The injury patterns, management and outcomes of retroperitoneal haemorrhage caused by lumbar arterial bleeding at a Level-1 Trauma Centre: A 10-year retrospective review.

PURPOSE: Haemorrhagic shock remains a leading preventable cause of death amongst trauma patients. Failure to identify retroperitoneal haemorrhage (RPH) can lead to irreversible haemorrhagic shock. The arteries of the middle retroperitoneal region (i.e., the 1st to 4th lumbar arteries) are complicit in haemorrhage into the retroperitoneal space. However, predictive injury patterns and subsequent management implications of haemorrhage secondary to bleeding of these arteries is lacking. MATERIALS AND METHODS: We performed a retrospective cohort study of patients diagnosed with retroperitoneal haemorrhage who presented to our Level-1 Trauma Centre (2009-2019). We described the associated injuries, management and outcomes relating to haemorrhage of lumbar arteries (L1-4) from this cohort to assess risk and management priorities in non-cavitary haemorrhage compared to RPH due to other causes. RESULTS: Haemorrhage of the lumbar arteries (LA) is associated with a higher proportion of lumbar transverse process (TP) fractures. Bleeding from branches of these vessels is associated with lower systolic blood pressure, increased incidence of massive transfusion, higher shock index, and a higher Injury Severity Score (ISS). A higher proportion of patients in the LA group underwent angioembolisation when compared to other causes of RPH. CONCLUSION: This study highlights the injury patterns, particularly TP fractures, in the prediction, early detection and management of haemorrhage from the lumbar arteries (L1-4). Compared to other causes of RPH, bleeding of the LA responds to early, aggressive haemorrhage control through angioembolisation. These injuries are likely best treated in Level-1 or Level-2 trauma facilities that are equipped with angioembolisation facilities or hybrid theatres to facilitate early identification and management of thoracolumbar bleeds.

Utility of healthcare-worker-targeted antimicrobial stewardship interventions in hospitals of low- and lower-middle-income countries: a scoping review of systematic reviews.

BACKGROUND: Antimicrobial stewardship (AMS) initiatives in hospitals often include the implementation of clustered intervention components to improve the surveillance and targeting of antibiotics. However, impacts of the individual components of AMS interventions are not well known, especially in low- and lower-middle-income countries (LLMICs). OBJECTIVE: A scoping review was conducted to summarize evidence from systematic reviews (SRs) on the impact of common hospital-implemented healthcare-worker-targeted components of AMS interventions that may be appropriate for LLMICs. METHODS: Major databases were searched systematically for SRs of AMS interventions that were evaluated in hospitals. For SRs to be eligible, they had to report on at least one intervention that could be categorized according to the Effective Practice and Organisation of Care taxonomy. Clinical and process outcomes were considered. Primary studies from LLMICs were consulted for additional information. RESULTS: Eighteen SRs of the evaluation of intervention components met the inclusion criteria. The evidence shows that audit and feedback, and clinical practice guidelines improved several clinical and process outcomes in hospitals. An unintended consequence of interventions was an increase in the use of antibiotics. There was a cumulative total of 547 unique studies, but only 2% (N=12) were conducted in hospitals in LLMICs. Two studies in LLMICs reported that guidelines and educational meetings were effective in hospitals. CONCLUSION: Evidence from high- and upper-middle-income countries suggests that audit and feedback, and clinical practice guidelines have the potential to improve various clinical and process outcomes in hospitals. The lack of evidence in LLMIC settings prevents firm conclusions from being drawn, and highlights the need for further research.

Denosumab utilization among older adults in Ontario: patient characteristics, persistence with therapy, and return to therapy after an extended gap.

