GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55-74 at enrollment in 1993-2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI.

Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF (p = 0.010), CMRO2 (p < 0.001) and DC (p = 0.002), and increased PmO2 (p = 0.043) in patients compared to controls. No significant differences were observed for CBVdHb (p = 0.389), OEF (p = 0.358), or GM volume (p = 0.302). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS. Our findings may be indicative of reduced oxygen demand or utilisation in the MS brain and mitochondrial dysfunction. Our results suggest changes in brain physiology may precede MRI-detectable GM loss and may contribute to disease progression and neurodegeneration.

Superficial surgical site infection in delayed primary vs primary. Wound closure in complicated appendicitis.

<b><br>Introduction:</b> Wound infection is the most common post-operative complication encountered after open appendectomy. Various studies have compared the risk of superficial surgical site infection (SSI) in primary closure (PC) and delayed primary closure (DPC) of wounds. However, there is no uniform consensus regarding the method of wound closure.</br> <b><br>Aim:</b> The aim of this study is to compare the two wound closure techniques.</br> <b><br>Material and methods:</b> This is a prospective study which enrolled 50 patients who underwent open appendectomy. The patients' demographics, characteristics, and operative findings were recorded. Those who were older than 18 years and had an appendectomy with a right lower quadrant incision were included. Patients with any comorbidity, morbid obesity, or pregnancy were excluded. Patients were randomized to undergo two techniques of wound closure: PC and DPC. During follow- -up at 1 week and 1 month, SSI, post-op pain, and LOS were compared among the two groups. Clinical assessment included the Visual Analog Scale (1-10) for pain.</br> <b><br>Results:</b> In our study, the incidence of SSI in the DPC group was significantly lower than in the PC group (p = 0.0002), while post-op pain and LOS were not significantly different between the two groups.</br> <b><br>Conclusions:</b> We concluded that DPC was superior to PC in terms of reducing the incidence of superficial SSI, but with respect to post-op pain and LOS, the two techniques of wound closure were not different.</br>.

Metformin Enhances the Anti-Cancer Efficacy of Sorafenib via Suppressing MAPK/ERK/Stat3 Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) incidence, as well as related mortality, has been steadily increasing in the USA and across the globe, partly due to the lack of effective therapeutic options for advanced HCC. Though sorafenib is considered standard-of-care for advanced HCC, it only improves median survival by a few months when compared to placebo. Sorafenib is also associated with several unpleasant side effects that often lead to early abatement of therapy. Here, we investigate whether a combination regimen including low-dose sorafenib and a non-toxic dose of anti-diabetic drug metformin can achieve effective inhibition of HCC. Indeed, combining metformin with low-dose sorafenib inhibited growth, proliferation, migration, and invasion potential of HCC cells. We observed a 5.3- and 1.9-fold increase in sub-G1 population in the combination treatment compared to sorafenib alone. We found that the combination of metformin enhanced the efficacy of sorafenib and inhibited the MAPK/ERK/Stat3 axis. Our in vivo studies corroborated the in vitro findings, and mice harboring HepG2-derived tumors showed effective tumor reduction upon treatment with low-dose sorafenib and metformin combination. This work sheds light on a therapeutic strategy aiming to augment sorafenib efficacy or dose-de-escalation that may prove beneficial in circumventing sorafenib resistance as well as minimizing related side effects.

The case of spontaneous stoma closure in patient with loop ileostomy.

INTRODUCTION: An ileostomy is a mean to empty the contents of the bowel via ileum rather than usual anal route to prevent distal anastomotic leak. It is considered a controlled entero-cutaneous (EC) fistula which prevents contamination of peritoneal cavity, protecting the peri-stomal skin from effluent and excoriation. Spontaneous closure of ileostomy is a very rare phenomenon. Thus, we hereby report a case of spontaneous closure of ileostomy. CASE PRESENTATION: An 18-years male presented with complaints of pain abdomen, vomiting for 6 days. Chest X-ray showed free air under the right dome of diaphragm suggestive of pneumo-peritoneum. So explorative laparotomy with primary repair of ileal perforation with diversion loop ileostomy (2 ft proximal to ileocecal junction) was performed. Over the months stoma retracted and eventually spontaneous closure of stoma took place after 4 months of surgery. DISCUSSION: Retraction of stoma depends on multiple factors. Firstly, on patient's general condition, if he/she is malnourished/obese/immunocompromised then retraction occurs due to poor healing of wound. Secondly, it results from inadequate mobilization of bowel. Separation of stoma with muco-cutaneous fascial planes leads to gradual retraction of stoma which is primary mechanism of spontaneous closure of stoma. CONCLUSION: To summarize, gradual retraction of stoma (complication of an ileostomy) and healing of EC fistula has to be correlated to know the complex mechanism of spontaneous closure of an ileostomy.

