Knotted lanugo in a newborn: Cultural practices revealed.

Across the world, there are varied cultural practices applied in the newborn period that pediatric dermatologists need to be familiar with. This report details a 9-day-old girl who presented with black, spike-like hairs across the back after her mother had been rubbing breast milk on her back in a circular motion for the first 7 days of life. On dermatoscopic exam, these lesions were found to be tight bundles of lanugo hairs, consistent with a diagnosis of knotted lanugo. Improved understanding of cultural practices and newborn skin care routines is critical for diagnosis, treatment, and counseling.

Palliative Care and Hospice in the Pandemic: A Review of State Planning and Lessons Not Yet Learned.

CONTEXT: Written Crisis Standards of Care guidelines have been published federally in the United States for several decades to assisted in planning for a variety of disasters, and planning documents exist in most states. Federal and state crisis planning guidelines, both before and during the early COVID pandemic, focused on saving the most lives. Palliative care (PC) and hospice shortages were exacerbated by the COVID pandemic but recognized late and incompletely. OBJECTIVES: 1) Quantify the number of state crisis standard planning documents that include recognition of potential PC and hospice crisis needs in a pandemic. 2) Assess the range of practical plans in existing state Crisis Standards of Care plans. 3) Outline elements of recommendations from existing guidelines and literature. METHODS: Internet searches for state-based "crisis standards of care" completed and results categorized regarding PC and hospice planning as: 1) absent, 2) mentioned only in relation to critical care triage, 3) described only in general principles, 4) describing potential concrete plans to address PC and hospice needs. RESULTS: Of the 50 states and Washington, DC, 45 states have electronically available "crisis standards of care" or emergency preparedness documents; 35 of these were written or updated since 2020. Only 20 states mention any concrete aspects of planning for potential palliative care or hospice service shortages. Guidelines most often involved alternate care sites, protective equipment, and specialist resources. Visitation policy was rarely mentioned. CONCLUSIONS: Concrete planning for PC and hospice needs in state crisis planning occurs in less than half of state documents, even three years after the start of this pandemic. Failure to address these needs will result in avoidable suffering for patients in a wide range of settings. It is important to identify and address gaps before the next disaster.

Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors.

BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.

The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration.

Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture of cell types, and superior imaging properties. Regeneration of the embryonic zebrafish tail requires development of a blastema, a mass of dedifferentiated cells capable of replacing lost tissue, a crucial step in all known examples of appendage regeneration. Using this model, we show that tail amputation triggers an obligate metabolic shift to promote glucose metabolism during early regeneration similar to the Warburg effect observed in tumor forming cells. Inhibition of glucose metabolism did not affect the overall health of the embryo but completely blocked the tail from regenerating after amputation due to the failure to form a functional blastema. We performed a time series of single-cell RNA sequencing on regenerating tails with and without inhibition of glucose metabolism. We demonstrated that metabolic reprogramming is required for sustained TGF-ß signaling and blocking glucose metabolism largely mimicked inhibition of TGF-ß receptors, both resulting in an aberrant blastema. Finally, we showed using genetic ablation of three possible metabolic pathways for glucose, that metabolic reprogramming is required to provide glucose specifically to the hexosamine biosynthetic pathway while neither glycolysis nor the pentose phosphate pathway were necessary for regeneration.

Integrating structural and evolutionary data to interpret variation and pathogenicity in adapter protein complex 4.

Genetic variation in the membrane trafficking adapter protein complex 4 (AP-4) can result in pathogenic neurological phenotypes including microencephaly, spastic paraplegias, epilepsy, and other developmental defects. We lack molecular mechanisms responsible for impaired AP-4 function arising from genetic variation, because AP-4 remains poorly understood structurally. Here, we analyze patterns of AP-4 genetic evolution and conservation to identify regions that are likely important for function and thus more susceptible to pathogenic variation. We map known variants onto an AP-4 homology model and predict the likelihood of pathogenic variation at a given location on the structure of AP-4. We find significant clustering of likely pathogenic variants located at the interface between the ß4 and N-µ4 subunits, as well as throughout the C-µ4 subunit. Our work offers an integrated perspective on how genetic and evolutionary forces affect AP-4 structure and function. As more individuals with uncharacterized AP-4 variants are identified, our work provides a foundation upon which their functional effects and disease relevance can be interpreted.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

BACKGROUND: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AIMS: Identification of genomic disorders in DD/ID. MATERIALS AND METHODS: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. RESULTS: We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION AND CONCLUSION: We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

Resurgence of Vaccine-Preventable Diseases in the United States: Anesthetic and Critical Care Implications.