We studied 46,797 older adults who initiated denosumab in Ontario, Canada. Patient characteristics remained relatively stable over time and aligned with public reimbursement restrictions. Almost half of patients persisted with therapy for at least 3 years. Fifty-nine percent of patients who discontinued denosumab returned to treatment within 3.6 years. INTRODUCTION: The purpose of this study was to describe the characteristics of patients who initiated denosumab and estimate persistence with therapy. METHODS: We identified older adults (aged ≥ 66 years) in Ontario who initiated denosumab between 2012/02 and 2015/03 and followed them to 2016/03. Patient characteristics were summarized using medical and pharmacy claims in the year before starting denosumab and osteoporosis drug use considered since 1996/10. Persistence with denosumab and return after discontinuation (> 90-day gap) were estimated using Kaplan-Meier curves. Analyses were stratified by community and long-term care (LTC) residence. RESULTS: We identified 46,797 patients (monthly mean = 1263, SD = 187); 97% female, 13% LTC. Community-dwelling patients had a higher prevalence of bone mineral density testing (62% vs. 5%), yet were younger (mean age 78.5 vs. 86.6 years) and had lower prevalence of hip fractures (3% vs. 10%) compared to LTC patients. Eighty-two percent of patients had used osteoporosis medications in the past; 99% of whom took an oral bisphosphonate. Persistence was similar between community-dwelling and LTC patients: 59% persisted ≥ 2 years, 48% ≥ 3 years, and 38% ≥ 4 years, yet a larger proportion of LTC patients returned to denosumab after discontinuation (76% vs. 57%). CONCLUSIONS: Denosumab utilization is increasing at a steady rate in Ontario. However, persistence remains a concern given the highly reversible pharmacokinetic profile of denosumab that results in a rapid increased fracture risk following discontinuation. Over 80% of patients had a history of oral bisphosphonate therapy, which may persist in bone despite discontinuing denosumab. Consequently, better understanding of denosumab safety and effectiveness among real-world users is important.

Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes.

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

Muscle specific kinase protects dystrophic mdx mouse muscles from eccentric contraction-induced loss of force-producing capacity.

KEY POINTS: Adeno-associated viral vector was used to elevate the expression of muscle specific kinase (MuSK) and rapsyn (a cytoplasmic MuSK effector protein) in the tibialis anterior muscle of wild-type and dystrophic (mdx) mice. In mdx mice, enhanced expression of either MuSK or rapsyn ameliorated the acute loss of muscle force associated with strain injury. Increases in sarcolemmal immunolabelling for utrophin and ß-dystroglycan suggest a mechanism for the protective effect of MuSK in mdx muscles. MuSK also caused subtle changes to the structure and function of the neuromuscular junction, suggesting novel roles for MuSK in muscle physiology and pathophysiology. ABSTRACT: Muscle specific kinase (MuSK) has a well-defined role in stabilizing the developing mammalian neuromuscular junction, but MuSK might also be protective in some neuromuscular diseases. In the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy, limb muscles are especially fragile. We injected the tibialis anterior muscle of 8-week-old mdx and wild-type (C57BL10) mice with adeno-associated viral vectors encoding either MuSK or rapsyn (a cytoplasmic MuSK effector protein) fused to green fluorescent protein (MuSK-GFP and rapsyn-GFP, respectively). Contralateral muscles injected with empty vector served as controls. One month later mice were anaesthetized with isoflurane and isometric force-producing capacity was recorded from the distal tendon. MuSK-GFP caused an unexpected decay in nerve-evoked tetanic force, both in wild-type and mdx muscles, without affecting contraction elicited by direct electrical stimulation of the muscle. Muscle fragility was probed by challenging muscles with a strain injury protocol consisting of a series of four strain-producing eccentric contractions in vivo. When applied to muscles of mdx mice, eccentric contraction produced an acute 27% reduction in directly evoked muscle force output, affirming the susceptibility of mdx muscles to strain injury. mdx muscles overexpressing MuSK-GFP or rapsyn-GFP exhibited significantly milder force deficits after the eccentric contraction challenge (15% and 14%, respectively). The protective effect of MuSK-GFP in muscles of mdx mice was associated with increased immunolabelling for utrophin and ß-dystroglycan in the sarcolemma. Elevating the expression of MuSK or rapsyn revealed several distinct synaptic and extrasynaptic effects, suggesting novel roles for MuSK signalling in muscle physiology and pathophysiology.

[The impact of persistent high ambient fine particulate matters exposures on mortality in the 40 districts/counties of China, 2013-2015].

