A transcriptional switch controls sex determination in Plasmodium falciparum.

Sexual reproduction and meiotic sex are deeply rooted in the eukaryotic tree of life, but mechanisms determining sex or mating types are extremely varied and are only well characterized in a few model organisms1. In malaria parasites, sexual reproduction coincides with transmission to the vector host. Sex determination is non-genetic, with each haploid parasite capable of producing either a male or a female gametocyte in the human host2. The hierarchy of events and molecular mechanisms that trigger sex determination and maintenance of sexual identity are yet to be elucidated. Here we show that the male development 1 (md1) gene is both necessary and sufficient for male fate determination in the human malaria parasite Plasmodium falciparum. We show that Md1 has a dual function stemming from two separate domains: in sex determination through its N terminus and in male development from its conserved C-terminal LOTUS/OST-HTH domain. We further identify a bistable switch at the md1 locus, which is coupled with sex determination and ensures that the male-determining gene is not expressed in the female lineage. We describe one of only a few known non-genetic mechanisms of sex determination in a eukaryote and highlight Md1 as a potential target for interventions that block malaria transmission.

Photocurrent-driven transient symmetry breaking in the Weyl semimetal TaAs.

Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry changes a critical step in developing future technologies that rely on such control. Topological materials, like topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second harmonic generation spectroscopy as a sensitive probe of symmetry changes, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast timescales.

Ultrafast Suppression of the Ferroelectric Instability in KTaO_{3}.

We use an x-ray free-electron laser to study the lattice dynamics following photoexcitation with ultrafast near-UV light (wavelength 266 nm, 50 fs pulse duration) of the incipient ferroelectric potassium tantalate, KTaO_{3}. By probing the lattice dynamics corresponding to multiple Brillouin zones through the x-ray diffuse scattering with pulses from the Linac Coherent Light Source (LCLS) (wavelength 1.3 Å and <10 fs pulse duration), we observe changes in the diffuse intensity associated with a hardening of the transverse acoustic phonon branches along Γ to X and Γ to M. Using force constants from density functional theory, we fit the quasiequilibrium intensity and obtain the instantaneous lattice temperature and density of photoexcited charge carriers. The density functional theory calculations demonstrate that photoexcitation transfers charge from oxygen 2p derived π-bonding orbitals to Ta 5d derived antibonding orbitals, further suppressing the ferroelectric instability and increasing the stability of the cubic, paraelectric structure.

Knowledge, attitudes and practices of neonatal professionals regarding pain management.

Pain management is an important issue which impacts the prognosis of neonates in neonatal intensive care units. Evidence has shown that professionals' knowledge and attitudes regarding pain management can impact the quality of their practice. The purpose of this study was to evaluate the knowledge, attitudes, and practices of neonatal professionals regarding neonatal pain management. A cross-sectional study was performed involving neonatal physicians and nurses, using a research questionnaire to investigate the knowledge and attitudes of professionals as well as to assess their practice of pain management. Research found an apparent discrepancy between the knowledge levels of neonatologists and nurses regarding pain assessment and management, with nurses displaying weaker professional knowledge and more negative attitudes toward pain management than did neonatologists. Additionally, research revealed a lack of knowledge and negative attitudes among participants regarding the provision of sufficient opioid analgesics to sick infants during invasive procedures and even for dying neonates. There is an urgent need for continuing education regarding neonatal pain management with the goal of empowering neonatal professionals; further research is needed into the question of how to translate education into more reliable practice.Conclusion: This research provides useful information regarding the knowledge, attitudes, and clinical practice of neonatal pain management among neonatologists and nurses and points out some differences in the knowledge levels of these two groups. What is Known: •Neonates can perceive and respond to pain stimuli by showing their biological signals similarly to children and adults. •Untreated or insufficient pain management for high-risk neonates has short-term. negative effects and may also induce long-term negative effects. What is New: •The level of knowledge, the attitudes, and the practices regarding neonatal pain in intensive care are different among neonatal professionals. •There is an urgent need to provide interdisciplinary continuing education to improve the knowledge of neonatal professionals and encourage them to more highly prioritize neonatal pain management.

