Citations

Abstract SARS-CoV-2 infection disrupts iron homeostasis in organs such as the lung. Emerging evidence suggests similar dysregulation in the placenta may impair function and fetal growth. Ferroptosis, an iron-dependent form of cell death, is driven by the accumulation of labile ferrous iron, catalyzing the peroxidation of polyunsaturated fatty acids in the absence of sufficient iron storage or antioxidant defenses. This pathway has been implicated in SARS-CoV-2-related tissue damage in other organs and may contribute to placental dysfunction during pregnancy. However, the influence of infection timing, symptom severity, and fetal sex on placental iron regulation remains unexamined. We analyzed placental samples from a cohort of SARS-CoV-2-exposed pregnancies in the first (n = 6), second (n = 14), or third trimester (n = 30), classified by symptom severity (asymptomatic n = 23, symptomatic n = 27) and fetal sex, alongside unexposed controls (n = 47). We assessed placental iron deposition, lipid peroxidation, and mRNA and protein expression of ferroptosis markers. Publicly available RNA-sequencing datasets from human placenta tissue, exposed or not to SARS-CoV-2, were analyzed to assess ferroptosis-related gene expression. SARS-CoV-2 infection, particularly in symptomatic cases, was associated with reduced placental weight and birth weight. Asymptomatic cases showed increased placental iron deposition, which correlated with lower birthweight and was accompanied by elevated expression of nuclear receptor coactivator 4, a cytosolic adaptor protein that mediates the selective autophagic degradation of ferritin (ferritinophagy) and iron release. Placentas from symptomatic patients exhibited evidence of altered iron transport and sex-specific down-regulation of antioxidant defenses. Transcriptomic analyses further suggested widespread disruption of ferroptosis pathways in placentas from infected patients. Our findings reveal that SARS-CoV-2 infection alters placental iron homeostasis and is associated with ferroptosis-related changes, with distinct molecular responses based on timing of infection, symptom severity, and fetal sex.

Abstract Background High-sensitivity cardiac troponin (hs-cTn) assays are recommended for the diagnosis of acute myocardial infarction. Here, we characterize the analytical performance of a next-generation hs-cTn assay, Elecsys® Troponin T hs Gen 6 (Roche Diagnostics International). Methods Surplus lithium-heparin plasma or serum samples from patients or healthy volunteers were run on Cobas® e 801, e 402, and Pro analyzers. Limits of blank (LoB), limits of detection (LoD), and limits of quantitation (LoQ) were determined according to CLSI EP17-A2, with target values of 1.0 and 1.5 ng/L for LoB/LoD and 3.0 ng/L (10% CV) and 1.5 ng/L (20% CV) for LoQ, respectively. Precision was measured, per CLSI EP17-A2, using 3 QC samples (approximately 4, 30, and 220 ng/L), 12 native samples, and 3 reagent lots. Linearity, per CLSI EP06-Ed2, was determined by diluting samples with cardiac troponin T (cTnT) concentration above the measuring range with a low/blank sample. Interference (per Glick) with endogenous and assay components at 5 cTnT concentrations was assessed. Results Measured values for LoB, LoD, and LoQ at 10% and 20% CV were 0.1 to 0.7 ng/L, 0.3 to 1.4 ng/L, 1.0 to 2.9 ng/L, and 0.4 to 1.2 ng/L, respectively. Repeatability CVs were 1.0 to 5.8% for mean cTnT concentrations of 2.6 to 9230 ng/L in lithium-heparin plasma. High precision was shown across lots, and linearity was observed across the measuring range (1.5 to 9500 ng/L, all Pearson's r = 1.00). No interferences were observed, specified up to ≤1000 mg/dL hemoglobin, ≤50 mg/dL [≤855 µmol/L] icterus/bilirubin, and ≤1200 ng/mL biotin. Conclusions The analytical performance characterization of the assay demonstrated high sensitivity, high precision at the low end and across the measuring range, and resistance to interference.