Objective: To investigate the impact of persistent high ambient fine particulate matters (PM(2.5)) exposures on mortality in the polluted areas of 40 districts/counties in China. Methods: Using a convenient sampling method, we selected 40 districts/counties as research sites from the Beijing-Tianjin-Hebei Metropolitan Region, the Yangtze River Delta, the Pearl River Delta, and Heilongjiang, Shanxi, and Sichuan province. The daily concentrations of PM(2.5), meteorological data and population death data from January 1, 2013 to December 31, 2015 were collected. The six persistent PM(2).5 pollution episode scenarios were defined by the average daily concentration of PM(2.5) (75 µg/m(3), P(75) and P(90) of the average daily concentration of each district/county respectively) and the duration (≥2 days or 3 days). Generalized linear models and meta analyses were used to explore the impact of PM(2.5) pollution episodes on mortality in 40 districts/counties. Results: The mean±SD and P(50) (P(25), P(75)) of average daily temperature, relative humidity and PM(2.5) were (15.26±10.48) ℃, 17.20 (7.50, 23.70) ℃, (67.31±19.26)%, 72.00% (57.00%, 81.00%), (72.81±60.93) µg/m(3) and 55.38 (33.77, 91.45) µg/m(3), respectively in 40 districts/counties during 2013-2015. The average number of non-accidental, cardiovascular and cerebrovascular diseases deaths per day were (12±7), (5±4) and (2±2) in each district/county, respectively. When the daily concentrations of PM(2.5) were ≥75 µg/m(3) (≥2 days), ≥P(75) (≥2 days), ≥P(90) (≥2 days), ≥75 µg/m(3) (≥3 days), and ≥P(75) (≥3 days), the excess risk (95%CI) of the total non-accidental deaths and cardiovascular diseases deaths were 1.77% (0.89%,2.66%), 2.69% (1.06%,4.35%), 1.67% (0.59%,2.76%), 2.31% (0.67%, 3.97%), 0.71% (-0.75%, 2.20%), 1.95% (0.08%, 3.86%), 1.15% (0.12%, 2.18%), 1.85% (0.25%, 3.47%), 1.39% (0.15%, 2.64%), 2.29% (0.39%, 4.23%), respectively. Conclusion: Persistently high PM(2.5) exposures were associated with total non-accidental deaths and cardiovascular disease deaths.

[Association of ambient fine particulate matters with anxiety in middle-aged and elderly people].

Objective: To investigate the association of ambient fine particulate matters (PM(2.5)) exposure with anxiety in middle-aged and elderly people in China. Methods: Using a stratified random sampling method, 5 997 middle-aged and elderly people (aged 40-89) who resided in the region for more than 2 years and had no hearing or language impairment were selected from 32 districts/counties in the key areas for air pollution prevention and control in China from October 10(th), 2017 to February 7(th), 2018. Information about demographic characteristics, socioeconomic factors and health status were collected by questionnaire survey and physical examination. The anxiety symptoms were assessed by 7-item Generalized Anxiety Disorder Scales. Three-year moving average concentrations of PM(2.5) were calculated to estimate exposure level. The multivariate logistic regression model was conducted to assess the association between PM(2.5) exposure and anxiety. The interaction of age, gender, overweight, education, smoking, drinking and chronic diseases was also analyzed by likelihood ratio test. Results: There were 2 995 (49.94%) males subjects, 4 092 (68.23%) subjects with education of secondary school or above and 2 576 (42.95%) subjects with self-reported chronic diseases among the 5 997 middle-aged and elder participants. The prevalence of anxiety was 6.64% (n=398). The mean±SD of 3-year moving average concentrations of PM(2.5), O(3) and SO(2) were (53.50±13.38), (90.58±13.26) and (40.29±12.56) µg/m(3), respectively. PM(2.5) had significantly association with anxiety, and the corresponding OR value was 1.17 (95%CI: 1.05,1.31) with a 10 µg/m(3) increment of 3-year moving average concentrations of PM(2.5). Compared with female (OR (95%CI)=1.07 (0.93,1.23)), those with no chronic diseases (OR (95%CI)=1.06 (0.93,1.20)) and those with primary school degree or below (OR (95% CI)=0.90 (0.75,1.09)), the association between PM(2.5) and anxiety was stronger among male (OR (95%CI)=1.35 (1.12,1.63)) and those with chronic diseases (OR (95%CI)=1.77 (1.31,2.38)), middle school education (OR (95%CI)=1.43 (1.22,1.67)), college education and above (OR (95%CI)=1.68 (1.05, 2.67)), all the P interaction values were <0.05. Conclusion: PM(2.5) exposure has significantly positive association with anxiety. The associations are stronger in male, people with higher educational qualifications and patients with chronic diseases.

