Involvement of phospholipase D2 in lysophosphatidate-induced transactivation of platelet-derived growth factor receptor-beta in human bronchial epithelial cells.
Lysophosphatidate (LPA) mediates multiple cellular responses via heterotrimeric G protein coupled LPA-1, LPA-2, and LPA-3 receptors. Many G protein-coupled receptors stimulate ERK following tyrosine phosphorylation of growth factor receptors; however, the mechanism(s) of transactivation of receptor tyrosine kinases are not well defined. Here, we provide evidence for the involvement of phospholipase D (PLD) in LPA-mediated transactivation of platelet-derived growth factor receptor-beta (PDGF-R beta). In primary cultures of human bronchial epithelial cells (HBEpCs), LPA stimulated tyrosine phosphorylation of PDGF-R beta and threonine/tyrosine phosphorylation of ERK1/2. The LPA-mediated activation of ERK and tyrosine phosphorylation of PDGF-R beta was attenuated by tyrphostin AG 1296, an inhibitor of PDGF-R kinase, suggesting transactivation of PDGF-R by LPA. Furthermore, LPA-, but not PDGF beta-chain homodimer-induced tyrosine phosphorylation of PDGF-R beta was partially blocked by pertussis toxin, indicating coupling of LPA-R(s) to Gi. Exposure of HBEpCs to LPA activated PLD. Butan-1-ol, which acts as an acceptor of phosphatidate generated by the PLD pathway, blocked LPA-mediated transactivation of PDGF-R beta. This effect was not seen with butan-3-ol, suggesting PLD involvement. The role of PLD1 and PLD2 in the PDGF-R beta transactivation by LPA was investigated by infection of cells with adenoviral constructs of wild type and catalytically inactive mutants of PLD. LPA activated both PLD1 and PLD2 in HBEpCs; however, infection of cells with cDNA for wild type PLD2, but not PLD1, increased the tyrosine phosphorylation of PDGF-R beta in response to LPA. Also, the LPA-mediated tyrosine phosphorylation of PDGF-R beta was attenuated by the catalytically inactive mutant mPLD2-K758R. Infection of HBEpCs with adenoviral constructs of wild type hPLD1, mPLD2, and the inactive mutants of hPLD1 and mPLD2 resulted in association of PLD2 wild type and inactive mutant proteins with the PDGF-R beta compared with PLD1. These results show for the first time that transactivation of PDGF-R beta by LPA in HBEpCs is regulated by PLD2.


Novel chemotherapeutic and renal protective effects for the green tea (EGCG): role of oxidative stress and inflammatory-cytokine signaling.
The green tea catechin, epigallocatechin-gallate (EGCG) is a superb nature's medicine candidate. We evaluated the chemotherapeutic/chemoenhancing effects of EGCG in mice bearing the solid Ehrlich ascites carcinoma (EAC) tumor, and jointly monitored levels of serum C-reactive protein (CRP), lipid peroxidation (as malondialdehyde: MDA) and leukocytosis (LC). Besides, we verified whether; and how then, EGCG would protect against a devastating CP-induced nephrotoxicity in rats. In particular, renal proinflammatory (TNF-α) and oxidant stress signals have been investigated. (EAC)-bearing mice displayed elevated serum-LC (2-fold), -CRP (11-fold) and -MDA levels (2.7-fold). EGCG (20, 40 mg/kg) significantly shrank tumors (by 48% and 92%, respectively), and reduced LC, CRP and MDA levels. Such responses for CP were less prominent than those of EGCG (40 mg/kg). Further, EGCG (20 mg/kg) markedly augmented such functional and biochemical responses to CP. Correlation studies showed positive association between tumor size and each of CRP (r=0.97) and LC (r=0.83). Additionally; in rats, CP (10 mg/kg) caused a prominent nephrotoxicity that was manifested as deteriorated glomerular filtration rate (GFR, 2-5-fold rise in serum creatinine/urea levels) after 4 days, and unanimous animal fatalities after 7 days. Kidney homogenates from CP-treated rats showed significantly higher MDA- and TNF-α-, and -depleted GSH levels. Rats treated with EGCG (50 mg/kg, but not 25 mg/kg) devoid the nephrotoxic effects of CP and their consequences; while their homogenates had appreciably lower MDA and TNF-α, and higher GSH levels. Notable correlation was detected between serum creatinine level and each of MDA (r=0.85), TNF-α (r=0.85) and GSH (r=-0.81). This study shows remarkable cytotoxic/chemoenhancing effects for EGCG and introduces CRP as a predictor of both tumor's progression and responsiveness to chemotherapy. Further, this study is the first to reveal that EGCG can obliterate the lethal CP-induced nephrotoxicity. Mechanistically, EGCG acts by suppressing leukocytosis, systemic inflammation, oxidative stress, and their sequelae.


Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital Chagas disease.
Trypanos o ma cruzi (T. cruzi or Tc) is the causative agent of Chagas disease (CD). It is common for patients to suffer from non-specific symptoms or be clinically asymptomatic with acute and chronic conditions acquired through various routes of transmission. The expecting women and their fetuses are vulnerable to congenital transmission of Tc. Pregnant women face formidable health challenges because the frontline antiparasitic drugs, benznidazole and nifurtimox, are contraindicated during pregnancy. However, it is worthwhile to highlight that newborns can be cured if they are diagnosed and given treatment in a timely manner. In this review, we discuss the pathogenesis of maternal-fetal transmission of Tc and provide a justification for the investment in the development of vaccines against congenital CD.


A systematic review on the modifications of extracellular vesicles: a revolutionized tool of nano-biotechnology.
Tailoring extracellular vesicles (EVs) can bequeath them with diverse functions and efficient performance in nano-biotechnology. Engineering and modification of EVs improves the targeted drug delivery efficiency. Here, we performed systematic review of various methods for EVs modifications. PubMed, Scopus, ISI Web of Science, EMBASE, and Google Scholar were searched for available articles on EVs modifications (up to March 2021). In total, 1208 articles were identified and assessed, and then only 36 articles were found eligible and included. Six studies demonstrate the application of click chemistry, seven studies used co-incubation, two studies used chemical transfection, four studies implicated electroporation and sonication approach for modification of EVs. Moreover, two studies utilized microfluidics as suitable approach for loading cargo into EVs, while eight studies showed freeze-thaw method as feasible for these biological nanoparticles. Freeze-thaw approach is found to be convenient and popular among researchers for performing modifications in EVs for the purpose of targeted drug delivery loading. Clinical-grade EVs production with good clinical practices (GCPs) is challenging in the current scenario. More studies are needed to determine the best suitable approach for cargo loading of EVs that may be exploited for research and therapeutic use.


Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid.
Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15-25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.


Interaction Between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Environment with Susceptibility to Ischemic Stroke in Chinese Population.
To investigate the association of several single-nucleotide polymorphisms (SNPs) within methylenetetrahydrofolate reductase (MTHFR) gene, and additional gene-environment interaction with ischemic stroke (IS) risk. Testing for Hardy-Weinberg equilibrium in controls was conducted using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among four SNPs within MTHFR gene and smoking or alcohol drinking. The frequency of the rs4846049-A allele was 28.6% in IS patients and 19.1% in normal controls, in addition, the frequency of the rs3737967-T allele was 27.9% in IS patients and 20.3% in normal controls, which was also indicating a statistically significant difference. The rs4846049-A and rs3737967-T were associated with an increased risk of IS risk; adjusted odds ratios (ORs) (95% confidence interval [CI]) were 1.76 (1.28-2.13) and 1.51 (1.13-1.97), respectively. GMDR model found significant gene-alcohol drinking interaction combination, but no significant gene-tobacco smoking interaction combinations. In order to obtain the odds ratios and 95% CI for the joint effects of gene-alcohol drinking on IS, we conducted stratified analysis for interaction effect using logistic regression. We found that alcohol drinkers with rs4846049-CA/AA genotype also have the highest IS risk, compared with never drinkers with rs4846049-CC genotype, OR (95% CI) = 3.12 (1.83-4.45), after adjustment for age, smoke, and smoking status. The rs4846049-A and rs3737967-T, gene-environment interaction between rs1764391 and rs918592, gene-environment interaction between rs4846049 and alcohol drinking were all associated with increased IS risk.


Effect of methionine-enkephalin plus ZnCl2 on active T cell rosettes.
Methionine-enkephalin (Met-Enk) and ZnCl2 in combination enhances active T cell rosette formation of human peripheral blood lymphocytes to a greater degree than either of the agents used separately. Enhancement of rosette formation by Met-Enk plus ZnCl2 was not inhibited by the opiate receptor antagonist naloxone but was completely blocked by the zinc chelator 1,10-phenanthroline. The results suggest a relationship between zinc and Met-Enk and that zinc may be a modulator of enkephalin binding and function in the immune system as well as the nervous system.


