Characteristics and complications of acute promyelocytic leukemia in children: an analysis of a national database.

Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia (AML) that was previously one of the most fatal forms of acute leukemia. With advances in diagnosis and treatment, APL has become one of the most curable myeloid leukemias. The major reason for treatment failure in APL is early death after initiation of treatment. We performed a retrospective cross-sectional analysis of the Healthcare Cost and Utilization Project 2016 and 2019 Kids' Inpatient Database, with the diagnosis of APL or AML not in remission as defined by ICD-10-CM codes. We compared complications and outcomes associated with APL and AML (exclusive of APL) in hospitalized children in the U.S. and described yearly national incidence. The national incidence of APL was 2.2 cases per million children per year. Children with APL were more likely to have cardiopulmonary complications (OR 1.79; CI 1.20-2.67; p = 0.004), coagulation abnormalities or DIC (OR 7.75; CI 5.81-10.34; p < 0.001), pulmonary hemorrhage (OR 2.18; CI 1.49-3.17; p < 0.001), and intracranial hemorrhage (OR 10.82; CI 5.90-19.85; p < 0.001) and less likely to have infectious complications (OR 0.48; CI 0.34-0.67; p < 0.001) compared to children with AML. In-hospital mortality rates were similar in children with APL and AML (4.2% vs 2.6%; OR 1.62; CI 0.86-3.06; p = 0.13), while the median length of stay for children who died from APL was shorter compared to AML (2 (IQR: 1-7) versus 25 (IQR: 5-66) days; p < 0.05). Hemorrhagic complications occur more often, and infectious complications occur less often in hospitalized children with APL compared to AML.

A Retrospective Review of Patient-reported Outcomes after Postaxial Polydactyly Ligation and Surgical Excision.

Background: Interventions for type B postaxial polydactyly include suture ligation and surgical excision, yet there is a paucity of literature comparing the outcomes of these procedures. This study sought to compare patient-reported long-term outcomes of postaxial digit excision. Methods: A six-question survey was distributed from January 2021 to March 2022 to patients who underwent treatment for type B postaxial polydactyly at a single pediatric institution from 2010 to 2016. Patients were queried about the incidence of pain sensitivity, keloid healing, and/or persistent presence of bump ("nubbin") at the treatment site. Results: A total of 158 responses accounting for 258 digits were attained for a 53% response rate. The majority of digits (67.4%, n = 174) were surgically excised. Median age at procedure was 49 days: 13.0 days for ligation, 63.0 days for surgical excision. Median age at survey was 8 [IQR 5.4-10.2] years. Short-term (<30 days after procedure) complications rate was 1.6%. The rate of a raised or sensitive scar was 39.5% (ligation 51.5% versus surgery 35.4%, P < 0.05). The likelihood of postoperative sensitivity (P = 0.80) was similar among groups. However, the odds of a residual bump or raised scar at the surgical site was significantly higher in the ligation group (P = 0.001). These findings remained significant in the adjusted analysis. Conclusion: This study suggests that suture ligation can be used in select cases without increasing the prevalence of long-term pain or sensitivity, albeit with greater risk of a bump or raised scar at the excision site compared with surgical excision.

Epidemiology of Adenovirus Infection in Hospitalized Children in the United States From 1997 to 2019.

OBJECTIVE: The study aimed to explore the prevalence, clinical features, resource utilization, temporal trends and outcomes associated with adenoviral infections in hospitalized children. METHODS: A retrospective analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997 to 2019 was performed. Children aged 29 days to 17 years with adenoviral infection were selected. Chi-square, Kruskal-Wallis tests, linear trend analysis and multivariable analysis were used for data analysis. RESULTS: A total of 40,135 children under 18 years of age with adenoviral infection were discharged in the United States with an overall prevalence of 18.9 per 10,000 discharges and 6.9 children per 100,000 population. By linear trend analysis, the hospitalization rate has significantly increased with the highest prevalence in 2019. Adenoviral infection was more prevalent in Black children, in winter months, in the Midwest region, in children with government insurance and in the lowest income quartile. The majority (85%) of adenovirus-related hospitalizations occurred under 6 years of age. Mechanical ventilation, extracorporeal membrane oxygenation support, acute kidney injury and liver failure were documented in 11.9%, 0.4%, 2.7% and 0.4%, respectively. The overall case fatality rate was 1.4%, which decreased from 1997 to 2019 (P < 0.05). By regression analysis, an increased mortality rate was associated with the need for mechanical ventilation, the presence of complex chronic conditions, immune deficiency, central nervous system infection and pneumonia/bronchiolitis. CONCLUSIONS: Most human adenovirus infections occur in children under 6 years of age and cause mild illness. Human adenovirus can lead to serious illness in children with complex chronic conditions and immune deficiency conditions.

