Structural and Resting-State Brain Alterations in Trauma-Exposed Firefighters: Preliminary Results.
To analyze the altered brain regions and intrinsic brain activity patterns in trauma-exposed firefighters without posttraumatic stress disorder (PTSD). Resting-state functional MRI (rsfMRI) was performed for all subjects. Thirty-one firefighters over 40 years of age without PTSD (31 men; mean age, 49.8 ± 4.7 years) were included. Twenty-six non-traumatized healthy controls (HCs) (26 men; mean age, 65.3 ± 7.84 years) were also included. Voxel-based morphometry was performed to investigate focal differences in the brain anatomy. Seed-based functional connectivity analysis was performed to investigate differences in spontaneous brain characteristics. The mean z-scores of the Seoul Verbal Learning Test for immediate and delayed recall, Controlled Oral Word Association Test (COWAT) score for animals, and COWAT phonemic fluency were significantly lower in the firefighter group than in the HCs, indicating decreased neurocognitive function. Compared to HCs, firefighters showed reduced gray matter volume in the left superior parietal gyrus and left inferior temporal gyrus. Further, in contrast to HCs, firefighters showed alterations in rsfMRI values in multiple regions, including the fusiform gyrus and cerebellum. Structural and resting-state functional abnormalities in the brain may be useful imaging biomarkers for identifying alterations in trauma-exposed firefighters without PTSD.


Molecular determinants for selective recognition of antidepressants in the human serotonin and norepinephrine transporters.
Inhibitors of the serotonin transporter (SERT) and norepinephrine transporter (NET) are widely used in the treatment of major depressive disorder. Although SERT/NET selectivity is a key determinant for the therapeutic properties of these drugs, the molecular determinants defining SERT/NET selectivity are poorly understood. In this study, the structural basis for selectivity of the SERT selective inhibitor citalopram and the structurally closely related NET selective inhibitor talopram is delineated. A systematic structure-activity relationship study allowed identification of the substituents that control activity and selectivity toward SERT and NET and revealed a common pattern showing that SERT and NET have opposite preference for the stereochemical configuration of these inhibitors. Mutational analysis of nonconserved SERT/NET residues within the central substrate binding site was performed to determine the molecular basis for inhibitor selectivity. Changing only five residues in NET to the complementary residues in SERT transferred a SERT-like affinity profile for R- and S-citalopram into NET, showing that the selectivity of these compounds is determined by amino acid differences in the central binding site of the transporters. In contrast, the activity of R- and S-talopram was largely unaffected by any mutations within the central substrate binding site of SERT and NET and in the outer vestibule of NET, suggesting that citalopram and talopram bind to distinct sites on SERT and NET. Together, these findings provide important insight into the molecular basis for SERT/NET selectivity of antidepressants, which can be used to guide rational development of unique transporter inhibitors with fine-tuned transporter selectivity.


Importance of free fatty acids as a determinant of myocardial oxygen consumption and myocardial ischemic injury during norepinephrine infusion in dogs.
Increased delivery of free fatty acids raises myocardial oxygen consumption (MVO(2)) without influencing mechanical performance. The effects of norepinephrine on MVO(2) and on the size of ischemic injury after acute coronary occlusion were therefore studied before and during inhibition of lipolysis with beta-pyridylcarbinol. In spite of similar mechanical responses to norepinephrine, MVO(2) increased by 57+/-11% before and significantly less, 31+/-6%, (P < 0.01) during inhibition of lipolysis. After coronary occlusion the ischemic injury associated with norepinephrine infusion, as evidenced by epicardial mapping of S-T segment elevation, was larger before (7.9+/-1.1 mV) than during inhibited lipolysis (2.8+/-0.4 mV; P < 0.005). Average S-T segment elevation associated with norepinephrine infusion during inhibited lipolysis (2.8+/-0.4 mV) was even lower (P < 0.05) than during control occlusion alone, before drug administration (4.4+/-0.7 mV). In conjunction with an antilipolytic agent, norepinephrine was shown to reduce the extent and magnitude of the myocardial ischemic injury produced by acute coronary occlusion; this could be due to an improved balance between myocardial oxygen supply and requirement.


Telemonitoring readiness among Austrian diabetic patients: A cross-sectional validation study.
Digitalized healthcare services offer remote and cost-effective treatment of diabetes patients. Thus, the present online study analyzed the readiness to use telemonitoring among Austrian diabetes patients. We developed and validated a German version of the patient telehealth readiness assessment tool and performed quantitative context analysis of free-text comments on perceived barriers and benefits of telemonitoring. Participants (n = 41, 42.6% females) achieved a medium average readiness level for telemonitoring. The three top benefits were intensified care, shorter travel and waiting times, and better therapy adjustment. The top three barriers were data privacy issues, loss of personal communication and focus on blood sugar, and teledoctor competence. Diabetes patients represent a suitable target group for remote treatment opportunities. However, a shift from traditional face-to-face medical care to exclusive telemonitoring treatment from diagnosis to consultation and treatment requires fundamental new legal framework conditions.


Immunoreceptor tyrosine-based inhibitory motif of the IL-4 receptor associates with SH2-containing phosphatases and regulates IL-4-induced proliferation.
Immunoreceptor tyrosine-based inhibitory motifs (ITIM) have been implicated in the negative modulation of immunoreceptor signaling pathways. The IL-4R alpha-chain (IL-4Ralpha) contains a putative ITIM in the carboxyl terminal. To determine the role of ITIM in the IL-4 signaling pathway, we ablated the ITIM of IL-4Ralpha by deletion and site-directed mutagenesis and stably expressed the wild-type (WT) and mutant hIL-4Ralpha in 32D/insulin receptor substrate-2 (IRS-2) cells. Strikingly, 32D/IRS-2 cells expressing mutant human (h)IL-4Ralpha were hyperproliferative in response to IL-4 compared with cells expressing WT hIL-4Ralpha. Enhanced tyrosine phosphorylation of Stat6, but not IRS-2, induced by hIL-4 was observed in cells expressing mutant Y713F. Using peptides corresponding to the ITIM of hIL-4Ralpha, we demonstrate that tyrosine-phosphorylated peptides, but not their nonphosphorylated counterparts, coprecipitate SH2-containing tyrosine phosphatase-1, SH2-containing tyrosine phosphatase-2, and SH2-containing inositol 5'-phosphatase. The in vivo association of SH2-containing inositol 5'-phosphatase with IL-4Ralpha was verified by coimmunoprecipitation with anti-IL-4Ralpha Abs. These results demonstrate a functional role for ITIM in the regulation of IL-4-induced proliferation.


Cellular compartmentation of Ehrlich ascites tumor cells.
The digitonin method for the study of cellular compartmentation in mitochondrial and cytosolic fractions was applied to Ehrlich ascites tumor cells. The volume of mitochondrial and cytosolic water spaces are calculated to be 1.62 microliter/30 x 10(6) cells respectively, by the technique of 3H2O permeable and (14C)-sucrose impermeable spaces. The validity of the methods was tested by the distribution of cytosolic (lactate dehydrogenase) and mitochondrial (citrate synthase and glutamate dehydrogenase) marker enzymes. As occurs in normal hepatic cells, an asymmetric distribution of ATP and ADP was observed. The ATP/ADP ratio in the cytosolic fraction was 7 times higher than in the mitochondrial fraction.


Experimental evidence of masculinization by continuous illumination in a temperature sex determination teleost (Atherinopsidae) model: is oxidative stress involved?
The present study evaluates the influence of continuous light on phenotypic sex ratios in Chirostoma estor, a temperature sex determination animal model. Relative gene expression levels of 5 day old larvae were performed on two early gonad differentiation genes (sox9 and foxl2), two stress axis activation genes (gcr1 and crf) and four reactive oxygen species (ROS) antagonist effector genes (sod2, ucp2, gsr and cat). Two light treatments were applied from fertilization; control (12L:12D) simulated natural photoperiod and a continuous illumination photoperiod. By the end of the trial (12 weeks after hatching), differentiated and normal gonads were clearly identifiable in both treatments by histological observations. Regarding sex ratio, 73% of phenotypic males were found in continuous illumination compared with 40% in controls. Consistently, the sox9 gene (involved in early testis differentiation) showed an over expression in 64% of the individual larvae analysed compared with foxl2 (ovarian differentiation) suggesting a masculinization tendency in continuous illumination. On the other hand, only 36% of individuals showed the same tendency in the control treatment consistent with phenotypic sex ratios found under normal culture conditions. Relative gene expression results did not show significant difference in sod2, ucp2 and gcr1 levels, but cat, gsr and crf showed significantly higher expression levels in the continuous illumination treatment suggesting that both, the stress axis and ROS response mechanisms were activated at this time. This study suggests, a link between continuous light, oxidative stress and environmental sex determination in vertebrates. However, further research is necessary to describe this possible upstream mechanism that may drive some aspects of sexual plasticity in vertebrates.


Increased use of colorectal cancer tests--United States, 2002 and 2004.
Colorectal cancer is the second leading cause of cancer-related death (after lung/bronchus cancer) in the United States. In 2002, a total of 139,534 adults in the United States had colorectal cancer diagnosed, and 56,603 died. The U.S. Preventive Services Task Force and other national organizations recommend that adults aged >/=50 years be screened for colorectal cancer with one or more of the following tests: fecal occult blood testing (FOBT) every year, sigmoidoscopy or double-contrast barium enema every 5 years, or colonoscopy every 10 years. To estimate current rates of use of colorectal cancer screening tests and to evaluate changes in test use, CDC compared data from the 2002 and 2004 Behavioral Risk Factor Surveillance System (BRFSS) surveys. This report describes the results of that comparison, which indicated that the proportion of BRFSS respondents reporting use of FOBT and/or sigmoidoscopy or colonoscopy had increased overall from 2002 to 2004. Measures to increase awareness and encourage regular colorectal cancer screening must be continued to reduce mortality from colorectal cancer.


