A Viral Exposure Signature Defines Early Onset of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with its global incidence and mortality rate continuing to rise, although early detection and surveillance are suboptimal. We performed serological profiling of the viral infection history in 899 individuals from an NCI-UMD case-control study using a synthetic human virome, VirScan. We developed a viral exposure signature and validated the results in a longitudinal cohort with 173 at-risk patients who had long-term follow-up for HCC development. Our viral exposure signature significantly associated with HCC status among at-risk individuals in the validation cohort (area under the curve: 0.91 [95% CI 0.87-0.96] at baseline and 0.98 [95% CI 0.97-1] at diagnosis). The signature identified cancer patients prior to a clinical diagnosis and was superior to alpha-fetoprotein. In summary, we established a viral exposure signature that can predict HCC among at-risk patients prior to a clinical diagnosis, which may be useful in HCC surveillance.

An interbacterial NAD(P)(+) glycohydrolase toxin requires elongation factor Tu for delivery to target cells.

Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD(+) and NADP(+). Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tu (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.

The Emergence and Functional Fitness of Memory CD4+ T Cells Require the Transcription Factor Thpok.

Memory CD4+ T cells mediate long-term immunity, and their generation is a key objective of vaccination strategies. However, the transcriptional circuitry controlling the emergence of memory cells from early CD4+ antigen-responders remains poorly understood. Here, using single-cell RNA-seq to study the transcriptome of virus-specific CD4+ T cells, we identified a gene signature that distinguishes potential memory precursors from effector cells. We found that both that signature and the emergence of memory CD4+ T cells required the transcription factor Thpok. We further demonstrated that Thpok cell-intrinsically protected memory cells from a dysfunctional, effector-like transcriptional program, similar to but distinct from the exhaustion pattern of cells responding to chronic infection. Mechanistically, Thpok- bound genes encoding the transcription factors Blimp1 and Runx3 and acted by antagonizing their expression. Thus, a Thpok-dependent circuitry promotes both memory CD4+ T cells' differentiation and functional fitness, two previously unconnected critical attributes of adaptive immunity.

A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation.

The generation of high-affinity neutralizing antibodies, the objective of most vaccine strategies, occurs in B cells within germinal centers (GCs) and requires rate-limiting "help" from follicular helper CD4+ T (Tfh) cells. Although Tfh differentiation is an attribute of MHC II-restricted CD4+ T cells, the transcription factors driving Tfh differentiation, notably Bcl6, are not restricted to CD4+ T cells. Here, we identified a requirement for the CD4+-specific transcription factor Thpok during Tfh cell differentiation, GC formation, and antibody maturation. Thpok promoted Bcl6 expression and bound to a Thpok-responsive region in the first intron of Bcl6. Thpok also promoted the expression of Bcl6-independent genes, including the transcription factor Maf, which cooperated with Bcl6 to mediate the effect of Thpok on Tfh cell differentiation. Our findings identify a transcriptional program that links the CD4+ lineage with Tfh differentiation, a limiting factor for efficient B cell responses, and suggest avenues to optimize vaccine generation.

IKKα-deficient lung adenocarcinomas generate an immunosuppressive microenvironment by overproducing Treg-inducing cytokines.

The tumor microenvironment (TME) provides potential targets for cancer therapy. However, how signals originating in cancer cells affect tumor-directed immunity is largely unknown. Deletions in the CHUK locus, coding for IκB kinase α (IKKα), correlate with reduced lung adenocarcinoma (ADC) patient survival and promote KrasG12D-initiated ADC development in mice, but it is unknown how reduced IKKα expression affects the TME. Here, we report that low IKKα expression in human and mouse lung ADC cells correlates with increased monocyte-derived macrophage and regulatory T cell (Treg) scores and elevated transcription of genes coding for macrophage-recruiting and Treg-inducing cytokines (CSF1, CCL22, TNF, and IL-23A). By stimulating recruitment of monocyte-derived macrophages from the bone marrow and enforcing a TNF/TNFR2/c-Rel signaling cascade that stimulates Treg generation, these cytokines promote lung ADC progression. Depletion of TNFR2, c-Rel, or TNF in CD4+ T cells or monocyte-derived macrophages dampens Treg generation and lung tumorigenesis. Treg depletion also attenuates carcinogenesis. In conclusion, reduced cancer cell IKKα activity enhances formation of a protumorigenic TME through a pathway whose constituents may serve as therapeutic targets for KRAS-initiated lung ADC.