Presence of microchimerism in labial salivary glands in systemic sclerosis but not in Sjögren's syndrome.
To determine whether microchimerism can be implicated in Sjögren's syndrome (SS) by studying minor salivary glands, one of the targets of the disease. Labial salivary gland (LSG) biopsy specimens from 16 female patients with primary SS and 11 with systemic sclerosis (SSc) (a disease in which microchimerism is frequently detected) were analyzed. All 27 women had a history of pregnancy with a male baby. Specimens were microdissected, and polymerase chain reaction (PCR) was performed using the unique sex-determining region Y gene probe. The sensitivity of PCR for detecting male cells in LSG was high; the presence of 3 male cells was consistently detected in DNA extracted from a normal female LSG specimen to which male DNA had been added, and 1 male cell was detected in 50% of specimens analyzed. Male DNA was not found in any of the specimens from the 16 SS patients but was detected in 5 (45%) of 11 SSc specimens (P = 0.006). No differences in the rate of detection were found between patients with diffuse and limited SSc (male DNA detected in 2 of 3 and 3 of 8, respectively; P = 0.55) or between patients with and those without secondary SS (1 of 6 and 4 of 5, respectively; P = 0.08). The results of our study strengthen the possibility that microchimerism is implicated in SSc. This is the first study to demonstrate the presence of chimeric cells in LSG from 45% of SSc patients, independent of the presence of secondary SS. However, microchimerism was not detected in LSG from patients with primary SS, suggesting that the pathogenesis of the 2 diseases is different.


Transtracheal drainage of lung abscesses in children.
Experience with three patients with primary lung abscesses indicates that transtracheal catheter drainage of lung abscesses is a safe and beneficial procedure in childhood. The ability to drain abscesses not easily reached percutaneously will promote emptying and collapse of the abscess and provide bacteriological information which will enable the physician to select the correct antibiotics.


Immunological components and antioxidant activity in human milk processed by different high pressure-thermal treatments at low initial temperature and flash holding times.
The effect of high pressure thermal (HPT) processing on the immunoglobulin (IgM, IgA and IgG), and cytokine content (IL-6, IL-8, IL-10, and TNF-α), and antioxidant activity of human milk was analyzed after the application of different treatments between 200, and 800 MPa at low initial temperatures (between -15, and 50 °C) and for 1 s (flash treatments). Low pressures intensities did not induce changes in Igs while at 800 MPa, all combinations reduced the control levels. IL-6 and IL-10 were not affected by any of the treatments applied while IL-8 and TNF-α were reduced at treatments which combined temperatures at 50 °C. In general antioxidant activity was not affected at the processing conditions chosen. The flash HPT treatment applied at 600 MPa and at 0 °C could be the best choice to preserve immunological parameters and the antioxidant activity of human milk.


[Prevalence and prognostic meaning of comorbidity in heart failure].
Heart failure (HF) predominantly affects elderly individuals and has a significant impact on the health systems of developed countries. Comorbidities are present in most patients with HF by acting as the cause, the consequence or a mere coincidence. In addition to their high prevalence, they have considerable relevance because they can mask symptoms, impede the diagnosis and treatment, contribute to progression and negatively influence the prognosis of HF. Most of the associated comorbidities result in a greater number of hospitalisations, poorer quality of life and increased mortality. Given that many of these comorbidities are underdiagnosed, their detection could improve the outcome and quality of life of patients with HF. This article reviews the prevalence and prognostic meaning of the most prevalent comorbidities associated with HF.


Chlordecone (Kepone) induced ultrastructural and morphometric alterations in the cells of the immature quail oviduct.
Groups of sexually immature Japanese quail females, kept in a reduced photoperiod, received either daily intraperitoneal injections of 40 micrograms estradiol-17 beta for 26 days or were fed diets containing 0, 10, 40, 80 or 160 ppm chlordecone for the same duration. Estradiol-17 beta induced rapid cellular hypertrophy, cytodifferentiation, tubular gland formation, organelle proliferation and secretory granule formation in different cells of the quail oviduct. Higher chlordecone doses mimicked these estradiol-17 beta actions, but in addition induced atypical cell and organelle morphology, such as protruding or swollen cell apices, increased mitochondrial volume densities and diameters and disorganized Golgi apparati. The possible effects of these chlordecone-induced atypical cell alterations on avian reproduction are discussed.


Purkinje cell vulnerability and autism: a possible etiological connection.
Autism is a neurological disorder of unknown etiology. The onset of the abnormal growth and development within the brain is also not known. Current thought by experts in autism is that the time of onset is prenatal, occurring prior to 30 weeks gestation. However, autism comprises a heterogeneous population in that parents report either that their child was abnormal from birth, or that their child was developmentally normal until sometime after birth, at which time the child began to regress or deteriorate. Anecdotal reports suggest that some children with autism have significant illness or clinical events prior to the development of autistic symptoms. Conceivably, these children may become autistic from neuronal cell death or brain damage sometime after birth as result of insult. To support this theory is that marked Purkinje cell loss, the most consistent finding in the autistic disorder, can result from insult. Evidence suggests that the Purkinje cell is selectively vulnerable. This article discusses a theory that the selective vulnerability of the Purkinje cell may play a role in the etiology of autism, and suggests that a future direction in autism research may be to investigate the possibility of neuronal cell loss from insult as a cause of autism. Results of a small pilot survey are also discussed.


The impact of mucormycosis (black fungus) on SARS-CoV-2-infected patients: at a glance.
The emergence of various diseases during the COVID-19 pandemic made health workers more attentive, and one of the new pathogens is the black fungus (mucormycosis). As a result, millions of lives have already been lost. As a result of the mutation, the virus is constantly changing its traits, including the rate of disease transmission, virulence, pathogenesis, and clinical signs. A recent analysis revealed that some COVID-19 patients were also coinfected with a fungal disease called mucormycosis (black fungus). India has already categorized the COVID-19 patient black fungus outbreak as an epidemic. Only a few reports are observed in other countries. The immune system is weakened by COVID-19 medication, rendering it more prone to illnesses like black fungus (mucormycosis). COVID-19, which is caused by a B.1.617 strain of the SARS-CoV-2 virus, has been circulating in India since April 2021. Mucormycosis is a rare fungal infection induced by exposure to a fungus called mucormycete. The most typically implicated genera are Mucor rhyzuprhizopusdia and Cunninghamella. Mucormycosis is also known as zygomycosis. The main causes of infection are soil, dumping sites, ancient building walls, and other sources of infection (reservoir words "mucormycosis" and "zygomycosis" are occasionally interchanged). Zygomycota, on the other hand, has been identified as polyphyletic and is not currently included in fungal classification systems; also, zygomycosis includes Entomophthorales, but mucormycosis does not. This current review will be focused on the etiology and virulence factors of COVID-19/mucormycosis coinfections in COVID-19-associated mucormycosis patients, as well as their prevalence, diagnosis, and treatment.


Oscillatory potentials of visually inattentive children.
The oscillatory potentials (OPs) are probably generated in the proximal retina. The OPs of 20 visually inattentive infants and children were recorded. All 20 had evidence of abnormalities of the visual parts of the brain. The a- and b-waves, indices of distal retinal function, were normal in 10 patients, abnormal in the other 10. Among the patients with abnormal, attenuated a- and b-waves, OP amplitudes were more attenuated than among those with normal a- and b-waves. However, the timing of the OP wavelets was not correlated with distal retinal activity. These results suggest that in humans OP amplitude may be determined by inputs from the distal retina, but OP latency and periodicity are governed by processes within the proximal retina.


Characterisation of a navelbine-resistant bladder carcinoma cell line cross-resistant to taxoids.
A bladder carcinoma cell line (J82) was selected for resistance to the new vinca alkaloid navelbine. The resistance factor of the resistant subline (J82-NVB) to navelbine was 17. P-glycoprotein was not detected in the membrane of J82-NVB cells. The lack of cross-resistance to multidrug-resistant (MDR) drugs such as doxorubicin, epipodophyllotoxins and colchicine, the absence of increase in navelbine efflux and the fact that a reduced accumulation of the drug cannot account for the resistance level confirmed that the phenotype of resistance of J82-NVB cells is not a classical MDR phenotype. Moreover, verapamil did not reverse the resistance of J82-NVB cells. The cells were cross-resistant to vinca alkaloids and taxoids which share the same target protein: tubulin. Analysis of microtubules using immunofluorescence showed that disassembly of the microtubular network occurred for the same concentration of navelbine in sensitive and resistant cells. However, after treatment with a concentration of navelbine inducing depolymerisation in both sensitive and resistant cells, reassembly of the microtubular network was observed only in resistant cells. This study suggests that the mechanism of resistance of J82-NVB cells involves recovery from the inhibition of microtubule dynamics induced by drug treatment.


