Clevelandkilic6649

Dexanabinol is a synthetic analogue of tetrahydrocannabinol identified as a potential anti-cancer therapeutic by e-Therapeutics PLC. Sunitinib nmr Dexanabinol was selected for further investigation based on its preclinical tumoricidal activity. This phase I dose-escalation trial examined the safety, drug penetration into the central nervous system (CNS), preliminary antitumor activity, and recommended phase II dose.

Dexanabinol formulated in cremophor/ethanol was administered once weekly via 3-hour intravenous infusion to patients with brain cancer.

A total of 26 patients were dosed once weekly at 2, 4, 8, 16, 24, 28, and 36 mg/kg. Two patients at 36 mg/kg were nonevaluable for dose level confirmation, having withdrawn early for reasons unrelated to study treatment. A recommended phase II dose of dexanabinol was established at 28 mg/kg due to related, reversible adverse events at higher dose levels that required medications for symptomatic relief. The most common drug-related toxicities were the depressed level of consciousness and lightheadedness, diarrhea, itching, fatigue, chest discomfort, and tingling in the mouth. Systemic exposure to dexanabinol (AUC

and



) increased from 2 to 36 mg/kg, with dose nonproportionality apparent at the highest dose; dexanabinol was present in appreciable levels in the cerebrospinal fluid (CSF), which implies the possibility of exposure of intracranial tumors to drug. Five of 24 efficacy-evaluable patients (21%) experienced stable disease with a median duration of 2 cycles (28-day cycle) as the best response.

Dexanabinol administered weekly by intravenous infusion was safe and well-tolerated up to 28 mg/kg in brain cancer patients, but has limited antitumor activity in patients with brain cancer.

Dexanabinol administered weekly by intravenous infusion was safe and well-tolerated up to 28 mg/kg in brain cancer patients, but has limited antitumor activity in patients with brain cancer.

Combined whole-exome sequencing (WES) and somatic copy number alteration (SCNA) information can separate

-wildtype glioblastoma into two prognostic molecular subtypes, which cannot be distinguished by epigenetic or clinical features. The potential for radiographic features to discriminate between these molecular subtypes has yet to be established.

Radiologic features (

= 35 340) were extracted from 46 multisequence, pre-operative magnetic resonance imaging (MRI) scans of

-wildtype glioblastoma patients from The Cancer Imaging Archive (TCIA), all of whom have corresponding WES/SCNA data. We developed a novel feature selection method that leverages the structure of extracted MRI features to mitigate the dimensionality challenge posed by the disparity between a large number of features and the limited patients in our cohort. Six traditional machine learning classifiers were trained to distinguish molecular subtypes using our feature selection method, which was compared to least absolute shrinkage and secularly-defined risk-stratifying IDH1/2-wildtype glioblastoma patient groups.

There is mounting evidence of a high burden of antimicrobial-resistant infections in children in low- and middle-income countries (LMICs).

To detect the frequency of ESBL-producing

in clinical specimens from paediatric patients attending Yangon Children's Hospital in Myanmar.

All children attending Yangon Children's Hospital who had clinical specimens submitted to the hospital diagnostic microbiology laboratory from June 2019 to December 2019 were included in the study. Specimens were processed routinely using standard methods with BD Phoenix used for pathogen identification and susceptibility testing. Presence of ESBLs was determined using the cephalosporin/clavulanate combination disc method with confirmation by PCR.

From 3462 specimens submitted to the Microbiology Laboratory, a total of 123

were isolated. Among them, 100 isolates were phenotypically ESBL producers, 94 (76.4%) of which were confirmed by PCR [82/94 (87%) CTX-M, 72/94 (77%) TEM, 1/94 (1%) SHV]. Most of the ESBL-producing

were isolated from urine samples (52.1%, 49/94) and the majority were from the surgical unit (61.7%, 58/94). Only 34/94 (36%) isolates were susceptible to meropenem.

This study confirms a high proportion of infections caused by ESBL-producing and MDR

in children hospitalized in Yangon, where access to effective second-line antimicrobials is limited.

This study confirms a high proportion of infections caused by ESBL-producing and MDR E. coli in children hospitalized in Yangon, where access to effective second-line antimicrobials is limited.Weight gain is often associated with the pleasure of eating food rich in calories. This idea is based on the findings that people with obesity showed increased neural activity in the reward and motivation systems of the brain in response to food cues. Such correlations, however, overlook the possibility that obesity may be associated with a metabolic state that impacts the functioning of reward and motivation systems, which in turn could be linked to reactivity to food and eating behaviour and weight gain. In a study involving 44 female participants [14 patients with obesity, aged 20-63 years (mean 42, SEM 3.2 years), and 30 matched lean controls, aged 22-60 years (mean 37, SEM 1.8 years)], we investigated how ventromedial prefrontal cortex seed-to-voxel resting-state connectivity distinguished between lean and obese participants at baseline. We used the results of this first step of our analyses to examine whether changes in ventromedial prefrontal cortex resting-state connectivity over 8 months could formaloss surgery-induced changes in ventromedial prefrontal cortex-ventral striatum resting-state connectivity to surgery-induced changes in homeostatic hormone regulation. More specifically, we focussed on changes in fasting state systemic leptin, a homeostatic hormone signalling satiety, and inhibiting reward-related dopamine signalling. We found that the surgery-induced increase in ventromedial prefrontal cortex-ventral striatum resting-state connectivity was correlated with a decrease in fasting-state systemic leptin. These findings establish the first link between individual differences in brain connectivity in reward circuits in a more tonic state at rest, weight change over time and homeostatic hormone regulation.