Methyl jasmonate-induced senescence results in alterations in the status of chlorophyll precursors and enzymatic antioxidants in rice plants.

We examined the control of chlorophyll biosynthesis and protective mechanisms during leaf senescence induced by methyl jasmonate (MeJA). After MeJA treatment, rice plants displayed evidence of great oxidative stress regarding senescence symptoms, disruption of membrane integrity, H2O2 production, and decreased chlorophyll content and photosynthetic efficiency. After 6 h of MeJA treatment, plants greatly decreased not only their levels of chlorophyll precursors, including protoporphyrin IX (Proto IX), Mg-Proto IX, Mg-Proto IX methylester, and protochlorophyllide, but also the expression levels of the chlorophyll biosynthetic genes CHLD, CHLH, CHLI, and PORB, with the greatest decreases at 78 h. MeJA-treated plants showed a noticeable degradation of light-harvesting chlorophyll-binding proteins (LHCB) at 78 h after MeJA treatment but began to downregulate expression of LHCB at 6 h. Photoprotection, as indicated by nonphotochemical quenching, slightly increased only at 6 h after MeJA treatment. In parallel to the increased activities of superoxide dismutase, catalase (CAT), ascorbate peroxidase (APX), and peroxidase, MeJA-treated plants responded to senescence by markedly upregulating the expression of APX and CAT. Our study demonstrates that rice plants developed protective mechanisms for mitigating oxidative stress by scavenging phototoxic chlorophyll precursors and activating enzymatic antioxidant responses during MeJA-induced senescence.

A germline 1;3 translocation disrupting the VHL gene: a novel genetic cause for von Hippel-Lindau.

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary tumour susceptibility disease caused by germline pathogenic variation of the VHL tumour suppressor gene. Affected individuals are at risk of developing multiple malignant and benign tumours in a number of organs.In this report, a male patient in his 20s who presented to the Urologic Oncology Branch at the National Cancer Institute with a clinical diagnosis of VHL was found to have multiple cerebellar haemangioblastomas, bilateral epididymal cysts, multiple pancreatic cysts, and multiple, bilateral renal tumours and cysts. The patient had no family history of VHL and was negative for germline VHL mutation by standard genetic testing. Further genetic analysis demonstrated a germline balanced translocation between chromosomes 1 and 3, t(1;3)(p36.3;p25) with a breakpoint on chromosome 3 within the second intron of the VHL gene. This created a pathogenic germline alteration in VHL by a novel mechanism that was not detectable by standard genetic testing.Karyotype analysis is not commonly performed in existing genetic screening protocols for patients with VHL. Based on this case, protocols should be updated to include karyotype analysis in patients who are clinically diagnosed with VHL but demonstrate no detectable mutation by existing genetic testing.

Putting non-communicable disease data to work in Vietnam: an investigation of community health surveillance capacity.

INTRODUCTION: Despite the public health system's critical role in non-communicable disease (NCD) surveillance in Vietnam, limited evidence exists on the implementation of NCD surveillance activities within these systems and the need for capacity building across different system levels to meet expected NCD surveillance goals. This study aimed to evaluate the status of and describe factors affecting the implementation of NCD surveillance activities and to identify the NCD surveillance capacity building needs of the public health system in Vietnam. METHODS: We used a mixed-methods approach in four provinces, conducting self-completed surveys of staff from six Preventive Medicine Institutes (PHI), 53 Centres for Disease Control (CDC) and 148 commune health stations (CHS), as well as 14 in-depth interviews and 22 focus group discussions at four PHI, four CDC, and eight district health centres and CHS. RESULTS: Study findings highlighted that although Vietnam has a well-functioning NCD surveillance system, a number of quality issues related to NCD surveillance data were salient. Multifactorial reasons were identified for incomplete, unconfirmed, and inaccurate mortality data and current disease surveillance data. Data on NCD management and treatment were reported to be of better quality than data for screening, targeted treatment, and counselling communication. Main factors affected the effective implementation of NCD surveillance, namely lack of complete and specific guidelines for NCD surveillance, limitations in human resource capacity within NCD departments, and shortage of funding for NCD surveillance activities. CONCLUSION: Study findings provide practical strategies for strengthening health system capacity for NCD surveillance through developing policies, guidelines, and standardised tools to guide NCD surveillance and a road map for integrated NCD surveillance, developing training packages and manuals for all levels of the health system, and conducting utilisation-focused surveillance training programs.

