Technology III: in-line vaporizer with reflector

As the clinical advantages of vapor anesthesia (VA) for sedation of patients in ICU become more apparent, the ergonomics, economy and safety issues need to be better addressed. Here we describe the use of a new commercial digital in-line anesthetic vaporizer that can be attached to the inspiratory limb of a ventilator. If used with a simple, and easily assembled secondary circuit and anesthetic reflector, the circuit remains remote from the patient, the VA consumption approaches a physical minimum, VA level is controlled and monitored, and the tidal volume size is not limited.     

The Effect of Pain on Major Cognitive Impairment in Older Adults

Older adults frequently report pain; cross-sectional studies have shown that pain is associated with worse cognitive function. However, longitudinal studies are lacking. We prospectively studied 441 participants without dementia, including 285 with pain, aged 65 years and older, enrolled in the Central Control of Mobility in Aging study, a prospective cohort study. We analyzed the longitudinal association between pain (measured with the Medical Outcomes Study pain severity scale) and major cognitive impairment (measured with the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test Delta) using Cox regression analysis adjusted for age, gender, ethnicity, and education. Over a mean follow-up of 2.75 years (standard deviation?=?1.94), there was no difference in the risk of developing cognitive impairment between participants with pain and participants without pain. However, among those with pain, risk for developing major memory impairment was higher among those with high levels of pain than those with low levels of pain (adjusted hazard ratio?=?3.47, 95% confidence interval?=?1.42–8.46). The association with pain and incident impairments in attention or executive function was not significant. We did not find that pain is associated with incident cognitive impairment in general, but among older adults with pain, a high level of pain is associated with increased risk of developing incident memory impairment.

Improved Differentiation of Low-Grade and High-Grade Gliomas and Detection of Tumor Proliferation Using APT Contrast Fitted from Z-Spectrum

Purpose

The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation.

Procedures

This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3 T scanner. After B₀ correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around ??1.5, 0, and +?3.5 ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated.

Results

Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58?±?0.99 vs. 6.79?±?1.05 %, p?<?0.05) than con_APT (4.34?±?0.95 vs. 4.05?±?2.02 %, p?>?0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC?=?0.723) than con_APT (AUC?=?0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75 %), diagnostic accuracy (78.2 %), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r?=?0.451, p?=?0.018) is better correlated with Ki-67 than con_APT (r?=?0.331, p?=?0.092).

Conclusions

Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

     

The Association between Choroidal Thickness Variations and Response to Intravitreal Bevacizumab in Central Serous Chorioretinopathy

PurposeTo analyze differences in the subfoveal choroidal thickness (SFChT) between bevacizumab responders (BevRs) and nonresponders (BevNRs) in patients with idiopathic central serous chorioretinopathy (CSC).MethodsThe medical records of 30 unilateral chronic CSC patients who were treated with intravitreal bevacizumab (IVB) as a first line treatment were reviewed. Patients were categorized as BevNRs when CSC did not completely resolve after a minimum of 3 IVB treatments. Enhanced depth imaging-optical coherence tomography was used and SFChT was measured before and after treatment. Choroidal hyperpermeability was also evaluated using indocyanine angiography.ResultsTwenty and 10 eyes were classified as BevRs or BevNRs, respectively. The mean number of IVB treatments was 2.22 ± 0.89 in BevRs, and 4.80 ± 1.03 in BevNRs. Compared with BevNRs, BevRs demonstrated significantly greater pretreatment SFChT (441.25 ± 88.09 vs. 364.10 ± 61.97 µm); SFChT reduction following IVB was significantly greater in BevRs than BevNRs. SFChT in the unaffected eyes was also greater in BevRs than BevNRs. Choroidal hyperpermeability was detected less frequently in BevNRs (hypofluorescence on late-phase, 0.0% and 33.3% in BevNRs and BevRs, respectively; p= 0.049).ConclusionsCompared with CSC eyes that did not respond well to IVB, BevRs demonstrated significantly thicker SFChT at baseline, greater reduction in SFChT after IVB treatment, and hyperfluorescence on late-phase indocyanine green angiography. We recommend IVB injection as the first-line therapy for CSC eyes with relatively high SFChT and hyperfluorescence on late-phase indocyanine green angiography.     

Microbiota That Affect Risk for Shigellosis in Children in Low-Income Countries

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17–0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8–220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.–induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.     

Fatigue is cross-sectionally not associated with objective assessments of inflammation,but changes in fatigue are associated with changes of disease activity assessments during biologic treatment of patients with established rheumatoid arthritis

Clinical Rheumatology - The associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients...     

Infection of human gastrointestinal cells by HIV-1

Human immunodeficiency virus (HIV-1) infected and replicated in primary cultures of normal human ileal and colonic epithelial cells. Monocyte-tropic strains (ADA, 24, and 36) were better able to replicate in the gastrointestinal (GI) cells than the T-cell-tropic HIV strain HTLV-IIIB. In some cultures, virus replication persisted through several months. Intestinal epithelium may be an initial target and reservoir for HIV and a vector for virus dissemination and transmission.     

Hepatitis C virus entry and neutralization

The processes of hepatitis C virus (HCV) entry and antibody-mediated neutralization are intimately linked. The high frequency of neutralizing antibodies (nAbs) that inhibit E2-CD81 interaction(s) suggests that this is a major target for the humoral immune response. The observation that HCV can transmit to naive cells by means of CD81-dependent and -independent routes in vitro awaits further investigation to assess the significance in vivo but may offer new strategies for HCV to escape nAbs. The identification of claudins in the entry process highlights the importance of cell polarity in defining routes of HCV entry and release, with recent experiments suggesting a polarized route of viral entry into cells in vitro. In this review, the authors summarize the current understanding of the mechanism(s) defining HCV entry and the role of nAbs in controlling HCV replication.     

Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of major depressive disorder. A number of studies have shown that this dysregulation is correlated with impaired forebrain glucocorticoid receptor (GR) function. To determine whether a primary, acquired deficit in forebrain GR signaling is an etiologic factor in the pathogenesis of depression, we generated a line of mice with time-dependent, forebrain-specific disruption of GR (FBGRKO). These mice develop a number of both physiological and behavioral abnormalities that mimic major depressive disorder in humans, including hyperactivity of the HPA axis, impaired negative feedback regulation of the HPA axis and, increased depression-like behavior. Importantly, a number of these abnormalities are normalized by chronic treatment with the tricyclic antidepressant, imipramine. Our findings suggest that imipramine's proposed activities on forebrain GR function are not essential for its antidepressant effects, and that alteration in GR expression may play a causative role in disease onset of major depressive disorder.