A Rare Case of Dermatofibrosarcoma in a Pediatric Patient.

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant fibroblastic tumor. DFSP has an insidious onset, slow growth, and heterogeneous presentation that can create a delay in diagnosis and increase morbidity. In this case report, we present a child with DFSP that presented as a large, slow-growing mass over the dorsum of the left foot. She underwent successful surgical excision with no functional sequelae.

Racial Inequities in Mortality Rate in Hospitalized Children.

BACKGROUND AND OBJECTIVES: Racial/ethnic inequities for inpatient mortality in children at a national level in the U.S. have not been explored. The objective of this study was to evaluate differences in inpatient mortality rate among different racial/ethnic groups, using the Kids' Inpatient Database. METHODS: A cross-sectional study of children of ages greater than 28 days and less than 21 years discharged during 2012 and 2016. Racial/ethnic groups - White, Black, Hispanic, Asian and Pacific Islander and Native Americans were analyzed in two cohorts, Cohort A (all discharges) and Cohort B (ventilated children). RESULTS: A total of 4,247,604 and 79,116 discharges were included in cohorts A and B, respectively. Univariate analysis showed that the inpatient mortality rate was highest among Asian and Pacific Islander children for both cohorts: A (0.47% [0.42-0.51]), B (10.9% [9.8-12.1]). Regression analysis showed that Asian and Pacific Islander and Black children had increased odds of inpatient mortality compared to White children: A (1.319 [1.162-1.496], 1.178 [1.105-1.257], respectively) and B (1.391 [1.199-1.613], 1.163 [1.079-1.255], respectively). Population-based hospital mortality was highest in Black children (1.17 per 10,000 children). CONCLUSIONS: Inpatient mortality rates are significantly higher in U.S. children of Asian and Pacific Islander and Black races compared to White children. U.S. population-based metrics such as hospitalization rate, ventilation rate, and hospital mortality rate are highest in Black children. Our data suggest that lower median household income alone may not account for a higher inpatient mortality rate. The causes and prevention of racial and ethnic inequities in hospitalized children need to be explored further.

Epidemiology and Outcomes of Cerebral Edema in Hospitalized Children.

BACKGROUND: Cerebral edema can be a consequence of multiple disease processes. Untreated cerebral edema can be fatal, and even with aggressive management, it can be devastating. The objective of this study was to describe the prevalence, underlying causes, and outcomes of cerebral edema in hospitalized children. METHODS: A retrospective cross-sectional study using the 2016 Kids' Inpatient Database was performed. Children aged one month to 20 years were included. Sample weighting was employed to produce national estimates. Univariate analyses were used to compare those who died and survived. Multivariable logistic regression was performed to assess the influence of demographic variables and etiologic factors on mortality. RESULTS: Cerebral edema was documented in 4903 children of 2,210,263 (2.2 of 1000) discharges. Among children with cerebral edema, males were 57%, white children were 47.9%, and adolescents were 48.9%. The three most common etiologies associated with cerebral edema in this cohort were stroke (21.7%), anoxic injury (21.4%), and central nervous system (CNS) malignancy (16%). The overall hospital mortality rate was 29.4%. The adjusted mortality rate was significantly higher when cerebral edema was associated with anoxic injury (84%). The mortality was lower when cerebral edema was associated with CNS malignancy (9.5%) or diabetic ketoacidosis (DKA) (4.3%). CONCLUSIONS: Cerebral edema is uncommon in hospitalized children but has a high mortality. Stroke and anoxic brain injury are the two most common etiologies for cerebral edema in hospitalized children in the United States. Among all etiologies for cerebral edema in children, anoxic brain injury has the highest mortality, whereas DKA has the lowest mortality.

Botulinum Toxin to Improve Scar Quality in Cleft Lip Repair: A Systematic Review.

