Increased Intracranial Pressure Attenuates the Pulsating Component of Cerebral Venous Outflow

Neurocritical Care - The underlying physiology of the intracranial pressure (ICP) curve morphology is still poorly understood. If this physiology is explained it could be possible to extract...     

Phenotypic Modification of Human Airway Epithelial Cells in Air–Liquid Interface Culture Induced by Exposure to the Tobacco-Specific Nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco-specific carcinogen. We used an air–liquid interface epithelial cell culture system to model changes associated with NNK exposure relative to pathologies documented in human tobacco-related illnesses. Although in vitro systems exhibit certain limitations, they often offer accentuation of subtle pathologies. While the distribution of cell types in control cultures typically favors the ciliated cell phenotype, NNK-exposed cultures transitioned to non-ciliated cell phenotypes as well as reflecting features consistent with squamous metaplasia. We conclude that NNK impacts normal growth and differentiation of human airway epithelium in a short interval of time in vitro.     

What to expect when you're expecting a hepatopancreatobiliary surgeon: self-reported experiences of HPB surgeons from different training pathways

BackgroundHepatopancreatobiliary (HPB) surgery fellowship training has multiple paths. Prospective trainees and employers must understand the differences between training pathways. This study examines self-reported fellowship experiences and current scope of practice across three pathways.MethodsAn online survey was disseminated to 654 surgeons. These included active Americas Hepato-Pancreato-Biliary Association (AHPBA) members and recent graduates of HPB, transplant–HPB and HPB–heavy surgical oncology fellowships.ResultsA total of 416 (64%) surgeons responded. Most respondents were male (89%) and most were practising in an academic setting (83%). 290 (70%) respondents underwent formal fellowship training. Although fellowship experiences varied, current practice was largely similar. Minimally invasive surgery (MIS) and ultrasound were the most commonly identified areas of training deficiencies and were, respectively, cited as such by 47% and 34% of HPB-, 49% and 50% of transplant-, and 52% and 25% of surgical oncology-trained respondents. Non-HPB cases performed in current practice included gastrointestinal (GI) and general surgery cases (56% and 49%, respectively) for HPB-trained respondents, transplant and general surgery cases (87% and 21%, respectively) for transplant-trained respondents, and GI surgery and non-HPB surgical oncology cases (70% and 28%, respectively) for surgical oncology-trained respondents.ConclusionsFellowship training in HPB surgery varies by training pathway. Training in MIS and ultrasound is deficient in each pathway. The ultimate scope of non-transplant HPB practice appears similar across training pathways. Thus, training pathway choice is best guided by the training experience desired and non-HPB components of anticipated practice.     

Thiol‐water proton exchange of glutathione,cysteine, and N‐acetylcysteine: Implications for CEST MRI

Amide‐, amine‐, and hydroxyl‐water proton exchange can generate MRI contrast through chemical exchange saturation transfer (CEST). In this study, we show that thiol‐water proton exchange can also generate quantifiable CEST effects under near‐physiological conditions (pH = 7.2 and 37°C) through the characterization of the pH dependence of thiol proton exchange in phosphate‐buffered solutions of glutathione, cysteine, and N‐acetylcysteine. The spontaneous, base‐catalyzed, and buffer‐catalyzed exchange contributions to the thiol exchange were analyzed. The thiol‐water proton exchange of glutathione and cysteine was found to be too fast to generate a CEST effect around neutral pH due to significant base catalysis. The thiol‐water proton exchange of N‐acetylcysteine was found to be much slower, yet still in the fast‐exchange regime with significant base and buffer catalysis, resulting in a 9.5% attenuation of the water signal at pH 7.2 in a slice‐selective CEST NMR experiment. Furthermore, the N‐acetylcysteine thiol CEST was also detectable in human serum albumin and agarose phantoms.     

Subconjunctival Orbital Fat Prolapse: An Update on Diagnosis and Management

Subconjunctival prolapse of orbital fat is an uncommon clinical entity in which intraconal orbital fat herniates into the subconjunctival space. Its diagnosis is mainly clinical in character and usually based on palpation, patient clinical history, and lesion features along with a slit lamp examination. Its pathophysiology remains unclear. Although frequently asymptomatic, clinical features may simulate conditions such as a prolapsed lacrimal gland, orbital lymphoma or dermolipoma and may worsen over time. In such cases, surgical removal or repositioning of the herniated fat may be necessary. While several surgical techniques have been described, no reports exist of a customized approach to manage this condition. This paper reviews the diagnosis and management of subconjunctival orbital fat prolapse.     