[A review on the research progress related to ambient air pollution and depression].

It is reported that depression has caused heavy disease burden across the world, with an possible association between ambient air pollution and depressive symptoms. In this paper, we reviewed relative literature in this field and summarized the research events on association between ambient air pollution and depression, both in China and abroad and found that the results of the existed studies were inconsistent, with most studies showing that there existed a positive correlation between the exposure of air pollution and depression, but few studies showing the negative correlation or no correlation between the two.

Acute effect of multiple ozone metrics on mortality by season in 34 Chinese counties in 2013-2015.

BACKGROUND: Although numerous multicentre studies have estimated the association between ozone exposure and mortality, there are currently no nationally representative multicentre studies of the ozone-mortality relationship in China. OBJECTIVE: To investigate the effect on total (nonaccidental) and cause-specific mortality of short-term exposure to ambient ozone, and examine different exposure metrics. METHODS: The effects of short-term exposure to ozone were analysed using various metrics (daily 1-h maximum, daily 8-h maximum and daily average) on total (nonaccidental) and cause-specific (circulatory and respiratory) mortality from 2013 to 2015 in 34 counties in 10 cities across China. We used distributed lag nonlinear models for estimating county-specific relative risk of mortality and combined the county-specific relative rates by conducting a random-effects meta-analysis. RESULTS: In all-year analyses, a 10 µg m-3 increase in daily average, daily 1-h maximum and daily 8-h maximum ozone at lag02 corresponded to an increase of 0.6% (95% CI: 0.33, 0.88), 0.26% (95% CI: 0.12, 0.39) and 0.37% (95% CI: 0.2, 0.55) in total (nonaccidental) mortality, 0.66% (95% CI: 0.28, 1.04), 0.31% (95% CI: 0.11, 0.51) and 0.39% (95% CI: 0.16, 0.62) in circulatory mortality, and 0.57% (95% CI: -0.09, 1.23), 0.11% (95% CI: -0.22, 0.44) and 0.22% (95% CI: -0.28, 0.72) in respiratory mortality, respectively. These estimates had a different seasonal pattern by cause of death. In general, the seasonal patterns were consistent with the times of year when ozone concentrations are highest. CONCLUSIONS: Our findings suggest that in China, the acute effects of ozone are more closely related to daily average exposure than any other metric.

Estimation of Day-Specific Probabilities of Conception during Natural Cycle in Women from Babylon.

BACKGROUND: Identifying predictors of the probabilities of conception related to the timing and frequency of intercourse in the menstrual cycle is essential for couples attempting pregnancy, users of natural family planning methods, and clinicians diagnosing for possible causes of infertility. The aim of this study is to estimate the days in which the likelihood of conception happened by using first trimester ultrasound fetal biometry in natural cycles and spontaneous pregnancy, and to explore some factors that may affect them. MATERIALS AND METHODS: This study is retrospective cohort study, with random sampling. It involved 60 pregnant ladies at first trimester; the date of conception was estimated using: i. Crown-rump length biometry (routine ultrasound examinations were performed at a median of 70 days following Last menstrual period or equivalently 10 weeks), ii. Date of last menstrual cycle. Only women with previous infertility and now conceiving naturally with a certain date of Last menstrual period were selected. RESULTS: The distribution of conception showed a sharp rise from day 8 onwards, reaching its maximum at day 13 and decreasing to zero by day 30 of Last menstrual period. The older and obese women had conceive earlier than younger women but there was insignificants difference between the two groups (P>0.05). According to the type of infertility, the women with secondary infertility had conceived earlier than those with primary infertility. There was a significant difference between the two groups (P<0.05). CONCLUSION: Day specific of conception may be affected by factors such as age, BMI, and type of infertility. This may be confirmed by larger sample size in metacentric study.

