Clinical outcomes of biliary drainage of malignant biliary obstruction due to colorectal cancer metastases : a systematic review

Background and aims: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC). Biliary drainage is frequently performed to relieve symptoms of jaundice or enable palliative systemic therapy, but effective drainage can be difficult to accomplish. The aim of this study is to summarize literature on clinical outcomes of biliary drainage in mCRC patients with malignant biliary obstruction.& nbsp; Methods: We searched Medline and EMBASE for studies that included patients with malignant biliary obstruction secondary to mCRC, treated with endoscopic and/or percutaneous biliary drainage. We summarized available data on technical success, clinical success, adverse events, systemic therapy administration and survival after biliary drainage.& nbsp; Results: After screening 3584 references and assessing 509 full-text articles, seven cohort studies were included. In these studies, rates of technical success, clinical success and adverse events varied between 63%-94%, 42%81%, and 19%-39%, respectively. Subsequent chemotherapy was administered in 17%-56% of patients. Overall survival varied between 40 and 122 days across studies (278-365 days in patients who received subsequent chemotherapy, 42-61 days in patients who did not).& nbsp; Conclusions: Successful biliary drainage in mCRC patients can be challenging to achieve and is frequently associated with adverse events. Overall survival after biliary drainage is limited, but is significantly longer in patients treated with subsequent systemic therapy. Expected benefits of biliary drainage should be carefully weighed against its risks

Severe Daily Headache as an Uncommon Manifestation of Widespread Skull Base Osteomyelitis

Temporal bone osteomyelitis has been recognized for decades as a complication of otitis externa, specifically in elderly patients with diabetes. A much less prevalent form is skull base osteomyelitis. We report a 70-year-old man with diabetes who presented to our outpatient clinic with severe chronic daily complaints of headache. The headache was located frontoparietally and kept him awake at night. Imaging (nonenhanced computed tomography [CT], magnetic resonance imaging, and positron emission tomography/CT) showed a hypermetabolic mass on the right side of the skull base, in the middle ear, and in the mastoid process, with invasion and partial destruction of the surrounding elements of the petrous bone, the occipital bone, and the sphenoid bone on the right, with extension by way of the clivus into the apex of the left petrous bone. Diagnostic puncture revealed Streptococcus pneumoniae.The final diagnosis was severe daily headache due to central skull base osteomyelitis. Our case emphasizes the need for proper clinical and radiological investigation keeping the diagnosis of skull base osteomyelitis in mind with patients with diabetes or otherwise immunocompromised status who present with chronic daily headache and otalgia

The bidirectional association between sleep problems and autism spectrum disorder

Background: Sleep difficulties are prevalent in children with autism spectrum disorder (ASD). The temporal nature of the association between sleep problems and ASD is unclear because longitudinal studies are lacking. Our aim is to clarify whether sleep problems precede and worsen autistic traits and ASD or occur as a consequence o

SK channel-mediated metabolic escape to glycolysis inhibits ferroptosis and supports stress resistance in C. elegans

Metabolic flexibility is an essential characteristic of eukaryotic cells in order to adapt to physiological and environmental changes. Especially in mammalian cells, the metabolic switch from mitochondrial respiration to aerobic glycolysis provides flexibility to sustain cellular energy in pathophysiological conditions. For example, attenuation of mitochondrial respiration and/or metabolic shifts to glycolysis result in a metabolic rewiring that provide beneficial effects in neurodegenerative processes. Ferroptosis, a non-apoptotic form of cell death triggered by an impaired redox balance is gaining attention in the field of neurodegeneration. We showed recently that activation of small-conductance calcium-activated K+ (SK) channels modulated mitochondrial respiration and protected neuronal cells from oxidative death. Here, we investigated whether SK channel activation with CyPPA induces a glycolytic shift thereby increasing resilience of neuronal cells against ferroptosis, induced by erastin in vitro and in the nematode C. elegans exposed to mitochondrial poisons in vivo. High-resolution respirometry and extracellular flux analysis revealed that CyPPA, a positive modulator of SK channels, slightly reduced mitochondrial complex I activity, while increasing glycolysis and lactate production. Concomitantly, CyPPA rescued the neuronal cells from ferroptosis, while scavenging mitochondrial ROS and inhibiting glycolysis reduced its protection. Furthermore, SK channel activation increased survival of C. elegans challenged with mitochondrial toxins. Our findings shed light on metabolic mechanisms promoted through SK channel activation through mitohormesis, which enhances neuronal resilience against ferroptosis in vitro and promotes longevity in vivo

Prenatal and early postnatal measures of brain development and childhood sleep patterns

BackgroundBrain development underlies maturation of sleep patterns throughout childhood. Intrauterine head growth - marker of early neurodevelopment - has not been associated with childhood sleep characteristics. We explored associations between ultrasonographic measures of prenatal and early postnatal neurodevelopment and childhood sleep.MethodsA total of 6,808 children from a population-based birth cohort (Generation R) were included. Head circumference (HC) and lateral ventricles size were assessed with mid- and late-pregnancy fetal ultrasounds, and with cranial ultrasound 3-20 weeks postnatally. Mothers reported children's sleep duration at 2 and 3 years, and sleep problems at 1.5, 3, and 6 years.ResultsLarger ventricular size, but not HC, was related to longer sleep duration at 3 years (β=0.06 h, 95% confidence interval (CI): 0.02; 0.10 in late-pregnancy and β=0.11 h, 95% CI: 0.02; 0.20 in early infancy, mid-pregnancy parameters were unrelated to sleep duration). Larger HC in mid-pregnancy was associated with a reduced risk for being a "problematic sleeper" up to the age of 6 years (odds ratio (OR): 0.94, 95% CI: 0.89; 0.99). Consistently, children with larger HC in early infancy were less likely to be "problematic sleepers" at 3 and 6 years.ConclusionsThis study shows that variations in fetal and neonatal brain size may underlie behavioral expression of sleep in childhood. Albeit small effect estimates, these associations provide evidence for neurodevelopmental origins of sleep

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals

Background: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. Aim: To determine the prevalence of Do No

Microbial degradation of furanic compounds: biochemistry, genetics, and impact

Microbial metabolism of furanic compounds, especially furfural and 5-hydroxymethylfurfural (HMF), is rapidly gaining interest in the scientific community. This interest can largely be attributed to the occurrence of toxic furanic aldehydes in lignocellulosic hydrolysates. However, these compounds are also widespread in nature and in human processed foods, and are produced in industry. Although several microorganisms are known to degrade furanic compounds, the variety of species is limited mostly to Gram-negative aerobic bacteria, with a few notable exceptions. Furanic aldehydes are highly toxic to microorganisms, which have evolved a wide variety of defense mechanisms, such as the oxidation and/or reduction to the furanic alcohol and acid forms. These oxidation/reduction reactions constitute the initial steps of the biological pathways for furfural and HMF degradation. Furfural degradation proceeds via 2-furoic acid, which is metabolized to the primary intermediate 2-oxoglutarate. HMF is converted, via 2,5-furandicarboxylic acid, into 2-furoic acid. The enzymes in these HMF/furfural degradation pathways are encoded by eight hmf genes, organized in two distinct clusters in Cupriavidus basilensis HMF14. The organization of the five genes of the furfural degradation cluster is highly conserved among microorganisms capable of degrading furfural, while the three genes constituting the initial HMF degradation route are organized in a highly diverse manner. The genetic and biochemical characterization of the microbial metabolism of furanic compounds holds great promises for industrial applications such as the biodetoxifcation of lignocellulosic hydrolysates and the production of value-added compounds such as 2,5-furandicarboxylic acid

Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−

The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions