Search

Gain-of-function (GOF) variants give rise to increased/novel protein functions whereas loss-of-function (LOF) variants lead to diminished protein function. Experimental approaches for identifying GOF and LOF are generally slow and costly, whilst available computational methods have not been optimized to discriminate between GOF and LOF variants. We have developed LoGoFunc, a machine learning method for predicting pathogenic GOF, pathogenic LOF, and neutral genetic variants, trained on a broad range of gene-, protein-, and variant-level features describing diverse biological characteristics. LoGoFunc outperforms other tools trained solely to predict pathogenicity for identifying pathogenic GOF and LOF variants and is available at https://itanlab.shinyapps.io/goflof/ ., (© 2023. The Author(s).)

This study aimed to investigate the inhibitory effect of 12- epi -napelline on leukemia cells and its possible mechanisms. The inhibitory effects of 12- epi -napelline on K-562 and HL-60 cells were evaluated using the CCK-8 assay, cell cycle arrest and apoptosis were detected by flow cytometry, and the expression of related proteins was measured by western blot. A K-562 tumor model was established to evaluate the antitumor effect of 12- epi -napelline in vivo . A reduction in leukemia cell viability was observed after treatment with 12- epi -napelline. It was determined that the cell cycle was arrested in the G 0/ G 1 phase, and the cell apoptosis rate was increased. Moreover, caspase-3 and Bcl-2 were downregulated, whereas cleaved caspase-3 and caspase-9 were upregulated. Further study revealed that 12- epi -napelline could suppress the expression of PI3K, AKT, p-AKT, and mTOR. Insulin-like growth factor 1 (IGF-1) attenuated 12- epi -napelline-induced apoptosis and ameliorated the repression of PI3K, AKT, p-AKT, and mTOR by 12- epi -napelline. Animal experiments clearly showed that 12- epi -napelline inhibited tumor growth. In conclusion, 12- epi -napelline restrained leukemia cell proliferation by suppressing the PI3K/AKT/mTOR pathway in vitro and in vivo., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Jia Han et al.)