Assessing the Impact of COVID-19 on Facial Aesthetic Surgery Search Interest.

ABSTRACT: The global COVID-19 pandemic reshaped many components of modern health care practice. Before the pandemic, research was beginning to demonstrate the impact of self-facing cameras, selfie images, and webcams on patient interest in head and neck (H&N) aesthetic surgery. We sought to determine temporal changes in patient interest in aesthetic surgery of the H&N as compared with the rest of the body because of COVID-19, and the subsequent surge in Web-conferencing and telecommunication. The 2020 Plastic Surgery Trends Report produced by the American Society of Plastic Surgeons was used to identify the 5 most common aesthetic surgical procedures performed on the H&N and the rest of the body for 2019: blepharoplasty, face lift, rhinoplasty, neck lift, cheek implant, and breast lift, liposuction, tummy tuck, breast augmentation, and breast reduction, respectively. Google Trends filters, which provide relative search interest for greater than 85% of Internet searches, were applied to gauge interest from January 2019 to April 2022. Relative search interest and mean interest were plotted as a function of time for each term. Our findings demonstrate a sharp decline in online aesthetic surgery interest in March 2020, coinciding with the beginning of the COVID-19 pandemic for both the H&N and the rest of the body. Search interest increased shortly after March 2020 and reached values greater than those of the prepandemic year (2019) in 2021 for rest of the body procedures. After March 2020, there was a brief, sharp increase in search interest for rhinoplasty, neck lift, and facelift, whereas patient interest in blepharoplasty increased more gradually. There was no increase in search interest for H&N procedures as a result of COVID-19 when using the mean values of the included procedures, although current interest has returned to prepandemic levels. The COVID-19 pandemic caused a disruption of normal trends in aesthetic surgery interest, with a sharp decline in search interest in March 2020. Afterward, there was a sharp increase in rhinoplasty, face lift, neck lift, and blepharoplasty interest. Patient interest in blepharoplasty and neck lift has remained elevated compared with 2019. Interest in rest of the body procedures has returned to and even surpassed prepandemic levels.

Outcomes of Surgical Treatment of Malar Mounds and Festoons.

BACKGROUND: Malar mounds (congenital) and festoons (acquired) are persistent puffiness in the prezygomatic space between the orbicularis retaining ligament (ORL) and zygomatico-cutaneous ligament (ZCL). Non-surgical treatments often yield unsatisfactory results. This paper aims to demonstrate a surgical approach for the treatment of malar bags by outlining the author's surgical technique of treating malar mounds and festoons and reviewing outcomes in 89 cases. METHODS: Correction of malar mounds and festoons was achieved with subciliary skin-muscle flap, release of the ORL and ZCL, midface lift, canthopexy, and muscle suspension. We performed a retrospective study of 89 patients, all of whom had surgical correction of malar mounds or festoons in the past 10 years and a follow-up period of at least 6 months. This study was conducted over the course of the past year and involved reviewing patient charts in the office. Specifically, patient data spanning 2012 to 2022 were analyzed. The predictor variable in this study is the specific class of malar bags the patient has, as determined by the underlying pathophysiology. Outcome variables include the presence or absence of prolonged lid or malar edema, necessary re-excision of excess orbicularis oculi of the subciliary area, lid malposition, permanent visual changes, the need for additional non-operative treatment, and recurrence requiring reoperation. RESULTS: The majority of patients presented with acquired festoons (81/89) with prior attempts of correction (49/89). The mean follow-up is 11.2 months. Persistent malar edema (> 6 weeks) was documented in 14 patients and mainly resolved with Medrol Dosepak (methylprednisolone) and hydrochlorothiazide. A two-proportion Z-test was conducted, comparing the proportion of patients with poor protoplasm who experienced postoperative malar edema to the proportion of those with excellent protoplasm who experienced postoperative malar edema. A p-value of 3.414e-7 was obtained, indicating a statistically significant difference of proportions between the two groups. Five patients received additional injections of deoxycholic acid and two needed fillers for smoother contour of the lower eyelids. Two patients with severe malar mounds required multiple reoperations including direct excision in one patient. One incidence of transient lid retraction was reported in a patient with previous facelift and facial nerve injury. CONCLUSION: Malar mounds and festoons present a unique challenge to plastic surgeons. They are persistent in nature and require close-interval, long-term follow-up as additional injections and reoperations are warranted. Our approach to malar mound and festoon correction is safe and effective and provides long-lasting results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells.