Identifying key gait features associated with the radiological grade of knee osteoarthritis.

PURPOSE: Knee osteoarthritis (KOA) is characterized by pain and decreased gait function. This study assessed key features that can be used as mechanical biomarkers for KOA severity and progression. The identified features were validated statistically and were further examined by developing a classification model based on a machine-learning algorithm. METHODS: The study included 227 volunteers with various grades of KOA. The severity of KOA was graded using the Kellgren-Lawrence (KL) system. A total of 165 features were extracted from the gait data. The key features were selected using neighborhood component analysis. The selected features were validated using the t-test. Then, the features were examined by building a classification model using a random forest algorithm. RESULTS: Twenty features were identified that could discriminate the grade of KOA, including nine features extracted from the knee joint, seven from the hip, two from the ankle and two from the spatiotemporal gait parameters. The t-test showed that some features differed significantly between health and sever group, while some were significantly different among the severe group, and others were significantly different for all KL grades. The areas under the receiver operating characteristic curves for classification were 0.974, 0.992, 0.845, 0.894, and 0.905 for KL grades 0 through 4, respectively. CONCLUSION: Key gait features reflecting the grade of KOA were identified. The results of the statistical analysis and machine-learning algorithm show that the features can discriminate the severity of disease according to the KL grade.

Susceptibility of Anopheles gambiae complex mosquitoes to microbial larvicides in diverse ecological settings in western Kenya.

The microbial larvicides Bacillus thuringiensis var. israelensis (Bti) and Bacillus sphaericus (Bs) (Bacillales: Bacillaceae) are well known for their efficacy and safety in mosquito control. In order to assess their potential value in future mosquito control strategies in western Kenya, the current study tested the susceptibility of five populations of Anopheles gambiae complex mosquitoes (Diptera: Culicidae), collected from five diverse ecological sites in this area, to Bti and Bs under laboratory conditions. In each population, bioassays were conducted with eight concentrations of larvicide (Bti/Bs) in four replicates and were repeated on three separate days. Larval mortality was recorded at 24 h or 48 h after the application of larvicide and subjected to probit analysis. A total of 2400 An. gambiae complex larvae from each population were tested for their susceptibility to Bti and Bs. The mean (± standard error of the mean, SEM) lethal concentration values of Bti required to achieve 50% and 95% larval mortality (LC50 and LC95 ) across the five populations were 0.062 (± 0.005) mg/L and 0.797 (± 0.087) mg/L, respectively. Corresponding mean (± SEM) values for Bs were 0.058 (± 0.005) mg/L and 0.451 (± 0.053) mg/L, respectively. Statistical analysis indicated that the five populations of An. gambiae complex mosquitoes tested were fully susceptible to Bti and Bs, and there was no significant variation in susceptibility among the tested populations.

Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.

Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS.

Prospective evaluation of skin and nipple-areola sensation and patient satisfaction after nipple-sparing mastectomy.

BACKGROUND: Sensation and quality of life (QOL) before and after nipple sparing mastectomy (NSM) are poorly understood. METHODS: Women electing mastectomy with immediate reconstruction and eligible for NSM were prospectively enrolled in a sensation and satisfaction/QOL study. Women self-selected skin-sparing mastectomy (SSM) or NSM. Skin sensation testing using Semmes Weinstein monofilaments and patient satisfaction/QOL surveys were administered preoperatively and at 1 year postoperatively. RESULTS: 53 patients were enrolled (n = 38, 72% NSM and n = 15, 28% SSM). Both groups had significant reduction in postoperative skin sensation. For NSM, measurable NAC sensation was preserved in both NAC for 26% of patients and in one NAC for 68%. QOL and satisfaction was similar between groups. Neither group was satisfied with sexual arousal with breast or nipple stimulation after surgery. CONCLUSION: Patients undergoing SSM and NSM have considerable loss in skin and NAC sensation following surgery. Satisfaction and QOL did not differ between groups. J. Surg. Oncol. 2016;114:11-16. © 2016 Wiley Periodicals, Inc.

Dual energy X-ray absorptiometry spine scans to determine abdominal fat in postmenopausal women.

Body composition may be a better predictor of chronic disease risk than body mass index (BMI) in older populations. OBJECTIVES: We sought to validate spine fat fraction (%) from dual energy X-ray absorptiometry (DXA) spine scans as a proxy for total abdominal fat. METHODS: Total body DXA scan abdominal fat regions of interest (ROI) that have been previously validated by magnetic resonance imaging were assessed among healthy, postmenopausal women who also had antero-posterior spine scans (n = 103). ROIs were (1) lumbar vertebrae L2-L4 and (2) L2-Iliac Crest (L2-IC), manually selected by two independent raters, and (3) trunk, auto-selected by DXA software. Intra-class correlation coefficients evaluated intra and inter-rater reliability on a random subset (N = 25). Linear regression models, validated by bootstrapping, assessed the relationship between spine fat fraction (%) and total abdominal fat (%) ROIs. RESULTS: Mean age, BMI, and total body fat were 66.1 ± 4.8 y, 25.8 ± 3.8 kg/m2 and 40.0 ± 6.6%, respectively. There were no significant differences within or between raters. Linear regression models adjusted for several participant and scan characteristics were equivalent to using only BMI and spine fat fraction. The model predicted L2-L4 (Adj. R2 : 0.83) and L2-IC (Adj. R2 : 0.84) abdominal fat (%) well; the adjusted R2 for trunk fat (%) was 0.78. Model validation demonstrated minimal over-fitting (Adj. R2 : 0.82, 0.83, and 0.77 for L2-L4, L2-IC, and trunk fat, respectively). CONCLUSIONS: The strong correlation between spine fat fraction and DXA abdominal fat measures make it suitable for further development in postmenopausal chronic disease risk prediction models. Am. J. Hum. Biol. 28:918-926, 2016. © 2016Wiley Periodicals, Inc.

Nasotracheal intubation in patients with limited mouth opening: a comparison between fibreoptic intubation and the Trachway®.

In patients with limited mouth opening, traditional laryngoscopy and videolaryngoscopes are not useful when performing nasotracheal intubation. Eighty patients with limited mouth opening who required nasotracheal intubation were randomly assigned to either fibreoptic intubation (n = 40) or the Trachway(®) (n = 40). Using the modified nasal intubation difficulty scale, 22 (55%) patients who received fibreoptic intubation were categorised as no difficulty compared with 40 (100%) patients in the Trachway group (p < 0.001). Mean (SD) total intubation time was 71.8 (23.3) s in patients who received fibreoptic intubation compared with 35.4 (9.8) s in the Trachway group (p < 0.001). We conclude that the Trachway technique for nasotracheal intubation is quicker and easier compared with fibreoptic intubation in patients with limited mouth opening.

Intracortical modulation, and not spinal inhibition, mediates placebo analgesia.

Suppression of spinal responses to noxious stimulation has been detected using spinal fMRI during placebo analgesia, which is therefore increasingly considered a phenomenon caused by descending inhibition of spinal activity. However, spinal fMRI is technically challenging and prone to false-positive results. Here we recorded laser-evoked potentials (LEPs) during placebo analgesia in humans. LEPs allow neural activity to be measured directly and with high enough temporal resolution to capture the sequence of cortical areas activated by nociceptive stimuli. If placebo analgesia is mediated by inhibition at spinal level, this would result in a general suppression of LEPs rather than in a selective reduction of their late components. LEPs and subjective pain ratings were obtained in two groups of healthy volunteers - one was conditioned for placebo analgesia while the other served as unconditioned control. Laser stimuli at three suprathreshold energies were delivered to the right hand dorsum. Placebo analgesia was associated with a significant reduction of the amplitude of the late P2 component. In contrast, the early N1 component, reflecting the arrival of the nociceptive input to the primary somatosensory cortex (SI), was only affected by stimulus energy. This selective suppression of late LEPs indicates that placebo analgesia is mediated by direct intracortical modulation rather than inhibition of the nociceptive input at spinal level. The observed cortical modulation occurs after the responses elicited by the nociceptive stimulus in the SI, suggesting that higher order sensory processes are modulated during placebo analgesia.

Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan.

BACKGROUND: Obstructive uropathy and chronic urinary tract infection increase the risk of urinary tract cancer. Urinary tuberculosis (UTB) can cause chronic urinary tract inflammation, lead to obstructive uropathy, and potentially contribute to the development of urinary tract cancer. However, the association between UTB and urinary tract cancer has not been studied. METHODS: This study enrolled 135 142 tuberculosis (TB) cases (male, 69%) from a nationwide health insurance research database in Taiwan and investigated the risk factors for urinary tract cancer, with emphasis on a history of UTB. The incidence of urinary tract cancer in the general population without TB was also calculated for comparison. RESULTS: The TB patients had a mean age of 57.5 ± 19.5 years. Of the 1287 UTB and 133 855 non-UTB patients, 15 (1.2%) and 396 (0.3%) developed urothelial carcinoma, respectively (P<0.001); and 2 (0.2%) and 96 (0.1%) developed renal cell carcinoma, respectively (P=0.240). Cox regression analysis revealed that age, male sex, end-stage renal disease, obstructive uropathy, arsenic intoxication, organ transplantation, and UTB (hazard ratio: 3.38 (2.01-5.69)) were independent risk factors for urothelial carcinoma. The hazard ratio of UTB was higher among female patients (5.26 (2.12-13.06)) than that among male patients (2.96 (1.57-5.60)). CONCLUSION: Urinary tuberculosis had a strong association with urothelial carcinoma, but not with renal cell carcinoma. In TB endemic areas, the urinary tract of TB patients should be scrutinised. It is also imperative that these patients be followed-up carefully in the post-treatment period, and urinalysis, ultrasonography or endoscopy should be an integral part of the follow-up.

Chondrogenic potentials of human synovium-derived cells sorted by specific surface markers.

OBJECTIVE: We aimed to evaluate expression levels of nine candidate surface markers for chondrogenic potential in human synovial cells and to determine whether cell pellets positively sorted by each specific marker would have valuable chondrogenic potential. METHODS: The expression levels of the selected nine leading surface markers in synovial cells from knee joints in 15 patients with primary knee osteoarthritis were evaluated at the stage of isolation and after cultivation using flow cytometry. We obtained positive and negative cells for each surface marker using a magnetically activated cell sorting method and compared chondrogenic potentials between the positive and the negative cell pellets. RESULTS: CD29, CD44, CD73, and CD90 were expressed on the most synovial cells at the isolation stage and on almost all cells at stage of P0 and P1. CD133 was rarely expressed at any stages of the evaluated cells. CD166 was expressed in 7.1% of cells at the isolation stage on average, but this expression increased after cell passages. The expressions of CD10 and CD105 also increased after cell passages while the expression of CD49a made no significant difference at progressive stages of isolation and passage. Comparison of chondrogenic potentials between positive and negative cell pellets for each marker revealed that only CD105- and CD166-positive cell pellets showed better chondrogenic potentials (type II collagen gene expression, cartilage matrix formation, and GAG expression) than the corresponding negative cell pellets. CONCLUSION: Our study suggests that CD105 and CD166 would be valuable surface markers associated with chondrogenic potential; thus, CD105- and CD166-enriched cells derived from human synovium would be practical and valuable sources for cartilage regeneration.

The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis.