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-sensitive mutations benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR- TKIs). However, drug resistance is a major cause of therapeutic failure. This study examined whether saikosaponin-d (SSD) enhances the anti-tumor effect of gefitinib in NSCLC cells. Cell Counting Kit-8 (CCK-8) was used to determine cell viability. Cell apoptosis was examined by flow cytometry. Signal transducer and activator of transcription (STAT3), phosphor-STAT3 (P-STAT3), and B-cell lymphoma 2 (Bcl-2) were detected by Western blot. An HCC827/GR tumor model was established to observe the effect of combination therapy in vivo. The combination of SSD with gefitinib had an enhanced inhibitory effect by reducing cell viability and inducing cells apoptosis in NSCLC cells. Furthermore, SSD decreased and increased the expression of P-STAT3 and Bcl-2, respectively. Down-regulated STAT3 promoted the sensitivity of lung cancer cells to gefitinib. The results of animal experiments also showed that SSD enhanced the anti-tumor effect of gefitinib. These results indicated that the combination of SSD with gefitinib had an increased antitumor effect in NSCLC cells and that the molecular mechanisms were associated with the inhibition of STAT3/Bcl-2 signaling pathway. Our findings suggest a promising approach for the treatment of NSCLC patients with EGFR-TKI resistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The lack of autograft donor site is one of the greatest limiting factors for the treatment of extensive burn. Micrografting is an important revolution in burn surgery where autografts are cut into small pieces for wide and rapid coverage of burn wound. Our early experiences with the current standard micrografting technique were fraught with poor graft take as well being time and labor intensive. We have improvised our technique, where we combined the use of allograft to serve as a carrier for the micrograft. The objective of this paper is to share our experience in micrografting and several technical tips which had enhanced our micrografting results. The improvisation in our technique includes: (1) Single-stage 'micrograft-allograft sandwich method' where allograft served as a direct carrier for the micrografts. Micrografts were laid uniformly 1cm apart onto allograft sheets, creating a 1:9 expansion ratio. This technique replaced the original two stage method. (2) The use of the Meek device (Humeca, Netherlands) to prepare micrograft. The Meek device can rapidly produce 3mm micrografts for easy transfer with a fine forceps. (3) The use of slow-acting fibrin sealant to promote graft take and hemostasis. (4) A two-team approach for micrograft preparation where one team processes micrograft and another prepares the allograft sheets. This reduces the lag time between micrograft preparation and grafting, and reduces the overall surgery time. Micrografting remains an important treatment for major burn surgery. The aim of micro-allograft combination is to allow autografts re-epithelization under a reliable temporary skin coverage in a single stage procedure. A prospective study is warranted to measure the objective outcome of this renewed technique., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Objective: Diabetic burns patients may be at risk of worse clinical outcomes. This study aims to further investigate the impact of diabetes mellitus on clinical outcomes in burns patients in Singapore., Methods: A 3-year retrospective review was performed at the Singapore General Hospital Burns Centre (2011-2013). Pure inhalational burns were excluded. Diabetic (N=53) and non-diabetic (N=533) patients were compared, and the impact of diabetes on clinical outcomes, adjusting for confounders, was investigated using multivariate logistic regression., Results: The diabetic group had a significantly higher incidence of wound infection and severe renal impairment, as well as a longer length of stay, higher number of operations and higher rate of unplanned readmission. ICU admission was significantly associated with hyperglycaemia (OR 5.44 [2.61-11.35], p<0.001) and a higher total body surface area of burn (OR per 1% TBSA 1.07 [1.05-1.09], p<0.001). Unplanned readmission was significantly associated with wound infection (OR 4.29 [1.70-10.83], p=0.002), and mortality associated with a higher TBSA (OR per 1% TBSA 1.1 [1.07-1.14], p<0.001). After adjusting for confounders, diabetes mellitus was not significantly associated with unplanned readmission or mortality., Conclusions: Diabetic burns patients have an increased risk of worse clinical outcomes, including wound infections, renal impairment and longer length of stay., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: Singapore General Hospital (SGH) is a regional burns centre in Southeast Asia and is the only dedicated burns facility providing specialized burns care in Singapore., Methods: A cohort study was performed for burns patients admitted to SGH from 2011 to 2013. We compared our data with earlier studies and observed the trends of burns epidemiology in Singapore. Results were analyzed using the SPSS programme., Results: 655 patients were admitted during this study period, a 35.9% increase from 2003 to 2005. Scalding by water and flame injury remain the top causes of burns and the mean extent of burn is 9.5%. TBSA correlates with the incidence of burn infection, bacteremia and mortality. Patients with ≥20% TBSA are at a higher risk of bacteremia, and ≥ 34% TBSA is a predictor of mortality. 4.9% (n=32) of our patients developed bacteremia. Bacteremia was associated with a surgical duration of ≥80min. Patients with bacteremia incurred longer hospitalization, and had higher mortality rates. Overall mortality rate of our burns patients has decreased from 4.5% to 2.7% (n=18). Key factors of mortality include inhalational injury, bacteremia and ≥20% TBSA., Conclusion: This is a large epidemiology study of a tropical region burns centre. A total of 655 burns cases over a 3-year period were analyzed. We analysed the key factors associated with adverse outcomes including burns infection, bacteremia and mortality, factors associated with mortality, and discussed strategies on the optimization of burns care., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

The management of extensive burns with their associated high fluid exudate following burn excision and skin grafting has always posed a challenge in burn wound care. The ideal dressing should protect the wound from physical damage and micro-organisms; be comfortable and durable; allow high humidity at the wound; and be able to allow maximal activity for wound healing without retarding or inhibiting any stage of the process. The dressing technique described in this paper fulfils all the criteria above and at the same time provides an efficient channel to effectively clear the excessive exudate produced while keeping the wounds moist. Advantages conferred include accurate charting of wound exudate; reduced frequency of dressing changes; lower infection rates through prevention of strike-through; and securing and improving the viability of skin grafts. An enhancement to a technique previously described by us through the use of long thin strips of VAC sponges to transmit negative pressure, the enhanced Total Body Wrap aims to provide ideal conditions to promote healing in burns. Using negative pressure wound therapy (NPWT), this technique is simple and straightforward enough to be applied in majority of tertiary centres around the world., (Copyright © 2013. Published by Elsevier Ltd.)