The determination and application of (87) Sr/(86) Sr ratio in verifying geographical origin of wheat.

As 87 Sr/86 Sr ratio plays a significant role in authenticating the geographical origin of foodstuff, it is important to identify where the 87 Sr/86 Sr signature in food comes from, and the methods of 87 Sr/86 Sr ratio analysis in food and environmental samples. Wheat with three genotypes, soil and groundwater samples were collected from three regions of China during harvest time of 2014. The 87 Sr/86 Sr ratios in the samples were determined by thermal ionization mass spectrometer in order to investigate the possible source of 87 Sr/86 Sr in wheat, and the concentrations of Rb and Sr in wheat and soils were also detected by inductively coupled plasma mass spectrometry and combined with 87 Sr/86 Sr ratio in order to trace the geographical origin of wheat. The 87 Sr/86 Sr ratio, the contents Rb and Sr, and Rb/Sr ratio of wheat and soil samples showed significant differences among three regions. The 87 Sr/86 Sr ratios and the concentrations of Rb and Sr in soils were higher than those in corresponding wheat. The 87 Sr/86 Sr ratio in wheat was identical to that corresponding soil NH4 NO3 extracts (labile fraction of soil) and groundwater. Wheat uptake more Rb than Sr. 3D distribution of 87 Sr/86 Sr, Rb and Sr could identify wheat samples from different regions clearly. The 87 Sr/86 Sr ratio of wheat reflects the 87 Sr/86 Sr ratio of the associated environment including soil and groundwater. It is expected that the use the parameters of 87 Sr/86 Sr ratio, the contents of Rb and Sr will allow to trace geographical origin of wheat. Copyright © 2017 John Wiley & Sons, Ltd.

[Air pollution and adverse birth outcome in China: a comprehensive review].

Objective: To summarize the progress in the research of the association between air pollution and adverse birth outcomes in China. Methods: A literature retrieval was conducted by using the databases of CNKI, Wanfang, Pubmed, Science Direct, and Web of Science to select relevant research papers published before 30(th), June 2016 in China according to inclusion criteria. Finally, 27 papers were included in analysis. Results: Exposure to particulate matter (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), total suspended particles (TSP) during pregnancy might increase risk for low birth weight; exposure to PM(10), SO(2), NO(2) during pregnancy might increase risk for premature birth; and exposure to SO(2), NO(2), ozone (O(3)), and PM(10) during pregnancy might increase risk for congenital heart diseases and other birth defects. Conclusion: Exposure to air pollutants during pregnancy might increase the risk for adverse birth outcomes, and further studies are needed to prove the association.

Diagnostic roles of calretinin in hirschsprung disease: A comparison to neuron-specific enolase.

BACKGROUND/AIM: Diagnosis of Hirschsprung's disease (HD) can be hard and requires good experience, principally for pathologists who infrequently encounter the disease. However, diagnosis is not always possible with hematoxylin and eosin (H and E) because staining has limitations in the identification of immature ganglion cells in neonates and the submucosal area. AIM: To assess the diagnostic role of calretinin immunostaining in HD in comparison to neuron-specific enolase. PATIENTS AND METHODS: Formalin-fixed paraffin tissue blocks of full-thickness distal colonic and rectal biopsies for 48 patients who clinically presented with symptoms suspicious for HD were collected for the period from December 2012 to January 2016. All biopsies were already studied by routine H and E histopathological examination for the presence or absence of ganglion cells. Further confirmation of ganglion cells and nerve fibers was performed by immunohistochemical study for neuron-specific enolase and calretinin, respectively, in a private pathology laboratory. RESULTS: According to the histopathological assessment, cases with absent ganglionic cells were considered to be HD, which comprised 40 cases out of the total 48 cases. The mean age for HD cases was 19.43 months. The male-to-female ratio in HD cases was 2.34:1. All HD cases showed negative expression of calretinin in small nerve fibers of the lamina propria, musularis mucosae, and submucosa, and negative expression of neuron-specific enolase in ganglionic cells. The sensitivity, specificity, positive predictive value, and negative predictive values for both the markers in the confirmation of diagnosis of HD were all 100%. CONCLUSION: Calretinin immunostaining, similar to that of neuron-specific enolase, is a highly sensitive and specific diagnostic aid to histopathological examination in suspected HD.