Vaccine-preventable diseases (VPDs) such as measles and pertussis are becoming more common in the United States. This disturbing trend is driven by several factors, including the antivaccination movement, waning efficacy of certain vaccines, pathogen adaptation, and travel of individuals to and from areas where disease is endemic. The anesthesia-related manifestations of many VPDs involve airway complications, cardiovascular and respiratory compromise, and unusual neurologic and neuromuscular symptoms. In this article, we will review the presentation and management of 9 VPDs most relevant to anesthesiologists, intensivists, and other hospital-based clinicians: measles, mumps, rubella, pertussis, diphtheria, influenza, meningococcal disease, varicella, and poliomyelitis. Because many of the pathogens causing these diseases are spread by respiratory droplets and aerosols, appropriate transmission precautions, personal protective equipment, and immunizations necessary to protect clinicians and prevent nosocomial outbreaks are described.

Unchanging pattern of prevalence of esophageal cancer, overall and by histological subtype, in the endoscopy service of the main referral hospital in the central region of Rio Grande do Sul State, in Southern Brazil.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the two main histological types of esophageal cancer. Southern Brazil has the highest rates of esophageal cancer in South America, and the most prevalent subtype of esophageal cancer has been SCC. This study assessed the trend changes in the histological types of esophageal cancer, in a 20-year period, in the central region of Rio Grande do Sul State, Brazil. We searched all cases of esophageal cancer from 1993 to 2012 by their histological diagnosis, grouping the patients in 4-year time periods to evaluate time trends. Among 18 441 upper gastrointestinal endoscopies we identified 686 cases of esophageal cancer. Histological study confirmed the diagnosis of SCC in 640 (93.3%) patients and ADC in 46 (6.7%). Overall, 522 men were diagnosed with esophageal carcinoma; from these, 489 (93.6%) presented SCC, and 33 (6.3%) ADC. Among women, 164 had the diagnosis of esophageal cancer, 151 (92%) SCC, and 13 (7.9%) ADC. The proportion found among men and women was 3.1:1, respectively. The prevalence rate of esophageal cancer, along a 20 year-period, remained stable, as well as the rates of SCC and ADC. SCC was the most common type of esophageal cancer, and ADC presented very low prevalence.

Complications of particle embolization of meningiomas: frequency, risk factors, and outcome.

BACKGROUND AND PURPOSE: Particle embolization is widely used in the treatment of meningiomas. We assessed the frequency and outcome of complications of embolization of meningiomas and tried to identify risk factors. MATERIALS AND METHODS: Between 1994 and 2009, a total of 198 patients with 201 meningiomas underwent embolization. Indication for embolization was preoperative in 165 meningiomas and adjunctive to radiosurgery in 8. In the remaining 28 meningiomas, embolization was initially offered as a sole therapy. There were 128 women and 70 men with a mean age of 54.4 years (median age, 54 years; range, 15-90 years). Complications were defined as any neurologic deficit or death that occurred during or after embolization. Logistic regression was used to identify the following possible risk factors: age above median, female sex, tumor size above median, meningioma location in 5 categories, use of small particle size (45-150 microm), the presence of major peritumoral edema, and arterial supply in 3 categories. RESULTS: Complications occurred in 11 patients (5.6%; 95% confidence interval [CI], 3.0%-9.8%). Ten complications were hemorrhagic, and 1 was ischemic. Six of 10 patients with hemorrhagic complications underwent emergency surgery with removal of the hematoma and meningioma. Complications of embolization resulted in death in 2 and dependency in 5 patients (7/198, 3.5%; 95% CI, 1.6%-2.0%). The use of small particles (45-150 mum) was the only risk factor for complications (odds ratio [OR], 10.21; CI, 1.3-80.7; P = .028). CONCLUSIONS: In this series, particle embolization of meningiomas had a complication rate of 5.6%. We believe that the use of small polyvinyl alcohol (PVA) particles (45-150 microm) should be discouraged.

Real-time MR artifacts filtering during continuous EEG/fMRI acquisition.