OBJECTIVE: Cleft lip repair (CLR) can be complicated by hypertrophic scar or keloid. Botulinum toxin type A (BTA) may improve postoperative scarring by reducing muscle tension and cytokine activity at the scar site. This systematic review analyzes the available evidence regarding the effect of BTA on scar quality after CLR. DESIGN: The search was conducted in 6 different databases in accordance with PRISMA guidelines (PubMed, Scielo, Embase, Scopus, Web of Science, and Cochrane) using "botulinum toxin" and "cleft lip" as keywords. SETTING: Academic hospital. PATIENTS: Exclusive to patients who underwent CLR and BTA injection. OUTCOME MEASURES: Mean visual analog scores (VAS), mean Vancouver scar scale (VSS), scar width, and BTA or CLR-related complications. RESULTS: Five studies for a total of 216 patients met inclusion criteria. Four studies reported on primary CLR during infancy while 1 study recruited older patients seeking revision. All patients had BTA (range: 1-2 units/kg) injected in the orbicularis oris muscle. One study documented BTA injections in additional perioral muscles. All 4 studies that measured scar width and had a saline control arm found a significant decrease in width with BTA injection. Improvement of VAS and VSS with BTA was reported in 3 of 5 studies and 2 of 5 studies, respectively. There were no reports of complications associated with BTA or CLR. CONCLUSION: The existing studies support the use of BTA injection to improve scar quality following CLR with low concern for complication. Further investigations with a greater number of patients are necessary.

Epidemiology and Clinical Features of Human Metapneumovirus and Respiratory Syncytial Viral Infections in Children.

BACKGROUND: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are 2 common causes of acute respiratory tract infections in infants and young children. The objective of this study is to compare the demographics and outcomes of children hospitalized with HMPV and RSV infections in the United States. METHODS: We performed a retrospective cohort analysis of children 1 month to less than 3 years old discharged during 2016 with HMPV or RSV infection using the Kids' Inpatient Database. Children with HMPV and RSV coinfection were excluded. Data were weighted for national estimates. RESULTS: There were 6585 children with HMPV infection and 70,824 with RSV infection discharged during the study period. The mean age of children with HMPV infection was higher than that of children with RSV infection (0.73 ± 0.8 vs. 0.42 ± 0.7 years; P < 0.05). The mortality rate was significantly higher in children with the presence of any complex chronic conditions compared to those without, in both HMPV [odds ratio (OR): 32.42; CI: 9.931-105.857; P < 0.05] as well as RSV (OR: 35.81; CI: 21.12-57.97; P < 0.05) groups. The adjusted median length of stay was longer (4.64 days; CI: 4.52-4.76 days vs. 3.33 days; CI: 3.31-3.35 days; P < 0.001) and total charges were higher ($44,358; CI: $42,145-$46,570 vs. $22,839; CI: $22,512-$23,166; P < 0.001), with HMPV infection. The mortality rate was similar in HMPV infection compared to RSV infection on multivariable analysis (OR: 1.48; P > 0.05). CONCLUSION: In hospitalized children in the United States, HMPV infection is less common than RSV infection. Complex chronic conditions are more prevalent in children hospitalized with HMPV infection. Hospitalization with HMPV is associated with longer length of stay and higher hospital charges. The adjusted mortality is similar with both infections.

Impaired aldehyde detoxification exacerbates motor deficits in an alpha-synuclein mouse model of Parkinson's disease.

INTRODUCTION: The discovery of biogenic aldehydes in the postmortem parkinsonian brain and the ability of these aldehydes to modify and cross-link proteins has called attention to their possible role in Parkinson's disease. For example, many in vitro studies have found that the aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL), induces the formation of stable, neurotoxic alpha-synuclein oligomers. METHODS: To study this in vivo, mice deficient in the two aldehyde dehydrogenase enzymes (Aldh1a1 and Aldh2, DKO) primarily responsible for detoxification of DOPAL in the nigrostriatal pathway were crossed with mice that overexpress human wild-type alpha-synuclein. DKO overexpressing human wild-type alpha-synuclein (DKO/ASO) offspring were evaluated for impairment on motor tasks associated with Parkinsonism. RESULTS: DKO/ASO mice developed severe motor deficits greater than that of mice overexpressing human wild-type alpha-synuclein alone. CONCLUSION: These results provide evidence to support the idea that biogenic aldehydes such as DOPAL interact with human wild-type alpha-synuclein, directly or indirectly, in vivo to exacerbate locomotor deficits in Parkinson's disease.