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI.

One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method's viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10-3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

Comparison of modified Glasgow-Imrie, Ranson, and Apache II scoring systems in predicting the severity of acute pancreatitis.

<b>Aim:</b> The course of acute pancreatitis is variable with patients at risk of poor outcomes. The purpose of this study was to compare Modified Glasgow-Imrie, Ranson, and APACHE II scoring systems in predicting the severity of acute pancreatitis. </br></br> <b> Material and Methods: </b> After a brief history, clinical examination and qualifying inclusion criteria, 70 patients (41 women, 29 men) diagnosed with acute pancreatitis were included in the study. The three scores were calculated for each patient and evaluated for their role in the assessment of specific outcomes. </br></br> <b>Results:</b> 34.3% patients were diagnosed with severe acute pancreatitis, while 65.7% patients had mild acute pancreatitis. A strong positive correlation was found between all the prognostic scores and the severity of disease. In the prediction of the severity of disease according to AUC, it was found that Glasgow-Imrie score had an AUC of 0.864 (0.7560.973), followed very closely by APACHE II score with an AUC of 0.863 (0.7580.968). APACHE II had the highest sensitivity (79.17%) in predicting severity while Glasgow-Imrie score was the most specific (97.83%) of all the scores. Patients with a Glasgow-Imrie score above the cut-off value of 3 had more complications and a longer hospital stay. </br></br> <b>Conclusion:</b> The Glasgow-Imrie score was comparable to APACHE II score and better than Ranson score statistically in predicting the severity of acute pancreatitis. Its administration in predicting the severity of acute pancreatitis is recommended.

A comparison of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation on visual and motor cortical oscillations, using magnetoencephalography.

Studying changes in cortical oscillations can help elucidate the mechanistic link between receptor physiology and the clinical effects of anaesthetic drugs. Propofol, a GABA-ergic drug produces divergent effects on visual cortical activity: increasing induced gamma-band responses (GBR) while decreasing evoked responses. Dexmedetomidine, an α2- adrenergic agonist, differs from GABA-ergic sedatives both mechanistically and clinically as it allows easy arousability from deep sedation with less cognitive side-effects. Here we use magnetoencephalography (MEG) to characterize and compare the effects of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation, on visual and motor cortical oscillations. Sixteen male participants received target-controlled infusions of propofol and dexmedetomidine, producing mild-sedation, in a placebo-controlled, cross-over study. MEG data was collected during a combined visuomotor task. The key findings were that propofol significantly enhanced visual stimulus induced GBR (44% increase in amplitude) while dexmedetomidine decreased it (40%). Propofol also decreased the amplitudes of the Mv100 (visual M100) (27%) and Mv150 (52%) visual evoked fields (VEF), whilst dexmedetomidine had no effect on these. During the motor task, neither drug had any significant effect on movement related gamma synchrony (MRGS), movement related beta de-synchronisation (MRBD) or Mm100 (movement-related M100) movement-related evoked fields (MEF), although dexmedetomidine slowed the Mm300. Dexmedetomidine increased (92%) post-movement beta synchronisation/rebound (PMBR) power while propofol reduced it (70%, statistically non- significant). Overall, dexmedetomidine and propofol, at equi-sedative doses, produce contrasting effects on visual induced GBR, VEF, PMBR and MEF. These findings provide a mechanistic link between the known receptor physiology of these sedative drugs with their known clinical effects and may be used to explore mechanisms of other anaesthetic drugs on human consciousness.

Mesh fixation with fibrin glue versus tacker in laparoscopic totally extraperitoneal inguinal hernia repair.