The purpose of this study was the development of a real-time filtering procedure of MRI artifacts in order to monitor the EEG activity during continuous EEG/fMRI acquisition. The development of a combined EEG and fMRI technique has increased in the past few years. Preliminary "spike-triggered" applications have been possible because in this method, EEG knowledge was only necessary to identify a trigger signal to start a delayed fMRI acquisition. In this way, the two methods were used together but in an interleaved manner. In real simultaneous applications, like event-related fMRI study, artifacts induced by MRI events on EEG traces represent a substantial obstacle for a right analysis. Up until now, the methods proposed to solve this problem are mainly based on procedures to remove post-processing artifacts without the possibility to control electrophysiological behavior of the patient during fMRI scan. Moreover, these methods are not characterized by a strong "prior knowledge" of the artifact, which is an imperative condition to avoid any loss of information on the physiological signals recovered after filtering. In this work, we present a new method to perform simultaneous EEG/fMRI study with real-time artifacts filtering characterized by a procedure based on a preliminary analytical study of EPI sequence parameters-related EEG-artifact shapes. Standard EEG equipment was modified in order to work properly during ultra-fast MRI acquisitions. Changes included: high-performance acquisition device; electrodes/cap/wires/cables materials and geometric design; shielding box for EEG signal receiver; optical fiber link; and software. The effects of the RF pulse and time-varying magnetic fields were minimized by using a correct head cap wires-locked environment montage and then removed during EEG/fMRI acquisition with a subtraction algorithm that takes in account the most significant EPI sequence parameters. The on-line method also allows a further post-processing utilization.

Further evidence for histamine facilitating oestrogen action in the uterus.

The effect of doses of estradiol ranging from 0-0125 to 1-6 mug on the uterine weight of the spayed rat was studied 24 h after a single s.c. injection of the hormone. The lowest dose inducing a significant increase in uterine weight was 0-32 mug. When histamine dihydrochloride (50 mg) was simultaneously injected with the hormone, the effect of small doses of oestradiol (0-0125--0-2 mug) was significantly increased. When oestradiol and histamine were administered for 3 successive days, the uterine weight of animals receiving 0-0125 mug oestradiol, if compared with untreated controls, was increased only in the histamine-treated group. When 0-05 mug oestradiol was administered histamine did not modify the increase already produced by the hormone. Spermidine and burimamide, two substances structurally related to histamine, increased [3H]oestradiol uptake by the spayed rat uterus. The latter (an antihistamine drug acting on H2-receptors) as well as pyrathiazine (a histamine releaser having antihistamine properties) decreased the effect of histamine on oestradiol uptake whereas diphenhydramine (an antihistamine drug blocking H1-receptors) did not modify it. Pyrathiazine was itself able to diminish oestradiol uptake.

On the mechanism of action of oral contraceptives. I. Effect of lynestrenol on ovum implantation and oviductal morphology in the rat.

PIP: 2 experiments on virgin female rats (average weight 200 gm) were performed to study the effects of small doses of lynestrenol on the early pregnancy of the rat. In both experiments, the rats were caged with a mate overnight and if, on the following morning, spermatozoa were found on the vaginal smear, that day became Day 1 of pregnancy. In Experiment 1, the test group (15) received .1 mg lynestrenol sc and the control group (14) 1 ml propyleneglycol on Days 2, 3, 4, and 5 of pregnancy. Experiment 2 differed in that the rats received 1 mg dosages of lynestrenol. On Day 7 of pregnancy, Experiment 1 rats were killed and their ovaries and genital tracts were examined. In Experiment 2, the rats were permitted to live until Day 23 to see if they would achieve full-term pregnancy. If delivery did not occur, they were killed (Day 25) and examined for fetuses. In Experiment 1, the dose did not significantly increase the number of lost ova (20% in controls), as indicated by the implanted embryos/recent corpora lutea ratio counted on Day 7. There was an increase in the number of ciliated cells in the epithelium and a diminution of the deciduoid tissue of the stroma. No histological changes were seen in the ovaries, embyros, or uteri. The 1 mg dosage of lynestrenol prevented pregnancy in all of the rats. Doses were smaller than those needed to inhibit ovulation, and the time of administration of the doses excluded any action on sperm transport, capacitation, or penetration. Lynestrenol would appear to act on the pregnant rat's genital tract, as oviducts displayed evidence of estrogen stimulation.^ieng