Characteristics and Outcomes of Children with Cerebral Sinus Venous Thrombosis.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is an uncommon condition in children with potentially serious outcomes. Large epidemiological studies in children with CSVT are few. The objective of this study is to evaluate the epidemiology and in-hospital outcomes of hospitalized children with CSVT in the United States. METHODS: We performed a retrospective cross-sectional analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database for the combined years 2016 and 2019. The database was queried using the diagnoses for intracranial and intraspinal phlebitis and thrombophlebitis, nonpyogenic thrombosis of the intracranial venous system, and cerebral infarction due to cerebral venous thrombosis. Sample weighting was employed to produce national estimates. RESULTS: Of 12,165,621 discharges, 3202 had CSVT (in-hospital prevalence 26.3 per 100,000 discharges). Male patients accounted for 57% of CSVT discharges. The median age was 8 years (interquartile range 1-16), with a U-shaped distribution with peaks in patients younger than 4 years and patients aged between 18 and 20 years. A total of 19.3% of children with CSVT had either hemorrhagic or ischemic stroke. Patients with stroke were more likely to require mechanical ventilation (odds ratio [OR] 2.7; 95% confidence interval [CI] 2.1-3.3; p < 0.001) and have higher mortality (OR 2.3; 95% CI 1.6-3.4; p < 0.001). Mechanical ventilation was necessary for 25.2% of patients with CSVT, of whom the majority were neonates and young children. The need for mechanical ventilation was associated with increased mortality (OR 16.6; 95% CI 9.9-27.9; p < 0.001). The overall mortality rate for CSVT was 4.1%, and 16.5% of patients with CSVT were discharged with home health care or to a skilled nursing facility. CONCLUSIONS: CSVT, which has a U-shaped age distribution, is an uncommon condition in children. Stroke is common in children with CSVT, and it is associated with an increased need for mechanical ventilation and increased mortality. The need for mechanical ventilation is more common in infants, and it is associated with increased mortality across all age groups.

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration.

Digital technologies: students' expectations and experiences during their transition from high school to university.

University students' expectations of digital technologies in their studies are greatly influenced by their previous exposure both within the secondary school classroom and in their private lives. These expectations often play a powerful role in their approaches and learning strategies in their first-year university classes. In this work, we investigated students' expectations and utilisation of digital technologies in their transition from high school to tertiary studies. A survey encompassing the Expectancy-Disconfirmation Paradigm was conducted amongst second year students across the university. The results showed students expected to use advanced IT technologies and equipment at university. The high expectations were similar regardless of demographic parameters, such as gender, school type or field of studies. The findings also indicated that most students perceived little disconnection between the technology they used in high school and that of university. The majority of students seemed satisfied and even positively surprised by the use of technology in their university courses.

El cuidado y los procesos de atención-desatención como referentes analíticos y operativos para la salud colectiva / Care and Attention-Neglect Processes as Analytical and Operative Referents for Community Health / O cuidado e os processos de atenção-desatenção como referentes analíticos e operacionais para a saúde coletiva

Resumen "Cuidado" es un término polisémico, con un potencial referencial para la salud colectiva. En el marco de la reflexión actual sobre el papel y el alcance del cuidado en ese campo, la atención constituye una etapa inicial, esencial, pero insuficiente del cuidado, siendo este un proceso más amplio en los ámbitos individual y colectivo. Si bien el reconocimiento del proceso salud-enfermedad-atención expande la perspectiva de la salud pública, la "desatención", como tal y como contraparte dinámica de la atención, es invisibilizada, a pesar de su potencial analítico y operativo en el campo de la epidemiología y la salud colectiva. Ambos términos, integrados como procesos de atención-desatención, se analizan en este artículo desde las propuestas de la ética y la integralidad del cuidado, y desde una perspectiva decolonial e incluyente de la epidemiología. En el marco de la dinámica entre atención y desatención, se concreta y materializa la capacidad de prevenir o producir el daño evitable a la salud, en diversos niveles, alcances e itinerarios ilustrativos, específicos y evidenciables en la práctica.