Independent and Combined Effects of Nicotine or Chronic Tobacco Smoking and HIV on the Brain: A Review of Preclinical and Clinical Studies

Tobacco smoking is highly prevalent among HIV-infected individuals. Chronic smokers with HIV showed greater cognitive deficits and impulsivity, and had more psychopathological symptoms and greater neuroinflammation than HIV non-smokers or smokers without HIV infection. However, preclinical studies that evaluated the combined effects of HIV-infection and tobacco smoking are scare. The preclinical models typically used cell cultures or animal models that involved specific HIV viral proteins or the administration of nicotine to rodents. These preclinical models consistently demonstrated that nicotine had neuroprotective and anti-inflammatory effects, leading to cognitive enhancement. Although the major addictive ingredient in tobacco smoking is nicotine, chronic smoking does not lead to improved cognitive function in humans. Therefore, preclinical studies designed to unravel the interactive effects of chronic tobacco smoking and HIV infection are needed. In this review, we summarized the preclinical studies that demonstrated the neuroprotective effects of nicotine, the neurotoxic effects of the HIV viral proteins, and the scant literature on nicotine or tobacco smoke in HIV transgenic rat models. We also reviewed the clinical studies that evaluated the neurotoxic effects of tobacco smoking, HIV infection and their combined effects on the brain, including studies that evaluated the cognitive and behavioral assessments, as well as neuroimaging measures. Lastly, we compared the different approaches between preclinical and clinical studies, identified some gaps and proposed some future directions.

Independent and combined effects of HIV and tobacco/nicotine. Left top and bottom panels: Both clinical studies of HIV infected persons and preclinical studies using viral proteins in vitro or in vivo in animal models showed that HIV infection could lead to neurotoxicity and neuroinflammation. Right top and bottom panels: While clinical studies of tobacco smoking consistently showed deleterious effects of smoking, clinical and preclinical studies that used nicotine show mild cognitive enhancement, neuroprotective and possibly anti-inflammatory effects. In the developing brain, however, nicotine is neurotoxic. Middle overlapping panels: Clinical studies of persons with HIV who were smokers typically showed additive deleterious effects of HIV and tobacco smoking. However, in the preclinical studies, when nicotine was administered to the HIV-1 Tg rats, the neurotoxic effects of HIV were attenuated, but tobacco smoke worsened the inflammatory cascade.

     

Prevalence,Evolution, and Risk Factors for Advanced Liver Fibrosis in Adults Undergoing Intestinal Transplantation

Introduction

Intestinal failure–associated liver disease (IFALD) occurs commonly in intestinal transplant (ITx) candidates receiving parenteral nutrition (PN). The aim of this study is to establish the prevalence and risk factors for advanced liver fibrosis in adults at the time of ITx.

Methods

Retrospective chart review of all ITx was performed in adults between January 2000 and May 2014. Advanced liver fibrosis was defined as stage 3 or stage 4 fibrosis.

Results

Fifty‐three patients met the inclusion criteria. The mean age was 50.6 ± 10.9 years, and the majority were female (60.4%) and Caucasian (67.9%). The mean body mass index was 21.7 ± 3.8 kg/m² and the median duration of PN was 402 (interquartile range: 529) days. Advanced liver fibrosis at the time of ITx was found in 13 patients (24.5%). The multivariate analysis revealed that female gender and white race were significant predictors of advanced liver fibrosis. A total bilirubin >3.0 mg/dL for > a month prior to ITx was associated with an odds ratio of 8.9 for advanced fibrosis at the time of ITx but did not reach statistical significance (P = 0.055).

Conclusion

Close to one‐quarter of the ITx recipients had advanced liver fibrosis. In the current era of improved PN management, our data suggests that previously reported risk factors for IFALD, such as extreme short gut syndrome and PN duration, may have a lesser impact on development of liver fibrosis. A prolonged duration of bilirubin elevation may be associated with advanced liver fibrosis in patients with IFALD, but this requires validation in a larger cohort.