Only a few studies have investigated the use of PCT in the diagnosis of bone and joint infection, and these studies have had relatively small sample sizes. We performed a systematic review and meta-analysis of the diagnostic performance of serum procalcitonin (PCT) in the identification of osteomyelitis and septic arthritis in patients who present with fever and orthopedic symptoms. EMBASE, MEDLINE, and Cochrane databases and the reference lists of relevant articles were searched, with no language restrictions, through February 2012. All original studies that reported the use of serum PCT alone or in comparison with other biomarkers for diagnosis of osteomyelitis and septic arthritis were included. Seven studies qualified for inclusion. These studies enrolled a total of 583 patients with suspected bone or joint infection, 131 of whom had confirmed osteomyelitis or septic arthritis. Analysis of the PCT data indicated a bivariate pooled sensitivity of 0.67 (95 % CI: 0.37-0.88), specificity of 0.90 (95 % CI: 0.78-0.96), a positive likelihood ratio (LR+) of 6.48 (95 % CI: 2.28-14.6), and a negative likelihood ratio (LR-) of 0.37 (95 % CI: 0.16-0.84). Use of a lower PCT cut-off value (0.2-0.3 ng/mL) improved the LR + to 6.66 and the LR- to 0.15. Analysis of the three studies that also measured serum C-reactive protein (CRP) indicated that CRP had an LR + of 1.39 (95 % CI: 1.17-1.65) and an LR- of 0.40 (95 % CI: 0.12-1.36). Our results indicate that PCT may be more suitable as an aid for rule-in diagnosis rather than for exclusion of septic arthritis or osteomyelitis and that use of a lower cut-off value for serum PCT may improve its diagnostic performance.

Imaging pain: a potent means for investigating pain mechanisms in patients.

Chronic pain is a state of physical suffering strongly associated with feelings of anxiety, depression and despair. Disease pathophysiology, psychological state, and social milieu can influence chronic pain, but can be difficult to diagnose based solely on clinical presentation. Here, we review brain neuroimaging research that is shaping our understanding of pain mechanisms, and consider how such knowledge might lead to useful diagnostic tools for the management of persistent pain in individual patients.

Development and characterization of 22 polymorphic microsatellite markers for the balloon flower Platycodon grandiflorum (Campanulaceae).

The balloon flower (Platycodon grandiflorum A. DC.) is a perennial flowering plant of the Campanulaceae family; it is the only member of the genus Platycodon. Information on the genetic diversity of balloon flower populations is of great importance for the conservation and germplasm utilization of this flowering plant. Twenty-two polymorphic microsatellite loci were developed and characterized with eight balloon flower accessions collected from South Korea and China. Eighty-one alleles were detected among the eight balloon flower accessions. The number of alleles per locus ranged from two to six, with a mean of four alleles per locus. The observed and expected heterozygosity values ranged from 0.000 to 0.875 (mean = 0.355) and 0.117 to 0.766 (mean = 0.489), respectively. The polymorphic information content values ranged from 0.110 to 0.733, with a mean of 0.449. These new microsatellite markers will be useful for population and conservation genetic studies of P. grandiflorum.

Adolescent mothers and older mothers: who is at higher risk for adverse birth outcomes?

OBJECTIVES: To document the patterns of first-order fertility rates associated with extreme maternal ages in Taiwan; determine if there is a gap in adverse birth outcomes (specifically low birth weight and prematurity) between adolescent mothers and older mothers; and determine which factors are important in explaining the differences in adverse birth outcomes between adolescent mothers and older mothers. STUDY DESIGN: Government statistics and survey data [Taiwan Birth Cohort Survey (TBCS)]. METHODS: Descriptive statistics and logistic regression. RESULTS: Between 1989 and 2009, the first-order fertility rate for mothers aged 15-19 years decreased, whereas that for mothers aged 35-49 years increased. Analysis of TBCS data revealed that, in comparison with older mothers, adolescent mothers are not necessarily at higher risk for adverse birth outcomes. Birth complications, pregnancy-related risks, adequate number of prenatal care visits and weight gain are more important than socio-economic status and prevalence of smoking in determining birth outcomes among first-time mothers of extreme reproductive ages. Adolescent mothers are less likely to have birth complications and pregnancy-related risks, but are more likely to have an inadequate number of prenatal care visits and to gain an inadequate amount of weight compared with older mothers. CONCLUSIONS: The risks associated with adolescent mothers are easier to manage than the risks associated with older mothers. Their birth outcomes can be improved through good policy. Taiwan's health policy should target specific risks to reduce the number of adverse birth outcomes among adolescent mothers rather than try to prevent all childbearing during adolescence.

