Molecular Breast Imaging Biopsy with a Dual-Detector System.

Purpose To develop a molecular breast imaging (MBI)-guided biopsy system using dual-detector MBI and to perform initial testing in participants. Materials and Methods The Stereo Navigator MBI Accessory biopsy system comprises a lower detector, upper fenestrated compression paddle, and upper detector. The upper detector retracts, allowing craniocaudal, oblique, or medial or lateral biopsy approaches. The compression paddle allows insertion of a needle guide and needle. Lesion depth is calculated by triangulation of lesion location on the upper detector at 0° and 15° and relative lesion activity on upper and lower detectors. In a prospective study (July 2022-June 2023), participants with Breast Imaging Reporting and Data System category 2, 3, 4, or 5 breast lesions underwent MBI-guided biopsy. After injection of 740 MBq technetium 99m sestamibi, craniocaudal and mediolateral oblique MBI (2-minute acquisition per view) confirmed lesion visualization. A region of interest over the lesion permitted depth calculation in the system software. Upper detector retraction allowed biopsy device placement. Specimen images were obtained on the retracted upper detector, confirming sampling of the target. Results Of 21 participants enrolled (mean age, 50.6 years ± 10.1 [SD]; 21 [100%] women), 17 underwent MBI-guided biopsy with concordant pathology. No lesion was observed at the time of biopsy in four participants. Average lesion size was 17 mm (range, 6-38 mm). Average procedure time, including preprocedure imaging, was 55 minutes ± 13 (range, 38-90 minutes). Pathology results included invasive ductal carcinoma (n = 1), fibroadenoma (n = 4), pseudoangiomatous stromal hyperplasia (n = 6), and fibrocystic changes (n = 6). Conclusion MBI-guided biopsy using a dual-head system with retractable upper detector head was feasible, well tolerated, and efficient. Keywords: Breast Biopsy, Molecular Breast Imaging, Image-guided Biopsy, Molecular Breast Imaging-guided Biopsy, Breast Cancer Clinical trial registration no. NCT06058650 © RSNA, 2024.

Multiple isoforms of the Activin-like receptor baboon differentially regulate proliferation and conversion behaviors of neuroblasts and neuroepithelial cells in the Drosophila larval brain.

In Drosophila coordinated proliferation of two neural stem cells, neuroblasts (NB) and neuroepithelial (NE) cells, is pivotal for proper larval brain growth that ultimately determines the final size and performance of an adult brain. The larval brain growth displays two phases based on behaviors of NB and NEs: the first one in early larval stages, influenced by nutritional status and the second one in the last larval stage, promoted by ecdysone signaling after critical weight checkpoint. Mutations of the baboon (babo) gene that produces three isoforms (BaboA-C), all acting as type-I receptors of Activin-type transforming growth factor ß (TGF-ß) signaling, cause a small brain phenotype due to severely reduced proliferation of the neural stem cells. In this study we show that loss of babo function severely affects proliferation of NBs and NEs as well as conversion of NEs from both phases. By analyzing babo-null and newly generated isoform-specific mutants by CRISPR mutagenesis as well as isoform-specific RNAi knockdowns in a cell- and stage-specific manner, our data support differential contributions of the isoforms for these cellular events with BaboA playing the major role. Stage-specific expression of EcR-B1 in the brain is also regulated primarily by BaboA along with function of the other isoforms. Blocking EcR function in both neural stem cells results in a small brain phenotype that is more severe than baboA-knockdown alone. In summary, our study proposes that the Babo-mediated signaling promotes proper behaviors of the neural stem cells in both phases and achieves this by acting upstream of EcR-B1 expression in the second phase.

A Survey of Patient Experience During Molecular Breast Imaging.