Operative timing of liver transplantation for patients with severe hepatitis.
Fulminant hepatic failure manifests a rapid onset, serious complications, and a high mortality, but still there is a possibility of recovery. Once the patient is able to pass a crisis, the liver is able to regenerate completely and regain its normal function. Therefore it is of vital importance to determine the eligible timing for transplantation. Premature surgery might result in a loss of the chance of internal medical treatment and misuse of liver resources, whereas delayed surgery might increase the difficulty of treatment in the preoperative period and the possibility of complications and medical expense, which eventually result in decreased rate of success and survival. This problem remains worldwide how to choose the optional timing of operation. Thirty-six patients with severe hepatitis were treated by orthotopic liver transplantation. The distribution of MELD scores in these patients was: 10-19 in 8 patients, 20-29 in 10, 30-39 in 11, and 40 in 7. They were divided into two groups: MELD score <30 and MELD score >or=30. Parameters (1-year survival rate, complications, preoperative use of artificial liver, operative time, volume of bleeding and blood transfusion, and average hospital costs) were examined as prognostic factors after liver transplantation. The 1-year survival rate of the MELD score <30 group was higher than that of the >or=30 group (77.8% and 33.3%, P=0.007), and the rate of complications in the <30 group was lower (P=0.012). There were no differences in the timing of artificial liver treatment, operative time, operative hemorrhage, and transfusion between the two groups (P=0.742). But the average daily hospital cost in the MELD score >or=30 group was higher (P=0.008). This study shows that when the MELD score is <30 it may be the optimal time to perform liver transplantation for patients with severe hepatitis.


Quality of Breast Cancer Treatment at a Rural Cancer Center in Rwanda.
As breast cancer incidence and mortality rise in sub-Saharan Africa, it is critical to identify strategies for delivery of high-quality breast cancer care in settings with limited resources and few oncology specialists. We investigated the quality of treatments received by a cohort of patients with breast cancer at Butaro Cancer Center of Excellence (BCCOE), Rwanda's first public cancer center. We reviewed medical records of all female patients diagnosed with invasive breast cancer at BCCOE between July 2012 and December 2013. We evaluated the provision of chemotherapy, endocrine therapy, surgery, and chemotherapy dose densities. We also applied modified international quality metrics and estimated overall survival using interval-censored analysis. Among 150 patients, 28 presented with early-stage, 64 with locally advanced, and 53 with metastatic disease. Among potentially curable patients (ie, those with early-stage or locally advanced disease), 74% received at least four cycles of chemotherapy and 63% received surgery. Among hormone receptor-positive patients, 83% received endocrine therapy within 1 year of diagnosis. Fifty-seven percent of potentially curable patients completed surgery and chemotherapy and initiated endocrine therapy if indicated within 1 year of biopsy. Radiotherapy was not available. At the end of follow-up, 62% of potentially curable patients were alive, 24% were dead, and 14% were lost to follow-up. Appropriate delivery of chemotherapy and endocrine therapy for breast cancer is possible in rural sub-Saharan African even without oncologists based on site. Performing timely surgery and ensuring treatment completion were key challenges after the opening of BCCOE. Further investigation should examine persistent quality gaps and the relationship between treatment quality and survival.


Bacterial cell wall nanoimaging by autoblinking microscopy.
Spurious blinking fluorescent spots are often seen in bacteria during single-molecule localization microscopy experiments. Although this 'autoblinking' phenomenon is widespread, its origin remains unclear. In Deinococcus strains, we observed particularly strong autoblinking at the periphery of the bacteria, facilitating its comprehensive characterization. A systematic evaluation of the contributions of different components of the sample environment to autoblinking levels and the in-depth analysis of the photophysical properties of autoblinking molecules indicate that the phenomenon results from transient binding of fluorophores originating mostly from the growth medium to the bacterial cell wall, which produces single-molecule fluorescence through a Point Accumulation for Imaging in Nanoscale Topography (PAINT) mechanism. Our data suggest that the autoblinking molecules preferentially bind to the plasma membrane of bacterial cells. Autoblinking microscopy was used to acquire nanoscale images of live, unlabeled D. radiodurans and could be combined with PALM imaging of PAmCherry-labeled bacteria in two-color experiments. Autoblinking-based super-resolved images provided insight into the formation of septa in dividing bacteria and revealed heterogeneities in the distribution and dynamics of autoblinking molecules within the cell wall.


Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults.
Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here, we sought to translate our preclinical findings to humans and determine the safety and efficacy of MitoQ. Twenty healthy older adults (60-79 years) with impaired endothelial function (brachial artery flow-mediated dilation <6%) underwent 6 weeks of oral supplementation with MitoQ (20 mg/d) or placebo in a randomized, placebo-controlled, double-blind, crossover design study. MitoQ was well tolerated, and plasma MitoQ was higher after the treatment versus placebo period (P<0.05). Brachial artery flow-mediated dilation was 42% higher after MitoQ versus placebo (P<0.05); the improvement was associated with amelioration of mitochondrial reactive oxygen species-related suppression of endothelial function (assessed as the increase in flow-mediated dilation with acute, supratherapeutic MitoQ [160 mg] administration; n=9; P<0.05). Aortic stiffness (carotid-femoral pulse wave velocity) was lower after MitoQ versus placebo (P<0.05) in participants with elevated baseline levels (carotid-femoral pulse wave velocity >7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of oxidative stress, also was lower after MitoQ versus placebo (P<0.05). Participant characteristics, endothelium-independent dilation (sublingual nitroglycerin), and circulating markers of inflammation were not different (all P>0.1). These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02597023.


Postprandial glycaemic response: how is it influenced by characteristics of cereal products?
Cereal products exhibit a wide range of glycaemic indexes (GI), but the interaction of their different nutrients and starch digestibility on blood glucose response is not well known. The objective of this analysis was to evaluate how cereal product characteristics can contribute to GI and insulinaemic index and to the parameters describing glycaemic or insulinaemic responses (incremental AUC, maximum concentration and Δpeak). Moreover, interactions between the different cereal products characteristics and glycaemic response parameters were assessed for the first time. Relationships between the cereal products characteristics and the glycaemic response were analysed by partial least square regressions, followed by modelling. A database including 190 cereal products tested by the usual GI methodology was used. The model on glycaemic responses showed that slowly digestible starch (SDS), rapidly digestible starch (RDS) and fat and fibres, and several interactions involving them, significantly explain GI by 53 % and Δpeak of glycaemia by 60 %. Fat and fibres had important contributions to glycaemic response at low and medium SDS contents in cereal products, but this effect disappears at high SDS levels. We showed also for the first time that glycaemic response parameters are dependent on interactions between starch digestibility (interaction between SDS and RDS) and nutritional composition (interaction between fat and fibres) of the cereal products. We also demonstrated the non-linear effect of fat and fibres (significant effect of their quadratic terms). Hence, optimising both the formula and the manufacturing process of cereal products can improve glucose metabolism, which is recognised as strongly influential on human health.


Lasing in a three-dimensional photonic crystal of the liquid crystal blue phase II.
Photonic-bandgap materials, with periodicity in one, two or three dimensions, offer control of spontaneous emission and photon localization. Low-threshold lasing has been demonstrated in two-dimensional photonic-bandgap materials, both with distributed feedback and defect modes. Liquid crystals with chiral constituents exhibit mesophases with modulated ground states. Helical cholesterics are one-dimensional, whereas blue phases are three-dimensional self-assembled photonic-bandgap structures. Although mirrorless lasing was predicted and observed in one-dimensional helical cholesteric materials and chiral ferroelectric smectic materials, it is of great interest to probe light confinement in three dimensions. Here, we report the first observations of lasing in three-dimensional photonic crystals, in the cholesteric blue phase II. Our results show that distributed feedback is realized in three dimensions, resulting in almost diffraction-limited lasing with significantly lower thresholds than in one dimension. In addition to mirrorless lasing, these self-assembled soft photonic-bandgap materials may also be useful for waveguiding, switching and sensing applications.


Addressing Moral Distress in Correctional Nursing: A Call to Action.
In 1984, Jameton defined moral distress in nursing practice as the negative experience that occurs "…when one knows the right thing to do, but institutional constraints make it nearly impossible to pursue…" (p. 6). Little research has been done about the magnitude and impact of moral distress among nurses working in correctional settings. All correctional nurses (CNs) will experience some form of moral distress during their careers. Consequences include burnout syndrome, blurred professional boundaries, and impaired ethical reasoning. There is a need for strong CN leaders who model professional behavior and provide orientation and mentoring for new CNs. A research agenda is needed to inform strong orientation and continuing education programs to introduce the concept of moral distress and related resources to CNs and to assist them in preventing or mitigating the consequences of moral distress.


Magnetic structures produced by the small-scale dynamo.
Small-scale dynamo action has been obtained for a flow previously used to model fluid turbulence, where the sensitivity of the magnetic field parameters to the kinetic energy spectrum can be explored. We apply quantitative morphology diagnostics, based on the Minkowski functionals, to magnetic fields produced by the kinematic small-scale dynamo to show that magnetic structures are predominantly filamentary rather than sheetlike. Our results suggest that the thickness, width, and length of the structures scale differently with magnetic Reynolds number as R(m)(-2/(1-s)) and R(m)(-0.55} for the former two, whereas the latter is independent of R(m), with s the slope of the energy spectrum.


Sympathomimetic preference and ethnicity in male felons.
A disproportionate number of Euro-American inmates given either an amphetamine- or cocaine-abuse diagnosis upon admission to prison were given a diagnosis of amphetamine abuse. A disproportionate number of African-American inmates were given a cocaine-abuse diagnosis. Of the 800 consecutively admitted inmates who were given one diagnosis or the other, 68% of the cocaine abusers, but only 4% of the amphetamine abusers, were African American.


Dengue virus type-3 envelope protein domain III; expression and immunogenicity.
Production of a recombinant and immunogenic antigen using dengue virus type-3 envelope protein is a key point in dengue vaccine development and diagnostic researches. The goals of this study were providing a recombinant protein from dengue virus type-3 envelope protein and evaluation of its immunogenicity in mice. Multiple amino acid sequences of different isolates of dengue virus type-3, corresponding to the envelope protein domain III, were achieved from GenBank. Clustal V alignment tool was used to provide a consensus amino acid sequence. Nucleotide sequence of the coding gene was optimized using "Optimizer". The origami (DE3) strain of Escherichia coli was used as the host in order to express the protein. A commercial affinity chromatography method was used to purify the recombinant protein. Immunogenicity of the recombinant protein was evaluated in mice using ELISA, MTT and cytokine assays. A consensus amino acid sequence corresponding to the most important region of dengue virus type-3 envelope protein (domain III) was provided. A high concentration (≥ 20 mg/L culture medium) of soluble recombinant antigen (EDIII3) was achieved. Immunized mice developed specific antibody responses against EDIII3 protein. The splenocytes from EDIII3-immunized mice showed a high proliferation rate in comparison with the negative control. In addition, the concentrations of two measured cytokines (IFN-γ and IL-4) were increased markedly in immunized mice. The results showed that the expressed recombinant EDIII3 protein is an immunogenic antigen and can be applied to induce specific immune responses against dengue virus type-3.