Preliminary clinical study of the accuracy of a digital axiographic recording system for the assessment of sagittal condylar inclination.
The aim of this study was to clinically evaluate the accuracy of a digital axiographic recording system in tracing the sagittal condylar inclination. An axiographic examination that records the sagittal condylar path during protrusive/retrusive movement was performed on ten patients. Each subject was registered five different times by two different systems: 1) the Cadiax Gamma Diagnostic 4 computerized system as the control; 2) the Zebris Jaw Motion Analyser+ Optic System as the tested digital axiographic recording system. The records obtained allow to calculate the kinematic terminal transverse horizontal axis and the sagittal condylar inclination (SCI) at 3 and 5 mm along the pro-retrusive path. A linear mixed model was used to analyze if there was a statistically significant difference between the two systems. The mean left SCI value recorded by Zebris system were 49.81 ± 10.64° at 3 mm, 48.10 ± 11.04° at 5 mm, while the values recorded by Gamma system were 55.16° at 3 mm, 52.18° at 5 mm. The mean right SCI value recorded by Zebris system were 54.53 ± 10.26° at 3 mm, 51.85 ± 8.55° at 5 mm, while the values recorded by Gamma system were 49.68° at 3 mm, 48.23° at 5 mm. Linear mixed model showed no significant statistical difference between the two systems. Based on preliminary results, the Zebris Jaw Motion Analyzer+ Optic System demonstrates comparable accuracy to the Cadiax Gamma Diagnostic 4 when measuring sagittal condylar inclination. The digital axiographic recording system enables to evaluate sagittal condylar inclination and to adjust virtual articulators in a digital workflow.


Displaced trochanteric fragments lead to poor functional outcome in pertrochanteric fractures treated by cephalomedullary nails.
The importance of the greater trochanter and its attached abductor muscles for physiological gait is well accepted. However the influence of a displaced greater trochanter fracture after a pertrochanteric fracture is unknown. The aim of this study is to determine if there is an association between the greater trochanter position and the level of patient mobility following internal fixation of pertrochanteric fractures. One hundred and thirty-three consecutive elderly patients with a median age of 85 (interquartile range [IQR] 79-91) years, who were treated for pertrochanteric fractures at a level I trauma centre, were recruited. AO 31 A3.1 and A3.2 fracture types were excluded from the statistical analysis. Patient mobility was prospectively assessed before the fracture and one year following fracture treatment using the Parker mobility score. In a multivariable analysis, the influence of a displaced greater trochanter on patient mobility at one-year follow-up was assessed. The analysis was adjusted for age, gender, body mass index, Charlson comorbidity index, AO fracture classification, varus-/valgus malposition of the neck-shaft fragments, and Parker mobility score before fracture. Post-operative X-rays were available in 125 patients, out of which 66 (53%) patients were identified with a displaced or migrated greater trochanter. One year mortality rate was 22% (n=27). In the 82 patients who had functional assessment one year post-operatively, the median Parker mobility score before fracture and at one-year follow-up was 7 (IQR 4-9) and 7 (IQR 3-9) in patients without, and 7 (IQR 4-9) and 3 (IQR 2-5) in patients with a displaced greater trochanter. In multivariable analysis, a displaced greater trochanter was significantly associated with a lower Parker mobility score (-1.74, 95% confidence interval -2.37, -1.12, p<0.01). Greater trochanter displacement following internal fixation of extracapsular hip fractures with a cephalomedullary nail is associated with a poor functional outcome. Greater attention to achieve adequate reduction and stabilisation of this fragment during internal fixation of pertrochanteric hip fractures should be aimed for despite the inability of current cephalomedullary implants to do so. III prognostic and epidemiological study.


The nitric oxide synthesis inhibitor nitro-L-arginine (L-NNA) attenuates nicotine abstinence syndrome in the rat.
Nitric oxide synthesis contributes to opiate tolerance and dependence. Nicotine dependence and abstinence syndrome in the rat appear to involve opiate mechanisms. Therefore, it was postulated that nitric oxide synthase (NOS) activity might be essential for the expression of nicotine abstinence syndrome. Twenty-one rats were rendered dependent by SC infusion of 9 mg/kg per day nicotine tartrate via Alzet osmotic minipump. Rats were pretreated SC with vehicle alone, or with 18 or 30 mg/kg of the NOS inhibitor L-NNA (nitro-L-arginine). Thirty minutes later, rats were challenged by 1 mg/kg of the nicotinic antagonist mecamylamine SC and observed for 30 additional minutes. Rats pretreated with vehicle displayed a total of 68.7+/-8.0 mecamylamine-precipitated abstinence signs (mean+/-SEM), while those receiving 18 or 30 mg/kg L-NNA had 12.7+/-2.0 and 5.1+/-1.7 signs, respectively. All three groups differed significantly from one another according to Dunn's post-hoc procedure. Rats pretreated with L-NNA combined with an excess of the NOS substrate L-arginine had significantly more mecamylamine-precipitated abstinence signs than rats receiving L-NNA combined with D-arginine. Also, D-NNA, which does not selectively bind to NOS, was significantly less effective than L-NNA in preventing mecamylamine-precipitated abstinence syndrome. Additional studies determined the effect of L-NNA on spontaneous nicotine abstinence syndrome. Rats were assessed for abstinence signs at 17 and 20 h after termination of nicotine infusion. They received injections of 9, 18, or 30 mg/kg L-NNA SC or vehicle alone immediately before the 20-h observation; all rats were observed for 30 min. Signs at 20 h (post-injection) as a percentage of signs at 17 h (pre-injection) declined significantly as a function of L-NNA dose. Once again, this effect was attenuated significantly more by co-administration of L-arginine than by D-arginine. The overall pattern of results suggests that nitric oxide synthesis is critical to the expression of nicotine abstinence syndrome.


Type of goals and perceived control for goal achievement over time. The mediating role of motivational persistence.
This study tested how type of goals (i.e., performance and mastery goals) influence perceived control for goal achievement over time (i.e., after 12 months) while controlling for motivational persistence, gender, self-efficacy, initial perceived control, emotional involvement, and perceived difficulty. Goals and self-reported data from 1220 students were analyzed. Comparative test indicated that students describing a mastery goal display more motivational persistence and more perceived control for goal achievement, compared to those describing a performance goal. Type of goals directly and significantly predict perceived control of goal achievement at 12 months. Motivational persistence directly, positively, and significantly predicts perceived control of goal achievement at 12 months. In addition, motivational persistence positively and significantly mediates the relation between type of goals and perceived control of goal achievement at 12 months. Results support a partial mediation model.


Effects of coping flexibility on cardiovascular reactivity to task difficulty.
Coping flexibility refers to an individual's ability to effectively modify his or her coping behavior to better fit the nature of each stressful situation they encounter. More flexible coping is believed to produce more adaptive psychological functioning and physical health. We examined the relationship between coping flexibility and cardiovascular reactivity (CVR) to psychological stress. Challenging tasks of two difficulty levels were presented to 24 men and 24 women aged 18 to 24years. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure were measured. Change scores (from baseline to reactivity) for SBP and HR responses in the difficult task were higher than those in the easy task and were negatively correlated with coping flexibility during the difficult task but not the easy one. The findings suggest that more flexible coping is associated with reduced CVR to a difficult task.


Effects of the Ambient Fine Particulate Matter on Public Awareness of Lung Cancer Risk in China: Evidence from the Internet-Based Big Data Platform.
In October 2013, the International Agency for Research on Cancer classified the particulate matter from outdoor air pollution as a group 1 carcinogen and declared that particulate matter can cause lung cancer. Fine particular matter (PM2.5) pollution is becoming a serious public health concern in urban areas of China. It is essential to emphasize the importance of the public's awareness and knowledge of modifiable risk factors of lung cancer for prevention. The objective of our study was to explore the public's awareness of the association of PM2.5 with lung cancer risk in China by analyzing the relationship between the daily PM2.5 concentration and searches for the term "lung cancer" on an Internet big data platform, Baidu. We collected daily PM2.5 concentration data and daily Baidu Index data in 31 Chinese capital cities from January 1, 2014 to December 31, 2016. We used Spearman correlation analysis to explore correlations between the daily Baidu Index for lung cancer searches and the daily average PM2.5 concentration. Granger causality test was used to analyze the causal relationship between the 2 time-series variables. In 23 of the 31 cities, the pairwise correlation coefficients (Spearman rho) between the daily Baidu Index for lung cancer searches and the daily average PM2.5 concentration were positive and statistically significant (P<.05). However, the correlation between the daily Baidu Index for lung cancer searches and the daily average PM2.5 concentration was poor (all r2s<.1). Results of Granger causality testing illustrated that there was no unidirectional causality from the daily PM2.5 concentration to the daily Baidu Index for lung cancer searches, which was statistically significant at the 5% level for each city. The daily average PM2.5 concentration had a weak positive impact on the daily search interest for lung cancer on the Baidu search engine. Well-designed awareness campaigns are needed to enhance the general public's awareness of the association of PM2.5 with lung cancer risk, to lead the public to seek more information about PM2.5 and its hazards, and to cope with their environment and its risks appropriately.


