Facial Hypertrophy as a Complication of Weight Gain in Autologous Fat Graft Patients: Considerations and Recommendations.

Fat grafting can restore facial volume for reconstructive and cosmetic indications. Common practice often involves extracting lipoaspirate from the most abundant anatomic location. However, grafted fat retains the phenotypic characteristics of its original location and can undergo exaggerated hypertrophy with patient weight fluctuations. The aim of this study was to systematically assess the literature to summarize the reported effects of postoperative weight gain on facial hypertrophy in patients after facial fat grafting and to determine potentially avoidable factors. A search through PubMed/MEDLINE was conducted on October 4, 2022, to identify relevant articles with appropriate search terms. No lower date limit was applied and all eligible nonanimal clinical articles in English were included for review. Reports were summarized and presented as descriptive statistics. The search generated 714 articles. After abstract and full-text review of the initial set of articles, 6 were included in our analysis. All articles described poor cosmetic outcomes resulting from nonanatomic hypertrophy of the grafted fat. None of the articles reported a thorough methodology for selecting the donor site to minimize fat hypertrophy with potential future weight fluctuations. Grafted facial fat is susceptible to exaggerated hypertrophy as a result of changes in patient weight. Specifically, harvesting lipoaspirate from maximally abundant areas of the body may increase this risk. Individualizing the area of fat donation may attenuate unwanted fat growth and further contribute to increased patient quality of life.

TREM2 macrophages induced by human lipids drive inflammation in acne lesions.

Acne affects 1 in 10 people globally, often resulting in disfigurement. The disease involves excess production of lipids, particularly squalene, increased growth of Cutibacterium acnes, and a host inflammatory response with foamy macrophages. By combining single-cell and spatial RNA sequencing as well as ultrahigh-resolution Seq-Scope analyses of early acne lesions on back skin, we identified TREM2 macrophages expressing lipid metabolism and proinflammatory gene programs in proximity to hair follicle epithelium expressing squalene epoxidase. We established that the addition of squalene induced differentiation of TREM2 macrophages in vitro, which were unable to kill C. acnes. The addition of squalene to macrophages inhibited induction of oxidative enzymes and scavenged oxygen free radicals, providing an explanation for the efficacy of topical benzoyl peroxide in the clinical treatment of acne. The present work has elucidated the mechanisms by which TREM2 macrophages and unsaturated lipids, similar to their involvement in atherosclerosis, may contribute to the pathogenesis of acne.

Chalcone Derivatives as Potential Inhibitors of P-Glycoprotein and NorA: An In Silico and In Vitro Study.

The human P-glycoprotein (P-gp) and the NorA transporter are the major culprits of multidrug resistance observed in various bacterial strains and cancer cell lines, by extruding drug molecules out of the targeted cells, leading to treatment failures in clinical settings. Inhibiting the activity of these efflux pumps has been a well-known strategy of drug design studies in this regard. In this manuscript, our earlier published machine learning models and homology structures of P-gp and NorA were utilized to screen a chemolibrary of 95 in-house chalcone derivatives, identifying two hit compounds, namely, F88 and F90, as potential modulators of both transporters, whose activity on Staphylococcus aureus strains overexpressing NorA and resistant to ciprofloxacin was subsequently confirmed. The findings of this study are expected to guide future research towards developing novel potent chalconic inhibitors of P-gp and/or NorA.

Characterization of Virulence Function of Pseudomonas cichorii Avirulence Protein E1 (AvrE1) during Host Plant Infection.

Pseudomonas cichorii secretes effectors that suppress defense mechanisms in host plants. However, the function of these effectors, including avirulence protein E1 (AvrE1), in the pathogenicity of P. cichorii, remains unexplored. In this study, to investigate the function of avrE1 in P. cichorii JBC1 (PcJBC1), we created an avrE1-deficient mutant (JBC1ΔavrE1) using CRISPR/Cas9. The disease severity caused by JBC1ΔavrE1 in tomato plants significantly decreased by reducing water soaking during early infection stage, as evidenced by the electrolyte leakage in infected leaves. The disease symptoms caused by JBC1ΔavrE1 in the cabbage midrib were light-brown spots compared to the dark-colored ones caused by PcJBC1, which indicates the role of AvrE1 in cell lysis. The avrE1-deficient mutant failed to elicit cell death in non-host tobacco plants. Disease severity and cell death caused by JBC1ΔavrE1 in host and non-host plants were restored through heterologous complementation with avrE1 from Pseudomonas syringae pv. tomato DC3000 (PstDC3000). Overall, our results indicate that avrE1 contributes to cell death during early infection, which consequently increases disease development in host plants. The roles of PcJBC1 AvrE1 in host cells remain to be elucidated.

The cellular architecture of the antimicrobial response network in human leprosy granulomas.

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1ß. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.

Virtual Interviews During COVID-19: Perspectives of Female Pelvic Medicine and Reconstructive Surgery Program Directors.