BACKGROUND: The advent of mesh was a breakthrough in the field of hernia surgery. Mechanical methods of mesh fixation are hypothesized to cause more tissue trauma than nonmechanical methods. The present study was conducted to study the outcomes of mesh fixation using fibrin glue, a nonmechanical method versus tackers in totally extraperitoneal repair (TEP) of unilateral inguinal hernia. METHODS: A randomized controlled single blinded study was conducted in India from June 2017 to March 2019. Patients diagnosed with unilateral uncomplicated inguinal hernia with a hernial sac of size not more than 5 cm were invited to participate in the study. Sample size was 60 patients randomized into groups just before mesh fixation. In group A mesh was fixed using tackers while in group B mesh was fixed using fibrin glue. Patients were followed-up prospectively for 3 months. RESULTS: There was no statistical difference between the two groups with respect to operating time. Average hospital stay and pain scores at all follow-ups were better for fibrin glue group. There was no difference in the incidence of postoperative urinary retention, seroma formation and hematoma formation between the two groups. Patients of fibrin glue group had early restart of daily activities at 15 days follow-up when compared to tacker group. CONCLUSION: Fibrin glue fixation technique should be advocated over tackers for mesh fixation in TEP considering the better outcomes and cost-effectiveness of the technique.

Gossypiboma - Successful retrieval through laparoscopy: A case report.

INTRODUCTION: Numerous complications can occur after a surgery, but gossypiboma is undoubtedly the most unwanted and undesirable complication of a procedure for any surgeon with legal implications. Once suspected, the minimally invasive surgical approach should be considered for its management. PRESENTATION OF CASE: An adult P1L1E1 female presented to the surgery OPD with a painless abdominal mass which progressively increased in size in the past 4 months. She underwent emergency surgery for a ruptured ectopic pregnancy 6 months back at some other health centre. On computed tomography scan of the abdomen, a well-defined heterogenous cystic lesion of size 9.8 cm × 9.2 cm × 7 cm was noted intraperitoneally. Few air foci with a hyperdense tubular structure within the lesion were seen, suggestive of a retained surgical sponge with its radio-opaque marker also visualised. The retained sponge was successfully retrieved by the laparoscopic approach. DISCUSSION: Traditionally, the open approach for the removal of the sponge was more accepted compared to the laparoscopic approach. This was due to the belief that intense foreign body reaction and dense adhesions around the sponge may make the laparoscopic approach difficult. However, laparoscopy can prove to be beneficial with its advantages of early ambulation, reduced post-op pain, cosmetically improved results and shorter length of hospital stay. CONCLUSION: All precautions must be taken to avoid retention of surgical sponge post-surgery. Case reports in which laparoscopy is used to retrieve gossypiboma are rare. The authors recommend the use of laparoscopy as a therapeutic option in the event of such mishaps.

Induction of STK11-dependent cytoprotective autophagy in breast cancer cells upon honokiol treatment.

Cancer cells hijack autophagy pathway to evade anti-cancer therapeutics. Many molecular signaling pathways associated with drug-resistance converge on autophagy induction. Honokiol (HNK), a natural phenolic compound purified from Magnolia grandiflora, has recently been shown to impede breast tumorigenesis and, in the present study, we investigated whether breast cancer cells evoke autophagy to modulate therapeutic efficacy and functional networks of HNK. Indeed, breast cancer cells exhibit increased autophagosomes-accumulation, MAP1LC3B-II/LC3B-II-conversion, expression of ATG proteins as well as elevated fusion of autophagosomes and lysosomes upon HNK treatment. Breast cancer cells treated with HNK demonstrate significant growth inhibition and apoptotic induction, and these biological processes are blunted by macroautophagy/autophagy. Consequently, inhibiting autophagosome formation, abrogating autophagosome-lysosome fusion or genetic-knockout of BECN1 and ATG7 effectively increase HNK-mediated apoptotic induction and growth inhibition. Next, we explored the functional impact of tumor suppressor STK11 in autophagy induction in HNK-treated cells. STK11-silencing abrogates LC3B-II-conversion, and blocks autophagosome/lysosome fusion and lysosomal activity as illustrated by LC3B-Rab7 co-staining and DQ-BSA assay. Our results exemplify the cytoprotective nature of autophagy invoked in HNK-treated breast cancer cells and put forth the notion that a combined strategy of autophagy inhibition with HNK would be more effective. Indeed, HNK and chloroquine (CQ) show synergistic inhibition of breast cancer cells and HNK-CQ combination treatment effectively inhibits breast tumorigenesis and metastatic progression. Tumor-dissociated cells from HNK-CQ treated tumors exhibit abrogated invasion and migration potential. Together, these results implicate that breast cancer cells undergo cytoprotective autophagy to circumvent HNK and a combined treatment with HNK and CQ can be a promising therapeutic strategy for breast cancer.