Coherent helicity-dependent spin-phonon oscillations in the ferromagnetic van der Waals crystal CrI3.

The discovery of two-dimensional systems hosting intrinsic magnetic order represents a seminal addition to the rich landscape of van der Waals materials. CrI3 is an archetypal example, where the interdependence of structure and magnetism, along with strong light-matter interactions, provides a new platform to explore the optical control of magnetic and vibrational degrees of freedom at the nanoscale. However, the nature of magneto-structural coupling on its intrinsic ultrafast timescale remains a crucial open question. Here, we probe magnetic and vibrational dynamics in bulk CrI3 using ultrafast optical spectroscopy, revealing spin-flip scattering-driven demagnetization and strong transient exchange-mediated interactions between lattice vibrations and spin oscillations. The latter yields a coherent spin-coupled phonon mode that is highly sensitive to the driving pulse's helicity in the magnetically ordered phase. Our results elucidate the nature of ultrafast spin-lattice coupling in CrI3 and highlight its potential for applications requiring high-speed control of magnetism at the nanoscale.

Highly efficient multipotent differentiation of human periodontal ligament fibroblasts induced by combined BMP4 and hTERT gene transfer.

Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of stem cell properties. In this study we report for the first time that the combined ectopic expression of BMP4 and hTERT significantly enhanced the multipotent differentiation efficiency and capacity of human PDL fibroblasts (PFs), as shown by osteogenic, adipogenic and neurogenic differentiation in vitro, and cementum/PDL-like tissue regeneration in vivo. These findings may be attributed, at least in part, to the original upregulation of important stem cell markers, such as scleraxis, Stro-1 and CD146, and the extremely lowered threshold for BMP concentration to activate BMP signaling by enhanced basal phosphorylation levels of Smad 1/5/8. In addition, the significantly reduced expression levels of CD146 and CD90 with the presence of Noggin confirms the direct effect of BMP4 on the stem cell-like phenotype of genetically modified PF cells (BT-PFs). Furthermore, BT-PFs exhibited a high neural differentiation capacity (>75%). After transplantation into NOD/SCID mice, genetically modified-PFs generated cementum/PDL-like structures on the surface of the carrier. The multipotency of these modified cells potentially provides an attractive source of stem cells for therapeutic purposes and regenerative medicine.

Distinct association between aberrant methylation of Wnt inhibitors and genetic alterations in acute myeloid leukaemia.

BACKGROUND: Aberrant activation of Wnt signalling through hypermethylation of Wnt inhibitor genes is involved in several human malignancies, including acute myeloid leukaemia (AML). It remains unclear whether hypermethylation of Wnt inhibitors is associated with molecular gene mutations in the development of AML. METHODS: We investigated the association of the promoter hypermethylation of six Wnt inhibitors (Wif-1, SFRP1, SFRR2, SFRP4, SFRP5, and DKK1) with gene aberrations in the leukaemogenesis of 269 AML patients. RESULTS: In total, 166 patients (61.7%) had hypermethylation of at least one Wnt inhibitor. The majority (68.5%) of patients with Wnt inhibitor hypermethylation had concurrent Class II gene mutations that affect transcription factors or cofactors. There was a close association of Wif-1 hypermethylation with t(15;17) (P=0.0005) and CEBPA mutation (P<0.0001), DKK1 hypermethylation with t(8;21) (P<0.0001) and ASXL1 mutation (P=0.0078), SFRP-1 hypermethylation with t(8;21) (P<0.0001), SFRP-2 hypermethylation with AML1/RUNX1 mutation (P=0.0012), and SFRP-5 hypermethylation with MLL/PTD (P=0.0505). On the other side, hypermethylation of Wnt inhibitors was always negatively associated with NPM1 mutation and FLT3/ITD. CONCLUSION: There was distinct association between hypermethylation of individual Wnt inhibitors and specific gene aberrations, especially Class II mutations. The Wnt inhibitor hypermethylation might interact with genetic alterations in the leukaemogenesis.