The serotonin transporter gene polymorphism (SLC6A4) and risk for psychiatric morbidity and comorbidity in the Baltimore ECA follow-up study.
The human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sample. 628 participants, mean age 48.3 years old, were assessed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. Associations between 5HTTLPR and the prevalence, comorbidity, and time-to-diagnoses for 16 psychiatric conditions were evaluated, using several analytical approaches. The SERT S allele was significantly associated with an increased lifetime prevalence of panic disorder. There was a "protective" association between SERT gene S allele carrier status and the risk of obsessive-compulsive disorder (OCD) in time-to-event analysis. Carriers of the S allele had a significant increased risk of two specific comorbid disorder pairs: major depressive disorder (MDD) and social phobia, and MDD and agoraphobia. Overall, there was no increased risk of receiving an initial or an additional diagnosis for a mental disorder in the SERT S allele carriers CONCLUSIONS: The findings suggest that the S allele carrier status is associated with an increased prevalence of panic disorder in a community sample. There was an increased risk for comorbidity in a more homogeneous subgroup of cases with MDD and social phobia, as well as or agoraphobia. Our findings suggest a specific effect of the SERT promoter gene polymorphism on a subgroup of individuals identifiable by their comorbidity.


Functional characterization and oligomerization of a recombinant xyloglucan-specific endo-β-1,4-glucanase (GH12) from Aspergillus niveus.
Xyloglucan is a major structural polysaccharide of the primary (growing) cell wall of higher plants. It consists of a cellulosic backbone (beta-1,4-linked glucosyl residues) that is frequently substituted with side chains. This report describes Aspergillus nidulans strain A773 recombinant secretion of a dimeric xyloglucan-specific endo-β-1,4-glucanohydrolase (XegA) cloned from Aspergillus niveus. The ORF of the A. niveus xegA gene is comprised of 714 nucleotides, and encodes a 238 amino acid protein with a calculated molecular weight of 23.5kDa and isoelectric point of 4.38. The optimal pH and temperature were 6.0 and 60°C, respectively. XegA generated a xyloglucan-oligosaccharides (XGOs) pattern similar to that observed for cellulases from family GH12, i.e., demonstrating that its mode of action includes hydrolysis of the glycosidic linkages between glucosyl residues that are not branched with xylose. In contrast to commercial lichenase, mixed linkage beta-glucan (lichenan) was not digested by XegA, indicating that the enzyme did not cleave glucan β-1,3 or β-1,6 bonds. The far-UV CD spectrum of the purified enzyme indicated a protein rich in β-sheet structures as expected for GH12 xyloglucanases. Thermal unfolding studies displayed two transitions with mid-point temperatures of 51.3°C and 81.3°C respectively, and dynamic light scattering studies indicated that the first transition involves a change in oligomeric state from a dimeric to a monomeric form. Since the enzyme is a predominantly a monomer at 60°C, the enzymatic assays demonstrated that XegA is more active in its monomeric state.


Leptin receptor deficiency induces early, transient and hyperglycaemia-independent blood-brain barrier dysfunction.
Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer's disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability in Leprdb/db obesity-related diabetic mice. Surprisingly, significant BBB leakage was observed only in young mice at the pre-hyperglycemic stage. Thorough examination of barrier permeability at later diabetic stages showed no evidence for significant BBB leakage during the hyperglycemic state. Electron microscopy imaging of mice with short-term hyperglycaemia supported normal BBB permeability but indicated other stress-related changes in capillary ultrastructure, such as mitochondrial degeneration. Based on our study with this mouse genetic model of obesity-related DM, we suggest that previously reported hyperglycaemia-induced BBB leakage is most likely not the underlying mechanism of DM-related CNS pathologies. Finally we propose that BBB hyper-permeability might be an early and transient phenomenon while stress-related endothelial pathologies do correlate with a short-term diabetic state.


Temporal Variations of O3 and NO x in the Urban Background Atmosphere of Nanjing, East China.
Rapid economic growth has given rise to a significant increase in ozone (O3)-precursor emissions in many regions of China. An improved understanding of O3 formation in response to different precursor emissions is imperative to address the highly nonlinear O3 problem and to provide a solid scientific basis for efficient O3 abatement in these regions. To this end, this study was performed in Nanjing using a set of observational data from June 1, 2013, to May 31, 2014. The results showed that O3 concentrations were positively correlated with wind speed and temperature and were significantly negatively correlated with relative humidity. The highest monthly daytime, nighttime, and daily average O3 concentrations were observed in summer with values of approximately 46, 18 and 30 ppb, respectively. The lowest O3 concentrations were observed in November through January with values as low as 17, 4, and 9 ppb for the daytime, nighttime, and daily concentrations, respectively. The highest daytime average NO and NO2 concentrations were observed in December, whereas the lowest concentrations were observed in July. A unimodal O3 peak was observed with the highest O3 levels in summer followed by spring and then autumn; the lowest levels observed in the winter. The O3 concentration reached maximum levels at 14:00 to 15:00 h (local standard time). It was found that the crossover occurred with approximately several hours difference with the earliest occurring in summer (06:00 h) followed by spring (08:00 h), autumn (09:00 h), and winter (10:30 h). Furthermore, the highest constant rate of O3 accumulation was observed in summer (5.6 ppb/h) followed by autumn (4.8 ppb/h), spring (4.5 ppb/h), and winter (2.7 ppb/h). The oxidant intercept ranged from 28.4 ppb in January to 58.6 ppb in June, although the slope also shows substantial variation from 0.18 in June to 0.67 in August. The weekend effect is stronger in spring and summer than in autumn and winter and is more intense on Sundays than on Saturdays. Thus, the decrease of O3 levels during weekends suggests that it may be NO x -sensitive.


Mutations in mitochondrial ribosomal protein MRPL12 leads to growth retardation, neurological deterioration and mitochondrial translation deficiency.
Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and are associated with a wide range of clinical symptoms. We report a subject, born to consanguineous parents, with growth retardation and neurological deterioration. Multiple respiratory chain deficiency was found in muscle and fibroblasts of the subject as well as abnormal assembly of complexes I and IV. A microsatellite genotyping of the family members detected only one region of homozygosity on chromosome 17q24.2-q25.3 in which we focused our attention to genes involved in mitochondrial translation. We sequenced MRPL12, encoding the mitochondrial ribosomal protein L12 and identified a c.542C>T transition in exon 5 changing a highly conserved alanine into a valine (p.Ala181Val). This mutation resulted in a decreased steady-state level of MRPL12 protein, with altered integration into the large ribosomal subunit. Moreover, an overall mitochondrial translation defect was observed in the subject's fibroblasts with a significant reduction of synthesis of COXI, COXII and COXIII subunits. Modeling of MRPL12 shows Ala181 positioned in a helix potentially involved in an interface of interaction suggesting that the p.Ala181Val change might be predicted to alter interactions with the elongation factors. These results contrast with the eubacterial orthologues of human MRPL12, where L7/L12 proteins do not appear to have a selective effect on translation. Therefore, analysis of the mutated version found in the subject presented here suggests that the mammalian protein does not function in an entirely analogous manner to the eubacterial L7/L12 equivalent.


First-trimester biochemical markers of placentation in screening for gestational diabetes mellitus.
To investigate whether first-trimester biochemical markers of placentation, including pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF), are altered in women that subsequently develop gestational diabetes mellitus (GDM) and to examine their potential value in improving the performance of screening for GDM by maternal characteristics and medical history. The study population of 31,225 singleton pregnancies, including 787 cases that developed GDM, was drawn from women undergoing routine prospective screening for pregnancy complications at 11-13 weeks' gestation. Maternal serum PAPP-A and PLGF were measured and the levels were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and medical history. The performance of screening for GDM by maternal factors and MoM values of PAPP-A and PLGF was evaluated by receiver operating characteristic (ROC) curves. In the GDM group, compared to the unaffected group, the median PAPP-A was reduced (0.949, 95% CI 0.913-0.987 MoM) (p=0.0009) and median PLGF was increased (1.053, 95% CI 1.023-1.083 MoM) (p=0.004). The performance of screening for GDM by maternal factors was not improved by the addition of PAPP-A and/or PLGF. First trimester maternal serum PAPP-A and PLGF are not useful in screening for GDM.