An investigation of the use of app technology to support clinical management of patients with chronic myeloid leukaemia (CML).
The availability of healthcare apps to support patient self-management of various medical conditions, including cancer, has increased considerably in the past decade. However, there are limited published data on the role of apps in the management of chronic myeloid leukaemia (CML). The primary aim of this study was to investigate the current and future role of apps as a means of supporting patients with CML. A 31-item questionnaire was developed and distributed to patients via three on-line CML support groups. Responses were received from 286 patients. There was an approximate 2:1 female: male split and the majority (54%, n = 155) resided in the United Kingdom. 91% (n = 260) of respondents were currently receiving drug treatment for their CML. 23.4% (n = 67) of respondents were aware that apps were available to support their CML management and 11.5% (n = 33) had experience of using such an app. 94.1% (n = 238) of those who had not used a patient support app in the past stated that they would consider using an app in the future to help manage their disease. App awareness was significantly higher amongst male patients (30.3% vs. 19.9%). Likelihood of being a current or previous app user was higher amongst younger patients (16.3% for <55 years old vs. 5.6% for ≥55 years old) whilst younger patients and those with a more recent diagnosis of CML were both more likely to be interested in using an app in the future. When asked about potential app functionality, a drug interaction checker was the feature of greatest interest to respondents. We have identified both a lack of awareness of and a low uptake of patient support apps amongst CML patients. Importantly, we have demonstrated a clear interest in CML-specific apps amongst this population. Based on the functionality that study participants were most interested in, we will work with health care professionals, app developers and patients to develop a new app to deliver holistic support to CML patients.


Retinal detachment in highly myopic eyes due to macular holes and epiretinal traction.
We operated on four highly myopic eyes with recurrent retinal detachment due to macular holes. A thin layer of epiretinal tissue was present over the posterior retina in each eye, probably causing tangential traction on the retina and accounting for the recurrent detachment. Biopsy of the tissue from one case showed mainly acellular material resembling cortical vitreous. Recognizing this clinical condition may permit successful treatment of certain cases with recurrent retinal detachment in highly myopic eyes with macular holes.


Elucidating Stress-Strain Relations of ZrB12 from First-Principles Studies.
Transition-metal boron-rich compounds exhibit favorable synthesis conditions and mechanical properties that hold great promise for wide-ranging applications. However, the complex bonding networks of these compounds produce diverse structural and mechanical behaviors that require in-depth studies. A notable case is ZrB12, which has been reported to possess high Vickers hardness comparable to those of ReB2 and WB4. Surprisingly, first-principles calculations of stress-strain relations reveal unexpected low indentation strengths of ZrB12 well below those of ReB2 and WB4. Such contrasting results are reconciled by noting that the additional presence of a boron-rich phase of ZrB50 in the experimental synthesis process likely plays a key role in the extrinsic strengthening. These findings uncover mechanisms for the higher measured strength of ZrB12 and offer insights for elucidating extrinsic hardening phenomena that may exist in other transition-metal compounds.


Changes in Use of Postacute Care Associated With Accountable Care Organizations in Hip Fracture, Stroke, and Pneumonia Hospitalized Cohorts.
To examine changes in more and less discretionary condition-specific postacute care use (skilled nursing, inpatient rehabilitation, home health) associated with Medicare accountable care organization (ACO) implementation. 2009-2014 Medicare fee-for-service claims. Difference-in-difference methodology comparing postacute outcomes after hospitalization for hip fracture and stroke (where rehabilitation is fundamental to the episode of care) to pneumonia, (where it is more discretionary) for beneficiaries attributed to ACO and non-ACO providers. Across all 3 cohorts, in the baseline period ACO patients were more likely to receive Medicare-paid postacute care and had higher episode spending. In hip fracture patients where rehabilitation is standard of care, ACO implementation was associated with 6%-8% increases in probability of admission to a skilled nursing facility or inpatient rehabilitation (compared with home without care), and a slight reduction in readmissions. In a clinical condition where rehabilitation is more discretionary, pneumonia, ACO implementation was not associated with changes in postacute location, but episodic spending decreased 2%-3%. Spending decreases were concentrated in the least complex patients. Across all cohorts, the length of stay in skilled nursing facilities decreased with ACO implementation. ACOs decreased spending on postacute care by decreasing use of discretionary services. ACO implementation was associated with reduced length of stay in skilled nursing facilities, while hip fracture patients used institutional postacute settings at higher rates. Among pneumonia patients, we observed decreases in spending, readmission days, and mortality associated with ACO implementation.


Source-Sink Manipulation Affects Accumulation of Zinc and Other Nutrient Elements in Wheat Grains.
To better understand the source-sink flow and its relationships with zinc (Zn) and other nutrients in wheat (Triticum aestivum L.) plants for biofortification and improving grain nutritional quality, the effects of reducing the photoassimilate source (through the flag leaf removal and spike shading) or sink (through the removal of all spikelets from one side of the spike, i.e., 50% spikelets removal) in the field of the accumulation of Zn and other nutrients in grains of two wheat cultivars (Jimai 22 and Jimai 44) were investigated at two soil Zn application levels. The kernel number per spike (KNPS), single panicle weight (SPW), thousand kernel weight (TKW), total grain weight (TGW) sampled, concentrations and yields of various nutrient elements including Zn, iron (Fe), manganese (Mn), copper (Cu), nitrogen (N), phosphorus (P), potassium (K), calcium (Ca) and magnesium (Mg), phytate phosphorus (phytate-P), phytic acid (PA) and phytohormones (ABA: abscisic acid, and the ethylene precursor ACC: 1-aminocylopropane-1-carboxylic acid), and carbon/N ratios were determined. Soil Zn application significantly increased the concentrations of grain Zn, N and K. Cultivars showing higher grain yields had lower grain protein and micronutrient nutritional quality. SPW, KNPS, TKW (with the exception of TKW in the removal of half of the spikelets), TGW, and nutrient yields in wheat grains were most severely reduced by half spikelet removal, secondly by spike shading, and slightly by flag leaf removal. Grain concentrations of Zn, N and Mg consistently showed negative correlations with SPW, KNPS and TGW, but positive correlations with TKW. There were general positive correlations among grain concentrations of Zn, Fe, Mn, Cu, N and Mg, and the bioavailability of Zn and Fe (estimated by molar ratios of PA/Zn, PA/Fe, PA × Ca/Zn, or PA × Ca/Fe). Although Zn and Fe concentrations were increased and Ca was decreased in treatments of half spikelet removal and spike shading, the treatments simultaneously increased PA and limited the increase in bioavailability of Zn and Fe. In general, different nutrient elements interact with each other and are affected to different degrees by source-sink manipulation. Elevated endogenous ABA levels and ABA/ACC ratios were associated with increased TKW and grain-filling of Zn, Mn, Ca and Mg, and inhibited K in wheat grains. However, the effects of ACC were diametrically opposite. These results provide a basis for wheat grain biofortification to alleviate human malnutrition.


Automatic Biological Cell Counting Using a Modified Gradient Hough Transform.
We present a computational method for pseudo-circular object detection and quantitative characterization in digital images, using the gradient accumulation matrix as a basic tool. This Gradient Accumulation Transform (GAT) was first introduced in 1992 by Kierkegaard and recently used by Kaytanli & Valentine. In the present article, we modify the approach by using the phase coding studied by Cicconet, and by adding a "local contributor list" (LCL) as well as a "used contributor matrix" (UCM), which allow for accurate peak detection and exploitation. These changes help make the GAT algorithm a robust and precise method to automatically detect pseudo-circular objects in a microscopic image. We then present an application of the method to cell counting in microbiological images.


Responding to Distress Choosing Between Care and Food: Attachment Orientation and Emotion Regulation.
According to attachment theory, care-seeking is the primary coping strategy in threatening situations. However, anxious and avoidant individuals often use secondary regulation strategies. The purpose of this study was to test whether, in a potentially threatening situation, the participants' attachment orientation affects whether they prefer to resort to care or food to regulate their negative emotions. Ninety-two participants took part in an experimental situation in which they had to choose between pictures of care or food, following the presentation of threatening images randomly alternating with neutral ones. Results showed that care pictures were chosen to a greater extent in the threatening condition compared to the food pictures and the neutral condition, without distinction of attachment orientation. In addition, in threatening condition, anxious individuals chose to care less than non-anxious individuals. Finally, avoidant participants chose care pictures to a lesser extent than individuals low on avoidance in the neutral condition, but not in the threatening condition. In conclusion, attachment anxiety was associated with more difficulty in the choice of representation of care in a threatening condition, while avoidant individuals show their defensive strategies in the neutral condition rather than in the threatening condition.


Development and iterative refinement of an internet-based service for Chinese family caregivers of people with Alzheimer Disease.
This poster reports on the developmental phase of a new internet-based support services (ICSS) for Chinese caregivers of people with Alzheimer Disease (AD): a specialized email application and an informational website. Bilingual Chinese caregivers wanted internet-based information in both Chinese and English. Usability testing and heuristic evaluation results revealed that the interface successfully supported the core functionality, but can be refined to improve usability.


Beverage intake in low-income parent-child dyads.
Beverage consumption adds to daily energy intake and often exceeds the recommended amount for discretionary energy. Previous research has shown that children are consuming sugar-sweetened beverages (SSB) in greater frequency and the relationship between parent-child dyads in beverage consumption is meaningful due to the parental influence on the development of beverage consumption behaviors. In particular, low-income families are at greater risk for obesity and higher levels of SSB consumption. The current investigation assessed habitual beverage intake among low-income parent-child dyads (N=95) with children between the ages of 9-17 years. The sample (46% African American; 45% Caucasian) had a mean body mass index (BMI) for the parents of 31.8±8.9 kg/m(2), while the mean BMI percentile for age and gender for the children was 70.3±31.3. Both parents and children consumed fewer nutrient-dense beverages and more energy-dense beverages than the recommended amount. The mean daily energy intake from beverages was 451±236 kcal for the parents and 457±237 kcal for the children. Correlations between parent-child dyad intake was also evident, identifying parents as potential role models and gatekeepers of the home food environment. Future interventions to prevent childhood obesity in low-income populations should address beverage intake, particularly SSB consumption, and determine the degree to which this behavior is learned behavior in the home.


