The Ray Method: Aesthetic and Simple Technique for Prosthesis Coverage in Prepectoral Breast Reconstruction.

In prepectoral breast reconstruction, the acellular dermal matrix (ADM) is commonly used to envelop breast implants. Various wrapping methods have been proposed. We present a simple but aesthetic method (ie, the ray method) for wrapping in prepectoral breast reconstruction. Without any complicated design, we folded the four corners of one large ADM and sewed them together to completely envelop the implant. Then, the 6 o'clock corner of the ADM envelope was folded up and sutured to make a pentagonal shape. The other corners of the ADM envelope were quilted to determine the position and movement of the internal implant. Additional sutures were placed on the ADM envelope to separate the implant from the host tissue. The folded 6 o'clock corner was cut to a convex contour and had a diagonal gap to prevent the collection of fluid in the ADM envelope. Finally, the wrapped implant was inserted in the postmastectomy space, and the ADM envelope was spread widely to support soft tissue effectively. This simple design is straightforward for inexperienced surgeons and reduces operation time. The position and movement of the breast implant in the ADM envelope can be easily controlled by using quilted sutures. Subclavian depression and step-off deformities can be minimized by this wide-stretched ADM. By total coverage with a large ADM, the breast implant is separated from the surrounding tissue, and foreign body reactions are reduced. This method is reliable for maximizing the aesthetic advantages of prepectoral direct-to-implant breast reconstruction.

Next generation risk assessment of biocides (PHMG-p and CMIT/MIT)-induced pulmonary fibrosis using adverse outcome pathway-based transcriptome analysis.

Next-generation risk assessment (NGRA) has emerged as a promising alternative to non-animal studies owing to the increasing demand for the risk assessment of inhaled toxicants. In this study, NGRA was used to assess the inhalation risks of two biocides commonly used as humidifier disinfectants: polyhexamethylene guanidine phosphate (PHMG-p) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT). Human bronchial epithelial cell transcriptomic data were processed based on adverse outcome pathways and used to establish transcriptome-based points of departure (tPODs) for each biocide. tPOD values were 0.00500-0.0510 µg/cm2 and 0.0342-0.0544 µg/cm2 for PHMG-p and CMIT/MIT, respectively. tPODs may provide predictive power comparable to that of traditional animal-based PODs (aPODs). The tPOD-based NGRA determined that both PHMG-p and CMIT/MIT present a high inhalation risk. Moreover, the identified PHMG-p posed a higher risk than CMIT/MIT, and children were identified as more susceptible population compared to adults. This finding is consistent with observations from actual exposure events. Our findings suggest that NGRA with transcriptomics offers a reliable approach for risk assessment of specific humidifier disinfectant biocides, while acknowledging the limitations of current models and in vitro systems, particularly regarding uncertainties in pharmacokinetics (PK) and pharmacodynamics (PD).

Incidence and Characteristics of Cerebral Infarction After Microsurgical Clipping of Unruptured Anterior Circulation Cerebral Aneurysms: Diffusion-Weighted Imaging-Based Analysis of 600 Patients.

BACKGROUND AND OBJECTIVES: Postclipping cerebral infarction (PCI) remains a major concern after treatment for unruptured intracranial aneurysms (UIAs). However, studies of microsurgical clipping based on diffusion-weighted imaging are limited. We aimed to present the incidence, risk factors, and types of PCI and its radiological and clinical characteristics. METHODS: This was a retrospective single-center study in which patients were scheduled to undergo microsurgical clipping for anterior circulation UIAs. The overall incidence and risk factors were calculated. Based on the operation and relevant artery, we categorized PCI on diffusion-weighted imaging into 4 types and presented their radiological and clinical characteristics. RESULTS: We reviewed the radiological and clinical data of 605 patients. The overall incidence of PCI was 16.7% (101/605), of which asymptomatic infarction was 14.9% (90/605) and symptomatic infarction was 1.8% (11/605). Hypertension (adjusted odds ratio [aOR], 2.258; 95% confidence interval [CI]: 1.330-3.833), temporary clipping (aOR, 1.690; 95% CI: 1.034-2.760), multiple aneurysm locations (aOR, 1.832; 95% CI: 1.084-3.095), and aneurysm dome size (aOR, 1.094; 95% CI: 1.006-1.190) were independent risk factors for PCI. Type II (perianeurysmal perforator) infarction was the most common type of PCI (48.6%) and the most common cause of symptomatic infarction (72.7%). Types II and III (distal embolic) infarctions correlated with atherosclerotic changes in the aneurysm wall and temporary clipping (62.4% and 70.6%, respectively). The type IV (unrelated) infarction group had a higher incidence of systemic atherosclerosis (55%). CONCLUSION: Microsurgical clipping is a safe and viable option for the treatment of anterior circulation UIAs. However, modification of the surgical technique, preoperative radiological assessment, and patient selection are required to reduce the incidence of PCI.

