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SQSTM1/p62 droplets play crucial roles in droplets-based macroautophagy/autophagy including selective autophagy and bulk autophagy. We observed that under several stress milieus, SQSTM1 droplets entirely colocalize with P-body markers, and these stress-induced SQSTM1 droplets contain mRNAs. We thus determined that under certain stress conditions, autophagic SQSTM1 droplets are converted to a type of enlarged P-bodies, designated SQSTM1/p62-dependent P-bodies (pd-PBs). Stress-enhanced SQSTM1 droplet formation drives the nucleation of pd-PBs through the interaction between SQSTM1 and the RNA-binding protein DDX6. Furthermore, pd-PBs sequester PYCARD, facilitating the assembly of NLRP3 inflammasomes, and in turn induce inflammation-related cytotoxicity. Our study suggests that under stress settings, autophagic SQSTM1 droplets are transformed to pd-PBs, underlining a critical role of SQSTM1 in P-body condensation.

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs). p62 phase separation is essential for the nucleation of pd-PBs. Mechanistically, pd-PBs are triggered by enhanced p62 droplet formation upon stress stimulation through the interactions between p62 and DDX6, a DEAD-box ATPase. Functionally, pd-PBs recruit the NLRP3 inflammasome adaptor ASC to assemble the NLRP3 inflammasome and induce inflammation-associated cytotoxicity. Our study shows that p62 droplet-to-PB transformation acts as a stress response to activate the NLRP3 inflammasome process, suggesting that persistent pd-PBs lead to NLRP3-dependent inflammation toxicity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hand infections are a common reason for presenting to hospital and can be associated with significant morbidity and prolonged antibiotic use. Factors recognized to influence patient outcomes include resistant organisms and delayed presentation. Surgeons working around Australia may assume that hand infections and appropriate treatment algorithms will be similar between sites. This is the first study to examine differences between hand infections presenting in Darwin (with its tropical climate) vs. those in a more temperate city (Adelaide)., Methods: This is a two-site retrospective study, where diagnostic discharge codes were used to identify cases for a 12-month period and patient age, sex and rurality, duration of hospital stay, microbiology results and subsequent trips to theatre were reviewed., Results: Despite significant differences in rurality between FMC and RDH patients, there was no significant difference in length of hospital stay, duration of intravenous antibiotics or return trips to theatre across the two sites. RDH reported a 25% rate of MRSA, compared to 18% at FMC, as well as a statistically significant increase in uncommon microbes, with 30% compared to 12% of patients growing microbes that may not be covered by antibiotics routinely administered in metropolitan areas. A limitation of this study was that compliance with antibiotics and hospital stay were not accounted for., Conclusion: It is often our training years that determine our norms of everyday practice, but fewer Australian surgical training posts are located in tropical centres. The results of this study highlight the importance of not assuming that the spectrum of organisms causing hand infections are the same as that in the surgeons' state of origin., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Purpose: To evaluate the risk factors for the development of concurrent or delayed-onset rhegmatogenous retinal detachment (RRD) related to endophthalmitis as well as the anatomic and visual outcomes with subsequent RRD repair. Methods: In this retrospective case study, a 2-tailed t test (continuous) and Fisher exact test were used to determine statistical significance of the observed findings. The relative risk (RR) and 95% CIs were calculated to assess statistical significance. Results: Of the 170 patients included, 22 were found to have a concurrent or subsequent RRD. Initial treatment with pars plana vitrectomy (PPV) (RR, 3.544; 95% CI, 1.650-7.614), aphakia (RR, 4.150; 95% CI, 1.434-12.011), endogenous endophthalmitis (RR, 2.684; 95% CI, 1.065-6.764), and posterior synechiae (RR, 3.026; 95% CI, 1.408-6.505) were statistically significant risk factors for RRD. Anatomically successful repair was achieved in 77.7% of patients. Conclusions: In addition to preexisting risk factors, the initial treatment of endophthalmitis may be a significant risk factor for RRD development, with a higher incidence of subsequent RRD in patients who have PPV as the initial treatment for endophthalmitis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Women with larger breasts tend not to participate in high-intensity exercise and exercise less frequently. This study investigates how breast size impacts exercise habits and how breast reduction surgery changes women's participation in recreational exercise. Recruitment was generated via parkrun Limited (Richmond, UK), an organization offering weekly community-based runs. Female parkrun members aged over 18 years with no history of breast cancer were invited to complete a survey, including questions about their exercise habits, breast size, any breast alteration surgery, and BREAST-Q questionnaires. A total of 1987 women completed the survey, including 56 women who had undergone breast reduction. Results demonstrate that women with bigger breasts believe that reducing their breast size would improve their exercise performance and participation and that their breast size significantly impacts their type of exercise. Women who had undergone breast reduction reported increased overall frequency, enjoyment, and willingness to exercise in a group. Additionally, women that have undergone breast reduction report higher BREAST-Q scores than their non-surgical counterparts. This study supports the existing literature that breast size can impact exercise habits and demonstrates that women who have undergone breast reduction participate in healthier lifestyle practices. We suggest that if breast size impacts women's participation in sport and fitness, health practitioners and policymakers should advocate for better access to reduction mammoplasty in the publicly funded health sector., (© 2023 The Authors.)