Nontraumatic central fracture dislocation of the hip in a patient with chronic kidney disease and post gastrectomy.
PATIENTs with secondary hyperparathyroidism caused by chronic kidney disease (CKD) develop secondary osteoporosis, which increases fracture risk. We report a case of insufficiency fractures complicated by secondary osteoporosis caused by chronic renal failure and gastrectomy. A 78-year-old man with a medical history of nephrotic syndrome and gastric cancer experienced an occult intertrochanteric fracture of his left femur after falling. Ten days after the first fracture, the patient was treated with hemodialysis for acute uremic symptoms. Eight weeks after this fracture, he sustained a right insufficiency acetabular fracture and was treated with total hip arthroplasty (THA). For patients with CKD, effective fracture prevention is difficult. THA with reconstruction of the acetabulum was an effective therapy in a patient with nontraumatic central fracture dislocation of the hip.


[Role of different scale structures of titanium implant in the biological behaviors of human umbilical vein endothelial cells].
To study the role of different scale structure of Ti implants on the biological behaviors of human umbilical vein endothelial cell (HUVECs) and to reveal the role of material surface topographical features on peri-implant angiogenesis. Titanium (Ti) discs with different surface structures (Ti discs with smooth surface, Ti discs with nano scale structure, Ti discs with micro scale structure and Ti discs with micro/nano scale structure, named as SM-Ti, Nano-Ti, Micro-Ti and Micro/Nano-Ti, respectively) were prepared and their surface topographical features were confirmed via scanning electron microscopy (SEM) observation. HUVECs were cultured on these Ti discs. Biological outcomes of HUVECs on different surfaces were carried out, including cell adhesive capacity, proliferation, vascular endothelial growth factor (VEGF) production and intracellular expression of Ca(2+). The results of SEM images and immunofluorescence double staining of rhodamine-phalloidin and DAPI showed that compared with the SM-Ti and Nano-Ti group, the adhesive capacity and proliferation behavior of HUVECs on the surfaces of Micro-Ti and Micro/Nano-Ti was decreased. The results of culturing HUVECs on different groups of Ti discs after 24 hours showed that the cells number grew from (18±4) to (42±6)/ vision on SM-Ti, (28±6) to (52±10)/vision on Nano-Ti, (20±4) to (21±6)/vision on Micro-Ti and (16±4) to (18±6)/vision on Micro/Nano-Ti. Moreover, compared with the adhesion and proliferation of HUVECs on SM-Ti group and Nano-Ti, the adhesion and proliferation of HUVECs on Micro-Ti group and Micro/Nano-Ti group was significantly reduced (P<0.05).The results of enzyme-linked immunosorbent assay (ELISA) showed that the VEGF productions of SM-Ti, Nano-Ti, Micro-Ti and Micro/Nano-Ti were (690±35) ng/L, (560±20) ng/L, (474±43) ng/L and (517±29) ng/L, respectively. Moreover, compared with the VEGF production of HUVECs on SM-Ti group, the VEGF production of HUVECs on Micro-Ti group and Micro/Nano-Ti group was significantly reduced (P<0.05). The results of Ca(2+) ion detection showed that the Ca(2+) expression of HUVECs on Micro-Ti and Micro/Nano-Ti was significantly higher than that on the surface of SM-Ti and Nano-Ti. These results implied that the over expressed Ca(2+) might contributed to the impaired biological function of HUVECs on Micro-Ti and Micro/Nano-Ti. Different topographical features on titanium influenced the biological behaviors of the HUVECs, which may illustrate how topographical features of Ti implant affect peri-implant angiogenesis. These results also suggest that the biological behaviors of HUVECs might be relative to the changed expression of intracellular Ca(2+).


The use of virtual reality tools in surgical education.
Advances in computing, specifically those used for simulation and games technology has allowed for exciting developments in dental and surgical education. At the same time concerns are being raised that students with relatively little training, practise to improve their skill on patients with all of the inherent risks that may occur. Simulation in dentistry has been practised for many years and so the concept is not new to the profession. New tools have been developed that both enhance teaching and learning and are also useful for assessment of students and trainees. The challenge of virtual and simulated reality tools is to have the required fidelity to improve teaching and learning outcomes over the currently utilized methodology.


Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions.
The natural polyamines putrescine, cadaverine, spermidine, and spermine are found in all cells. These (poly)cations exert interactions with anions, e.g., DNA and RNA. This feature represents their best-known direct physiological role in cellular functions: cell growth, division, and differentiation. The lung and, more specifically, alveolar epithelial cells appear to be endowed with a much higher polyamine uptake system than any other major organ. In the lung, the active accumulation of natural polyamines in the epithelium has been studied in various mammalian species including rat, hamster, rabbit, and human. The kinetic parameters (Michaelis-Menten constant and maximal uptake) of the uptake system are the same order of magnitude regardless of the polyamine or species studied and the in vitro system used. Also, other pulmonary cells accumulate polyamines but never to the same extent as the epithelium. Although different uptake systems exist for putrescine, spermidine, and spermine in the lung, neither the nature of the carrier protein nor the reason for its existence is known. Some pulmonary toxicological and/or pathological conditions have been related to polyamine metabolism and/or polyamine content in the lung. Polyamines possess an important intrinsic toxicity. From in vitro studies with nonpulmonary cells, it has been shown that spermidine and spermine can be metabolized to hydrogen peroxide, ammonium, and acrolein, which can all cause cellular toxicity. In hyperoxia or after ozone exposure, the increased polyamine synthesis and polyamine content of the rat lung is correlated with survival of the animals. Pulmonary hypertension induced by monocrotaline or hypoxia has also been linked to the increased polyamine metabolism and polyamine content of the lung. In a small number of studies, it has been shown that polyamines can contribute to the suppression of immunologic reactions in the lung.


Pulmonary Metastases of Chondroblastoma in a Pediatric Patient: A Case Report and Review of Literature.
Chondroblastoma is a locally destructive, cartilaginous bone tumor that accounts for a small percentage of cases of primary bone tumors. Although considered a benign tumor, chondroblastoma can locally recur and can rarely metastasize. Here, we report a rare presentation of a locally recurrent chondroblastoma with pulmonary metastases. A 13-year-old female presented with palpitations, dry cough, difficulty breathing, and chest tightness four years after her original surgical resection of tibial chondroblastoma. On chest CT, multiple pulmonary soft tissue nodules with confluent punctate areas of calcification were seen. The patient underwent robotic-assisted bilateral pulmonary wedge resections. She is now undergoing denosumab therapy. This case underlined the importance of suspecting metastatic disease in patients with a history of chondroblastoma when pulmonary nodules are detected on imaging.


Microbiological quality of topical drug formulations: efficacy of antimicrobial preservation against Paecilomyces lilacinus.
Microbiological quality of topical products comprises both, the microbiological purity of the unopened product and the efficacy of the antimicrobial preservation system. Subsequent to an outbreak of invasive Paecilomyces lilacinus mycosis among patients of an isolation ward, probably caused by a contaminated skin care product, the microbiological quality of different skin care products from the market was investigated. The different products were investigated for their efficacy of antimicrobial preservation in general and especially against P. lilacinus according to a pharmacopoeial routine method slightly adopted for the purpose of this investigation. The products did partially not comply with the British Pharmacopoeia 1993 test for efficacy of antimicrobial preservation. The antimicrobial preservation systems were less effective against P. lilacinus than against the pharmacopoeial reference germs. The antimicrobial preservation efficacy decreased towards the end of the shelf-life of the product. A decreased P. lilacinus inoculum dose was related to an increased growth of the micro-organisms. Topical products are, unless not labelled otherwise, non-sterile preparations and their preservation systems are only tested against pharmacopoeial key micro-organisms. The microbiological behaviour following contamination with other germs remains unknown.


Immunotherapy for EGFR-mutant advanced non-small-cell lung cancer: Current status, possible mechanisms and application prospects.
Immune checkpoint inhibitors (ICIs) are effective against advanced and even perioperative non-small-cell lung cancer (NSCLC) and result in durable clinical benefit, regardless of programmed death ligand-1 (PD-L1) expression status in cancer. Existing clinical evidence shows that the effect of immunotherapy in patients with EGFR-mutant NSCLC after the development of tyrosine kinase inhibitor (TKI) resistance is not satisfactory. However, compared with monotherapy, ICIs combined with chemotherapy can improve the efficacy. Encouragingly, compared with that of patients with sensitive mutations, the progression-free survival of patients with rare mutations who were treated with ICIs was increased. Adequately maximizing the efficacy of ICIs in EGFR-mutant NSCLC patients is worth exploring. In this review, we described preclinical and clinical studies of ICIs or combined therapy for EGFR-mutant NSCLC. We further focused on EGFR mutations and the cancer immune response, with particular attention given to the role of EGFR activation in the cancer-immunity cycle. The mechanisms for the natural resistance to ICIs were explored to identify corresponding countermeasures that made more EGFR-mutant NSCLC patients benefit from ICIs.


Spinal surgery in children with idiopathic and neuromuscular scoliosis. What's the difference?
We compared children who were hospitalized for the management of idiopathic scoliosis (IS) and neuromuscular scoliosis (NMS) via analysis of the 2000 Healthcare Cost and Utilization Project Kid Inpatient Database. Children with NMS had longer lengths of stay (9.2 vs. 6.1 days, P < 0.001), higher total charges (66,953 US dollars vs. 47,463 US dollars, P < 0.001), more diagnoses (6.3 vs. 2.5, P < 0.001), and more total procedures (4.2 vs. 3.0, P < 0.001) than did children with IS. Children with NMS more frequently developed pneumonia (3.5% vs. 0.7%, P < 0.001), respiratory failure (24.1% vs. 9.2%, P < 0.001), urinary tract infections (5.3% vs. 0.7%, P < 0.001), and surgical wound infections (1.3% vs. 0.3%, P < 0.001). Overall, 1570 children with NMS underwent spinal surgery, totaling to 105 US dollars million in hospital charges and 14,444 hospital days. We conclude that children with NMS experience significantly more complicated and costly hospitalizations than do children with IS. These results may add information on preoperative care, surgical decision-making, discussions of informed consent, and the provision of anticipatory guidance for children and their caregivers.