Molecular breast imaging (MBI) is one of several options available to patients seeking supplemental screening due to mammographically dense breasts. Patient experience during MBI may influence willingness to undergo the test but has yet to be formally assessed. We aimed to assess patient comfort level during MBI, to compare MBI comfort with mammography comfort, to identify factors associated with MBI discomfort, and to evaluate patients' willingness to return for future MBI. Methods: A 10-question survey was sent by e-mail to patients undergoing MBI between August and December 2022 to obtain quantitative assessments and qualitative opinions about MBI. Results: Of 561 invited patients, 209 (37%) completed the survey and provided study consent. Their average age was 60.1 y (range, 40-81 y). Of the 209 responders, 202 (97%) were presenting for screening MBI, 195 (94%) had dense breasts, and 46 (22%) had a personal history of breast cancer. The average rating of MBI comfort was 2.9 (SD, 1.5; median, 3.0) on a 7-point scale (1 indicating extremely comfortable and 7 indicating extremely uncomfortable). The rating distribution was as follows: 140 (67%) comfortable (rating, 1-3); 24 (12%) neither comfortable nor uncomfortable (rating, 4); and 45 (22%) uncomfortable (rating, 5 or 6). No responders gave a 7 rating. The most frequently mentioned sources of discomfort included breast compression (n = 16), back or neck discomfort (n = 14), and maintaining position during the examination (n = 14). MBI comfort was associated with responder age (74% ≥55 y old were comfortable, versus 53% <55 y old [P = 0.003]) and history of MBI (71% with prior MBI were comfortable, versus 61% having a first MBI [P = 0.006]). Of 208 responders with a prior mammogram, 148 (71%) said MBI is more comfortable than mammography (a significant majority [P < 0.001]). Of 202 responders to the question of whether they were willing to return for a future MBI, 196 (97%) were willing. A notable factor in positive patient experience was interaction with the MBI nuclear medicine technologist. Conclusion: Most responders thought MBI to be a comfortable examination and more comfortable than mammography. Patient experience during MBI may be improved by ensuring back support and soliciting patient feedback at the time of positioning and throughout the examination. Methods under study to reduce imaging time may be most important for improving patient experience.

Extensive scintigraphic gastric motor function testing with concurrent symptom recording predicts prospectively measured daily dyspeptic symptoms.

BACKGROUND: Absent "organic" disease, dyspeptic symptoms may arise from abnormal gastric sensation, accommodation, motility or emptying (GE). Extensive gastric sensorimotor evaluation is rarely undertaken because testing is prolonged, invasive, poorly tolerated or unavailable. AIMS: To investigate whether gastric antral motor function, evaluated with scintigraphy, predicts GE. To explore whether motor testing with symptom recording predicts day-to-day symptoms in patients with dyspepsia. METHODS: GE was determined using a scintigraphic solid-meal protocol (296 kcal, 35% fat). Antral motility was estimated from 10 min of scintigraphic time-activity curves acquired 40 min after meal consumption. An antral motility index (MI) was derived from contraction amplitude and frequency. Intra-gastric distribution of the meal on scintograms at 1 h (IGD1) was determined. Meal-induced symptoms were evaluated by questionnaire. Patients completed the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) for 14 days. RESULTS: Twelve healthy participants and 23 prospectively recruited patients completed the study. Nine patients had delayed, and 2 had rapid, GE. In univariate analysis MI explained 42% of GE half-time. In multivariate analysis MI and GE half-time explained 25% of the variance in meal-induced symptoms. While scintigraphic evaluation of gastric motor function with symptom recording explained 80% of the variance in the GCSI-DD, meal-induced symptoms were the only significant predictor. However, among patients with delayed GE, MI, GE half-time, IGD1, and meal-induced symptoms all significantly predicted GCSI-DD. CONCLUSIONS: Antral motility predicts GE. In exploratory analyses, only meal-induced symptoms predicted daily symptoms among patients with dyspepsia. However, motor function also predicted symptoms in patients with delayed GE.

The utility of nasal nitric oxide in the diagnostic evaluation of primary ciliary dyskinesia.

