Immungenetics (Germany)

Repetitive mild traumatic brain injury (rmTBI) produces cumulative cellular stress that can lead to progressive brain dysfunction, yet the mechanisms governing vulnerability to repeated injury remain unclear. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) regulates cellular proteostasis through the unfolded protein response and is implicated in neurodegeneration and acute brain injury. Here, we directly tested the role of PERK deficiency in shaping the brain’s response to rmTBI. Using a mouse model of neuronal PERK deficiency, we combined spatial proteomics and tissue analyses with resting-state functional MRI and diffusion tensor imaging to assess molecular, functional, and structural outcomes after rmTBI. PERK deficiency increased susceptibility to rmTBI-induced disruption of protein homeostasis, altered large-scale functional connectivity, and exacerbated white matter microstructural changes consistent with axonal and myelin damage. Molecular alterations were spatially aligned with imaging-defined network and white matter abnormalities. These findings identify PERK signaling as a key determinant of brain resilience to repetitive mild injury and link ER stress dysregulation to network-level dysfunction following rmTBI.

The advent of high-throughput data generation and artificial intelligence has transformed allergy research. Open-access database (OAD) and cohort-based database (CBD) provide essential resources for machine learning (ML)-driven algorithms for risk stratification and decision support. It is crucial for allergologists to understand their construction, strengths, and limitations. We review recently published databases with a focus on how these datasets can be combined to enhance research. OAD, including environmental monitoring resources, omics repositories, and electronic health records, offer scale, diversity, and opportunities for new hypotheses, but are often limited by sparse clinical annotation, heterogeneous data generation, and incomplete linkage to patient-level outcomes. CBD provide well-phenotyped patients, longitudinal follow up, and high-quality clinical and immunological measurements, yet face constraints in sample size, population diversity, and data sharing. Studies integrating OAD breadth with CBD label fidelity report improved predictive performance when paired with disciplined evaluation. Federated learning and portable feature specifications are emerging to enable privacy-preserving collaborations. Allergologists play a central role in building ML-ready resources. By ensuring rigorous clinical annotation, standardization of data, transparent methods, and independent validation, they can maximize the utility of OAD and CBD and their combination to accelerate progress toward precision allergy medicine.

Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research.

ABSTRACTBackground/ObjectivesTwo Phase III randomized controlled trials were conducted in the US (ULTRA I) and Germany (ULTRA II) to investigate the efficacy of incobotulinumtoxinA for simultaneous treatment of upper facial lines (UFLs: glabellar frown lines [GFLs], horizontal forehead lines [HFLs] and lateral canthal lines [LCLs]).Patients/MethodsHealthy adults with moderate to severe GFLs, HFLs, and symmetrical LCLs were enrolled. Participants were randomized 2:1:1 to three groups: placebo, UFLs, and GFLs & HFLs (ULTRA I) or LCLs (ULTRA II). All participants received up to 64 units of incobotulinumtoxinA in the main period (MP) and were eligible for two additional treatment cycles in the open‐label extensions (OLEX). Endpoints included participant‐ and investigator‐assessed Global Aesthetic Improvement Scale (pGAIS and iGAIS, respectively; any improvement defined as ≥ +1 score versus baseline) and the percentage of GFL, HFL, and LCL responders, defined as ≥ 1‐grade improvement in Merz Aesthetics Scale (MAS) score versus baseline at maximum contraction.ResultsFor pGAIS at Day 30, the proportion of participants with any improvement was very high (> 97%) across all three treatment cycles. iGAIS results were similar and slightly higher than pGAIS results. In the MP, investigator and participant MAS assessments were similar, with > 78% of participants showing a positive treatment response for UFLs up to Day 90; responses in the placebo groups remained low at all time points (< 13%). MAS results in the OLEX were consistent with the MP.ConclusionsAdditional endpoints, including pGAIS, iGAIS, and MAS scores, corroborate prior ULTRAI/II findings and demonstrate the efficacy of incobotulinumtoxinA for simultaneous treatment of UFLs.Trial RegistrationULTRA I: NCT04594213; ULTRA II: NCT04622254

Cervico-vaginal fluid represents an important biological fluid due to its proximity to gestational tissues, such as the cervix, fetal membranes, and myometrium. Here, we present a protocol to isolate cervico-vaginal fluid cells from Macaca mulatta. We describe steps for cervico-vaginal fluid collection, cervico-vaginal cell isolation for nuclear staining and immunophenotyping by flow cytometry, and protein-level detection and quantification by ELISA. This protocol can provide insights into altered immunological changes at the cervico-vaginal interface.