Bivalent effects of human growth hormone in experimental myocardial infarcts. Protective when administered alone and aggravating when combined with beta blockers.
Human growth hormone (hGH) administered alone revealed itself as a useful drug to prevent ventricular aneurysm formation in experimental myocardial infarctions in rats and is also able to diminish and change the usually expected pattern of wall necrosis. A protective action on the collagen framework of myocytes has been confirmed as one of the main causes responsible for the above mentioned findings. There are other positive metabolic actions on the myocardial cell although not completely known yet. These actions are revealed by an atypical picture of infarction which appears regionally reduced and with a patchy intracellular distribution. In an opposite fashion, when hGH was administered together with beta blockers, a rapid and extensive deleterious action occurred at the ventricular wall, a very high incidence of ventricular aneurysms and an increased extension of myocardial infarcts were the most outstanding features. The histologic picture in this series resembles that of a rapidly evolving diabetic cardiomyopathy.


Toward an ideal animal model to trace donor cell fates after stem cell therapy: production of stably labeled multipotent mesenchymal stem cells from bone marrow of transgenic pigs harboring enhanced green fluorescence protein gene.
The discovery of postnatal mesenchymal stem cells (MSC) with their general multipotentiality has fueled much interest in the development of cell-based therapies. Proper identification of transplanted MSC is crucial for evaluating donor cell distribution, differentiation, and migration. Lack of an efficient marker of transplanted MSC has precluded our understanding of MSC-related regenerative studies, especially in large animal models such as pigs. In the present study, we produced transgenic pigs harboring an enhanced green fluorescent protein (EGFP) gene. The pigs provide a reliable and reproducible source for obtaining stable EGFP-labeled MSC, which is very useful for donor cell tracking after transplantation. The undifferentiated EGFP-tagged MSC expressed a greater quantity of EGFP while maintaining MSC multipotentiality. These cells exhibited homogeneous surface epitopes and possessed classic trilineage differentiation potential into osteogenic, adipogenic, and chondrogenic lineages, with robust EGFP expression maintained in all differentiated progeny. Injection of donor MSC can dramatically increase the thickness of infarcted myocardium and improve cardiac function in mice. Moreover, the MSC, with their strong EGFP expression, can be easily distinguished from the background autofluorescence in myocardial infarcts. We demonstrated an efficient, effective, and easy way to identify MSC after long-term culture and transplantation. With the transgenic model, we were able to obtain stem or progenitor cells in earlier passages compared with the transfection of traceable markers into established MSC. Because the integration site of the transgene was the same for all cells, we lessened the potential for positional effects and the heterogeneity of the stem cells. The EGFP-transgenic pigs may serve as useful biomedical and agricultural models of somatic stem cell biology.


[Thinking of current situation of animal model of tradition Chinese medicine combining disease and syndrome].
Combination disease and syndrome to construct animal model must be accord with the diagnosis and treatment mode of tradition Chinese medicine (TCM). The construct ion method should abide by the mode of combination prescription, syndrome, disease and efficacy. Prescription refers to those classic and effective formula. Syndrome refers to the symptoms and signs of prescription. Disease refers to model medical disease. Efficacy refers to the results of treatment. Constructing animal model should choose the classical prescription and formulate the clinical signs and symptoms. According to the main pathological process of modem diseases related to the syndrome to mine the methods of constructing animal models to express the main signs and symptoms, at last to testify the efficacy through the corresponding prescription. This method of constructing animal model is not only accord to the mode of diagnosis and treatment of TCM, but also affords a certain example of constructing animal model of combination model disease and syndrome.


Varicella-zoster virus (VZV) open reading frame 10 protein, the homolog of the essential herpes simplex virus protein VP16, is dispensable for VZV replication in vitro.
Varicella-zoster virus (VZV) open reading frame 10 (ORF10) protein in the homolog of the herpes simplex virus type 1 (HSV-1) protein VP16. VZV ORF10 transactivates the VZV IE62 gene and is a tegument protein present in the virion. HSV-1 VP16, a potent transactivator of HSV-1 immediate-early genes and tegument protein, is essential for HSV-1 replication in vitro. To determine whether VZV ORF10 is required for viral replication in vitro, we constructed two VZV mutants which were unable to express ORF10. One mutant had a stop codon after the 61st codon of the ORF10 gene, and the other mutant was deleted for all but the last five codons of the gene. Both VZV mutants grew in cell culture to titers similar to that of the parental virus. To determine whether HSV-1 VP16 alters the growth of VZV, we constructed a VZV mutant in which VP16 was inserted in place of ORF10. Using immune electron microscopy, we found that HSV-1 VP16 was present in the tegument of the recombinant VZV virions. The VZV VP16 substitution mutant produced smaller plaques and grew to a lower titer than parental virus. Thus, VZV ORF10 is not required for growth of the virus in vitro, and substitution of HSV-1 VP16 for VZV ORF10 impairs the growth of VZV.


A Microwave Polarimeter Demonstrator for Astronomy with Near-Infra-Red Up-Conversion for Optical Correlation and Detection.
This paper presents a 10 to 20 GHz bandwidth microwave polarimeter demonstrator, based on the implementation of a near-infra-red frequency up-conversion stage that allows both the optical correlation, when operating as a synthesized-image interferometer, and signal detection, when operating as a direct-image instrument. The proposed idea is oriented towards the implementation of ultra-sensitive instruments presenting several dozens or even thousands of microwave receivers operating in the lowest bands of the cosmic microwave background. In this work, an electro-optical back-end module replaces the usual microwave detection stage with Mach-Zehnder modulators for the frequency up-conversion, and an optical stage for the signals correlation and detection at near-infra-red wavelengths (1550 nm). As interferometer, the instrument is able to correlate the signals of large-format instruments, while operating as a direct imaging instrument also presents advantages in terms of the possibility of implementing the optical back end by means of photonic integrated circuits to achieve reductions in cost, weight, size, and power consumption. A linearly polarized input wave, with a variable polar angle, is used as a signal source for laboratory tests. The receiver demonstrator has proved its capabilities of being used as a new microwave-photonic polarimeter for the study of the lowest bands of cosmic microwave background.


Community eligibility and other provisions for universal free meals at school: impact on student breakfast and lunch participation in California public schools.
United States Department of Agriculture (USDA) school meal programs are an important part of the safety net for reducing food insecurity, yet not all students who qualify for free or reduced-price meals participate. In 2014-2015, the Community Eligibility Provision became available nationwide. This provision, along with Provisions 1, 2, and 3 of the USDA school meals programs, allows local school food authorities to offer universal free meals at schools with high student poverty. It is expected that adoption of a provision allowing universal free meals will increase rates of student participation in meal programs at schools where many students are at risk for food insecurity. This study examines school-level adoption of any provision for universal free meals and subsequent changes in student participation rates for the School Breakfast Program and National School Lunch Program in California from 2013-2014 to 2016-2017. A database was assembled for 10,343 public schools, including meals served, demographics, eligibility for provisions, and use of provisions in each year. Multilevel regression models were used to examine school adoption and student participation rates over time. Difference-in-difference calculations from lagged longitudinal models adjusting for school demographics showed that when eligible schools adopted provisions, participation rates increased an average of 3.48 percentage points for breakfast and 5.79 points for lunch the following year. By 2016-2017, over half of all eligible schools were using a provision for universal free meals. Among eligible schools, provision adoption was more common at schools that were larger, had predominantly Latino students, and were in rural areas. When eligible schools adopt provisions for universal free meals, student participation rates significantly increase, improving program reach among children most at risk for food insecurity. However, not all eligible schools adopt a provision for universal free meals and some adopters drop out in subsequent years. Research to better understand factors influencing the decision whether to adopt a provision or to continue it could inform policy and program leaders. Increases in breakfast participation are smaller than those for lunch, suggesting that other barriers to breakfast participation warrant further investigation.


[Psoas abscess as the initial manifestation of Crohn's disease. Report of 3 cases].
Psoas abcess complicating Crohn's disease is a rare condition. Diagnosis remains difficult, especially when it is the first sign of Crohn's disease. We report here 3 patients presenting with psoas abcess as the initial manifestation of the disease, among 118 patients with Crohn's disease seen between 1990 and 2006. Symptoms and signs were fever, lower abdominal quadrant pain or tenderness and psoitis. Diagnosis was confirmed in all cases by computed axial tomography. In 2 cases, psoas abcess secondary to a periappendicular abcess or a colonic neoplasm were suspected, and the etiology was made correctly only after operation. Effective therapy included antibiotics, drainage and bowel resection.


Three-Dimensional Slope Imaging Method for Ground-Based Real-Aperture Radar.
Traditional two-dimensional radar images can only reflect the target azimuth and slant range and thus suffer problems of geometric deformation and overlapping. The unique three-dimensional (3D) imaging capability of ground-based real-aperture radar can more accurately and directly achieve correlation between the radar image and the slope monitoring scenarios, thus providing reliable information for the early warning and forecasting of landslides and collapse disasters. The latest method of selecting a slope target from a high-resolution range profile includes two indexes: maximum amplitude and coherence, which will affect the accuracy of displacement measurement when there is an interference target. We present a three-dimensional slope imaging method based on smoothness constraints. On the basis of the latest method, the objective fact of the practically smooth and continuous distribution of slope surfaces is considered. This method can be used for image interpretation on strongly scattered targets within the slope. The independently developed ground-based real-aperture slope radar system was deployed in the Heidaigou Open-Pit Coal Mine in Inner Mongolia to carry out 3D slope imaging experiments. The effectiveness of this method in slope monitoring and imaging was confirmed by comparing the surface roughness and the spatial positions of the targets with the high-density point cloud data in the projective plane obtained during the same time period. We used RMSE function and roughness as two measures. It shows that the method presented in this paper is more suitable for actual three-dimensional slope imaging.


Protective effect of S-adenosyl-L-methionine in hepatic uroporphyria. Evaluation in an experimental model.
The potential use of S-adenosyl-L-methionine (SAMe) as therapy for human porphyria cutanea tarda was investigated in an experimental model of hepatic porphyria--that is, chronic treatment of female rats with 0.2% hexachlorobenzene (HCB) in the diet. Administration of SAMe (25 mg/kg subcutaneously twice daily) during the last 15 days of HCB administration halved porphyrin accumulation in the liver but did not alter HCB-induced massive inhibition of uroporphyrinogen decarboxylase. Equally unaffected were inhibition of glutathione peroxidase and stimulation of lipid peroxide formation induced by HCB. Hypothetically, the beneficial effect of SAMe on hepatic porphyrin accumulation might be linked to modifications of the cellular availability of adenosine triphosphate.


