CT-guided pretreatment biopsy diagnosis in patients with thymic epithelial tumours: diagnostic accuracy and risk of seeding.

AIM: To investigate the diagnostic performance of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) for thymic epithelial tumours (TETs) and the complication rate after PTNB including seeding after PTNB. MATERIALS AND METHODS: This retrospective study identified PTNBs for anterior mediastinal lesions between May 2007 and September 2021. The diagnostic performance for TETs and complications were investigated. The concordance of the histological grades of TETs between PTNB and surgery was evaluated. The factors associated with pleural seeding after PTNB were determined using Cox regression analysis. RESULTS: Of 387 PTNBs, 235 PTNBs from 225 patients diagnosed as TETs (124 thymomas and 101 thymic carcinomas) and 150 PTNBs from 133 patients diagnosed as other than TETs were included. The sensitivity, specificity, and accuracy for TETs were 89.4% (210/235), 100% (210/210), and 93.5% (360/385), respectively, with an immediate complication rate of 4.4% (17/385). The concordance rate of the histological grades between PTNB and surgery was 73.3% (77/105) after excluding uncategorised types of thymomas. During follow-up after PTNB (median duration, 38.8 months; range, 0.3-164.6 months), no tract seeding was observed. Pleural seeding was observed in 26 patients. Thymic carcinoma (hazard ratio [HR], 5.94; 95% confidence interval [CI], 2.07-17.08; p=0.001) and incomplete resection (HR, 3.29; 95% CI, 1.20-9.02; p=0.02) were associated with pleural seeding, while the biopsy approach type (transpleural versus parasternal) was not associated (p=0.12). CONCLUSIONS: Pretreatment biopsy for TETs was accurate and safe and may be considered for diagnosing TETs, particularly when the diagnosis is challenging and histological diagnosis is mandatory.

Fructose: A New Variable to Consider in SIADH and the Hyponatremia Associated With Long-Distance Running?

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be involved in some cases of vasopressin-induced hyponatremia, especially in situations where the cause is not fully known such as in the syndrome of inappropriate secretion of diuretic hormone (SIADH) and exercise-associated hyponatremia, which has been observed in marathon runners. Here we discuss the new science of fructose and vasopressin, and how it may play a role in some of these conditions, as well as in the complications associated with rapid treatment (such as the osmotic demyelination syndrome). Studies to test the role of fructose could provide new pathophysiologic insights as well as novel potential treatment strategies for these common conditions.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair.

In mammalian cells, the bulky DNA adducts caused by ultraviolet radiation are mainly repaired via the nucleotide excision repair (NER) pathway; some defects in this pathway lead to a genetic disorder known as xeroderma pigmentosum (XP). Ribosomal protein S3 (rpS3), a constituent of the 40S ribosomal subunit, is a multi-functional protein with various extra-ribosomal functions, including a role in the cellular stress response and DNA repair-related activities. We report that rpS3 associates with transcription factor IIH (TFIIH) via an interaction with the xeroderma pigmentosum complementation group D (XPD) protein and complements its function in the NER pathway. For optimal repair of UV-induced duplex DNA lesions, the strong helicase activity of the TFIIH complex is required for unwinding damaged DNA around the lesion. Here, we show that XP-D cells overexpressing rpS3 showed markedly increased resistance to UV radiation through XPD and rpS3 interaction. Additionally, the knockdown of rpS3 caused reduced NER efficiency in HeLa cells and the overexpression of rpS3 partially restored helicase activity of the TFIIH complex of XP-D cells in vitro. We also present data suggesting that rpS3 is involved in post-excision processing in NER, assisting TFIIH in expediting the repair process by increasing its turnover rate when DNA is damaged. We propose that rpS3 is an accessory protein of the NER pathway and its recruitment to the repair machinery augments repair efficiency upon UV damage by enhancing XPD helicase function and increasing its turnover rate.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Initial experience with a suprapubic single-port robotic right hemicolectomy in patients with colon cancer.

