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Infantile Bullous Pemphigoid in a 3-Month-Old Female: A Rare and Important Diagnostic Consideration
No full textAbstract:
Bullous pemphigoid (BP) is a rare autoimmune blistering disorder, infrequently seen in children and exceptionally rare in infants. Due to significant clinical overlap with infectious, genetic, and other autoimmune conditions, definitive diagnosis in infants relies heavily on histopathologic and immunopathologic evaluation. A three-month-old female presented with a five-day history of erythematous plaques on the hands and feet, which progressed to tense bullae and spread to the forearms and trunk. The infant remained afebrile and systemically well. The clinical differential included bullous pemphigoid, atypical coxsackievirus infection, epidermolysis bullosa, herpes simplex virus, varicella zoster virus, and bullous impetigo. Bacterial cultures and viral PCR testing were negative. Histopathologic examination of a lesional punch biopsy revealed spongiotic dermatitis with eosinophilic exocytosis overlying papillary dermal edema and perivascular lymphohistiocytic infiltrate. Direct immunofluorescence of perilesional skin demonstrated linear IgG and C3 deposition along the basement membrane zone, confirming the diagnosis of bullous pemphigoid. No family history of autoimmune or blistering disorders was reported, and maternal history was unremarkable. The presence of linear IgG deposition in this age group supports early autoimmune activation against hemidesmosomal components, reinforcing the pathophysiologic basis of disease even in the absence of known triggers. This case expands the clinicopathologic spectrum of early-onset BP and highlights the diagnostic triad essential for recognition in pediatric patients: subepidermal blistering, eosinophil-rich infiltrate, and linear IgG/C3 deposition. Presenting this case provides an opportunity to reinforce diagnostic precision, inform pathology-based algorithms for vesiculobullous disease in infants, and contribute meaningfully to the limited literature on neonatal autoimmune blistering disorders
The dynamics of cognitive decline toward Alzheimer's disease progression: Results from ADSP‐PHC's harmonized cognitive composites
No full textIntroduction: Accurately assessing the temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presents controversial conclusions likely due to the use of a single cohort and different analytical strategies.
Methods: Harmonized composite cognitive measures in memory, language, and executive functions from 13 cohorts in the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) were used. A double anchoring events-based sigmoidal mixed model was developed using time to incident AD diagnosis as the time scale.
Results: In general, decline in memory occurred before decline in language, followed by decline in executive function. This temporal order generally persisted within each subgroup of apolipoprotein E ε4 carrier status, sex, and race/ethnicity.
Discussion: This study demonstrated the use of harmonized data across multiple cohorts to characterize the temporal order of cognitive decline along AD progression. Using time to incident AD diagnosis as the time scale can enhance research reproducibility and clinical practice.
Highlights: Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium's harmonized composite cognitive measures from 13 cohort studies fitted with a novel double anchoring event-based sigmoidal mixed model reveal the following temporal order of cognitive decline toward AD progression: memory, language, and executive function. If only investigated using individual cohort studies, the temporal order of cognitive decline would vary due to the underlying heterogeneities across studies. This temporal order generally persisted within each subgroup of apolipoprotein E ε4 carrier status, sex, and race/ethnicity
Transmission dynamics and response strategies for the chikungunya outbreak in Southern China
No full textWho decides? Exploring decisional dynamics for periviable resuscitation among diverse family structures
No full textObjective: To investigate conflict resolution and decisional authority among diverse family structures in periviable resuscitation decision-making.
Methods: We recruited 60 parent dyads, including 30 with prior periviable delivery experience and 30 first-time expecting dyads between 22 and 26 weeks gestation. Our diverse sample included heterosexual and same-sex partnerships, married and unmarried partners. Virtual interviews explored decision-making, engagement, and conflict resolution.
Results: Four themes emerged: "Mom is the priority," highlighting maternal decisional authority; "partner involvement is crucial," emphasizing engagement; "parents prioritize who will be caring for the child," indicating caregiver considerations; and "parents want empathy and support," underscoring emotional needs.