Epithelial ovarian cancer (EOC) remains the fifth leading cause of cancer-related death in women worldwide, partly due to the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that promote disease relapse. We previously described a role for the NF-κB pathway in promoting TIC chemoresistance and survival through NF-κB transcription factors (TFs) RelA and RelB, which regulate genes important for the inflammatory response and those associated with cancer, including microRNAs (miRNAs). We hypothesized that NF-κB signaling differentially regulates miRNA expression through RelA and RelB to support TIC persistence. Inducible shRNA was stably expressed in OV90 cells to knockdown RELA or RELB; miR-seq analyses identified differentially expressed miRNAs hsa-miR-452-5p and hsa-miR-335-5p in cells grown in TIC versus adherent conditions. We validated the miR-seq findings via qPCR in TIC or adherent conditions with RELA or RELB knocked-down. We confirmed decreased expression of hsa-miR-452-5p when either RELA or RELB were depleted and increased expression of hsa-miR-335-5p when RELA was depleted. Either inhibiting miR-452-5p or mimicking miR-335-5p functionally decreased the stem-like potential of the TICs. These results highlight a novel role of NF-κB TFs in modulating miRNA expression in EOC cells, thus opening a better understanding toward preventing recurrence of EOC.

A Novel Alginate Film Based on Nanocoating Approach for Enteric-Release Tablets.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

Tris(4'-Nitrobiphenyl)amine─An Octupolar Chromophore with High Two-Photon Absorption Cross-Section and Its Application for Uncaging of Calcium Ions in the Near-Infrared Region.

Compounds with high two-photon absorption (2PA) performance in the near-infrared region have attracted great attention because of their application in the material and biological science. In this study, we have developed a simple and novel octupolar chromophore, tris(4'-nitrobiphenyl)amine 1, with three nitro peripheral groups attached to a triphenylamine core via biphenyl linkers. A mono-branched analogue 2 has also been prepared to investigate the effects of octupolar and dipolar systems on photophysical and 2PA behaviors. Compound 1, despite having a much simpler structure than the previous three-branched scaffolds, exhibits comparable σ2 values, reaching 1330 GM at 730 nm and 900 GM at 820 nm in toluene. Combined with an outstanding σ2/MW ratio (2.2 GM g-1 mol) and a high fluorescence quantum yield (0.51), 1 displays potential as a promising two-photon (2P) probe for bioimaging. Subsequently, the ethylene glycol tetraacetic acid-substituted derivatives featuring octupolar (3 and 5) or dipolar (4 and 6) character have been synthesized and their one-photon (1P) and 2P photochemical reactions have been examined. Finally, 1P- and 2P-triggered uncaging of Ca2+ from these calcium chelators has been confirmed.

Facile Addition of B-H and B-B Bonds to an Iron(IV) Nitride Complex.

The nitride ligand in the iron(IV) complex PhB(iPr2Im)3Fe≡N reacts with boron hydrides to afford PhB(iPr2Im)3FeN(B)H (B = 9-BBN (1), Bpin (2)) and with (Bpin)2 to afford PhB(iPr2Im)3FeN(Bpin)2 (3). The iron(II) borylamido products have all been structurally and spectroscopically characterized, demonstrating facile insertion into B-H and B-B bonds by PhB(iPr2Im)3Fe≡N. Density functional theory (DFT) calculations reveal that the quintet state (S = 2) is significantly lower in energy than the singlet (S = 0) and triplet (S = 1) states for all products. Stoichiometric reaction with (Bpin)2 does not produce the mono-borylated iron imido species PhB(iPr2Im)3FeN(Bpin). DFT calculations suggest that this is because PhB(iPr2Im)3FeN(Bpin) is unstable toward disproportionation to the starting iron(IV) nitride and PhB(iPr2Im)3FeN(Bpin)2. Attempts at B-C bond insertion using phenyl- and benzyl-pinacol borane were unsuccessful, which we attribute to unfavorable kinetics.

Dynamic Transcriptomic and Phosphoproteomic Analysis During Cell Wall Stress in Aspergillus nidulans.