Background: The rotation flap approach (RoFA) mastectomy is a skin-sparing technique that actively imports skin to the centre of the skin envelope and therefore aids in achieving natural ptosis to the reconstructed breast. The objective of this study was to compare clinical outcomes, aesthetics, patient satisfaction and health-related quality of life between the ROFA mastectomy and standard mastectomy approach., Methods: This study is a prospective randomised controlled trial of participants undergoing mastectomy using either the RoFA technique or standard technique with breast reconstruction. The BREAST-Q was administered pre-operatively and at 3-, 6-, 9- and 12-months following mastectomy. A panel assessment of clinical photographs was conducted to score aesthetics and outcomes of reconstruction., Results: A total of 100 participants were enrolled in the study; of these, 51 underwent RoFA incision, 47 underwent standard incision and 2 were lost to follow up. There were no statistically significant differences in BREAST-Q scores or panellist assessment between the mastectomy groups following breast reconstruction. The post-operative incidence of mastectomy skin flap tip necrosis was high in the RoFA incision group, with rates of other complications such as seroma being similar., Conclusion: The RoFA skin-sparing mastectomy incision showed no significant difference in results across patient-reported outcomes or aesthetics when compared to the standard approach, however, did rate higher for skin flap tip necrosis., (© 2022 Royal Australasian College of Surgeons.)

SQSTM1/p62 is an autophagy receptor, forming droplets to sequester intracellular polyubiquitinated cargo and mediate its delivery for autophagic clearance. SQSTM1 droplets can function as platforms to allow the formation of autophagosomes at their surfaces. It would be interesting to understand how SQSTM1-droplet formation is regulated. We have shown that inflammatory toxicity induces SQSTM1 cleavage by CASP6 at a novel cleavage site, D256. The C-terminal cleavage product is unlikely to be functional, because it is hardly detectable, possibly due to its rapid turnover. The SQSTM1 N-terminal cleavage product (SQSTM1-N) exerts a dominant-negative effect on SQSTM1-droplet production, in turn attenuating SQSTM1 droplets-based autophagosome formation. Our study suggests that the CASP6-SQSTM1 axis negatively regulates SQSTM1 droplets-based autophagy under certain stress conditions.

Genetic screens are a powerful approach to identify previously uncharacterized genes involved in specific biological processes. Several technologies have been developed for high-throughput screens using reagents such as RNAi or CRISPR, and each approach is associated with specific advantages and disadvantages. Variable Dose Analysis (VDA), is an RNAi-based method developed in Drosophila cells that improves signal-to-noise ratio compared to previous methods. VDA assays are performed by co-transfecting cells with a plasmid expressing shRNA, (a type of RNAi that can be easily expressed from a DNA plasmid) against a gene of interest and a second plasmid expressing a fluorescent reporter protein. Fluorescent protein expression, can be used as an indirect readout of shRNA expression and therefore target gene knockdown efficiency. Using this approach, we can measure phenotypes over a range of knockdown efficiencies in a single sample. When applied to genetic interaction screens, VDA results in improved consistency between screens and reliable detection of known interactions. Furthermore, because phenotypes are analyzed over a range of target gene knockdown efficiencies, VDA allows the detection of phenotypes and genetic interactions involving essential genes at sub-lethal knockdown efficiency. This therefore represents a powerful approach to high-throughput screening applicable to a wide range of biological questions., Competing Interests: Competing interestsThe authors have nothing to disclose., (Copyright © 2018 The Authors; exclusive licensee Bio-protocol LLC.)