BACKGROUND: We developed a novel suprapubic single-port robotic right hemicolectomy (spRHC) procedure for patients with right colon cancer using a da Vinci SP Surgical System. The aim of this study was to determine the safety and feasibility of this technique. METHODS: We performed the spRHC procedure on five patients with right colon cancers between July and September 2020. All procedures including colon mobilization, D3 lymphadenectomy, and intracorporeal anastomosis were completed using the single-port robotic platform through a mini-transverse suprapubic incision and an additional assistant port. Data regarding patient characteristics, perioperative outcomes and pathologic results were analyzed. RESULTS: Four of the five patients were males. The median age was 69 years (range, 58-77 years).Two patients received preoperative chemotherapy for advanced colon cancer. The median total operative time was 160 min (range, 150-240 min). The median docking time was 4 min 40 s (range, 2 min 10 s-5 min 10 s). The median console time was 105 min (range, 100-120 min). There were no conversions to multiport or open surgeries. The median hospital stay was 7 days (range, 5-12 days). One patient experienced a wound infection. The median number of harvested lymph nodes was 41 (range, 39-50 lymph nodes). CONCLUSIONS: SpRHC is safe and feasible. However, further comparative studies are needed to assess whether this procedure can provide patients with significant benefits compared with multiport robotic surgery.

An initial experience with a novel technique of single-port robotic resection for rectal cancer.

BACKGROUND: The da Vinci single-port (SP) system is designed to facilitate single-incision robotic surgery in a narrow space. We developed a new procedure of rectal resection using this system. The aim of the present study was to evaluate the technical feasibility and safety of SP robotic rectal resection for rectal cancer patients based on our initial experience. METHODS: A study was conducted on consecutive patients with mid or low rectal cancer who had SP robotic resection at our institution between July and September 2020. The demographic characteristics, perioperative data, and pathology results of the patients were retrospectively analyzed. RESULTS: There were 5 patients (3 males, 2 females, median age 57 years (range 36-73 years). The median tumor height from the anal verge was 4 cm (range 3-5 cm). Two patients received preoperative chemoradiotherapy for advanced rectal cancer. A single docking was conducted, and the median docking time was 4 min 20 s (range 3 min 30 s to 5 min). The median total operation time was 195 min (range 155-240 min), and the median time of pelvic dissection was 45 min (range 36-62 min). All patients had circumferential and distal tumor-free resection margins. One patient experienced an anastomosis-related complication. The median duration of hospital stay was 7 days (range 7-8 days). CONCLUSIONS: Our initial experience suggests that SP robotic rectal resection is safe and feasible. Further clinical trials comparing SP and multiport robotic rectal resection should be conducted to verify the superior aspects of this new system.

Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach.

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.

Blindness increases the risk for hip fracture and vertebral fracture but not the risk for distal radius fracture: a longitudinal follow-up study using a national sample cohort.

The risks for hip fracture and vertebral fracture, but not the risk for distal radius fracture, were significantly higher in the blindness group than in the control group with a maximum 12-year follow-up. PURPOSE: To evaluate the influence of visual impairment on the risk for osteoporotic fractures at common sites: hip, thoracic/lumbar vertebra, and distal radius. METHODS: This longitudinal follow-up study used a database of a national sample cohort from 2002 to 2013 provided by the Korean National Health Insurance Service. Of a total of 1,125,691 subjects, 3918 patients with visual impairment and age ≥ 50 years were enrolled in a 1:4 ratio; 15,672 control participants were matched for age, sex, income, and region of residence. Stratified Cox proportional-hazards models were used to evaluate the crude and adjusted (for steroid medication, rheumatoid arthritis, depression, osteoporosis, diabetes mellitus, and stroke history) hazard ratios (HRs) for each fracture site. Fracture diagnoses were based on the ICD-10 codes: hip fracture (S720, S721, S722), vertebral fracture (S220, S320), and distal radius fracture (S525). RESULTS: The HRs for hip and vertebral fracture were significantly higher in the blindness group (adjusted HR = 2.46, p < 0.001 for hip fracture; adjusted HR = 1.42, p = 0.020 for thoracic/lumbar vertebral fracture) than in the matched control group. However, the HR for distal radius fracture was not higher in the blindness group. The HRs for all three fracture sites were not significantly higher in the non-blindness visual impairment group after adjustment. CONCLUSION: The risks for hip fracture and vertebral fracture were significantly higher in the blindness group. However, the risk for distal radius fracture was not related to visual impairment including blindness.

The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis.

Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE: Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS: A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS: The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION: We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.

Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits.