Chicken xenobiotic receptor upregulates the BCRP/ABCG2 transporter.
The transporter breast cancer resistance protein (BCRP, encoded by ABCG2) influences the bioavailability and elimination of numerous substrate drugs during clinical therapy. The xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) reportedly regulate functional expression of BCRP in mammalian species. However, it is unknown whether chicken xenobiotic receptor (CXR) regulates the expression and activity of BCRP. This study aimed to investigate the role of CXR in regulation of BCRP in chicken using in vitro and in vivo models. CXR was expressed in the main drug-metabolizing tissues of chickens, and its expression correlated well with that of the prototypical target genes CYP2H1 and ABCG2. BCRP expression was upregulated, and transporter activity was increased, in chicken primary hepatocytes exposed to the CXR agonist metyrapone. Using RNA interference and ectopic expression techniques to manipulate the cellular CXR status, we confirmed that ABCG2 gene regulation depended on CXR. In vivo experiments showed that metyrapone induced BCRP in the liver, kidney, duodenum, and jejunum of chickens. Coadministration of metyrapone significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a lower Cmax (4.62 vs. 7.35 µg/mL, P < 0.01) and AUC0-t (15.83 vs. 24.18 h·mg/L, P < 0.01) as well as a higher Tmax (0.96 vs. 0.79 h, P < 0.05) and Cl/F (0.13 vs. 0.08 L/h/kg, P < 0.05). Together, our data suggest that CXR is involved in regulation of BCRP, and consequently, coadministration of a CXR agonist can affect the pharmacokinetic behavior of an orally administered BCRP substrate.


Mineralized tissue formation by bone morphogenetic protein-7-transfected pulp stem cells.
Recombinant human bone morphogenetic protein-7 (BMP-7) is a well-established agent to induce bone and dentin formation. Little is understood until now whether BMP-7 could be used to genetically modify human dental pulp stem cells for tissue engineering applications. This study was to determine the feasibility of mineralized tissue formation from human dental pulp-derived stem cells (DPSCs) transfected with adenoviral-mediated human BMP-7 gene through in vitro and in vivo evaluations. In vitro results of alkaline phosphatase, calcium content, and real-time polymerase chain reaction showed that BMP-7-transfected cells had the ability to differentiate towards the odontoblast phenotype and produce a calcified extracellular matrix. Transfected cell were seeded onto a porous ceramic scaffold and implanted subcutaneously in mice. Samples were retrieved after 4 and 8 weeks for histology evaluation. The results indicated that only the cultures with BMP-7 gene transfection showed obvious hard-tissue generation. Our data suggest that adenovirus-mediated BMP-7 expression can induce odontogenic differentiation of human DPSCs and show effectively mineralized tissue formation in vivo, which may provide support for gene therapy candidate of BMP-7 in dental tissue engineering.


Reversed actrocytic GLT-1 during ischemia is crucial to excitotoxic death of neurons, but contributes to the survival of astrocytes themselves.
During ischemia, the operation of astrocytic/neuronal glutamate transporters is reversed and glutamate and Na(+) are co-transported to the extracellular space. This study aims to investigate whether this reversed operation of glutamate transporters has any functional meanings for astrocytes themselves. Oxygen/glucose deprivation (OGD) of neuron/astrocyte co-cultures resulted in the massive death of neurons, and the cell death was significantly reduced by treatment with either AP5 or DHK. In cultured astrocytes with little GLT-1 expression, OGD produced Na(+) overload, resulting in the reversal of astrocytic Na(+)/Ca(2+)-exchanger (NCX). The reversed NCX then caused Ca(2+) overload leading to the damage of astrocytes. In contrast, the OGD-induced Na(+) overload and astrocytic damage were significantly attenuated in PACAP-treated astrocytes with increased GLT-1 expression, and the attenuation was antagonized by treatment with DHK. These results suggested that the OGD-induced reversal of GLT-1 contributed to the survival of astrocytes themselves by releasing Na(+) with glutamate via reversed GLT-1.


Construction of a novel immune-related prognostic-predicting model of gastric cancer.
Gastric cancer (GC) is a common primary stomach tumor of the central nervous system with a poor prognosis. In this study, 274 differentially expressed immune-related genes (DEIRGs) were identified among six cell subpopulations in GSE112302 single-cell RNA sequencing (scRNA-seq) data of GC. Those DEIRGs were able to divide GC patients into three distinct subtypes with different overall survivals and tumor microenvironment. By univariate Cox and LASSO regression analyses, eight immune-related genes, including CTGF, CXCL3, CXCR4, NRP1, OAS1, SP1, STC1 and TAP1, were identified as GC prognostic signatures. Accordingly, a risk score model for predicting GC prognosis was constructed in TCGA-GC training cohort and validated in the external GSE66229 dataset. Moreover, a nomogram for predicting the survival of GC patients was also established based on independent prognostic factors (age, grade, cancer status and risk score) identified by univariate and multivariate Cox regression analyses. In addition, Gene Set Variation Analysis (GSVA) analysis indicated that the prognostic immune signatures may regulate GC via inflammation and cell proliferation related pathways, such as DNA replication, complement and coagulation cascades, focal adhesion and TGF-β signaling pathway.


Effects of thyroid hormone manipulation on pre-nuptial molt, luteinizing hormone and testicular growth in male white-crowned sparrows (Zonotrichia leuchophrys gambelii).
Most seasonal species rely on the annual change in day length as the primary cue to appropriately time major spring events such as pre-nuptial molt and breeding. Thyroid hormones are thought to be involved in the regulation of both of these spring life history stages. Here we investigated the effects of chemical inhibition of thyroid hormone production using methimazole, subsequently coupled with either triiodothyronine (T3) or thyroxine (T4) replacement, on the photostimulation of pre-nuptial molt and breeding in Gambel's white-crowned sparrows (Zonotrichia leuchophrys gambelii). Suppression of thyroid hormones completely prevented pre-nuptial molt, while both T3 and T4 treatment restored normal patterns of molt in thyroid hormone-suppressed birds. Testicular recrudescence was blocked by methimazole, and restored by T4 but not T3, in contrast to previous findings demonstrating central action of T3 in the photostimulation of breeding. Methimazole and replacement treatments elevated plasma luteinizing hormone levels compared to controls. These data are partially consistent with existing theories on the role of thyroid hormones in the photostimulation of breeding, while highlighting the possibility of additional feedback pathways. Thus we suggest that regulation of the hypothalamic pituitary gonad axis that controls breeding may be more complex than previously considered.


Work-life balance of female versus male surgeons in Hong Kong based on findings of a questionnaire designed by a Japanese surgeon.
We evaluated the attitudes of female and male surgeons in Hong Kong to work, personal life, and work-life balance, through a questionnaire survey. We sent an online questionnaire survey designed by a female Japanese surgeon to 142 female surgeons practicing in Hong Kong, while its customized version was sent to 953 of their male counterparts. "Home life" and "Work" were the first and second priorities for both the women and the men. More of the female surgeons reported that they could not find enough time to participate in community activities (p = 0.038) or rest (p = 0.024). Both reported moderate satisfaction at work (p = 0.114) and in their life outside work (p = 0.346), as well as equality at home (p = 0.548) and at work (p = 0.177). Of the men, 89 % agreed with the necessity for granting paternity leave and reported that they would like to work part-time during the child-rearing years (p = 0.013). The number of female surgeons involved in key roles is increasing in parallel with the increasing number of female medical students. The introduction of paternity leave for male surgeons is an important concern. The issues of work-life balance may need to be addressed to attract more talent into an important specialty in Hong Kong and this is likely to apply to other parts of Asia as well.


The effects of gamma-irradiation on the hydration characteristics of DNA and polynucleotides. III. A comparative NMR study of frozen and liquid solutions.
The effects of gamma-irradiation and changes in the macromolecular structure on the water proton resonance spectra observed in frozen and liwuid solutions have been compared for the DNA and polynucleotide solutions, using H2O or mixed H2O/D2O solvents. The results indicate that in order to obtain information concerning the role of hydration water in mediating the overall radiation damage, the NMR studies must be performed in the frozen state.


A coupled bulk-surface model for cell polarisation.
Several cellular activities, such as directed cell migration, are coordinated by an intricate network of biochemical reactions which lead to a polarised state of the cell, in which cellular symmetry is broken, causing the cell to have a well defined front and back. Recent work on balancing biological complexity with mathematical tractability resulted in the proposal and formulation of a famous minimal model for cell polarisation, known as the wave pinning model. In this study, we present a three-dimensional generalisation of this mathematical framework through the maturing theory of coupled bulk-surface semilinear partial differential equations in which protein compartmentalisation becomes natural. We show how a local perturbation over the surface can trigger propagating reactions, eventually stopped in a stable profile by the interplay with the bulk component. We describe the behavior of the model through asymptotic and local perturbation analysis, in which the role of the geometry is investigated. The bulk-surface finite element method is used to generate numerical simulations over simple and complex geometries, which confirm our analysis, showing pattern formation due to propagation and pinning dynamics. The generality of our mathematical and computational framework allows to study more complex biochemical reactions and biomechanical properties associated with cell polarisation in multi-dimensions.