OBJECTIVE: The aim of the study was to evaluate female pelvic medicine and reconstructive surgery (FPMRS) fellowship program directors' opinions regarding the effectiveness of virtual interviews for selecting fellows and their future interview mode preferences. METHODS: This was a cross-sectional online survey of all FPMRS program directors in the United States conducted from April 29, 2020, to May 30, 2020. At the time of this study, there were 73 program directors and 69 obstetrics and gynecology and urology-accredited FPMRS programs nationwide. The primary outcome was to subjectively assess the effectiveness of virtual interviews as compared with in-person interviews for evaluating applicants. RESULTS: Fifty seven (82.6%) of the program directors completed the survey. A total of 80.7% (46/57) of the respondents had participated in interviews for the active match cycle. Of the programs that participated in the interview process, almost all conducted interviews using virtual platforms (97.8%, 45/46). Program directors who conducted interviews virtually found them effective in evaluating applicants (88.9%, 40/45) and were satisfied with the virtual interview process (86.7%, 39/45). A total of 31.1% of respondents (14/45) preferred a virtual platform to an in-person setting for future interviews, and 60% (27/45) reported that they will likely perform future interviews virtually. CONCLUSIONS: Although the pandemic resulted in a sudden reformatting of FPMRS fellowship interviews, most program directors nationally were satisfied with the process and found virtual interviews effective for assessing applicants. More than 50% of FPMRS program directors are likely to consider the virtual format for future interviews.

Second-Strand Synthesis-Based Massively Parallel scRNA-Seq Reveals Cellular States and Molecular Features of Human Inflammatory Skin Pathologies.

High-throughput single-cell RNA-sequencing (scRNA-seq) methodologies enable characterization of complex biological samples by increasing the number of cells that can be profiled contemporaneously. Nevertheless, these approaches recover less information per cell than low-throughput strategies. To accurately report the expression of key phenotypic features of cells, scRNA-seq platforms are needed that are both high fidelity and high throughput. To address this need, we created Seq-Well S3 ("Second-Strand Synthesis"), a massively parallel scRNA-seq protocol that uses a randomly primed second-strand synthesis to recover complementary DNA (cDNA) molecules that were successfully reverse transcribed but to which a second oligonucleotide handle, necessary for subsequent whole transcriptome amplification, was not appended due to inefficient template switching. Seq-Well S3 increased the efficiency of transcript capture and gene detection compared with that of previous iterations by up to 10- and 5-fold, respectively. We used Seq-Well S3 to chart the transcriptional landscape of five human inflammatory skin diseases, thus providing a resource for the further study of human skin inflammation.

The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis.

The febrile neutropenia (FN) rates reported with the docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) (TC) regimen given every 3 weeks vary from 4 to 69 % in early-stage breast cancer (ESBC) patients. This creates uncertainty as to whether patients receiving the TC regimen should also receive granulocyte colony-stimulating factor primary prophylaxis (G-CSFpp), which is recommended when chemotherapy regimens have ≥20 % FN rate. We conducted a meta-analysis of published studies to determine FN rate with the TC regimen, its dependence on patients' age, and the efficacy of G-CSFpp in reducing it in ESBC patients. We systematically searched the literature via PUBMED using the following terms: 'docetaxel', 'cyclophosphamide', 'febrile neutropenia', and 'breast cancer'. Inclusion criteria were full text peer-reviewed clinical studies in English reporting FN rates with TC regimen in relationship to G-CSFpp. Comprehensive meta-analysis software was used for all statistical analyses. Eight studies (N = 1542 patients) were included in our meta-analysis. The pooled mean FN rate was 23.2 % (95 % confidence interval (CI) 6.9-55.2 %; Q = 218.17, I (2) = 97.7). The FN risk in <65 years old patients was lower by 67.7 % compared to that in patients ≥65 years old (pooled odds ratio (OR) 0.323; 95 % CI 0.127-0.820; P = 0.017). The FN risk was reduced by 92.3 % with G-CSFpp (pooled OR 0.077; 95 % CI 0.013-0.460; P = 0.005). Our meta-analysis demonstrated that TC regimen was associated with ≥20 % FN risk, which was significantly higher in patients ≥65 years old and improved with G-CSFpp. G-CSFpp should be considered for all ESBC patients receiving TC regimen, especially those ≥65 years old.

Serum levels of trace elements and iron-deficiency anemia in adult Vietnamese.

This study was aimed at assessing the serum levels of vitamin A, copper, zinc, selenium, and iron among adult Vietnamese with and without iron-deficiency anemia. Blood was collected from adult Vietnamese living in the midland of northern Vietnam. One hundred twenty-three subjects in the age range 20-60 yr were included in the study. Anemia, where the concentration of hemoglobin in whole blood is less than 120 g/L in females and 130 g/L in males, was found in 30% (37/123) of the study population. The levels of vitamin Aand selenium in the sera of anemic subjects (n = 37) were significantly lower than that in nonanemic group (n = 86). On the other hand, no significant differences were observed in the concentrations of copper and zinc between the two groups. This study was the first to show serum levels of trace elements in adult Vietnamese, providing useful baseline information for further studies.