ABSTRACT Background Driving supports independence and quality of life in later life but is vulnerable to age‐related and/or disease‐related decline. While cognitive impairment is a well‐recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. Methods We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in‐vehicle GPS dataloggers between 2019 and 2025. Linear mixed‐effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). Results At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (−0.050 vs. −0.037 trips/month), long‐distance trips (> 20 miles; p < 0.001), and maximum trip distance ( p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self‐reported driving behaviors showed that participants with higher SMI drove fewer days per‐week and were more likely to avoid night driving ( p < 0.01). Rates of self‐reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self‐regulatory behaviors. Conclusion Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low‐cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving.

This is a concise literature-based delineation of dignity and its connections with important mental health issues in the Latin American continent. This review examines the relationship between dignity and mental health in Latin America, focusing mostly on Peruvian socio-cultural studies and clinical perspectives. Drawing on published literature, an introductory geographic description and a historical narrative supported by socio-demographic data and cultural realities of the region, the review explores how dignity is shaped by cultural identity and by the mestizaje process as a decisive ontological feature. A series of seven cases covering different aspects of the impact of clinical events on the dignity of the protagonists is presented. Dignity is explored from the perspective of native healers, mothers and human rights principles, as well as its fragility in the face of socio-political, racism-induced conflicts, and sectarian/religious deformations. The difficulties faced in overcoming reductionistic and alienating influences, as well as social inequalities affecting dignity, are discussed. The review emphasizes, in turn, its consideration as one of the central issues of psychotherapeutic approaches and much-needed investigation projects.

Objective: Battlefield acupuncture (BFA) has gained widespread clinical use for patients presenting to emergency departments (EDs). This systematic review of randomized controlled trials (RCTs) aims to assess the efficacy and safety of BFA in ED settings. Methods: A literature search was conducted in OVID and Scopus databases for RCTs involving BFA applied in ED settings. The risk of bias was evaluated using the Cochrane Collaboration risk of bias tool, while the methodological quality of RCTs was assessed using the Jadad score. Due to the heterogeneity of the included studies, a qualitative analysis was performed. Results: Seven studies involving 758 patients met the eligibility criteria. Among these, five studies evaluated traditional BFA in conjunction with standard analgesia care, while two studies assessed modified BFA alongside standard care. Most of the included studies were found to have a high risk of bias, leading to an overall classification of low quality according to the Jadad criteria. A descriptive analysis was performed due to heterogeneity in the interventions, observational timepoints, and outcomes reported in the included studies. Positive results were demonstrated in 71% of the studies. The most common conditions documented as the primary ED presentation included back pain, acute abdominal pain, lower extremity pain, neck pain, and acute sore throat. Notably, no severe adverse events were reported. Conclusion: BFA may offer a safe adjunct to standard care for pain management in ED settings. However, the limited methodological rigor and small number of existing RCTs reduce confidence in the current evidence. Well-designed, robust studies are needed to clarify their effectiveness and support stronger clinical recommendations.

Introduction This case describes the application of spinal cord stimulation for the treatment of phantom limb pain in a patient with a left transhumeral amputation. Treatment of pain involving a high frequency spinal cord stimulator allowed the patient to utilize his myoelectric prosthesis and improve his overall function. Clinical findings Severe, phantom limb pain with associated involuntary muscle contractions prevented the patient from wearing a prosthesis for more than three hours per day. He also had difficulty using his myoelectric prosthesis to use his left upper extremity for functional tasks. Therapeutic intervention A high frequency spinal cord stimulator was placed at the level of the cervical spine. The patient had improvement in pain and overall function. He was also able to tolerate wearing his prosthesis longer each day. Conclusion High frequency spinal cord stimulation may be an effective treatment option for individuals with phantom limb pain. Treatment of phantom limb pain may decrease barriers to prosthesis use and improve overall function.