The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons. Neural transcript expression of only one gene, encoding the Npas4 transcription factor, was >twofold altered (downregulated) in MET mice; strikingly, similar Npas4 downregulation occurred in the prefrontal cortex of human patients with schizophrenia. Finally, therapeutic actions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects in human schizophrenia patients. Our data support the validity of MET mice as a model for schizophrenia, and uncover methionine metabolism as a potential preventive and/or therapeutic target.

Biofilm inhibiting activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms.

AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml-1 ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml-1 ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability. CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.

Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo.

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

Prognostic value of CT attenuation and FDG uptake of adipose tissue in patients with pancreatic adenocarcinoma.

AIM: To investigate the prognostic significance of computed tomography (CT) attenuation and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) for predicting overall survival (OS) in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS: Data were collected retrospectively from 66 patients with pancreatic adenocarcinoma who had undergone pretreatment combined FDG positron-emission tomography (PET)/CT imaging and subsequent curative or palliative treatment. Metabolic parameters of primary tumour including total lesion glycolysis (TLG) and heterogeneity factor were measured. Volume, CT attenuation (attenuation), and FDG uptake of SAT and VAT were derived from PET/CT acquisitions. Survival analysis using Cox proportional hazard modelling was performed to assess the relationship between both attenuation and FDG uptake of fat tissue and OS. RESULTS: During follow-up, 33 patients (50%) died and the median OS was 12 months. There were significant positive correlations between attenuation and mean standardised uptake values of both SAT (p<0.001, r=0.697) and VAT (p<0.001, r=0.742). Attenuation and FDG uptake of adipose tissue were significantly associated with heterogeneity factor and T stage. Patients with high FDG uptake and attenuation of SAT and VAT had significantly worse OS than those with low values. On multivariate analysis, attenuation of SAT (p=0.047) and VAT (p=0.021), and FDG uptake of VAT (p=0.005) were correlated significantly with OS after adjusting for age, sex, body mass index, TNM stage, and TLG. CONCLUSIONS: CT attenuation of SAT and VAT, and FDG uptake of VAT significantly correlated with OS in patients with pancreatic adenocarcinoma, independent of TNM staging and TLG.

Epidemiology of myopia and prevention of myopia progression in children in East Asia: a review.

INTRODUCTION: Myopia (short-sightedness) exhibits high prevalence in East Asia. Methods to mitigate myopia progression are important in preventing the vision-threatening complications associated with high myopia. In this review, we examine the regional epidemiology of myopia and provide updated evidence regarding interventions to slow myopia progression in children. METHODS: We performed a literature search using PubMed from the date of inception through 25 June 2018. Studies involving myopia epidemiology and control of myopia progression were selected; only studies published in English were reviewed. Preference was given to prospective studies, as well as those conducted in Hong Kong or East Asia. RESULTS: Atropine eye drops and pirenzepine eye gel are highly effective for controlling myopia progression in children. Orthokeratology, peripheral defocus contact lenses, bifocal or progressive addition spectacles, and increased involvement in outdoor activities are also effective for controlling myopia progression; however, myopia undercorrection and single vision contact lenses are ineffective. CONCLUSION: Although various methods are effective for controlling myopia progression in children, no curative remedy exists for myopia. Health care professionals should be aware of the available methods, as well as their risks and benefits. Treatment should be individualised and based on the preferences of the patient's family, after full discussion of the risks and benefits of each modality.

Emerging treatment paradigms for brain metastasis in non-small-cell lung cancer: an overview of the current landscape and challenges ahead.

Advances in the last decade in genomic profiling and the identification of druggable targets amenable to biological agents have transformed the management and survival of a subgroup of patients with brain metastasis in non-small-cell lung cancer. In parallel, clinicians have reevaluated the role of whole brain radiotherapy in selected patients with brain metastases to reduce neurocognitive toxicity. Continual progress in this understudied field is required: optimization of the sequence of schedules for therapies in patients with brain metastases of differing genomic profiles, focusing on new strategies to overcome mechanisms of biological resistance and increasing drug penetrability into the central nervous system. This review summarizes the field to date and possible treatment strategies based on current evidence.

Identification of α-tocopherol as a bioactive component of Dicranopteris linearis with disrupting property against preformed biofilm of Staphylococcus aureus.