Abstract "Care" is a polysemous term that can serve as a reference for community health. Within the framework of current thinking about the role and extent of care in this field, attention constitutes an initial, essential, but insufficient stage of care, which is a broader process in the individual and collective spheres. Although acknowledging the health-illness-care process broadens the public health perspective, "neglect" as a concept and as a dynamic counterpart to attention remains hidden, despite its analytical and operational potential in epidemiology and community health. Both terms, combined as attention-neglect processes, are analyzed in this article from an ethical and integrative care viewpoint, as well as from a decolonial and inclusive epidemiological perspective. Within the dynamics of care and neglect, the ability to avoid or cause preventable harm to health materializes and arrives at various levels, scopes, and illustrative itineraries, all of which are specific and evident in practice.

Resumo "Cuidado" é um termo polissêmico, com um potencial referencial para a saúde coletiva. No marco da reflexão atual sobre o papel e o alcance do cuidado nesse campo, a atenção constitui uma etapa inicial, essencial, mas insuficiente do cuidado, sendo este um processo mais amplo nos âmbitos individual e coletivo. Ainda que o reconhecimento do processo saúde-enfermidade-atenção expande a perspectiva da saúde pública, a "desatenção", como tal e como contraparte dinâmica da atenção, é invisível, apesar do seu potencial analítico e operacional no campo da epidemiologia e da saúde coletiva. Ambos os termos, integrados como processos de atençãodesatenção, são analisados neste artigo desde as propostas da ética e a integralidade do cuidado, e desde uma perspectiva decolonial e inclusiva da epidemiologia. No marco da dinâmica entre atenção e desatenção se concretiza e se materializa a capacidade de prevenir ou produzir o prejuízo evitável à saúde em diversos níveis, abrangências e itinerários ilustrativos, específicos e evidenciáveis na prática.

A Case of a Lethal Diquat Ingestion in a Toddler.

BACKGROUND: Diquat is an herbicide that may cause rapid and profound systemic toxicity. It can cause multisystem organ failure, primarily via its effects on the gastrointestinal, renal, cardiovascular, and central nervous systems. Case fatality rates as high as 43% have been reported. There is a paucity of pediatric literature on diquat poisoning, and in this article, we will discuss an unfortunate pediatric case that highlights the severity of diquat toxicity. CASE REPORT: We present the case of a child who ingested diquat, which led to multisystem organ failure and death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of this herbicide's potential for significant morbidity and mortality, especially in children, in whom small quantities can be lethal. It is important that emergency physicians are aware of the significant toxicity of diquat and provide early gastric decontamination, as it is the only proven therapeutic strategy.

Takotsubo cardiomyopathy in children.

OBJECTIVE: To explore the epidemiology and outcomes of takotsubo cardiomyopathy in children. METHODS: A retrospective analysis of the Healthcare Cost and Utilization 2012 and 2016 Kids' Inpatient Database was performed. Patients admitted with the diagnosis of takotsubo cardiomyopathy in the age group of 1 month-20 years were identified using International Classification of Diseases (ICD)-9 code 429.83 and ICD-10 code I51.81. RESULTS: Among a total of 4,860,859 discharges, there were 153 with the diagnosis of takotsubo cardiomyopathy (3.1 per 100,000 discharges). Among patients with takotsubo cardiomyopathy, 55.0% were male, 62.4% were white, and 16.7% were black. Eighty-nine percent of patients were between 12 and 20 years. Psychiatric diagnosis was documented in 46% and substance use disorder in 36.2%. Sepsis was documented in 22.8% of patients. The median length of stay was 5 days (interquartile range: 2.7-15), and median total charges were $75,080 (interquartile range: 32,176-198,336). The overall mortality for takotsubo cardiomyopathy was 7%. On multivariable regression analysis, mortality was higher in the presence of anoxic injury (odds ratio = 34.42, 95% confidence interval: 4.85-320.11, p = 0.00). CONCLUSIONS: Takotsubo cardiomyopathy is uncommon in children and carries a mortality rate of 7%. Most children with takotsubo cardiomyopathy are adolescent males, many of whom have psychiatric disorder or substance use disorder or both. Takotsubo cardiomyopathy should be considered in the differential diagnosis for patients who present with cardiac dysfunction and have underlying psychiatric disorders or drug abuse.