Utility of Cellular Measurements of Non-Specific Endocytosis to Assess the Target-Independent Clearance of Monoclonal Antibodies.

Past studies have demonstrated higher clearance for monoclonal antibodies possessing increased rates of non-specific endocytosis. However, this metric is oftentimes evaluated indirectly using biophysical techniques or cell surface binding studies that may not provide insight into the specific rates of cellular turnover. Furthermore, few examples evaluating non-specific endocytosis have been reported for a therapeutic antibody that reached clinical assessment. In the current report, we evaluated a therapeutic human immunoglobulin G2 monoclonal antibody targeted against the interleukin-4 receptor alpha chain (IL-4Rα) that exhibited elevated target independent clearance in previous Phase 1 and 2 studies. We confirmed high non-specific clearance of the anti-IL-4Rα antibody as compared to a reference antibody during pharmacokinetic assessments in wild type mice where target-mediated disposition was absent. We then developed a cell-based method capable of measuring cellular protein endocytosis and demonstrated the anti-IL-4Rα antibody exhibited marked non-specific uptake relative to the reference compound. Antibody homology modeling identified the anti-IL-4Rα antibody possessed positive charge patches whose removal via targeted mutations substantially reduced its non-specific endocytosis. We then expanded the scope of the study by evaluating panels of both preclinical and clinically relevant monoclonal antibodies and demonstrate those with the highest rates of non-specific uptake in vitro exhibited elevated target independent clearance, low subcutaneous bioavailability, or both. Our results support the observation that high non-specific endocytosis is a negative attribute in monoclonal antibody development and demonstrate the utility of a generic cell-based screen as a quantitative tool to measure non-specific endocytosis of protein therapeutics at the single-cell level.

A systematic review and BMD modeling approach to develop an AOP for humidifier disinfectant-induced pulmonary fibrosis and cell death.

Dosimetry modeling and point of departure (POD) estimation using in vitro data are essential for mechanism-based hazard identification and risk assessment. This study aimed to develop a putative adverse outcome pathway (AOP) for humidifier disinfectant (HD) substances used in South Korea through a systematic review and benchmark dose (BMD) modeling. We collected in vitro toxicological studies on HD substances, including polyhexamethylene guanidine hydrochloride (PHMG-HCl), PHMG phosphate (PHMG-p), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), CMIT, and MIT from scientific databases. A total of 193 sets of dose-response data were extracted from 34 articles reporting in vitro experimental results of HD toxicity. The risk of bias (RoB) in each study was assessed following the office of health assessment and translation (OHAT) guideline. The BMD of each HD substance at different toxicity endpoints was estimated using the US Environmental Protection Agency (EPA) BMD software (BMDS). Interspecies- or interorgan differences or most critical effects in the toxicity of the HD substances were analyzed using a 95% lower confidence limit of the BMD (BMDL). We found a critical molecular event and cells susceptible to each HD substance and constructed an AOP of PHMG-p- or CMIT/MIT-induced damage. Notably, PHMG-p induced ATP depletion at the lowest in vitro concentration, endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), inflammation, leading to fibrosis. CMIT/MIT enhanced mitochondrial reactive oxygen species (ROS) production, oxidative stress, mitochondrial dysfunction, resulting in cell death. Our approach will increase the current understanding of the effects of HD substances on human health and contribute to evidence-based risk assessment of these compounds.

Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework.