Conclusions: Findings reveal maternal priority in decision-making, the importance of partner involvement, and a challenges with lacking inclusive legal and ethical guidance for non-heteronormative families. The study highlights the need for shared decision-making that considers family structures, legal aspects, and emotional complexities to enhance inclusive, informed decision-making processes for parents facing periviable delivery
Acute EtOH enhances septohippocampal coordination but disrupts intrinsic hippocampal theta dynamics during foraging
No full textTheta oscillations - rhythmic patterns of synchronous activity within discrete brain regions - are known to support memory, navigation, and behavioral coordination, and are sensitive to pharmacological manipulation. Acute ethanol (EtOH) exposure has been shown to alter theta oscillations, but its effects on transient theta bursts and cross-regional coordination during naturalistic behavior remain unclear. We recorded local field potentials (LFPs) from the medial septum (MS), hippocampal Cornu Ammonis 1 (CA1), and medial prefrontal cortex (mPFC) in freely foraging mice following intraperitoneal injection of EtOH (1.5 g/kg) or saline. We analyzed spectral power, theta burst dynamics, phase, and lag timing. Burst features from CA1 were used to train a machine learning classifier to predict session condition. EtOH impaired locomotion and reduced goal-directed behaviors, particularly early in the session. In CA1, theta power shifted toward lower frequencies and lagged coherence declined. EtOH increased the frequency but reduced the duration of theta bursts in CA1, and in MS, only burst count increased. EtOH enhanced the temporal alignment of MS-CA1 burst pairs. Phase-locking between CA1 and MS during coupled bursts remained present but showed altered structure. Our classifier achieved robust performance using burst features such as skew and entropy, and reliably distinguished treatment conditions. EtOH modulates septohippocampal dynamics by altering the timing and structure of theta bursts. These results suggest that burst-level features are sensitive markers of EtOH's circuit-level effects during naturalistic behavior
Carbohydrate Antigen-125: Endometrial Cancer or Heart Failure Biomarker?
No full textBackground: Carbohydrate antigen-125 (also known as cancer antigen-125) (CA-125) is a biomarker used to monitor for endometrial cancer progression, but it may also reflect other disease processes.
Case summary: A 70-year-old woman with metastatic endometrial cancer who was treated with paclitaxel, carboplatin, and pembrolizumab presented with new onset ascites and rising CA-125 levels concerning for cancer progression. She received a diagnosis of heart failure (HF) and normalized her CA-125 levels with loop diuretic agents without changing her oncologic treatment.
Discussion: CA-125 is a novel biomarker for HF monitoring because it correlates with increased intracardiac filling pressures. In this patient, concomitant endometrial malignant disease and HF complicated ascertainment of ascites and elevated biomarker origin. Therefore, clinicians should consider alternate causes of elevated CA-125 levels besides cancer progression.
Take-home message: CA-125 levels in patients with endometrial cancer may not always reflect cancer disease progression because levels can be influenced by the presence of HF
Disabled Youth's Cultural Ways of Knowing and Doing in Special Education: Implications and Strategies
No full textAs section leader of the ‘diversity/multicultural’ portion of the International Handbook of Special Education: Implications and Strategies, I have spent considerable time reflecting on the conceptualization of disability at the intersections of multiple non-dominant identity markers in relation to strategies benefiting disabled youth. My reflections have been heavily influenced by Waitoller and Thorius’s (2022) critical scholarship on centering and sustaining disabled youth’s assets within educational spaces. Their work alongside the scholarship of those with multiple intersectional identities (e.g., scholars of Color, disabled scholars, disabled scholars of Color), has supported an evolution of thinking around difference encapsulated in two main ideas: a) disability is part of the fabric of human variance encompassing identity formation, a connection to disability culture/s and communities, and a way of knowing that is contributive, beneficial, and evolving and (b) disability can be located as a counterhegemonic construct to disrupt “normalcy and its location in the bodies and minds of those with dominant identity markers” (Thorius, 2019, p. 212)
It is all about POCUS!: Participant Survey Data from a Statewide Gastric POCUS Workshop
No full textObjectives
POCUS education has grown significantly in the past two decades, impacting various medical specialties. This study aimed to assess practicing anaesthesiologists' confidence, knowledge, and skill in performing gastric POCUS before and after a focused workshop that used deliberate practice.
Methods
Attendees of the 2024 Indiana Society of Anesthesiologists annual meeting participated in an included hands-on gastric point-of-care ultrasound workshop. The workshop included 10 stations, each with a standardized patient model and anesthesiologist competent in gastric ultrasound to offer immediate feedback and assistance in obtaining images. Participants rotated through all 10 standardized patients and faculty, performing deliberate practice without realizing that’s what they were doing. Participants completed pre- and post-workshop surveys to assess their knowledge and confidence with gastric ultrasound with X questions using a 5-point Likert scale. The post-workshop survey also tested participant’s ability to correctly identify structures on classic gastric ultrasound images. This study is a prospective analysis of pre- and post-workshop survey data. Data was analysed using two-tailed Fisher's exact tests, with statistical significance set at p < 0.05.
Results
37 participants completed the pre-workshop survey, and 25 completed the post-workshop survey. Statistically significant differences were found in physicians' confidence in obtaining gastric images (p<0.0001), interpreting gastric ultrasound (p<0.0001), and confidence in incorporating gastric POCUS into practice (p=0.0003) [Fig. 1]. No significant difference was found in general POCUS confidence (p=0.5336).