Do Racial/Ethnic and Economic Factors Affect the Rate of Complicated Appendicitis in Children?

INTRODUCTION: Appendicitis continues to be one of the most common surgical conditions in the pediatric population. We set out to determine demographic and practice variations among children admitted with appendicitis and highlight the racial/ethnic and healthcare access role in relation to the rate of complicated appendicitis using the 2012 Kids' Inpatient Database (KID). Methodology. A retrospective cross-sectional database study was performed using the 2012 KID. All children (age 1 months to 20 years) with appendicitis were identified using the ICD-9 diagnosis codes. Children with a diagnosis of appendicitis were compared with all other discharges. Among children with appendicitis, demographic and practice variations and the rate of complicated appendicitis were evaluated. Univariate and multivariate analyses were done to analyze the data. Sample weighing was done to present national estimates. RESULTS: In 2012, a total of 89, 935 out of 2.7 million pediatric hospital discharges (3.3%) had a diagnosis of appendicitis. The incidence of appendicitis was higher in males (4.7%), 6-15-year age group (7.43%), Hispanics (5.2%), and in the Western region (5.2%) and was lower in infants (0.02%) and African American children (1.2%) (p < 0.0001). The proportion of children with peritonitis or abscess was higher in children's hospitals (48.2% vs. 29.0%; OR 2.3, 95% CI: 2.2-2.4). The risk of complicated appendicitis was inversely related to age, while racial and ethnic minority status, bottom quartile of the income group, and government insurance increased the risk. Laparoscopic appendectomy was performed more frequently at children's hospitals (84.8% vs. 74.3%; p < 0.0001). CONCLUSIONS: Appendicitis is more common in Hispanics, males, older children, and in the Western region. Complicated appendicitis is more common in younger children, minority groups, low-income group, and children with government insurance. Children's hospitals manage more children with complicated appendicitis and are more likely to perform laparoscopic appendectomy.

Radiosurgery for brain metastases from ovarian cancer: an analysis of 25 years' experience with Gamma Knife treatment.

PURPOSE: We present our results in the treatment of brain metastases (BM) from ovarian cancer using Gamma Knife Radiosurgery (GKRS) over the last 25 years in a single institution. BACKGROUND: Gamma Knife Radiosurgery has become increasingly important in the management of brain metastases from ovarian cancer due to improving results from systemic disease and the need for better outcomes. MATERIAL AND METHODS: The medical records of 9 patients with brain metastases from ovarian cancer treated with GKRS between 1993 and 2018 were reviewed. Median age at first treatment was 57 years (range 39-76). Forty-two brain metastases were treated with 16 procedures. Median tumor volume was 1.8cc ranging from 0.2 to 30.3cc (there were five patients with a tumor volume exceeding 10cc). Median prescription dose was 16 Gy. RESULTS: Using Kaplan Meier estimates, the median OS after diagnosis was 48.1 months and the median OS after GKRS was 10.6 months (ranging from 2.5 to 81 months). The Kaplan Meier survival rates were 31.3%, and 6.5% at 2 and 5 years after GKRS, respectively. Treatment procedure was well tolerated and no patient presented with acute or chronic toxicity. Two of 9 patients had a tumor requiring retreatment (local control of 95% 40/42). Two out of the 7 patients evaluated for cause of death expired due to progression of brain metastases and the remaining ones died of systemic disease with brain control. CONCLUSIONS: GKRS for BM from ovarian cancer is a safe and effective modality. Our findings are in agreement with the recent literature indicating that women with brain metastases from ovarian cancer will benefit with radiosurgery and may achieve long term survival with brain control.

Cardiolipin remodeling by ALCAT1 links mitochondrial dysfunction to Parkinson's diseases.