The fungal cell-wall integrity signaling (CWIS) pathway regulates cellular response to environmental stress to enable wall repair and resumption of normal growth. This complex, interconnected, pathway has been only partially characterized in filamentous fungi. To better understand the dynamic cellular response to wall perturbation, a ß-glucan synthase inhibitor (micafungin) was added to a growing A. nidulans shake-flask culture. From this flask, transcriptomic and phosphoproteomic data were acquired over 10 and 120 min, respectively. To differentiate statistically-significant dynamic behavior from noise, a multivariate adaptive regression splines (MARS) model was applied to both data sets. Over 1800 genes were dynamically expressed and over 700 phosphorylation sites had changing phosphorylation levels upon micafungin exposure. Twelve kinases had altered phosphorylation and phenotypic profiling of all non-essential kinase deletion mutants revealed putative connections between PrkA, Hk-8-4, and Stk19 and the CWIS pathway. Our collective data implicate actin regulation, endocytosis, and septum formation as critical cellular processes responding to activation of the CWIS pathway, and connections between CWIS and calcium, HOG, and SIN signaling pathways.

Addition of "Septal Window" to Lower Blepharoplasty for the Management of Fat of the Lower Eyelids.

BACKGROUND: The most common reason for dissatisfaction and reoperation in lower blepharoplasty patients is persistent bulging of the lateral fat pad. This compartment contributes the most to fat herniation and yet is the most commonly overlooked. The addition of a septal window, a small opening of the septum on the most prominent part of the lateral fat compartment, helps with precise removal of lateral fat and allows for additional fat excision after septal reset without disrupting the arcuate expansion. METHODS: Our lower blepharoplasty approach includes 1) a subcilliary incision; 2) aggressive lateral fat excision through a septal window; 3) central and medial fat excision, transposition, and septal reset; 4) canthopexy; 5) orbicularis oculi muscle suspension; and 6) no dissection of orbicularis oculi medially and no skin resected medially to avoid lid retraction. We performed a retrospective review of all lower blepharoplasty cases by a single surgeon over 10 years. Demographics and operative outcomes were queried. RESULTS: There were 224 cases, 90% were women with a mean age of 58.2 years. The most common postoperative occurrences were eyelid edema, malar edema, and chemosis, all of which were self-limiting. Two patients needed additional removal of lateral fat of their lower eyelids.Two patients had lid retraction, one of which had a previous facial nerve palsy and the other did not have a canthopexy and developed transient unilateral lid retraction that resolved with conservative treatment. Resumption of full activities and exercises at 6 weeks was typical. CONCLUSION: The septal window facilitates aggressive resection of the lateral fat pad and additional fat excision after septal reset to create a smooth lid-cheek junction. In our practice, it is a critical component of a successful lower blepharoplasty.

Sodium-Glucose Cotransporter 2 Inhibitor Use Associated With Fournier's Gangrene: A Review of Case Reports and Spontaneous Post-Marketing Cases.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective for glycemic control and have demonstrated cardiorenal benefits. The U.S. Food and Drug Administration (FDA) released a boxed warning in 2018 regarding the potential development of Fournier's gangrene (FG) with the use of SGLT2 inhibitors. FG is a serious perineal infection with a mortality rate of up to 88% in some cases. OBJECTIVES: To report spontaneous post-marketing cases from the FDA Adverse Event Reporting System (FAERS) database and case reports from the literature of FG associated with the use of SGLT2 inhibitors and to determine whether correlations exist with specific agents. METHODS: A search of the FAERS database was conducted to identify reported cases of FG associated with the use of any FDA-approved SGLT2 inhibitor between 1 March 2013 and 30 June 2020. Additionally, a literature search was conducted of PubMed, Embase, and the Cochrane library using PRISMA guidelines to identify case reports of FG with the use of SGLT2 inhibitors up to 9 October 2020. RESULTS: A total of 491 cases from the FAERS database were included for review. Descriptive analysis depicted more cases in the empagliflozin, canagliflozin, and dapagliflozin groups than in the ertugliflozin group. Nine case reports were included from the literature review; four attributed to dapagliflozin, three to empagliflozin, and two to canagliflozin. The median ages from cases reported in the FAERS database and from the literature review were 54 and 52 years, respectively. In both datasets, males had a higher incidence of FG than females. Additional data reported include clinical outcomes and concomitant antihyperglycemic medications. CONCLUSION: Consistent findings are noted in this systematic review and warrant further investigation to elucidate the association between SGLT2 inhibitor use and the development of FG. These results may drive enhanced prescribing patterns to consider patient-specific risk factors and timely monitoring, especially as more indications are approved related to these medications' cardiorenal protective properties.

Safety and Efficacy of Third-Generation Ultrasound-Assisted Liposuction: A Series of 261 Cases.