Single-round multiplex PCR with species-specific mitochondrial primers of P. falciparum, P. vivax/P. simium and P. malariae/P. brasilianum: Comparison with standard techniques.
A single-round multiplex PCR (mPCR) with species-specific primers (SSP) of three mitochondrial genes of Plasmodium, namely COX I, COX III and CYT B, was compared to microscopy and 18S rRNA semi-nested PCR, nested-PCR and Real Time PCRs (*PCRs). Each parasite has between 20 and 150 mitochondria and each mitochondria has one copy of each target gene, while 18S rRNA gene is repeated 4 to 8 times. The specificity of mPCR was assessed by testing Plasmodium from rodents and birds, parasites responsible for other endemic diseases in the country such as schistosomiasis, Chagas disease and leishmaniasis in addition to microorganisms that, like Plasmodium, can cause anemia (Bartonella henselae, Babesia vogeli, Rickettsia vini). No cross-reactions were detected. From a total of 149 specimens from suspected cases of malaria were tested, 97 were positive by microscopy (49 P. falciparum, 38 P. vivax, 6 P. malariae, 4 P. falciparum/P. vivax- mixed infections) and 52 were negative; 148 samples were positive by *PCRs (49 P. falciparum, 53 P. vivax, 7 P. malariae and 39 mixed infections) and one was negative; 146 were positive by mPCR (49 P. falciparum, 56 P. vivax, 9 P. malariae and 32 mixed infections) and three were negative. The comparison of groups found statistically significant differences between microscopy vs.*PCRs or vs. mPCR (p-values <0.0001), but no difference was found between mPCR vs. *PCRs (p=0.946). The agreement in the identification of Plasmodium species was only regular, with Kappa indices of 0.407 (microscopy vs. *PCRs), 0.433 (microscopy vs. mPCR) and 0.558 (*PCRs vs. mPCR). In conclusion, the diagnostic performance of mPCR was comparable to those of *PCRs, and superior to microscopy, although the identification of Plasmodium species showed many disagreements. In conclusion, a sensitive and specific one-round SSP multiplex PCR, capable of simultaneously detecting and identifying P. falciparum, P. vivax/P. simium and P. malariae/P. brasilianum may be useful in resource-constrained countries where quantitative amplifications are not yet fully accessible.


Projection of the lateral geniculate nucleus onto cortical area V2 in the macaque monkey.
Recent publications have demonstrated a projection of the lateral geniculate nucleus (LGN) onto extrastriate cortical regions in the old world monkey but have failed to identify a projection from this nucleus to V2, the area adjacent to the striate cortex. In this report we show that such a projection exists, as demonstrated by the retrograde transport of the fluorescent labels fast blue (FB) and diamidino yellow (DY). Neurons labelled after V2 injections are more scattered in the LGN than the cells backfilled by the V1 injections and mostly belong to the interlaminar zones and the S layers, regions which are largely devoid of neurons labelled by the V1 injections.


Genotyping analysis of the MNS blood group system of thalassemia patients with alloantibodies in Iran.
Serological methods are unreliable for accurate determination of blood group antigens in multi-transfused thalassemia patients. The MNS blood group system has five high-frequency antigens. Many studies demonstrated that some antibodies including anti-S, anti-s, and anti-U may cause acute and delayed transfusion reactions and hemolytic disease of the fetus and newborn. This study aimed to determine the genotype of the MNS blood group in thalassemia patients with alloantibodies by molecular methods. In this study, 104 blood samples from thalassemia patients were collected. The blood group phenotype for M, N, S and s antigens was determined by the tube hemagglutination method. MNS blood group genotyping was performed using PCR-SSP and DNA Sequencing methods. All patients were genotyped with a total of 6 pairs of primers. Discrepancies between genotype and phenotype were observed in 22 patients with S/s alleles and 2 patients with M/N alleles, however, there was full accordance between the results of SSP-PCR and DNA sequencing. The frequency of MNS blood group alleles was determined as follows: 25 % MNSs, 23 % MNss, 21 % MMSs, 9% MMSS, 9% MMss, 8% NNss, 2%MNSS, and NNSS, NNSs, MM genotypes at 1% each. In conclusion, molecular genotyping is more reliable than serological methods in multiple transfusion patients and can lead to a more compatible blood unit for transfusion in these patients.


Fabrication of bifunctional core-shell Fe3O4 particles coated with ultrathin phosphor layer.
Bifunctional monodispersed Fe3O4 particles coated with an ultrathin Y2O3:Tb3+ shell layer were fabricated using a facile urea-based homogeneous precipitation method. The obtained composite particles were characterized by powder X-ray diffraction, transmission electron microscopy (TEM), quantum design vibrating sample magnetometry, and photoluminescence (PL) spectroscopy. TEM revealed uniform spherical core-shell-structured composites ranging in size from 306 to 330 nm with a shell thickness of approximately 25 nm. PL spectroscopy confirmed that the synthesized composites displayed a strong eye-visible green light emission. Magnetic measurements indicated that the composite particles obtained also exhibited strong superparamagnetic behavior at room temperature. Therefore, the inner Fe3O4 core and outer Y2O3:Tb3+ shell layer endow the composites with both robust magnetic properties and strong eye-visible luminescent properties. These composite materials have potential use in magnetic targeting and bioseparation, simultaneously coupled with luminescent imaging.


Elevated pediatric age-adjusted shock-index (SIPA) in blunt solid organ injuries.
Shock index-pediatric age-adjusted (SIPA) is a proven tool to predict outcomes in blunt pediatric trauma. We hypothesized that an elevated SIPA in either the pre-hospital or in the emergency department (ED) would identify children with blunt liver or spleen injury (BLSI) needing a blood transfusion and those at risk for failure of non-operative management (NOM). Pediatric patients (1-18 years) in the ACS pediatric-TQIP database (2014-2016) with a BLSI were included. Patients were stratified by the need for a blood transfusion and/or abdominal operation. A total of 3561 patients had BLSI, of which 4% received a blood transfusion, and 4% underwent an abdominal operation. Patients who received blood had higher ISS scores (27.0 vs. 5.0, p < 0.001) and mortality (22% vs. 0.4%, p < 0.001). Those who failed NOM had higher ISS scores (17.0 vs. 5.0, p < 0.001) and mortality (7.9% vs. 0.9%, p < 0.001). On multivariable regression, an elevated SIPA score in either pre-hospital or ED was significantly associated with blood transfusion (odds ratio (OR) 8.2, 95% confidence intervals (CI) 5.8-11.5, p < 0.001) and failure of NOM (OR 2.3, CI 1.5-3.4, p < 0.001). Hemodynamic instability, represented by an elevated pre-hospital or ED SIPA, accurately identifies children with BLSI who may need blood products or an operative intervention. Retrospective Comparative Study. Level III.


Bilateral venous infarctions of the thalamus: a case report.
This is a mini-report of a case of bilateral nonhemorrhagic venous infarctions of the thalamus, complicated by a dural arteriovenous malformation.


Role of cystatin C in the detection of sight-threatening diabetic retinopathy in Asian Indians with type 2 diabetes.
To study the association between cystatin C and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2DM). In a cross-sectional study carried out at two tertiary centres in India in 2022, individuals with T2DM underwent clinical and ophthalmic assessments and estimation of serum cystatin C. Grading of DR was done by retina specialists. STDR was defined by the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) and/or diabetic macular edema. Receiver operating characteristic (ROC) curves were used to identify cystatin C cut-off value for detecting STDR. Among 420 individuals with T2DM (mean age 56 ± 9 years; mean duration of diabetes 14.5 ± 7.9 years), 121 (24.1 %) had No-DR, 119 (28.3 %) had No-STDR and 200 (49.6 %) had STDR. Mean cystatin C level was significantly higher in individuals with STDR compared to those with no-STDR and No-DR (1.34 vs 1.06 vs 0.93 mg/L, p < 0.001). Cystatin C cut-off value ≥1.11 mg/L had a C statistic of 0.944 (95 % CI: 0.909-0.968, p < 0.001), 96.8 % sensitivity and 78.2 % specificity for detection of STDR. Elevated serum cystatin C was strongly associated with STDR and could possibly be used as a biomarker for screening for sight-threatening diabetic retinopathy.