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine.

Cortical recordings of task-induced oscillations following subanaesthetic ketamine administration demonstrate alterations in amplitude, including increases at high-frequencies (gamma) and reductions at low frequencies (theta, alpha). To investigate the population-level interactions underlying these changes, we implemented a thalamo-cortical model (TCM) capable of recapitulating broadband spectral responses. Compared with an existing cortex-only 4-population model, Bayesian Model Selection preferred the TCM. The model was able to accurately and significantly recapitulate ketamine-induced reductions in alpha amplitude and increases in gamma amplitude. Parameter analysis revealed no change in receptor time-constants but significant increases in select synaptic connectivity with ketamine. Significantly increased connections included both AMPA and NMDA mediated connections from layer 2/3 superficial pyramidal cells to inhibitory interneurons and both GABAA and NMDA mediated within-population gain control of layer 5 pyramidal cells. These results support the use of extended generative models for explaining oscillatory data and provide in silico support for ketamine's ability to alter local coupling mediated by NMDA, AMPA and GABA-A.

Perineural local anaesthetic catheter after major lower limb amputation trial (PLACEMENT): results from a randomised controlled feasibility trial.

OBJECTIVES: To determine the feasibility of undertaking a randomised controlled effectiveness trial evaluating the use of a perineural catheter (PNC) after major lower limb amputation with postoperative pain as the primary outcome. DESIGN: Randomised controlled feasibility trial. SETTING: Two vascular Centres in South Wales, UK. PARTICIPANTS: 50 patients scheduled for major lower limb amputation (below or above knee) for complications of peripheral vascular disease. INTERVENTIONS: The treatment arm received a PNC placed adjacent to the sciatic or tibial nerve at the time of surgery, with continuous infusion of levobupivacaine hydrochloride 0.125% for up to 5 days. The control arm received neither local anaesthetic nor PNC. Both arms received usual perioperative anaesthesia and postoperative analgesia. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the proportion of eligible patients who were randomised and the proportion of recruited patients who provided primary effectiveness outcome data. Secondary outcomes were: the proportion of recruited patients reaching 2 and 6 month follow-up and supplying pain data; identification of key cost drivers; development of an economic analysis framework for a future effectiveness trial; identification of barriers to recruitment and site set-up; and identification of the best way to measure postoperative pain. RESULTS: Seventy-six of 103 screened patients were deemed eligible over a 10 month period. Fifty (64.5%) of these patients were randomised, with one excluded in the perioperative period. Forty-five (91.3%) of 49 recruited patients provided enough pain scores on a 4-point verbal rating scale to allow primary effectiveness outcome evaluation. Attrition rates were high; 18 patients supplied data at 6 month follow-up. Costs were dominated by length of hospital stay. Patients and healthcare professionals reported that trial processes were acceptable. CONCLUSIONS: Recruitment of patients into a trial comparing PNC use to usual care after major lower limb amputation with postoperative pain measured on a 4-point verbal rating scale is feasible. Evaluation of longer-term symptoms is difficult. TRIAL REGISTRATION NUMBER: ISRCTN: 85 710 690. EudraCT: 2016-003544-37.

Concomitant Inhibition of Cytoprotective Autophagy Augments the Efficacy of Withaferin A in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality, and despite recent advances in early diagnosis and therapeutics, HCC related morbidity and mortality rate continue to rise. Clearly, it is imperative to develop novel effective therapies for HCC to improve long-term survival of HCC patients. We found that Withaferin A (WFA), a bioactive compound derived from Withania somnifera, is an effective agent for HCC inhibition. Interestingly, we observed that in addition to inducing apoptotic cell death, WFA also induces autophagy in HCC cells. Utilizing mRFP-EGFP-LC3B, LC3B-GFP/Lysotracker and LC3B-GFP/Rab7-RFP, we show that WFA induces autophagosomes-lysosomes fusion. WFA-induced autolysosomes exhibit intact protein degradation activity as evident with cathepsin-D activation and DQ-BSA assays. Importantly, we present that inhibiting WFA-induced autophagy either by blocking autophagosome-formation or by elevating lysosomal pH (Chloroquine and Bafilomycin) enhances WFA-induced growth-inhibition and apoptosis, indicating the presence of cytoprotective autophagy. Indeed, WFA and CQ combination shows synergism and higher efficacy in comparison to either monotherapy. Collectively, we reveal that the efficacy of WFA is somewhat diminished by the concomitant induction of cytoprotective autophagy which can be successfully conquered by cotreatment with CQ, and we pave the way for development of a novel combination therapeutic strategy for HCC.