Objectives: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. Methods: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into 3 lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway-adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. Results: The integration of each AEP-AOP component for PHMG and CMIT/MIT led to the development of an AEP-AOP model, wherein disinfectants released from humidifiers in aerosol or gaseous form reached target sites, causing respiratory damage through molecular initiating events and key events. The model demonstrated high reliability and relevance to the pathogenesis of respiratory diseases. Conclusion: The AEP-AOP model developed in this study provides strong evidence that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Corrigendum: Therapeutically targeting type I interferon directly to XCR1+ dendritic cells reveals the role of cDC1s in anti-drug antibodies.

[This corrects the article DOI: 10.3389/fimmu.2023.1272055.].

Bio-Exercise (BioEx) - A biocreative orofacial myofunctional therapy: preliminary cephalometric study and clinical application

ABSTRACT Objective: To introduce newly structured and developed orofacial myofunctional therapy (OFMFT) protocols named Bio-Exercise (BioEx), and evaluate the treatment effect of this method, using lateral cephalometric analysis on malocclusion with low tongue posture in young patients. Methods: A retrospective preliminary study was performed using orthodontic records from 28 patients (mean age of 8.41±1.45-year-old, 13 males, 15 females) treated with BioEx therapy using tongue elevators for 18.14±9.04 months (range: 6 to 37 months). Pretreatment (T0) and post-BioEx therapy (T1) lateral cephalograms were subsequently analyzed for tongue posture changes by linear, anteroposterior and vertical measurements. The data were analyzed by paired t-test, considering a 5% significance level. Results: The tongue length (TGL) and tongue height (TGH) increased statistically significant between T0 and T1. The decrease of the dorsum of the tongue perpendicular to the palatal plane (Td-PP value) was statistically significant. The increase of the tip of the tongue perpendicular to the pterygomaxillary vertical line (TT-PMV) was not statistically significant. Conclusions: These preliminary cephalometric results indicate that BioEx can be an effective OFMFT modality in increasing the tonicity of the tongue muscles to establish more normalized tongue position at rest.

RESUMO Objetivo: Introduzir protocolos de terapia miofuncional orofacial (TMO) recém-estruturados e desenvolvidos, denominados Bio-Exercise (BioEx), e avaliar o efeito do tratamento com esse método, usando análise cefalométrica em radiografias laterais de jovens com má oclusão e postura baixa da língua. Métodos: Foi realizado um estudo preliminar retrospectivo com registros ortodônticos de 28 pacientes (idade média de 8,41±1,45 anos, 13 homens, 15 mulheres) tratados com terapia BioEx usando elevadores de língua por 18,14±9,04 meses (intervalo: 6 a 37 meses). As radiografias cefalométricas laterais pré-tratamento (T0) e pós-tratamento com BioEx (T1) foram analisadas quanto às alterações na postura da língua, por meio de medidas lineares, anteroposteriores e verticais. Os dados foram analisados pelo teste t pareado, considerando-se um nível de significância de 5%. Resultados: O comprimento da língua (CL) e a altura da língua (AL) aumentaram entre T0 e T1, com significância estatística. A diminuição do dorso da língua perpendicular ao plano palatino (valor Td-PP) foi estatisticamente significativa. O aumento da ponta da língua perpendicular à linha vertical pterigomaxilar (PL-PMV) não foi estatisticamente significativo. Conclusões: Esses resultados cefalométricos preliminares indicam que o BioEx pode ser uma modalidade de TMO eficaz no aumento da tonicidade dos músculos da língua, para estabelecer uma postura de língua adequada em repouso.

Terapia BioCriativa: o C-Implante / Terapia BioCriativa: o C-Implante

Muitos dos esforços dos ortodontistas do século passadoconsistiam em fundamentar a ancoragem para a uma mecânicaproposta. Com a utilização dos implantes na Odontologia, surgiu umnovo conceito de ancoragem na Ortodontia, denominado ancoragemesquelética, a qual não permite a movimentação da unidade de reação.Este artigo apresenta um conceito de ancoragem desenvolvida para aterapia biocriativa, que possui uma biomecânica desenvolvida associadaa diversos dispositivos de ancoragem. O C-Implante possui característicaspróprias, e sua eficiência é demonstrada em um relato de casoclínico. Com a introdução da ancoragem absoluta independente, abiomecânica ortodôntica contemporânea permite que, em diversassituações clínicas, as unidades anteriores mal posicionadas possamser retraídas sem a mudança de posição indesejada dos elementosposteriores durante todo o tratamento ativo.