AIMS: The potential of Dicranopteris linearis leaves' extract and its bioactive components were investigated for the first time for its disrupting ability against Staphylococcus aureus biofilms. METHODS AND RESULTS: The leaves of D. linearis were subjected to sonication-assisted extraction using hexane (HEX), dichloromethane, ethyl acetate and methanol (MeOH). It was found that only the MeOH fraction exhibited antimicrobial activity using broth microdilution assay; while all four fractions do not exhibit biofilm inhibition activity against S. aureusATCC 6538P, S. aureusATCC 43300, S. aureusATCC 33591 and S. aureusATCC 29213 using crystal violet assay. Among the four fractions tested, only the HEX fraction showed biofilm disrupting ability, with 60-90% disruption activity at 5 mg ml-1 against all four S. aureus strains tested. Bioassay-guided purification of the active fraction has led to the isolation of α-tocopherol. α-Tocopherol does not affect the cells within the biofilms but instead affects the biofilm matrix in order to disrupt S. aureus biofilms. CONCLUSIONS: α-Tocopherol was identified to be the bioactive component of D. linearis with disruption activity against S. aureus biofilm matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of α-tocopherol as a biofilm disruptive agent might potentially be useful to treat biofilm-associated infections in the future.

Investigation on the antimicrobial activities of gingers (Etlingera coccinea (Blume) S.Sakai & Nagam and Etlingera sessilanthera R.M.Sm.) endemic to Borneo.

AIMS: To investigate the antimicrobial properties of Etlingera coccinea and Etlingera sessilanthera and to isolate and identify the antimicrobial compounds. METHODS AND RESULTS: Extracts were obtained via sequential solvent extraction method using hexane, dichloromethane, ethyl acetate, methanol and water. Antimicrobial activity testing was done using broth microdilution assay against 17 strains of bacteria. The leaf hexane extract of E. coccinea and rhizome hexane extract of E. sessilanthera showed best antimicrobial activities, with minimum inhibitory concentration (MIC) values ranging from 0·016 to 1 mg ml-1 against Gram-positive bacteria. From these active extracts, two antimicrobials were isolated and identified as trans-2-dodecenal and 8(17),12-labdadiene-15,16-dial with MIC values ranging from 4 to 8 µg ml-1 against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus. CONCLUSION: Etlingera coccinea and E. sessilanthera demonstrated good antimicrobial activities against clinically relevant bacteria strains. The antimicrobial compounds isolated showed low MIC values, hence suggesting their potential use as antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to identify the potent antimicrobials from these gingers. The antimicrobials isolated could potentially be developed further for use in treatment of bacterial infections. Also, this study warrants further research into other Etlingera species in search for more antimicrobial compounds.

Predictor of fluid responsiveness in the 'grey zone': augmented pulse pressure variation through a temporary increase in tidal volume.

BACKGROUND: Pulse pressure variation (PPV) is widely used as a predictor of fluid responsiveness. However, a previous study has suggested a 'grey zone' between 9 and 13% in which PPV would be inconclusive to predict fluid responsiveness. Considering PPV is based on cardiopulmonary interactions, we evaluated whether an augmented PPV using a temporary increase in tidal volume (V T ) from 8 to 12 ml kg -1 has the predictability for fluid responsiveness in patients within the grey zone. METHODS: Adult patients requiring general anaesthesia were enrolled. During the period when PPV was within the range of 9-13%, haemodynamic variables such as stroke volume index (SVI) and PPV with an 8 ml kg -1 tidal volume ventilation (PPV8) were obtained before and after volume expansion (6 ml kg -1 ) under mechanical ventilation. Augmented PPV induced by 2-min ventilation with a V T of 12 ml kg -1 (PPV12) was also recorded immediately before volume loading. The patients whose SVI increased ≥10% after volume expansion were considered responders. RESULTS: In 38 enrolled patients, 20 were responders. Receiver operating characteristic curve analysis showed PPV12 had an excellent predictability for fluid responsiveness {area under the curve [AUC]=0.935 [95% confidence interval (CI) 0.805-0.989]; sensitivity 95%; specificity 72%; P <0.0001}. The optimal threshold for PPV12 was >17%. However, PPV8 failed to show significant predictability [AUC=0.668 (95% CI 0.497-0.812); sensitivity 65%; specificity 61%; P =0.06]. CONCLUSION: In mechanically ventilated patients, our augmented PPV successfully predicted fluid responsiveness in the previously suggested grey zone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02653469.