Crystal structure of a domain-swapped photoactivatable sfGFP variant provides evidence for GFP folding pathway.
Photoactivatable fluorescent proteins (PA-FPs) are a powerful non-invasive tool in high-resolution live-cell imaging. They can be converted from an inactive to an active form by light, enabling the spatial and temporal trafficking of proteins and cell dynamics. PA-FPs have been previously generated by mutating selected residues in the chromophore or in its close proximity. A new strategy to generate PA-FPs is the genetic incorporation of unnatural amino acids (UAAs) containing photocaged groups using unique suppressor tRNA/aminoacyl-tRNA synthetase pairs. We set out to develop a photoactivatable GFP variant suitable for time-resolved structural studies. Here, we report the crystal structure of superfolder GFP (sfGFP) containing the UAA ortho-nitrobenzyl-tyrosine (ONBY) at position 66 and its spectroscopic characterization. Surprisingly, the crystal structure (to 2.7 Å resolution) reveals a dimeric domain-swapped arrangement of sfGFP66ONBY with residues 1-142 of one molecule associating with residues 148-234 from another molecule. This unusual domain-swapped structure supports a previously postulated GFP folding pathway that proceeds via an equilibrium intermediate.


Social dynamics in an isolated, confined, and extreme workplace.
There can be few indoor workplaces that are more subject to the meteorological and atmospheric conditions of their locations than permanent stations on the high, inland polar plateau of Antarctica. The US Amundsen-Scott South Pole Station is such a workplace, totally isolated during the 8-9 months of the austral winter, more than 800 miles (1287 km) from the nearest other human habitation. The wintering party at the South Pole must deal with all the demands and stressors of an isolated, confined, and extreme environment without the prospect of relief from the outside world. In 1975, the seventeen men chosen to winter at the South Pole had an additional challenge. In February, as the austral winter was about to begin, a new geodesic-domed research station had just been completed. The station was the first of its kind, and the vagaries of its design and construction would be significant factors in the health and well-being of station residents as winter progressed. Potential physical and psychological problems from isolation literature are commented upon, and some significant events from this noteworthy winter are described. In addition, supporting quantitative data from current research at South Pole are used to better understand these events.


Accidental hand burns caused by operating room lights.
Three patients sustained burns of the hand in the operating room because of the lack of heat shields in the lights. A 54 degrees F increase in temperature in the operating field was noted when the heat shields were not in place.


The impact of mode of donor brain death on cardiac allograft vasculopathy: an intravascular ultrasound study.
We evaluated the association of mode of brain death with cardiac allograft vasculopathy. Explosive brain death (EBD) is accompanied by a sudden increase in intracranial pressure, with recruitment of pro-inflammatory cytokines, as well as adhesion cell and co-stimulatory molecules. Whether these early events influence the later development of cardiac allograft vasculopathy following heart transplantation remains unknown. An inception cohort of 61 consecutive heart transplant recipients between 1993 and 1995 who underwent intravascular ultrasound examination of the coronary arteries were evaluated. Based on the mode of donor brain death, this cohort was divided into either an EBD group (n = 27) or non-EBD (n = 34), and the development of intimal thickness and cardiac events (sudden cardiac death, myocardial infarction, and need for coronary revascularization via percutaneous techniques or surgical bypass) was assessed. Despite similar posttransplant survival and distribution of nonimmunological and immunological variables, heart transplant recipients with EBD demonstrated greater intimal thickening (0.59 +/- 0.1 vs. 0.32 +/- 0.2 mm; p = 0.02) and higher cardiac events (37% vs. 12%; p = 0.01) when compared to those with non-EBD donors. Hearts from donors with EBD had lower survival (63 +/- 19 vs. 72 +/- 17 months) than with non-EBD donors (p = 0.04). Explosive brain death is a significant determinant for the late development of cardiac allograft vasculopathy and influences long-term allograft survival. Thus, strategies focusing on limitation of vascular allograft injury in the pre-engraftment phase of cardiac transplantation are warranted.


Organic solvent exposure as a risk factor for multiple sclerosis: An updated review.
Organic solvents exposure has for a long time been suspected as a risk factor for developing multiple sclerosis. The evidence, containing case reports, case-control studies and cohort studies has been contradictory. An early meta-analysis, however, pointed to a doubled risk for MS. Recent major case-control studies confirm this, but also have elucidated the risk pattern, being dependent on another risk factor, i.e. smoking.


Identification of an HptB-mediated multi-step phosphorelay in Pseudomonas aeruginosa PAO1.
We herein demonstrate that the hybrid sensor PA1611 carries out specific signal transduction, through HptB (PA3345), to the response regulator PA3346 in Pseudomonas aeruginosa PAO1. As assessed by phenotypic changes in the hptB deletion mutant, the pathway is likely to be involved in the regulation of flagellar activity, the chemotaxis response, twitching motility, and biofilm formation in the bacteria.


Increased thrombin generation in persons with echogenic carotid plaques.
Echolucent carotid plaques are associated with higher risk for future ischemic cerebrovascular events (CVE) than echogenic plaques independent of the degree of stenosis. Elevated markers of thrombin generation are associated with atherosclerotic plaques and are increased in the acute and chronic phases of CVE. The present study was conducted to investigate the influence of plaque morphology on thrombin generation in persons with carotid stenosis. One hundred twenty-eight persons with carotid stenosis (>or=35% lumen diameter reduction) and 136 matched controls without stenosis were recruited from the health survey of the Tromsø Study. Blood samples were collected and plaque morphology determined by ultrasonography. Thrombin generation was assessed by thrombin-antithrombin complexes (TAT) and by prothrombin fragment 1+2 (F1+2). Persons with echogenic plaques (n = 63) had significantly higher levels of TAT (5.24 microg/l, 4.33-6.14) (mean, 95%CI) than persons with echolucent plaques (n = 65) (3.44 microg/l, 2.91-3.96, p < 0.001) and controls (n = 136) (3.33 microg/l, 3.06-3.60, p < 0.001). They also had significantly higher levels of F1+2 (2.14 nM, 1.83-2.45) than persons with echolucent plaques (1.54 nM, 1.38-1.71, p < 0.001) and controls (1.49 nM, 1.40-1.58, p < 0.001). TAT and F1+2 increased linearly with plaque echogenicity (p = 0.002 and p = 0.001, respectively) independent of the degree of stenosis. Increased thrombin generation was associated with a significant increase in plasma factor V levels among persons with echogenic plaques compared to echolucent plaques (p = 0.049) and controls (p = 0.025). The present findings indicate that increasing plaque echogenicity, rather than plaque echolucency and the degree of stenosis, is associated with thrombin generation in persons with carotid stenosis.


The urinary excretory ratio of nicotinamide catabolites was associated with the conversion ratio of tryptophan to nicotinamide in growing rats fed a niacin-free 20% casein diet.
Weaning rats were fed a niacin-free 20% casein diet. Twenty-four-h-urine samples were collected, and nicotinamide and its catabolites were measured. A correlation was found between the urinary excretory ratio of nicotinamide catabolites (N(1)-methyl-2-pyridone-5-carboxamide + N(1)-methyl-4-pyridone-3-carboxamide)/N(1)-methylnicotinamide and the tryptophan-nicotinamide conversion ratio during growing period of the rats. This indicates the possibility that the conversion ratio can be deduced from the excretory ratio.


Prognostic Value of Long Noncoding RNA SPRY4-IT1 on Survival Outcomes in Human Carcinomas: A Systematic Review and Meta-Analysis with TCGA Database.
Emerging evidences have shown that long noncoding RNA SPRY4-IT1 can be aberrantly expressed in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic mechanism of SPRY4-IT1 is still unclear. This study is aimed at evaluating its potential predictive value for cancer prognosis. We thoroughly searched PubMed, Embase, Web of Science, and MEDLINE databases so as to explore the relationship between SPRY4-IT1 expression and cancer prognosis value. Then, TCGA datasets were used to validate the results of our meta-analysis. In all, seventeen studies involving 1650 patients were included in this meta-analysis. Pooled results showed that high expression of SPRY4-IT1 was significantly correlated with poor OS (HR = 1.96, 95% confidence interval (CI) = 1.47-2.62, P < 0.001) in cancer patients. Furthermore, exploration of TCGA dataset further validated that SPRY4-IT1 was aberrantly expressed in various cancers, which partially confirmed our results in this meta-analysis. The present systematic review and meta-analysis implicated that the aberrant expressions of lncRNA SPRY4-IT1 were strongly associated with clinical survival outcomes in various cancers and therefore might serve as a promising biomarker for predicting prognosis of human cancers.