BACKGROUND: The introduction of third-generation ultrasound-assisted liposuction (3rd UAL) allows for a less invasive modality of both deep and superficial lipectomy while offering improved skin retraction and reduced rate of complications. This study examined the efficacy and safety profile of this technology over 15 years of clinical experience. METHODS: A consecutive series of patients treated from 2005-2020 by the senior author were reviewed for demographic and anthropometric measurements, intraoperative settings, surgical outcomes, and complications via retrospective chart review. Body-Q survey was used to assess patient satisfaction. RESULTS: A total of 261 patients underwent 3rd UAL in 783 areas. There were 238 female and 23 male patients with an average age of 43.5 years and BMI of 27.4 kg/m2. The most frequently treated areas were the trunk and lower limbs. An average of 2840 mL of wetting solution was used with an average of 2284 mL of lipocrit aspirate. About 65% of the cases were done in conjunction with another procedure. Overall complication rate was 4.6%, contour irregularity (1.9%), seroma (0.8%), cellulitis (0.8%), pigmentation changes (0.4%), and electrolyte imbalance (0.4%), with a minimum follow-up of 6 months. 78% of patient would undergo the procedure again and 86% would recommend it. CONCLUSION: Third-generation ultrasound-assisted liposuction can be used effectively and safely, either alone, or in conjunction with other plastic surgery procedures. VASER liposuction allows surgeons to address superficial fat plane and enhanced skin tightening. Rate of complications are lower than that of traditional liposuction with equivalent or higher patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Alteration of macrophage immune phenotype in a murine sepsis model is associated with susceptibility to secondary fungal infection.

BACKGROUND: Secondary fungal infection is a major complication in patients with sepsis-associated immunosuppression. However, sepsis-induced immune alterations related to fungal susceptibility have not been well characterized. OBJECTIVES: To determine kinetic changes in the immune phenotype by determining the proportion of T cells, B cells and macrophages, and especially the expression of an immune exhaustion marker PD-1, in murine sepsis. In addition, sepsis -induced alterations of these immune cells were assessed in relation to susceptibility to secondary fungal infection. METHODS: Cecal ligation and puncture (CLP) was used as a mouse sepsis model, with Candida albicans as the secondary systemic fungal infection. Splenic T cells, B cells and macrophages were assessed by flow cytometry. RESULTS: Alterations in T cell and B cell numbers and the proportion of PD-1 expressing T cells and B cells in CLP mice were not clearly related to susceptibility to secondary Candida infection. By contrast, changes in levels of CD86+-activated macrophages, and the proportion of the PD-1+ population among the CD86+ macrophages in CLP mice were found to be related to secondary fungal infection susceptibility. CONCLUSIONS: Macrophage activation and exhaustion might be a significant determinant in susceptibility to fungal infection, and outcomes of infection. This study provided more comprehensive knowledge pertinent to patient evaluation and therapeutics design in restoring host defenses against secondary fungal infection in those with sepsis.

[Major advancement in Ophthalmology in 2021]. / Ophtalmologie.

This year, we are seeing a major boost in the advancement of new targeted gene therapies in the fight against certain orphan ocular genetic diseases that cause blindness. The progressive introduction of computer tools with algorithms for the recognition of diabetic retinopathy should be noted. Progress has been made in other areas of ophthalmology, with particular interest in the fight against myopia, given the worrying and rapidly increasing incidence of this disease, in varying proportions throughout the world. There has also been a major effort to develop new ways of delivering specific ocular treatments without having to rely on patient compliance. Finally, we are discovering new diagnostic and clinical entities related to the side effects of systemic immunotherapy generally used in oncology.

Cette année, nous constatons un élan important dans l'avènement de nouvelles thérapies géniques ciblées dans la lutte contre certaines maladies génétiques orphelines oculaires, responsables de cécité. Relevons l'introduction progressive d'outils infor matiques dotés d'algorithme permettant une reconnaissance automatisée de la rétinopathie diabétique. Des avancées sont à relever dans la lutte contre la myopie, véritable problème de santé publique vu l'incidence inquiétante et en forte augmentation dans le monde. Ajoutons aussi un effort important dans le développement de nouveaux moyens de délivrer des traitements oculaires spécifiques sans faire appel à la compliance du patient. Finalement, nous découvrons de nouvelles entités diagnostiques et cliniques liées aux effets secondaires d'immunothérapie systémique utilisée en oncologie.