Discussion
Prior studies implementing POCUS into medical education through standardized workshops have been shown to improve knowledge and POCUS comfort. In one study, implementation of a 6-hour-workshop with faculty showed increased confidence in teaching POCUS to medical students, a 36% increase in POCUS knowledge, and an increase in correct identification of anatomic structures1. Likewise, hands-on training and asynchronous online modules increased PGY-1 residents’ confidence in obtaining POCUS images, recognizing anatomical structures, and incorporating POCUS into clinical practice2. Our study reinforces these findings in the population of practicing anesthesiologists of all ages for gastric ultrasound. In the face of increased use of GLP-1 agonists, gastric ultrasound is a vital tool for anesthesiologists to appraise a patient’s fasting status and determine a safe induction plan3. One of our more grey-haired attendees said, “Wow, I actually think I can now do this in clinical practice, and I did not think this workshop would be so helpful.”
Conclusion
Anesthesia faculty who attended the workshop reported increased confidence with gastric POCUS, demonstrated improved skills in identifying structures, and reported greater confidence in integrating it into clinical practice, suggesting the addition of deliberate practice was very positive.
References
1. Russell et al, PMID: 33415026.
2. Ferre et al, PMID: 39107748.
3. Gagey et al, PMID: 29265174
Thermodynamic and Structural Investigations of Protein Mutations Using λ-Dynamics
No full textIUIThe λ-dynamics (λD) alchemical free energy method is a powerful tool to
investigate the impact that an amino acid change has on the stability of a protein or a protein
complex. This method simultaneously calculates thermodynamic relative free energy
changes (ΔΔGs) due to protein perturbations and generates simulation trajectories that
allow the specific origin of the thermodynamic change to be identified. Historically,
alchemical investigations of protein mutations have encountered difficulties when the
perturbation involved buried small-to-large changes, changes to backbone flexibility,
and/or changes in charge. However, such perturbations frequently arise when studying
disease-linked protein mutations. In this thesis, λD was used to model mutations in the 20S
proteasome, the insulin receptor, and the RNA exosome complex, demonstrating its ability
to model each kind of challenging protein mutations listed above.
Using multisite λ-dynamics (MSλD), a series of thermal-sensitive mutants in the
proteasome subunit, Pup2 (C76R, T113M, and L204Q) were investigated. The
thermodynamic results revealed a large ΔΔGbind of 5 kcal/mol accompanying the C76R
mutation. Complimentary stabilization by the T113M and L204Q variants was observed at
lower temperatures (30 °C) but disappeared at higher temperatures (50 °C).
The insulin ValA3Leu mutation gives the clinically observed insulin Wakayama a
140-500-fold worse binding affinity for the insulin receptor. This loss of binding, along
with the binding trends of six other insulin A3 variants, were successfully captured with λD. Structural investigation revealed that the substantially worse impact from LeuA3 stems
from a steric clash with Leu’s second Cδ.
With λD, a series of challenging EXOSC3 mutations were analyzed, including the
neurodegenerative disorder-linked D132A, A139P, G191C, and G191D and the variant of
uncertain significance (VUS) G135R. All of these variants were found to destabilize
EXOSC3 folding while A139P, G191D, and G135R were also found to negatively impact
binding affinity. Structural analysis identified a clear rationale for the thermodynamic
impact of all EXOSC3 variants. This study concludes that the VUS G135R is likely
pathogenic. This work demonstrates the utility of λD in investigations including extremely
challenging protein mutations in macromolecular complexes and applies this tool to
explain disease-linked missense mutations and to predict the significance of a VUS
mutation
3D-Printable Photothermal and Temperature-Controlled Polycaprolactone Scaffolds Incorporating Gold Plasmonic Blackbodies for Bone Tissue Engineering
No full textThree-dimensional (3D) printing technology has revolutionized the design and fabrication of bone scaffolds, offering precise and customizable solutions for bone tissue engineering. In this study, we developed polycaprolactone (PCL) scaffolds that incorporated gold plasmonic blackbodies (AuPBs) to harness photothermal properties for temperature-controlled bone regeneration. The AuPB-PCL scaffolds demonstrated enhanced mechanical strength, a tunable thermal response under near-infrared (NIR) laser irradiation, and improved osteogenic potential. Photothermal stimulation effectively modulated cellular responses, promoting osteoblast proliferation, alkaline phosphatase (ALP) activity, and mineralization. Notably, mild hyperthermia (39-41 °C) induced by laser irradiation optimized osteogenesis, while excessive temperatures (≥42.5 °C) impaired cellular function due to mitochondrial stress and oxidative damage. These findings highlight the potential of AuPB-PCL scaffolds for controlled photothermal bone regeneration, offering a promising strategy for precise, completely noninvasive stimulation of bone repair