Cardiolipin (CL) is a mitochondrial signature phospholipid that is required for membrane structure, respiration, dynamics, and mitophagy. Oxidative damage of CL by reactive oxygen species is implicated in the pathogenesis of Parkinson's disease (PD), but the underlying cause remains elusive. This work investigated the role of ALCAT1, an acyltransferase that catalyzes pathological remodeling of CL in various aging-related diseases, in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP). We show that MPTP treatment caused oxidative stress, mtDNA mutations, and mitochondrial dysfunction in the midbrain. In contrast, ablation of the ALCAT1 gene or pharmacological inhibition of ALCAT1 prevented MPTP-induced neurotoxicity, apoptosis, and motor deficits. ALCAT1 deficiency also mitigated mitochondrial dysfunction by modulating DRP1 translocation to the mitochondria. Moreover, pharmacological inhibition of ALCAT1 significantly improved mitophagy by promoting the recruitment of Parkin to dysfunctional mitochondria. Finally, ALCAT1 expression was upregulated by MPTP and by α-synucleinopathy, a key hallmark of PD, whereas ALCAT1 deficiency prevented α-synuclein oligomerization and S-129 phosphorylation, implicating a key role of ALCAT1 in the etiology of mouse models of PD. Together, these findings identify ALCAT1 as a novel drug target for the treatment of PD.

Female-biased population divergence in the venom of the Hentz striped scorpion (Centruroides hentzi).

Sex-biased genes are expressed at higher levels in one sex and contribute to phenotypic differences between males and females, as well as overall phenotypic variation within and among populations. Venom has evolved primarily for predation and defense, making venom expression a highly variable phenotype as a result of local adaptation. Several scorpion species have shown both intraspecific and intersexual venom variation, and males have been observed using venom in courtship and mating, suggesting the existence of venom-specific, sex-biased genes that may contribute to population divergence. We used reversed-phase high-performance liquid chromatography (RP-HPLC), Agilent protein bioanalyzer chips, nano-liquid chromatography mass spectrometry (nLC/MS/MS), and median lethal dose (LD50) assays in fruit flies (Drosophila melanogaster) and banded crickets (Gryllodes sigillatus) to investigate proteomic and functional venom variation within and among three Florida populations of the Hentz striped scorpion (Centruroides hentzi). We found significant venom variation among populations, with females, not males, being responsible for this divergence. We also found significant variation in venom expression within populations, with males contributing more to within population variation than females. Our results provide evidence that male and female scorpions experience different natural and sexual selective pressures that have led to the expression of sex-biased venom genes and that these genes may be consequential in population divergence.

Airborne Bacteria in Earth's Lower Stratosphere Resemble Taxa Detected in the Troposphere: Results From a New NASA Aircraft Bioaerosol Collector (ABC).

Airborne microorganisms in the upper troposphere and lower stratosphere remain elusive due to a lack of reliable sample collection systems. To address this problem, we designed, installed, and flight-validated a novel Aircraft Bioaerosol Collector (ABC) for NASA's C-20A that can make collections for microbiological research investigations up to altitudes of 13.7 km. Herein we report results from the first set of science flights-four consecutive missions flown over the United States (US) from 30 October to 2 November, 2017. To ascertain how the concentration of airborne bacteria changed across the tropopause, we collected air during aircraft Ascent/Descent (0.3 to 11 km), as well as sustained Cruise altitudes in the lower stratosphere (~12 km). Bioaerosols were captured on DNA-treated gelatinous filters inside a cascade air sampler, then analyzed with molecular and culture-based characterization. Several viable bacterial isolates were recovered from flight altitudes, including Bacillus sp., Micrococcus sp., Arthrobacter sp., and Staphylococcus sp. from Cruise samples and Brachybacterium sp. from Ascent/Descent samples. Using 16S V4 sequencing methods for a culture-independent analysis of bacteria, the average number of total OTUs was 305 for Cruise samples and 276 for Ascent/Descent samples. Some taxa were more abundant in the flight samples than the ground samples, including OTUs from families Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae as well as the following genera: Clostridium, Mogibacterium, Corynebacterium, Bacteroides, Prevotella, Pseudomonas, and Parabacteroides. Surprisingly, our results revealed a homogeneous distribution of bacteria in the atmosphere up to 12 km. The observation could be due to atmospheric conditions producing similar background aerosols across the western US, as suggested by modeled back trajectories and satellite measurements. However, the influence of aircraft-associated bacterial contaminants could not be fully eliminated and that background signal was reported throughout our dataset. Considering the tremendous engineering challenge of collecting biomass at extreme altitudes where contamination from flight hardware remains an ever-present issue, we note the utility of using the stratosphere as a proving ground for planned life detection missions across the solar system.