BACKGROUND: There is no gold-standard test for primary ciliary dyskinesia (PCD), rather American Thoracic Society guidelines recommend starting with nasal nitric oxide (nNO) in children ≥5 years old and confirming the diagnosis with genetic testing or ciliary biopsy with transmission electron microscopy (TEM). These guidelines have not been studied in a clinical setting. We present a case series describing the PCD diagnostic process at our pediatric PCD center. METHODS: Diagnostic data from 131 patients undergoing PCD consultation were reviewed. RESULTS: In all participants ≥ 5 years old and who completed nNO using resistor methodology, the first diagnostic test performed was nNO in 77% (73/95), genetic testing in 14% (13/95), and TEM in <1% (9/95). nNO was the only diagnostic test performed in 75% (55/73) of participants who completed nNO first. Seventy-five percent (55/73) had a single above the cutoff nNO value and PCD was determined to be unlikely in 91% (50/55) without performing additional confirmatory testing. Eleven percent (8/73) had multiple below the cutoff nNO values, with 38% (3/8) being diagnosed with PCD by confirmatory testing and 50% (4/8) with negative confirmatory testing, but being managed as PCD. The genetic testing positivity rate was 50% in participants who completed nNO first and 8% when genetic testing was completed first. CONCLUSION: nNO is useful in three situations: an initial above the cutoff nNO value makes PCD unlikely and prevents additional confirmatory testing, repetitively below the cutoff nNO values without positive confirmatory testing suggests a probable PCD diagnosis and the yield of genetic testing is higher when nNO is performed first.

Exploring safety culture within inpatient mental health units: The results from participant observation across three mental health services.

In Australia, acute inpatient units within public mental health services have become the last resort for mental health care. This research explored barriers and facilitators to safe, person-centred, recovery-oriented mental health care in these settings. It utilised participant observations conducted by mental health nurses in acute inpatient units. These units were located in three distinct facilities, each serving different areas: a large metropolitan suburban area in a State capital, a mid-sized regional city, and a small city with a large rural catchment area. Our findings highlighted that, in the three inpatient settings, nurses tended to avoid common areas they shared with consumers, except for brief, task-related visits. The prioritisation of administrative tasks seemed to arise in a situation where nurses lacked awareness of alternative practices and activities. Consumers spent prolonged periods of the day sitting in communal areas, where the main distraction was watching television. Boredom was a common issue across these environments. The nursing team structure in the inpatient units provided a mechanism for promoting a sense of psychological safety for staff and were a key element in how safety culture was sustained.

Isolated Intracranial Hypertension as a Presentation of Pediatric Lyme Borreliosis: A Case Report and Literature Review.

BACKGROUND: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial. METHODS: Case report and literature review. RESULTS: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months. CONCLUSIONS: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children.

Hematological and biochemical parameters of giant pandas (Ailuropoda melanoleuca) in captive and semi-natural environments.

Physiological indexes like blood parameters have been widely used to monitor the health of free-roaming animals. Attempts to reintroduce one of China's most endangered species, the giant panda (Ailuropoda melanoleuca), have been hampered by a lack of data on its ecology and physiology. We examined three giant pandas' hematological and blood chemistry parameters in a soft release program and 30 captive giant pandas as controls and determined the reference intervals (RIs) for those blood parameters in the captive animals. Elevation, captivity status and the interaction of those factors were statistically significant for hematologic measures. Release pandas had significantly higher hemoglobin and hematocrit values after they moved to high elevation locations. We also found significant difference in the enzyme parameters between high and low elevation pandas such as higher aspartate aminotransferase, alanine aminotransferase, creatinine kinase, amylase and lower lactate dehydrogenase and alkaline phosphatase. Release pandas also had higher nutrition parameter values such as higher albumin, globulin and creatinine. The RI for blood parameters in our study provides a baseline to monitor the health of captive animals and forms the basis for assessing the health of free-roaming giant pandas in future reintroduction efforts.

Suppressor analysis links trans-translation and ribosomal protein uS7 to RluD function in Escherichia coli.