Systematic Comparison of Pancreatic Ductal Adenocarcinoma Models Identifies a Conserved Highly Plastic Basal Cell State.
Intratumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including pancreatic ductal adenocarcinoma (PDAC). As PDAC portends a dire prognosis, a better understanding of the mechanisms underpinning cellular diversity in PDAC is crucial. Here, we investigated the cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. Heterogeneity contracted significantly in two-dimensional and three-dimensional cell culture models but was restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquired cell states identified in autochthonous PDAC tumors, including a basal state exhibiting coexpression and coaccessibility of epithelial and mesenchymal genes. Lineage tracing combined with single-cell transcriptomics revealed that basal cells display high plasticity in situ. This work defines the impact of cellular growth conditions on phenotypic diversity and uncovers a highly plastic cell state with the capacity to facilitate state transitions and promote intratumoral heterogeneity in PDAC. This work provides important insights into how different model systems of pancreatic ductal adenocarcinoma mold the phenotypic space of cancer cells, highlighting the power of in vivo models.


Sharpening Host Defenses during Infection: Proteases Cut to the Chase.
The human immune system consists of an intricate network of tightly controlled pathways, where proteases are essential instigators and executioners at multiple levels. Invading microbial pathogens also encode proteases that have evolved to manipulate and dysregulate host proteins, including host proteases during the course of disease. The identification of pathogen proteases as well as their substrates and mechanisms of action have empowered significant developments in therapeutics for infectious diseases. Yet for many pathogens, there remains a great deal to be discovered. Recently, proteomic techniques have been developed that can identify proteolytically processed proteins across the proteome. These "degradomics" approaches can identify human substrates of microbial proteases during infection in vivo and expose the molecular-level changes that occur in the human proteome during infection as an operational network to develop hypotheses for further research as well as new therapeutics. This Perspective Article reviews how proteases are utilized during infection by both the human host and invading bacterial pathogens, including archetypal virulence-associated microbial proteases, such as the Clostridia spp. botulinum and tetanus neurotoxins. We highlight the potential knowledge that degradomics studies of host-pathogen interactions would uncover, as well as how degradomics has been successfully applied in similar contexts, including use with a viral protease. We review how microbial proteases have been targeted in current therapeutic approaches and how microbial proteases have shaped and even contributed to human therapeutics beyond infectious disease. Finally, we discuss how, moving forward, degradomics research can greatly contribute to our understanding of how microbial pathogens cause disease in vivo and lead to the identification of novel substrates in vivo, and the development of improved therapeutics to counter these pathogens.


Circulating Levels of Inflammatory Proteins and Survival in Patients with Gallbladder Cancer.
Although inflammation is central to gallbladder cancer (GBC) development and proliferation, no study has systematically investigated circulating inflammatory proteins and patient survival. We aimed to examine whether the circulating levels of inflammatory proteins is associated with all-cause mortality among such patients. We recruited 134 patients with newly diagnosed with GBC from 1997 to 2001 in a population-based study in Shanghai and an independent set of 35 patients from 2012 to 2013 in Chile. Cox proportional hazards regression models adjusted for covariates were used to evaluate the hazard ratios (HRs) for death by serum levels of 49 inflammatory proteins (quartiles). Of 49 evaluable proteins, eight were significantly associated with overall survival. Seven were associated with a poorer survival, while the highest levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were associated with an increase in survival (HR = 0.26, 95% CI = 0.14, 0.47). No substantial difference in the magnitude of the association was observed between early- and late-stages of GBC. Of seven proteins, five were validated in the patients from Chile. Reducing inflammation and targeting pathways associated with increased survival might improve GBC outcomes. The potential for using a TRAIL-related anticancer drug for GBC treatment merits further investigation.


[Clinical implications of pharmacology and pharmacokinetics of tiagabine].
Tiagabine is a new antiepileptic drug which acts by blocking neuronal and glial GABA uptake and it is indicated in the treatment of partial epilepsies. Its pharmacokinetics is lineal, being extensively metabolized in the liver by means of CYP3A4 isoenzyme. Plasma elimination half life ranges between 5-8 hours in healthy volunteers, being markedly reduced when the drug is administered concomitantly with enzyme-inducing antinconvulsants. Tiagabine does not induce nor inhibit hepatic enzymes and, consequently, it does not modify the kinetics of simultaneously prescribed antiepileptic drugs. No relevant kinetic differences have been observed between adults and elderly subjects. Renal impairment does not alter the pharmacokinetic profile of tiagabine; hepatic disease, however, significantly reduces tiagabine elimination and lower daily doses of the drug are necessary in these patients. Although tiagabine elimination half life is short, it has been ascertained that therapeutic efficacy is similar when administered in 2 or 4 divided doses. Tiagabine is usually well tolerated; its most frequent side effects include dizziness, asthenia, nervousness, tremor, diarrhea and depressed mood.


Immunoexpression of Relaxin and Its Receptors in Stifle Joints of Dogs with Cranial Cruciate Ligament Disease.
The etiology of spontaneous cranial cruciate ligament rupture in dogs is unknown despite being one of the most impacting orthopedic diseases in dogs. Numerous studies have contributed to the understanding of a multifactorial pathogenesis, this, however, without identifying a pivotal link to explain progressive collagen degeneration and osteoarthritic changes. In human medicine, recent reports have identified relaxin as a triggering factor in ligament ruptures in knee and metacarpal joints. We thus hypothesized that relaxin might also play a role in canine cruciate ligament rupture. Relaxin's primarily known property is connective tissue remodeling through collagenolysis. We therefore investigated relaxin and its cognate receptors LGR7/LGR8 in 18 dogs with cranial cruciate ligament disease (CCLD) and compared them to a group of dogs with normal stifle joints. Applying immunohistochemistry (IHC), double immunofluorescence (dIF), and western blot analysis (WB), we found strong and significantly increased expression of both relaxin and its receptors in ruptured cruciate ligaments, and in synovial membranes. Pattern of immuno-staining on dIF strongly suggests relaxin binding to primed receptors and activation of signaling properties, which in turn may have affected collagen matrix metabolism. Thus, in canine cranial cruciate ligament disease, relaxin/receptor signaling may be a primary trigger for collagen fiber degradation and collagen lysis, eventually followed by ligament rupture.


Behavioral phenotypes revealed during reversal learning are linked with novel genetic loci in diversity outbred mice.
Impulsive behavior and impulsivity are heritable phenotypes that are strongly associated with risk for substance use disorders. Identifying the neurogenetic mechanisms that influence impulsivity may also reveal novel biological insights into addiction vulnerability. Our past studies using the BXD and Collaborative Cross (CC) recombinant inbred mouse panels have revealed that behavioral indicators of impulsivity measured in a reversal-learning task are heritable and are genetically correlated with aspects of intravenous cocaine self-administration. Genome-wide linkage studies in the BXD panel revealed a quantitative trait locus (QTL) on chromosome 10, but we expect to identify additional QTL by testing in a population with more genetic diversity. To this end, we turned to Diversity Outbred (DO) mice; 392 DO mice (156 males, 236 females) were phenotyped using the same reversal learning test utilized previously. Our primary indicator of impulsive responding, a measure that isolates the relative difficulty mice have with reaching performance criteria under reversal conditions, revealed a genome-wide significant QTL on chromosome 7 (max LOD score = 8.73, genome-wide corrected p<0.05). A measure of premature responding akin to that implemented in the 5-choice serial reaction time task yielded a suggestive QTL on chromosome 17 (max LOD score = 9.14, genome-wide corrected <0.1). Candidate genes were prioritized (2900076A07Rik, Wdr73 and Zscan2) based upon expression QTL data we collected in DO and CC mice and analyses using publicly available gene expression and phenotype databases. These findings may advance understanding of the genetics that drive impulsive behavior and enhance risk for substance use disorders.


Behavioural and physiological responses to salinization and air exposure during the ontogeny of a freshwater South American snail.
Salinization is of global concern, threatening freshwater biodiversity. Salinity tolerance is highly variable and therefore needs to be evaluated on a species-specific basis. An estuarine population of Chilina dombeiana, a freshwater gastropod endemic to Chile and classified as vulnerable, has been recently found in the Biobío River's mouth, suggesting some degree of tolerance to brackish waters. This study evaluated the survival, behaviour (medium preference) and physiology of C. dombeiana when exposed to salinities higher than freshwater, thus elucidating the potential mechanisms used to survive salinization. Chilina dombeiana belongs to the Pulmonate group;, so we evaluated oxygen uptake in air and water, aiming to evaluate emersion as a potential avoidance response to a progressive salinity increase. Complete embryo development was observed for salinities ≤ 16 PSU (practical salinity units) but hatching rates above 50% were only achieved in freshwater (0 PSU). It was also found that salinity had stage-specific effects during embryonic development. In adults, acute exposure to brackish water (12 PSU) caused a decrease in oxygen consumption (compared to freshwater), in the ammonium excretion rates and in the percentage of muscular water content. Although C. dombeiana was able to take up oxygen in both mediums, survival in air decreased over time (days), which correlates with the behavioural preference to remain submerged, even at elevated salinities. Considering the survival of adults and embryos decreased as salinity increased and the lack of an avoidance behaviour or a physiological ability to maintain homeostasis at salinities higher than freshwater, our results suggest this snail could be adversely affected by salinization in the long term. Furthermore, given the ability of C. dombeiana to uptake oxygen in both mediums, it should be considered as a facultative air breather snail, rather than a strictly aquatic species.