Prophylactic hemodialysis has been employed in the treatment of 15 patients with acute renal failure due to acute tubular necrosis (12), bilateral renal cortical necrosis (two), and poststreptococcal glomerulonephritis (one). Dialyses, usually lasting six hours each, were begun before clinical evidence of uremia developed in each patient and/or before the nonprotein nitrogen reached 200 mg.%, and were repeated daily or often enough to maintain the nonprotein nitrogen below 150 mg.%. The hypothesis underlying this technic postulates (1) that wasting, sepsis and impaired wound healing in these patients may reflect tissue injury by the same dialyzable toxic agents which produce the uremic symptoms that are readily reversible by dialysis, and (2) that repeated dialyses should therefore prevent both clinical uremia and the later, often lethal sequelae. The results contrast dramatically with our own past experience in treating patients with acute renal failure with a carefully executed medical regimen together with hemodialysis on conventional indications. Except in one instance of crush injury with progressive intracerebral damage, and one brief occasion in another individual, these patients experienced a stable, convalescent clinical course, remained free of uremic symptoms or chemical imbalances, ate at least three meals daily which were unrestricted in amount and composition, and were ambulatory between dialyses unless confined to bed by associated disease. Wounds healed well. Infection either did not occur, or subsided after appropriate therapy. Fluid restriction was liberalized by means of ultrafiltration with dialysis. Regional heparinization of only the extracorporeal circuit eliminated actual or impending bleeding as a contraindication to dialysis. Chronic vessel cannulation made the frequent dialyses possible, but may have provided the route for repeated, transient bacterial contamination of the blood stream in the first hour of many dialyses. Marked anemia, despite reticulocytosis, moderate to mild weight loss and some mental deficit persisted in spite of the general clinical improvement and well-being. Three patients with tubular necrosis died after seven, 11 and 26 days of oliguria; both patients with bilateral renal cortical necrosis also succumbed, on the seventy-third and ninety-second days of renal failure, and after 29 and 40 dialyses, respectively. At autopsy, evidence of sepsis was conspicuously absent. The remaining 10 patients survived. Thus some, but not all, clinical manifestations of acute renal failure appear to be favorably influenced by prophylactic dialysis treatment. Our initial experience in this group of 15 patients does not of course prove that freedom from complications and a significantly better outlook for survival can be assured to patients with acute renal failure by these methods. However, it seems to offer a reasonable hope of this possibility which we cannot attach to management by medical measures alone, or by dialysis on conventional indications. If this hope is realized in greatly extended, subsequent series, then it seems inevitable that some form of prophylactic dialysis, or some equally effective alternative, should be adopted in treating the majority of patients with acute renal failure.

The effects of burn injury (30% of total body surface area) on the levels of oxidized and reduced glutathione, malondialdehyde, and on the activities of certain glutathione-dependent enzymes, have been determined in tissues of rabbit models. Thus, the malondialdehyde, glutathione (GSH), glutathione disulfide (GSSG) concentrations and the specific activities of glutathione peroxidase, glutathione S-transferase, and glutathione reductase were measured in liver and lung of 24-h burn rabbit models and compared to the corresponding values in 24-h sham burn (medicated, anesthetic/analgesic) rabbit models. It was found that the concentrations of malondialdehyde in liver and lung of burn models were increased by 17% and 29% respectively. Glutathione concentrations were decreased by 29% in liver and 13% in lung, and glutathione disulfide concentrations were increased by 35% in liver and 33% in lung, in burn versus sham burn models. It was also found that the specific activities of glutathione peroxidase decreased significantly, resultant to burn injury, by an average of 35% and 27% in liver and lung, respectively. Burn injury also decreased glutathione S-transferase specific activities by 14% in liver and 23% in lung tissues. In contrast, glutathione reductase specific activity was increased in liver tissues (22%), but was decreased (19%), as with the other enzymes studied, in lung tissues of burn models. Control model studies (no medication, no sham burn) show that these effects of burn injury are additional to effects elicited by medication associated with sham burn models. The data of this study are indicative of a major oxidative stress in liver and lung tissues due to burn injury at a remote site.

The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.

In this article we develop a calculation or formula for use in determining the potential dilution effect of fluids administered during patient treatment on serologic testing parameters. The formula uses basic principles of (a) fluid distribution over time from administration; (b) ratios of plasma and extravascular fluid volumes to body weight; and (c) common practices of fluid resuscitation. A dilution threshold of 50% was set using data from enzyme-linked immunosorbent assay human immunodeficiency virus antibody determinations performed on in vitro diluted seropositive serum samples. These data respond to issues raised by guidelines from the Centers for Disease Control and the U.S. Food and Drug Administration to achieve recipient safety without unnecessarily restricting the potential donor pool.

Two catalytically active proteases, dipeptidyl peptidase IV (DP IV) and aminopeptidase (AP), not previously reported as present in burn wound exudates, have been identified by substrate specificity and susceptibility to known enzyme inhibitors. The ratio of the two enzymes in exudates is significantly different from the ratio in plasma collected from the same patient during the same time interval, suggesting that measurement of exudate components may be more significant than plasma activities in evaluating local conditions in the wound. A number of biologically significant substances are DP IV substrates, and the list can be considerably extended by the sequential action of AP and DP IV. Some polypeptides are converted to their biologically active form by DP IV action, while others are degraded to inactive forms. Either action generates X-Pro dipeptides, which have a demonstrably beneficial effect on wound healing. Although not resolved by molecular sizing or anion exchange chromatography, DP IV and AP in a burn wound exudate were purified by affinity chromatography.