The pseudouridine (ψ) synthase, RluD is responsible for three ψ modifications in the helix 69 (H69) of bacterial 23S rRNA. While normally dispensable, rluD becomes critical for rapid cell growth in bacteria that are defective in translation-termination. In slow-growing rluD- bacteria, suppressors affecting termination factors RF2 and RF3 arise frequently and restore normal termination and rapid cell growth. Here we describe two weaker suppressors, affecting rpsG, encoding ribosomal protein uS7 and ssrA, encoding tmRNA. In K-12 strains of E. coli, rpsG terminates at a TGA codon. In the suppressor strain, alteration of an upstream CAG to a TAG stop codon results in a shortened uS7 and partial alleviation of slow growth, likely by replacing an inefficient TGA stop codon with the more efficient TAG. Inefficient termination events, such as occurs in some rluD- strains, are targeted by trans-translation. Inactivation of the ssrA gene in slow-growing, termination-defective mutants lacking RluD and RF3, also partially restores robust growth, most probably by preventing destruction of completed polypeptides on ribosomes at slow-terminating stop codons. Finally, an additional role for RluD has been proposed, independent of its pseudouridine synthase activity. This is based on the observation that plasmids expressing catalytically dead (D139N or D139T) RluD proteins could nonetheless restore robust growth to an E. coli K-12 rluD- mutant. However, newly constructed D139N and D139T rluD plasmids do not have any growth-restoring activity and the original observations were likely due to the appearance of suppressors.

Fourth Chromosome Resource Project: a comprehensive resource for genetic analysis in Drosophila that includes humanized stocks.

The fourth chromosome is the final frontier for genetic analysis in Drosophila. Small, heterochromatic, and devoid of recombination the fourth has long been ignored. Nevertheless, its long arm contains 79 protein-coding genes. The Fourth Chromosome Resource Project (FCRP) has a goal of facilitating the investigation of genes on this neglected chromosome. The project has 446 stocks publicly available at the Bloomington and Kyoto stock centers with phenotypic data curated by the FlyBase and FlyPush resources. Four of the five stock sets are nearly complete: (1) UAS.fly cDNAs, (2) UAS.human homolog cDNAs, (3) gene trap mutants and protein traps, and (4) stocks promoting meiotic and mitotic recombination on the fourth. Ongoing is mutagenesis of each fourth gene on a new FRT-bearing chromosome for marked single-cell clones. Beyond flies, FCRP facilitates the creation and analysis of humanized fly stocks. These provide opportunities to apply Drosophila genetics to the analysis of human gene interaction and function. In addition, the FCRP provides investigators with confidence through stock validation and an incentive via phenotyping to tackle genes on the fourth that have never been studied. Taken together, FCRP stocks will facilitate all manner of genetic and molecular studies. The resource is readily available to researchers to enhance our understanding of metazoan biology, including conserved molecular mechanisms underlying health and disease.

Clinical Characteristics of US Adolescents Hospitalized for Eating Disorders 2010-2022.

BACKGROUND AND OBJECTIVES: Eating disorders (EDs) affect a substantial number of American adolescents, with an increasing number seeking care for EDs during the coronavirus disease 2019 pandemic. We assessed the prevalence and clinical characteristics of adolescents hospitalized with EDs during 2010 to 2022. METHODS: We used data from a national database of 12 children's hospitals (PEDSnet). Adolescents aged 12 to 21 years hospitalized for ED, disordered eating, binge ED, anorexia nervosa, bulimia nervosa, avoidant-restrictive food intake disorder (ARFID), or other EDs were included. Patients with complex or chronic illness or with EDs hospitalized for another reason were excluded. We analyzed demographic data, clinical characteristics, cardiac manifestations, coexistence of psychiatric conditions, and hospital stay characteristics. RESULTS: We included 13 403 hospitalizations by 8652 patients in this study. We found a gradual increase in hospitalizations for patients with EDs before the pandemic and a large increase during the pandemic. Mean age was 15.8 years with 85.9% described as female and 71.8% as white. Anorexia nervosa was the most common ED (57.5%), though hospitalization for patients with ARFID is increasing. Patients' median BMI percentage was 90.3%. Patients' malnutrition was classified as none (50.9%), mild (25.0%), moderate (18.6%), or severe (5.4%). Significant numbers of patients had a diagnosis of depression (58.5%) or anxiety (57.0%); 21.9% had suicidal thoughts. Nearly one-quarter (23.6%) required rehospitalization for ED treatment within 1 year. CONCLUSIONS: Hospitalizations for EDs among American adolescents are increasing, with a spike during the coronavirus disease 2019 pandemic. Significant numbers of patients hospitalized with EDs have suicidal thoughts. Trends in patients with ARFID require monitoring.

Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain.

Introduction: Chronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketamine within a tertiary chronic pain management clinic. Methods: This study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale. Results: 73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p < 0.0001) on both numerical scores (41.6% decrease) and BPI scoring (mean decrease 2.61). Mood improved (p < 0.0001) across both PHQ-9 and BPI measurements. Patients also reported less difficulty with daily activities and improved QoL. The most common adverse reaction was drowsiness (21.9%), with 30.1% reporting no adverse reactions from Ketamine. Discussion: This work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key message: This real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions.

Ptth regulates lifespan through innate immunity pathway in Drosophila.

The prothoracicotropic hormone (Ptth) is well-known for its important role in controlling insect developmental timing and body size by promoting the biosynthesis and release of ecdysone. However, the role of Ptth in adult physiology is largely unexplored. Here we show that Ptth null mutants (both males and females) show extended lifespan and healthspan, and exhibit increased resistance to oxidative stress. Transcriptomic analysis reveals that age-dependent upregulation of innate immunity pathway is attenuated by Ptth mutants. Intriguingly, we find that Ptth regulates the innate immunity pathway, specifically in fly oenocytes, the homology of mammalian hepatocytes. We further show that oenocyte-specific overexpression of Relish shortens the lifespan, while oenocyte-specific downregulation of ecdysone signaling extends lifespan. Consistently, knocking down torso, the receptor of Ptth in the prothoracic gland also promotes longevity of the flies. Thus, our data reveal a novel function of the insect hormone Ptth in longevity regulation and innate immunity in adult Drosophila.

Navigating Informed Consent and Patient Safety in Surgery: Lessons for Medical Students and Junior Trainees.

AbstractIn the operating room, patient safety is of paramount importance. Medical students and junior trainees, despite their primary role as students, may play active roles in assessing patient safety and reporting suspected errors. Active consent is one layer of patient safety that is continuously assessed by several team members. This article examines an instance where patient consent may have been violated. Through the lens of trainee and senior perspectives, we discuss the ethical principles at stake and provide recommendations for medical student and junior trainee involvement in patient care when an error is suspected.

GraphVAMPnets for uncovering slow collective variables of self-assembly dynamics.

Uncovering slow collective variables (CVs) of self-assembly dynamics is important to elucidate its numerous kinetic assembly pathways and drive the design of novel structures for advanced materials through the bottom-up approach. However, identifying the CVs for self-assembly presents several challenges. First, self-assembly systems often consist of identical monomers, and the feature representations should be invariant to permutations and rotational symmetries. Physical coordinates, such as aggregate size, lack high-resolution detail, while common geometric coordinates like pairwise distances are hindered by the permutation and rotational symmetry challenges. Second, self-assembly is usually a downhill process, and the trajectories often suffer from insufficient sampling of backward transitions that correspond to the dissociation of self-assembled structures. Popular dimensionality reduction methods, such as time-structure independent component analysis, impose detailed balance constraints, potentially obscuring the true dynamics of self-assembly. In this work, we employ GraphVAMPnets, which combines graph neural networks with a variational approach for Markovian process (VAMP) theory to identify the slow CVs of the self-assembly processes. First, GraphVAMPnets bears the advantages of graph neural networks, in which the graph embeddings can represent self-assembly structures in high-resolution while being invariant to permutations and rotational symmetries. Second, it is built upon VAMP theory, which studies Markov processes without forcing detailed balance constraints, which addresses the out-of-equilibrium challenge in the self-assembly process. We demonstrate GraphVAMPnets for identifying slow CVs of self-assembly kinetics in two systems: the aggregation of two hydrophobic molecules and the self-assembly of patchy particles. We expect that our GraphVAMPnets can be widely applied to molecular self-assembly.