Background: Sinonasal malignancies (SNM) are rare cancers associated with poor prognosis and impaired quality of life (QOL). The 22-question Sino-Nasal Outcome Test (SNOT-22) has been used to assess QOL in patients with SNM. Objective: To determine the minimal clinically important difference (MCID) for the SNOT-22 in patients with SNM. Methods: About 264 patients with SNM were drawn from a prospective, longitudinal, multi-institutional study. SNOT-22 scores were collected at pre-treatment baseline and follow-up through 5 years post-treatment. Cronbach’s alpha was used to assess the internal consistency of the SNOT-22. Distribution-based approaches were used to estimate the MCID. Multivariable regression identified factors associated with SNOT-22 improvement exceeding the determined MCID. Results: Cronbach’s alpha was >.85. The estimated MCIDs were: 1.44 (Cohen’s effect size), 1.32 (standard error of the mean), 10.45 (1/2 of baseline standard deviation), and 3.67 (minimum detectable change). The mean MCID across methods was 4.22. Multivariable regression demonstrated higher odds of clinically meaningful improvement from baseline in patients with early-stage disease (odds ratio (OR) 3.510, P = .035), no neck irradiation (OR 11.050, P = .014), and neoadjuvant therapy (OR 16.667, P = .047). Conclusions: The SNOT-22 MCID was estimated as 4.22 in a large multi-center cohort of patients with SNM, suggesting that relatively small QOL changes are clinically relevant. When applying the MCID to the current cohort, advanced stage, treatment of neck disease, and not requiring neoadjuvant therapy were predictive of worse QOL.

Abstract Background Radiomics extracts quantitative imaging features from computed tomography (CT) data for clinical decision‐making. However, variations in acquisition parameters—particularly x‐ray tube voltage (kV)—introduce non‐biological variability in attenuation values, limiting the reproducibility of radiomic features across scanners, protocols, and institutions. Purpose To develop and evaluate a CT dAta harmoNiZAtion framework based on deep learNed vIrTual monoEnergetic imaging (TANZANITE), which leverages the keV flexibility of virtual monoenergetic images (VMIs) to enable cross‐kV scan translation and radiomics harmonization. Methods TANZANITE is a model hub consisting of multiple pre‐trained convolutional neural networks (CNNs), each designed to translate VMIs from 1 keV level to another. Phantom‐based calibration was first used to determine energy‐equivalent (Eff_E) keV levels corresponding to each tube potential (e.g., Eff_E(A) keV for source kV and Eff_E(B) keV for target kV). A CNN trained using 69 120 patches from seven patient cases to map VMIs from Eff_E(A) to Eff_E(B) was selected from the TANZANITE hub and applied directly to clinical CT images acquired at the source kV. This harmonized the images to match the attenuation characteristics of the target kV setting. Evaluation was conducted on independent dual‐energy CT datasets acquired at 100/Sn150 kV. Regions of interest (ROIs) were placed in the kidney, liver, and spine to assess CT number consistency and radiomic feature reproducibility. The concordance correlation coefficient (CCC) was calculated across 93 non‐shape radiomic features. Results After TANZANITE processing with 100 kV images, CT numbers in evaluated organs closely matched the Sn150 kV reference values in four testing patient cases. For example, mean kidney CT numbers changed from 320 HU (100 kV) to 156 HU (TANZANITE), approximating the Sn150 kV value of 160 HU. Similar changes were observed in the liver (157–105 HU vs. 104 HU reference) and spine (45–22 HU vs. 19 HU reference). Radiomic reproducibility improved substantially across organs: mean CCC increased from 0.590 to 0.995 in the liver, 0.300 to 0.970 in the kidney, and 0.630 to 0.968 in the spine. Post‐TANZANITE, over 98% of features exceeded the stability threshold (CCC ≥ 0.900) in all three representative organs. Conclusion TANZANITE provides a flexible, image‐domain harmonization framework by learning the keV‐to‐keV translation in the VMI domain and applying pre‐trained CNNs to clinical kV images. It improves CT number consistency and organ‐specific radiomic reproducibility without requiring raw projection data or scanner‐specific training. This approach supports consistent quantitative imaging across multiple‐kV acquisition protocols, enhancing radiomics reliability in clinical settings.