What's next in using CT scans to better understand cachexia?
Cachexia (CAX), a protein metabolism disorder commonly associated with cancer, can be evaluated by computed tomography (CT) scan assessment of skeletal muscle mass (SMM), a parameter associated with patient outcome. This review analyzes current barriers for using CT scans of SMM in routine management for defining prognostic risk groups, and proposes new areas of research to reach a better understanding of CAX mechanisms. Current research is focused on establishing a robust and relevant CAX staging system to reach a consensual definition. Previous biomarkers of CAX are poorly associated with outcome and do not exhibit clinical benefit. Systemic inflammatory marker, decrease in intake assessments, and/or nonnutritional criteria have been integrated to develop a multidimensional, highly complex CAX signature and CAX staging. A standardized definition of sarcopenia is essential, and its value in clinical practice should be evaluated in prospective interventional studies using skeletal muscle assessment. SMM loss may be a key element in defining early protein disorders occurring before weight loss and could be used as a trigger for initiating early nutritional support. Changes in SMM and body composition during follow-up are useful tools for exploring CAX mechanisms in terms of intrinsic factors or tumor evolution.


Effects of alpha-2 agonists on renal function in hypertensive humans.
Centrally acting adrenergic agonists, by decreasing peripheral adrenergic activity, are effective antihypertensive agents. The older agents, however, especially methyldopa, have been associated with weight gain, clinical edema, and antihypertensive tolerance when used as monotherapy. While acute studies in humans have demonstrated weight gain and sodium retention with clonidine and guanabenz, chronic administration results in a decrease in weight and plasma volume. The absence of chronic weight gain and of sodium retention could be the result of a counterbalance between hypotension-related antinatriuresis, secondary to a decrease in glomerular filtration rate and renal blood flow, and natriuretic activity, as a result of a decrease in renal sympathetic tone. Whereas natriuresis and water diuresis have been demonstrated in animals with acute clonidine or guanabenz administration, this has not been demonstrated in humans. Recent studies in which saline administration was used to precondition humans to a subsequent natriuretic stimulus (i.e., guanabenz-induced decreased renal adrenergic activity) resulted in stabilization of renal blood flow and natriuresis. Selective reduction renal sympathetic activity affecting salt and water transport may explain why guanabenz and probably also clonidine seem to be devoid of the sodium/fluid-retaining properties that are common with other antihypertensive agents. Because agents of this class have effects other than pure central alpha-2 agonism (such as alpha-1 activity), they might have confounding and counterbalancing side effects leading to sodium and water retention.


Imine-assisted C-F bond activation by electron-rich iron complexes supported by trimethylphosphine.
C-F bond activation of ortho-fluorinated benzalimines 2,6-F(2)C(6)R1R2R3-CH=N-R (1-3) using the electron-rich complex Fe(PMe(3))(4) is reported. With the assistance of the imine group as the anchoring group, bis-chelated iron(II) complexes (C(6)FR1R2R3-CH=N-R)(2)Fe(PMe(3))(2) (4-6) were formed. The reaction of 2,6-difluorobenzylidenenaphthalen-1-amine 2,6-F(2)C(6)H(3)-CH=N-C(10)H(7) (9) with Fe(PMe(3))(4) affords [CNC]-pincer iron(II) complex (C(6)H(3)F-CH=N-C(10)H(6))Fe(PMe(3))(3) (10) through both C-F and C-H bond activation and π-(C=N) coordinate iron(0) complex (C(6)H(3)F-CH=N-C(10)H(7))(2)Fe(PMe(3))(2) (11) with C,C-coupling, while a similar reaction with perfluorobenzylidenenaphthalen-1-amine C(6)F(5)-CH=N-C(10)H(7) (14) gave rise to only [CNC]-pincer iron(II) complex (C(6)F(4)-CH=N-C(10)H(6))Fe(PMe(3))(3) (15). The proposed formation mechanisms of these complexes are discussed. The structures of complexes 5, 6, 10 and 11 were confirmed by X-ray single crystal diffraction.


[Arthrosonography and biomarkers in the evaluation of destructive knee cartilage osteoarthrosis].
Knee osteoarthrosis (OA) is a degenerative disease with progressive loss of cartilage of joints and bone destruction. During this process, the release of fragments of connective tissue matrix is detected in the biological fluids such as human cartilage glycoprotein (YKL-40), cartilage oligomeric matrix protein (COMP) and collagen type I C terminal telopeptid (CTX-I). The aim of the study was to determine the degree of connection cartilage thickness measured by ultrasound with serum concentrations of biomarkers YKL-40, COMP and CTX-I in patients with primary knee OA. The analysis included 88 patients with the diagnosis of knee OA. Ultrasound examination of knees were done by two rheumatologists. The analysis of serum samples determined the concentration of COMP, YKL-40 and CTX-I by the ELISA method. The average age of patients was 69.97 +/- 9.37 years and the duration of knee OA 6.46 +/- 6.73 years. The average cartilage thickness of the femoral condyle was 1.33 +/- 0.20 mm; of the medial condyle (MC) (front access) 1.30 +/- 0.23 mm, (rear access) 1.30 +/- 0.29 mm and lateral condyli (LC) (front access) 1.39 +/- 0.27 mm. The average cartilage thickness of MC (front access) was 1.27 mm (0.98-1.42 mm), (rear access) 1.27 mm (0.84-1.46 mm) and LC (front access) 1.36 mm (1.01-1.57 mm) (p = 0.002). There was a significant connection in the negative direction between the patients' age and the cartilage thickness of MC (front and rear access) and LC (front access) (r = -0.253; p = 0.017). There was a significant negative direction of interrelationship between the cartilage thickness of MC (front access) (r = -0.259; p = 0.015) and LC (front access) and the disease duration (r = -0.259; p = 0.015). In patients with knee OA lasting for 5 years the measured cartilage thickness was 1.27 mm (1.16-1.49 mm), and 0.99 mm (0.94-1.23 mm) (p = 0.007) in those lasting for 20 years. There was a significant relationship in a negative direction between the concentration of YKL-40 and cartilage thickness of MC (front access) (r = -0.249; p = 0.019). The progressive loss of cartilage during the long-term evolution of osteoarthrosis is most extensive in the femoral MC. The increased serum levels of YKL-40 can be a good indicator of joint cartilage destruction.


Activated CD8+ T-effector/memory cells eliminate CD4+ CD25+ Foxp3+ T-suppressor cells from tumors via FasL mediated apoptosis.
Tumor-resident CD8(+) T cells display a quiescent effector/memory phenotype that is maintained in part by infiltrating CD4(+) CD25(+) Foxp3(+) T-suppressor cells. Intratumoral delivery of IL-12, in contrast, can restore cytotoxic function to tumor-associated CD8(+) T cells and induce the apoptotic death of T-suppressor cells. Depletion of CD8(+) T cells from tumors before IL-12 treatment resulted in the abrogation of treatment-mediated T-suppressor cell apoptosis revealing a link between CD8(+) T cell activation and T-suppressor elimination. Furthermore, IL-12 failed to induce T-suppressor cell loss in IFN-gamma- or FasL-deficient mice demonstrating a requirement for IFN-gamma and FasL in this process. Adoptive transfer of wild-type CD8(+) T cells to FasL-knockout mice restored posttherapy T-suppressor cell elimination from tumors establishing that expression of FasL on CD8(+) T cells was sufficient to promote T-suppressor cell death. IL-12 failed to induce FasL on T-effectors in IFN-gamma-knockout mice demonstrating a requirement for IFN-gamma in FasL up-regulation. Adoptive transfer of wild-type CD8(+) T cells induced T-suppressor cell death in IFN-gamma-knockout mice confirming that autocrine IFN-gamma was sufficient for CD8(+) T cell FasL expression. These findings reveal a mechanism by which cytotoxic T cells can abrogate regulatory cell activity.


Terminal-functionality effect of poly(N-isopropylacrylamide) brush surfaces on temperature-controlled cell adhesion/detachment.
Terminally functionalized poly(N-isopropylacrylamide) (PIPAAm) brush grafted glass surfaces were prepared by a surface-initiated reversible addition-fragmentation chain transfer radical (SI-RAFT) polymerization. SI-RAFT mediated PIPAAm chains possessed terminal dodecyl trithiocarbonate groups which can be substituted with various functional groups. In this study, dodecyl groups were substituted with hydrophilic maleimide groups for controlling the thermoresponsive character of PIPAAm brushes. PIPAAm brushes exhibited reversible temperature-dependent surface wettability changes around PIPAAm's lower critical solution temperature. Phase transition of dodecyl-terminated PIPAAm brushes clearly shifted to lower temperature than that of maleimide-terminated PIPAAm brushes, and this shift was attributed to promoted PIPAAm dehydration via terminal hydrophobes. By using this feature, the specific adhesion temperatures of bovine carotid artery endothelial cells (BAECs) on the PIPAAm brush surfaces were successfully controlled. BAECs were initiated to adhere on dodecyl-PIPAAm surfaces at 31 °C, while their adhesion was significantly suppressed on maleimide-PIPAAm surfaces under 33 °C. In contrast, terminal functionality scarcely affected the thermoresponsive behavior of PIPAAm brushes in the polymer rehydration process by reducing temperatures, and thus, the difference in spontaneous cell detachment from different PIPAAm-brush surface was negligible. Consequently, confluently cultured cells were able to be harvested as contiguous cell sheets from individual surfaces with comparable periods at 20 °C.


Supra-physiological doses of anabolic androgenic steroids impact erythropoietin and blood parameters.
Hematological parameters and erythropoiesis are known to be influenced by anabolic androgenic steroid (AAS) use. However, little is known in relation to supra-physiological doses of AAS. Therefore, the aim of this study was to evaluate the effect of supra-physiological doses of AAS on serum and urinary erythropoietin (EPO), and blood parameters, from self-reported AAS users. Serum EPO levels were higher in testosterone positive AAS users (11.83 mIU/mL ± 4.19) than nonpositive (6.60 mIU/mL ± 2.70, p = 0.03), while no differences in urinary EPO levels were noted. There were positive correlations between serum EPO and testosterone levels (rs = 0.46, p = 0.01) and reticulocyte percentage (rs = 0.43, p = 0.02). Individuals with AAS-induced hypogonadism (ASIH; luteinizing hormone levels <1.4 IU/L) had approximately 75% higher serum EPO (p < 0.05) and 140% higher high fluorescence reticulocyte fractions (p < 0.001), as well as other affected hematological parameters, compared with non-ASIH individuals. The results extend the knowledge of how endocrine and hematological biomarkers are affected by AAS doping.