Association of cigarette smoking with a past history and incidence of herpes zoster in the general Japanese population: the SHEZ Study.

Few studies have examined the impact of cigarette smoking on the risk for herpes zoster. The Shozu Herpes Zoster (SHEZ) Study is a community-based prospective cohort study over 3 years in Japan aiming to clarify the incidence and predictive and immunological factors for herpes zoster. We investigated the associations of smoking status with past history and incidence of herpes zoster. A total of 12 351 participants provided valid information on smoking status and past history of herpes zoster at baseline survey. Smoking status was classified into three categories (current, former, never smoker), and if currently smoking, the number of cigarettes consumed per day was recorded. The participants were under the active surveillance for first-ever incident herpes zoster for 3 years. We used a logistic regression model for the cross-sectional study on the association between smoking status and past history of herpes zoster, and a Cox proportional hazards regression model for the cohort study on the association with risk of incidence. The multivariable adjusted odd ratios (95% CI) of past history of herpes zoster for current vs. never smokers were 0·67 (0·54-0·80) for total subjects, 0·72 (0·56-0·93) for men and 0·65 (0·44-0·96) for women. The multivariable adjusted hazard ratios (95% CI) of incident herpes zoster for current vs. never smokers were 0·52 (0·33-0·81) for total subjects, 0·49 (0·29-0·83) for men and 0·52 (0·19-1·39) for women. Smoking status was inversely associated with the prevalence and incidence of herpes zoster in the general population of men and women aged ⩾50 years.

Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1).

We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. Multiple alignments of CD8α1 with known CD8α and CD8ß sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. For example, cysteine residues that are involved in disulfide bonding to form the V domain are conserved. In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A ß strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells.

Nitric oxide participates in IFN-gamma-induced HUVECs hyperpermeability.

The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.

Association of global DNA hypomethylation with clinicopathological variables in colonic tumors of Iraqi patients.

BACKGROUND/AIM: Colorectal cancer (CRC) ranks sixth among the most common 10 cancers in Iraq. It is a foremost public health dilemma and there is improved interest in understanding the fundamental principles of its molecular biology. DNA methylation in cancer has become the issue of passionate investigation. As compared with normal cells, the malignant cells show major disruptions in their DNA methylation patterns. We aimed to assess the association of global DNA hypomethylation in colonic adenomas and carcinomas of Iraqi patients, measured by immunohistochemistry of 5-methylcytosin, with different clinicopathological variables. PATIENTS AND METHODS: Thirty tissue paraffin blocks from patients with colorectal adenomas, 30 tissue paraffin blocks from patients with colorectal adenocarcinomas, and 30 samples of apparently normal colonic tissue taken from autopsy cases as a control group were included in the present study. From each block, two sections of 5 µm thickness were taken, one section was stained with Hematoxylin and Eosin for revision of histopathological diagnosis and one section was immunohistochemically stained for 5-methylcytosine (5mC) and digitally analyzed by AperioImageScope software. RESULTS: The mean digital value of 5mC immunohistochemical expression was sequentially decreased during neoplastic progression from normal colonic tissue into adenoma and then to carcinoma. The mean digital value of 5mC expression was significantly lower in large size adenomas (≥1 cm), and those with severe dysplasia. Concerning carcinoma cases, 5mC expression was significantly lower in stage C2. CONCLUSIONS: The immunohistochemical evaluation of 5mC yields refined information on colorectal tumor biology in adenoma and carcinoma. Global DNA hypomethylation reflected by low immunohistochemical expression of 5-mC is associated with advanced colorectal adenomatous polyps suggesting that it is an early event in colorectal carcinogenesis. Also this hypomethylation can reflect bad prognosis of patients with colorectal cancer by its correlation to higher tumor stage.