Correction: Characterizing multicity urban traffic conditions using crowdsourced data.

[This corrects the article DOI: 10.1371/journal.pone.0212845.].

Characterizing multicity urban traffic conditions using crowdsourced data.

Road traffic congestion continues to manifest and propagate in cities around the world. The recent technological advancements in intelligent traveler information have a strong influence on the route choice behavior of drivers by enabling them to be more flexible in selecting their routes. Measuring traffic congestion in a city, understanding its spatial dispersion, and investigating whether the congestion patterns are stable (temporally, such as on a day-to-day basis) are critical to developing effective traffic management strategies. In this study, with the help of Google Maps API, we gather traffic speed data of 29 cities across the world over a 40-day period. We present generalized congestion and network stability metrics to compare congestion levels between these cities. We find that (a) traffic congestion is related to macroeconomic characteristics such as per capita income and population density of these cities, (b) congestion patterns are mostly stable on a day-to-day basis, and (c) the rate of spatial dispersion of congestion is smaller in congested cities, i.e. the spatial heterogeneity is less sensitive to increase in delays. This study compares the traffic conditions across global cities on a common datum using crowdsourced data which is becoming readily available for research purposes. This information can potentially assist practitioners to tailor macroscopic network congestion and reliability management policies. The comparison of different cities can also lead to benchmarking and standardization of the policies that have been used to date.

Risk of automated driving: Implications on safety acceptability and productivity.

Autonomous Vehicles have captured the imagination of our society and have promised a future of safe and efficient mobility. However, there is a need to understand behaviour and its consequences in the use of autonomous vehicles. Using paradigms of behavioural and experimental economics, we show that risk attitudes play a role in acceptability of autonomous vehicles, productivity in autonomous vehicles and safety under risk of failures of autonomous systems. We found that risk attitudes and age have a significant impact on these. We believe these findings will help provide guidance to insurance agencies, licensing, vehicle design, and policies around automated vehicles.

Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells.

Withaferin A (WFA), a steroidal lactone, negatively regulates breast cancer growth however, its mechanisms of action remain largely elusive. We found that WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells. WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion. Autolysosomes display the characteristics of acidic compartments in WFA-treated cells; however, the protein degradation activity of lysosomes is inhibited. Blockade of autophagic flux reduces the recycling of cellular fuels leading to insufficient substrates for tricarboxylic acid (TCA) cycle and impaired oxidative phosphorylation. WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation. AMPK inhibition abrogates while AMPK activation potentiates WFA's effect. WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells. Genetic knockout of BECN1 and ATG7 fails to rescue cells from WFA treatment; in contrast, addition of methyl pyruvate to supplement TCA cycle protects WFA-treated cells. Together, these results implicate that WFA is a potent lysosomal inhibitor; energetic impairment is required for WFA-induced apoptosis and growth inhibition and combining WFA and 2-DG is a promising therapeutic strategy for breast cancer.

Mild Propofol Sedation Reduces Frontal Lobe and Thalamic Cerebral Blood Flow: An Arterial Spin Labeling Study.

Mechanisms of anesthetic drug-induced sedation and unconsciousness are still incompletely understood. Functional neuroimaging modalities provide a window to study brain function changes during anesthesia allowing us to explore the sequence of neuro-physiological changes associated with anesthesia. Cerebral perfusion change under an assumption of intact neurovascular coupling is an indicator of change in large-scale neural activity. In this experiment, we have investigated resting state cerebral blood flow (CBF) changes in the human brain during mild sedation, with propofol. Arterial spin labeling (ASL) provides a non-invasive, reliable, and robust means of measuring cerebral blood flow (CBF) and can therefore be used to investigate central drug effects. Mild propofol sedation-related CBF changes were studied at rest (n = 15), in a 3 T MR scanner using a PICORE-QUIPSS II ASL technique. CBF was reduced in bilateral paracingulate cortex, premotor cortex, Broca's areas, right superior frontal gyrus and also the thalamus. This cerebral perfusion study demonstrates that propofol induces suppression of key cortical (frontal lobe) and subcortical (thalamus) regions during mild sedation.