Right ventricular apex versus right ventricular outflow tract pacing: prospective, randomised, long-term clinical and echocardiographic evaluation.
In patients treated with permanent pacing, the electrode is typically placed in the right ventricular apex (RVA). Published data indicate that such electrode placement leads to an unfavourable ventricular depolarization pattern, while right ventricular outflow tract (RVOT) pacing seems to be more physiological. To compare long-term effects of RVOT versus RVA pacing on clinical status, left ventricular (LV) function, and the degree of atrioventricular valve regurgitation. Patients with indications for permanent pacing, admitted to hospital between 1996 and 1997, were randomised to receive RVA or RVOT pacing. In 2004 during a final control visit in 27 patients clinical status, echocardiographic parameters and QRS complex duration as well as NT-proBNP level were measured. Analysed parameters were compared between groups and in the case of data available during the perioperative period also their evolution in time was assessed. Out of 27 patients 14 were randomised to the RVA group and 13 to the RVOT group. No significant differences between groups were observed before the procedure with respect to age, gender, comorbidities or echocardiographic parameters. Mean duration of pacing did not differ significantly between the groups (89+/-9 months in RVA group vs 93+/-6 months in RVOT group, NS). In the RVA group significant LV ejection fraction decrease was observed (from 56+/-11% to 47+/-8%, p <0.05); in the RVOT group LV ejection fraction did not change (54+/-7% and 53+/-9%; NS). Progression of tricuspid valve regurgitation was also observed in the RVA group but not in the RVOT group. During the final visit NT-proBNP level was significantly higher in the RVA group: 1034+/-852 pg/ml vs 429+/-430 pg/ml (p <0.05). In patients with normal LV function permanent RVA pacing leads to LV systolic and diastolic function deterioration. RVOT pacing can reduce the unfavourable effect and can slow down cardiac remodelling caused by permanent RV pacing. Clinical and echocardiographic benefits observed in the RVOT group after 7 years of pacing are reflected by lower NT-proBNP levels in this group of patients.


Tumor intrinsic immunity related proteins may be novel tumor suppressors in some types of cancer.
Immune checkpoint blockade therapy (ICBT) can unleash T-cell responses against cancer. However, only a small fraction of patients exhibited responses to ICBT. The role of immune checkpoints in cancer cells is not well understood. In this study, we analyzed T-cell coinhibitory/costimulatory genes across more than 1100 samples of the Cancer Cell Line Encyclopedia (CCLE). Nearly 90% of such genes were not expressed or had low expression across the CCLE cancer cell lines. Cell line screening showed the enrichment of cancer cells deprived of the expression of CD27, CEACAM1, CTLA4, LRIG1, PDCD1LG2, or TNFRSF18, suggesting their role as tumor suppressor. The metagene expression signature derived from these six genes - Immu6Metagene was associated with prolonged survival phenotypes. A common set of five oncogenic pathways were significantly inhibited in different types of tumors of the cancer patients with good survival outcome and high Immu6Metagene signature expression. These pathways were TGF-β signaling, angiogenesis, EMT, hypoxia and mitotic process. Our study showed that oncoimmunology related molecules especially the six genes of the Immu6Metagene signature may play the tumor suppressor role in certain cancers. Therefore, the ICBT targeting them should be considered in such context to improve the efficacy.


At the intersection of the model minority myth and antiblackness: From Asian American triangulation to recommendations for solidarity.
Asian Americans are situated in a triangulated role in a black-white racial hierarchy designed to legitimize white supremacy (Kim, 1999). However, little is known about the lived experiences of Asian American triangulation and even less so in the context of anti-Asian racism. The present study was initially designed to examine anti-Asian racism at the outset of the COVID-19 pandemic. Yet, in a sociopolitical climate described as a "racial reckoning," our study evolved to capture the process of racial triangulation and the interplay of anti-Asian racism and antiblackness. Based on the online responses of 201 Asian Americans (from over 32 U.S. states), four themes emerged to showcase the ways in which Asian Americans suffered from and recapitulated racial oppression: (a) anti-Asian racism is overlooked in the black-white racial discourse, (b) anti-Asian racism is not taken seriously, (c) anti-Asian racism is also perpetrated by people of color (POC), and (d) anti-Asian racism is deprioritized in the presence of anti-Black racism. Regarding participant recommendations to combat anti-Asian racism, our second research question focused on areas of convergence with dismantling anti-Black racism. Two key themes emerged: (a) foster Asian American pan-ethnic solidarity and (b) build and strengthen cross-racial coalitions (POC solidarity and White allyship). Altogether, our study descriptively captured the process of racial triangulation to showcase the manifestation and recapitulation of anti-Asian racism and antiblackness. While Asian Americans suffered as victims and perpetrators of racial oppression, they also recognized the need to dismantle white supremacy with racial solidarity, coalition-building, and advocacy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Incidental detection of unsuspected pulmonary embolism on oncologic FDG PET/CT imaging.
Incidental findings are not infrequent on integrated FDG PET/CT scans by the virtue of obtaining images from skull base to mid thigh. These can be on the FDG PET portion or the CT portion of the study and can be clinically significant. We report a case of FDG PET/CT imaging performed for staging of head and neck cancer that led to the detection of unsuspected pulmonary embolism. Our case reinforces the importance of careful interpretation of incidental findings on FDG PET/CT imaging as they can have a significant effect on patient management.


Recent Advances in the Use of Molecular Analyses to Inform the Diagnosis and Prognosis of Patients with Polycythaemia Vera.
Genetic studies in the past decade have improved our understanding of the molecular basis of the BCR-ABL1-negative myeloproliferative neoplasm (MPN) polycythaemia vera (PV). Such breakthroughs include the discovery of the JAK2V617F driver mutation in approximately 95% of patients with PV, as well as some very rare cases of familial hereditary MPN caused by inherited germline mutations. Patients with PV often progress to fibrosis or acute myeloid leukaemia, both associated with very poor clinical outcome. Moreover, thrombosis and major bleeding are the principal causes of morbidity and mortality. As a result of increasingly available and economical next-generation sequencing technologies, mutational studies have revealed the prognostic relevance of a few somatic mutations in terms of thrombotic risk and risk of transformation, helping to improve the risk stratification of patients with PV. Finally, knowledge of the molecular basis of PV has helped identify targets for directed therapy. The constitutive activation of the tyrosine kinase JAK2 is targeted by ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor for PV patients who are resistant or intolerant to cytoreductive treatment with hydroxyurea. Other molecular mechanisms have also been revealed, and numerous agents are in various stages of development. Here, we will provide an update of the recent published literature on how molecular testing can improve the diagnosis and prognosis of patients with PV and present recent advances that may have prognostic value in the near future.


Dye-Loaded Nanoemulsions: Biomimetic Fluorescent Nanocarriers for Bioimaging and Nanomedicine.
Lipid nanoemulsions (NEs), owing to their controllable size (20 to 500 nm), stability and biocompatibility, are now frequently used in various fields, such as food, cosmetics, pharmaceuticals, drug delivery, and even as nanoreactors for chemical synthesis. Moreover, being composed of components generally recognized as safe (GRAS), they can be considered as "green" nanoparticles that mimic closely lipoproteins and intracellular lipid droplets. Therefore, they attracted attention as carriers of drugs and fluorescent dyes for both bioimaging and studying the fate of nanoemulsions in cells and small animals. In this review, the composition of dye-loaded NEs, methods for their preparation, and emerging biological applications are described. The design of bright fluorescent NEs with high dye loading and minimal aggregation-caused quenching (ACQ) is focused on. Common issues including dye leakage and NEs stability are discussed, highlighting advanced techniques for their characterization, such as Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS). Attempts to functionalize NEs surface are also discussed. Thereafter, biological applications for bioimaging and single-particle tracking in cells and small animals as well as biomedical applications for photodynamic therapy are described. Finally, challenges and future perspectives of fluorescent NEs are discussed.


Immune Checkpoint Blockers and Ovarian Cancer.
Although the idea, called "cancer immunotherapy," is very appealing and has previously been shown to work in several mouse models of cancer, it has in general been very difficult to translate cancer immunotherapy approaches to humans. Because of this frustration, by the 1990s, many scientists and biotechnology companies had given up on the idea of cancer immunotherapy. After few years, first detection T-cell suppression of effect of cytotoxic T-lymphocyte antigen-4 (CTLA4) molecule was established. Antibody (Ab) to CTLA4 could increase T-cell starting a completely new age of tumor immunology. Immune checkpoints are new ways in manipulation of immunological control over malignant tumors. It has lent an important measure to manage, especially recurrent and refractory cancers and those cancer where there is an unmet need like recurrent melanoma, renal cell carcinoma, and recurrent ovarian cancer. As a new development, this subject is experiencing rapid progress, and multiple avenues are opening up. Although there are many hurdles to overcome this needs constant updating, especially for students of ovarian cancer who are looking at it with much hope.


Effects of Schyzocotyle acheilognathi (Yamaguti, 1934) infection on the intestinal microbiota, growth and immune reactions of grass carp (Ctenopharyngodon idella).
Our understanding of interactions among intestinal helminths, gut microbiota and host is still in its infancy in fish. In this study, the effects of Schyzocotyle acheilognathi infection on the intestinal microbiota, growth and immune reactions of grass carp were explored under laboratory conditions. 16S rDNA amplification sequencing results showed that S. acheilognathi infection altered the composition of intestinal microbiota only at the genus level, with a significant increase in the relative abundance of Turicibacter and Ruminococcus (P < 0.05) and a significant decrease in the relative abundance of Gordonia, Mycobacterium and Pseudocanthomonas (P < 0.05). Schyzocotyle acheilognathi infection had no significant effect (P > 0.05) on the alpha diversity indices (including Chao1, ACE, Shannon, Simpson index) of intestinal microbiota in grass carp, but PERMANOVA analysis showed that microbial structure significantly (P < 0.01) differed between hindgut and foregut. PICRUST prediction showed that some metabolism-related pathways were significantly changed after S. acheilognathi infection. The relative abundance of Turicibacter was positively correlated with the fresh weight of tapeworm (foregut: r = 0.48, P = 0.044; hindgut: r = 0.63, P = 0.005). There was no significant difference in the body condition of grass carp between the S. acheilognathi infected group and the uninfected group (P > 0.05). Intestinal tissue section with HE staining showed that S. acheilognathi infection severely damaged the intestinal villi, causing serious degeneration, necrosis and shedding of intestinal epithelial cells. The real-time fluorescent quantitative PCR results showed that S. acheilognathi infection upregulated the mRNA expression of the immune-related genes: Gal1-L2, TGF-β1 and IgM.