Combined procedures involving elective breast surgery at the time of abdominoplasty are frequently performed procedures in aesthetic plastic surgery. While found to be safe outpatient procedures, many surgeons elect to perform combined abdominoplasty/breast surgery as inpatient surgery. This study was performed to explore the practice of performing the combined procedure as an inpatient in the United States. METHODS: The Nationwide Inpatient Sample database was evaluated using ICD-9CM procedural codes to identify hospitalizations where patients underwent abdominoplasty combined with breast surgery. We trended the frequency of this combined procedure, and evaluated the rate of acute post-operative complications, length of inpatient hospitalization, and total hospital charges. RESULTS: Between 2004 and 2011, 29,235 combined abdominoplasty/breast procedures were performed as inpatient in United States. The rate of major post-operative complications in the acute hospitalization period was 1.12% and included CVA (0.02%), respiratory failure (0.6%), pneumonia (0.3%), VTE (0.1%), and myocardial infarction (0.1%). Hospitalization averaged 1.8 days and resulted in $31,177 of hospital charges. The demographics of the combined procedure transitioned as i) frequency of inpatient surgeries decreased, ii) percent of patients >50 yr increased, and iii) hospital charges increased from 2004 to 2011. CONCLUSION: A significant number of surgeons are performing combined abdominoplasty and elective breast surgery as inpatient procedures in United States. The combined surgery is safe but is associated with small risk of major post-operative complications. A short inpatient hospitalization may be beneficial for high-risk patients interested in combined procedures, but must be analyzed against the rising costs of inpatient surgery.

Use of fenestrations in acellular dermal allograft in two-stage tissue expander/implant breast reconstruction.

UNLABELLED: The authors present a new technique of alteration of the acellular dermal matrix through strategically placed fenestrations, improving the reconstructive experience and overall cosmetic outcome. The authors present a retrospective chart review following two surgeons' experience at the University of California, Irvine, Department of Plastic Surgery using surgeon-designed fenestrated acellular dermal matrices in two-stage tissue expander breast reconstruction. The authors found that this leads to improved intraoperative fill volume, decreased number of postoperative expansions, increased expansion rate with subjectively less pain, decreased time to full expansion, and subjectively improved cosmetic outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Supraclavicular artery island flap innervation: anatomical studies and clinical implications.

BACKGROUND: Recently, the supraclavicular artery island flap has gained popularity as a regional flap for head and neck reconstruction. During clinical follow-up, some patients report referred sensation to the shoulder when there is contact with the flap skin island surface. The authors examine the anatomical origin/characteristics of the supraclavicular nerves (C3-4) to this flap and its relationship to the flap pedicle and anatomical boundaries. METHODS: SAI flap harvest and nerve dissection was performed in seven fresh frozen cadavers (n = 10) using loupe magnification in order to further elucidate the sensory nerve branches in a typical SAI flap. RESULTS: Branches of the supraclavicular nerve innervating the SAI flap were found to emerge from the deep fascia at a separate location from the vascular pedicle with the major nerve root exiting underneath the sternocleidomastoid muscle near the midpoint of the muscle belly. The nerve branches proximal to the pedicle with one branch exiting anterior to the flap and another running axially along the length of the flap. The majority (9/10) flaps had a major cutaneous nerves located 1-2 cm anterior to the pedicle. One (1/10) of the flaps had a major cutaneous nerve located 1-2 cm posterior to the pedicle toward the trapezius muscle. In 3 of the 10 flaps, smaller cutaneous nerves were also found posterior to the pedicle in a more distal location of the flap. CONCLUSIONS: The supraclavicular nerves innervating the SAI flap are easily identifiable and can be preserved or ligated, depending on the desired flap function, when present close to the pedicle. Further clinical investigation is warranted to confirm the potential benefit of using the SAI flap as a neurotized regional flap for head/neck reconstruction.