Background and Aims: Studies investigating hyperbaric oxygen treatment (HBOT) to improve outcome in burns have been inconclusive. In this study, we aimed to characterize early thermal burns injury in adult patients with < 40% total body surface area (TBSA) and to determine the effects of HBOT administered within 24 h to 48 h of a burn injury., Methods: Seventeen subjects were randomized into control (n = 9) and HBOT treatment (n = 8) arms. Burn depth, measured by laser Doppler imaging (LDI) and histologically, white blood cell (WBC) count and plasma cytokine inflammatory markers were assessed at 24 h (pre HBOT) and 48 h (post HBOT) post burn, as were immunohistochemistry and microbiology of burns tissue samples at 48 h post burn., Results: WBC count and serum interleukin (IL)-1β, IL-4, IL-6, IL-10 and interferon-γ were significantly elevated 24 h after burn, but no significant changes in any of these parameters were found with HBOT. HBOT had no significant effect on burn depth. Two HBOT patients and four control patients developed positive bacterial cultures., Conclusions: Slower than anticipated recruitment resulted in considerably fewer patients than planned being studied. Inflammatory markers were significantly increased at 24 h in patients with < 40% TBSA burn. Early HBOT had no apparent effects on any of the parameters measured in this small pilot study. HBOT may possibly have a broad-spectrum antimicrobial effect worthy of further study. We report our methodology in detail as a possible model for future burns studies.

Accessory axillary breast tissue can be fairly common occurring in 2-6% of women. Treatment modalities thus far include direct excision as well as liposuction. While direct excision allows for accessible and adequate tissue resection, it results in long unsightly scars and the creation of significant amount of dead space. This may be complicated by seroma and haematoma formation. Liposuction is not without its drawbacks either. It is often very difficult to remove fibro-glandular breast tissue resulting in inadequate excision, thus leaving behind a visible core of breast tissue. This has led some surgeons to use a combination of direct excision and liposuction to manage accessory axillary breast tissue. Hence, we present the use of the microdebrider for sharp and precise excision of accessory axillary breast tissue. This day procedure can be performed through a single 5-mm incision which is well hidden in the axillary skin folds while allowing the operator the amount of control needed to accurately remove fibro-glandular breast tissue and restore an aesthetically pleasing contour to the axilla., (Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Both negative wound pressure therapy (NPWT) and hyperbaric oxygen therapy (HBOT) are useful modalities in the treatment of problem wounds. However, none of the commercially available portable negative-pressure devices have been certified safe for use in a recompression chamber. Thus, the NPWT device is removed while the patient undergoes HBOT. The purpose of this study is to demonstrate that wound negative pressure can be effectively and safely maintained during HBOT., Patients and Methods: In a small, prospective, randomised crossover trial, we used commonly available clinical materials to connect the NPWT suction tubing to the negative suction generating device in the hyperbaric chamber. Six patients each underwent one HBOT session with continuous NPWT and one HBOT session without concurrent NPWT. We assessed the patient's pain score, the amount of exudate aspirated by the NPWT during HBOT, and the appearance of the wound dressing after each session was assessed in a blinded manner., Results: There were no differences in pain scores between the two HBOT sessions. The amount of exudate aspirated during HBOT with NPWT ranged from 5 to 12 ml. Five of the six patients had a better appearance scoring of their dressing when NPWT was maintained during HBOT (P = 0.006)., Conclusion: We successfully demonstrated a simple design that allows the maintenance of NPWT during HBOT without causing additional pain, and with continued extraction of exudate. The maintenance of NPWT during HBOT also allowed the dressing to be maintained undisturbed.

The regioselective palladium-catalyzed formate reduction of allylic acetates in five- to eight-membered heterocycles is reported. Reduction of allylic acetates under mild conditions using allylpalladium chloride dimer, phosphines, and formic acid/triethylamine in DMF gives the exo-cyclic olefins in good regioselectivities and high yields. Synthetic application in preparing N-tosyl-3-oxo-piperidine is also reported.

Thirty Chinese primiparous mothers were asked during the antenatal period their breastfeeding intention and then interviewed at delivery and 6 weeks post delivery. One mother had no intention to breastfeed. Ten mothers intended exclusive breastfeeding for one month and 19 for 6 weeks or more. At 6 weeks post delivery only 4 mothers were still breastfeeding. A total of 22 (73%) did not achieve their initial intention. For any future pregnancy, 5 chose exclusive breastfeeding, 22 complementary and 3 formula feeding. Chinese primiparous mothers have high breastfeeding intentions but the majority do not achieve them and their experience has discouraged them from exclusive breastfeeding in future pregnancies.