Prostaglandin biosynthesis by lapine articular chondrocytes in culture.
Secondary monolayer and spinner cultures of rabbit articular chondrocytes released into the culture medium prostaglandins the synthesis of which was inhibited by sodium meclofenamate. The prostaglandins measured by radioimmunoassay were, in order of decreasing abundance, prostaglandin E2, 6-oxo-prostaglandin F1 alpha (the stable metabolite of prostacyclin) and prostaglandin F2 alpha. Several lines of evidence indicated that chondrocytes synthesize little if any thromboxane B2 (the stable metabolite of thromboxane A2). The presence of prostaglandins was confirmed by radiometric thin-layer chromatography of extracts of culture media incubated with [3H]arachidonic acid-labeled cells. In monolayer culture, chondrocytes synthesized immunoreactive prostaglandins in serum-free as well as serum-containing medium. Monolayer chondrocytes produced higher levels of prostaglandin E2 relative to 6-oxo-prostaglandin F1 alpha than did spinner cells, but the latter synthesized more total prostaglandins. The identity of endogenous prostaglandins as well as those synthesized in short-term culture by rabbit cartilage slices was compared to those produced by chondrocytes in long-term culture. Chondrocytes synthesized all of the prostaglandins found in articular cartilage. Minimal quantities of thromboxane B2 were detected in cartilage. A higher percentage of 6-oxo-prostaglandin F1 alpha relative to other prostaglandins was found in cartilage than in either monolayer or spinner chondrocyte cultures. These results demonstrate that articular chondrocytes synthesize prostaglandins and prostacyclin. These prostaglandins may exert significant physiological effects on cartilage, since exogenous prostaglandins depress chondrocyte sulfated-proteoglycan synthesis and may even promote proteoglycan degradation.


Lateral carbon fluxes and CO2 evasion from a subtropical mangrove-seagrass-coral continuum.
Mangrove, seagrass, and coral habitats often lie adjacent to each other in the tropics and subtropics. Lateral carbon fluxes and their consecutive effects on CO2 dynamics and air-water fluxes along the ecosystem continuum are often overlooked. We measured the partial pressure of CO2 in water and associated biogeochemical parameters with a high temporal resolution and estimated air-water CO2 fluxes along the ecosystem continuum. Their lateral fluxes were estimated by using a biogeochemical mass-balance model. The results showed that the waters surrounding mangrove, seagrass, and coral habitats acted as a strong, moderate, and weak source of atmospheric CO2, respectively. The mangrove zone acted as a net source for TAlk, DIC, and DOC, but as a net sink for POC. The contribution of riverine and mangrove-derived OM was substantially high in mangrove sediment, indicating that net transport of POC towards the coastal sea was suppressed by the sediment trapping function of mangroves. The seagrass zone acted as a net source of all carbon forms and TAlk, whereas the coral zone acted as a net sink of TAlk, DIC, and DOC. The lateral transport of carbon from mangroves and rivers offset atmospheric CO2 uptake in the seagrass zone. DOC degradation might increase DIC, and other biogeochemical processes facilitate the functioning of the coral zone as a DOC sink. However, as a result of DIC uptake by autotrophs, mainly in the coral zone, the whole ecosystem continuum was a net sink of DIC and atmospheric CO2 evasion was lowered. We conclude that lateral transport of riverine and mangrove-derived DIC, TAlk, and DOC affect CO2 dynamics and air-water fluxes in seagrass and coral ecosystems. Thus, studies of lateral carbon fluxes at local and regional scales can improve global carbon budget estimates.


Sigmoid adenocarcinoma complicating ureterosigmoidostomy.
A 31-year-old man who died of metastatic adenocarcinoma of the sigmoid colon had undergone bilateral ureterosigmoidostomy for exstrophy of the bladder 20 years earlier. The patient never underwent a colonoscopy. Neoplastic transformation at the ureterosigmoid anastomosis must be considered as a possible severe complication, and therefore, periodic follow-up of these patients is mandatory.


Click-evoked oto-acoustic emission measurement in preterm infants.
Click-evoked oto-acoustic emissions (CEOAE) are acoustic responses produced by the inner ear, reflecting functional auditory integrity. We studied both the success rate of the CEOAE method and the CEOAE presence in preterm infants during their stay at the Neonatal Intensive Care Unit (NICU), by analysis of the results of longitudinal CEOAE measurements in 19 preterm infants. The CEOAE method proved to be feasible in the majority of the population under study; the CEOAE measurement failed in 8% of the total of 226 attempts. Within the range of 30-40 weeks post-conceptional age (PCA) the CEOAE presence increased from about 50% to 80%. These results show the possible clinical application of CEOAE in a NICU for the monitoring of cochlear function during treatment of preterm infants. Bedside CEOAE measurement in preterm infants in a NICU is feasible at a PCA as low as 30 weeks.


Post-transplant lymphoproliferative disorder after paediatric liver transplantation.
The purpose of this study was to analyse the clinical and pathological characteristics, treatments and outcomes of post-transplant lymphoproliferative disorder (PTLD) in paediatric liver transplant recipients. A retrospective analysis of records from nine paediatric liver transplant recipients with PTLD who were treated at our Liver Transplant Center over the period from June 2013 to August 2018. Of these nine patients, seven received liver transplantation in our centre and the remaining two patients at other hospitals. The overall incidence of PTLD in paediatric liver transplant recipients in our centre was 1.4% (7/485). The median onset of PTLD after liver transplantation was 11 months. Three cases were classified as infectious mononucleosis PTLD, one case was plasmacytic hyperplasia PTLD, one case was polymorphic PTLD and two cases were Burkitt lymphoma. One case showed diffuse large B-cell lymphoma and one was classical Hodgkin lymphoma-like PTLD. These patients presented with different clinical manifestations including fever, anaemia, diarrhoea, hypoproteinaemia, enlargement of lymph nodes, hepatosplenomegaly, jaundice, bowel obstruction and even intestinal perforation. Nine patients were positive for EBV-DNA in serum. After diagnosis, immunosuppressants were reduced or discontinued in all cases. Eight patients received anti-CD20 monoclonal antibody (Rituximab) therapy, four cases were treated with a combination of chemotherapy (R-CHOP, ABVD, COPP/ABV) and one case was combined with radiotherapy. Two cases received surgical treatment due to bowel obstruction. Eight of these patients achieved a complete remission and remained healthy when assessed at the time of final follow-up. One patient died as a result of PTLD progression. PTLD is one of the most serious and fatal complications after liver transplantation. The definitive diagnosis requires histopathology. Treatment varies and basically includes immunosuppression reduction, anti-CD20 antibody, surgery, radiotherapy and chemotherapy.


Surface enhanced Raman scattering-based lateral flow immunosensor for sensitive detection of aflatoxin M1 in urine.
Aflatoxin M1 (AFM1) is generally used as a biomarker in urine for the assessment of aflatoxin exposure in humans and animals. However, there is no approach for the rapid and on-site monitoring of AFM1 level in urine. Here, we report a surface enhanced Raman scattering (SERS)-based lateral flow immunosensor built for such a purpose. Raman molecule 5,5-dithiobis-2-nitrobenzoic acid and anti-AFM1 monoclonal antibody were conjugated with Au (core)@Ag (shell) nanoparticle to serve as SERS nanoprobe. AFM1-bovine serum albumin was conjugated with gold nanoparticle and then applied onto nitrocellulose membrane as a visible "GOLD" test line. Quantitation of AFM1 was performed by the readout of Raman signal from the SERS nanoprobes captured on the test line. After optimizing experimental parameters, the detection limit of this immunosensor can achieve as low as 1.7 pg/mL of AFM1 in urine, which is far below the recommended tolerable level (30 pg/mL) of AFM1 in urine. The spiking experiment yielded 93.8%-111.3% recovery with coefficients of variation below 17% demonstrating high assay accuracy and precision. Moreover, this immunosensing assay is fast with an assay time below 20 min. Therefore, the developed immunosensor is a promising tool for the rapid assessment of aflatoxin exposure in the field.


Moebius sequence: radiological approximations to molecular disturbances: an overview.
Moebius sequence is one of the rarest congenital cranial nerve abnormalities. Approximately 300 cases have been recorded in medical literature usually from single case report. Frequently characterized by either partial or complete agenesis of the VI and VII cranial nerves, Moebius sequence is also accompanied by vascular abnormalities and other alterations such as an aberrant or hypoplastic posterior fossa. We present 3 patients with Moebius sequence and their clinical and radiological features along with a discussion of their diagnostic approximations. The 3 patients (1 male and 2 females) with ages ranging from 24 days to 7 years in both outpatient and inpatient settings in a high complexity health center. Clinical and radiologic diagnosis with magnetic resonance imaging showed to be consistent with Moebius sequence. Moebius sequence initial diagnosis is based exclusively on nonunified clinical criteria, and there is an apparent genetic pattern of inheritance. Diagnostic clues include the child's inability for proper facial expressions, affectations in eye convergence, or diminished functional hearing. A radiological approach through the use of specific MRI sequences is often warranted in order to not only approximate cranial nerve abnormalities but also accompanying structural malformations.


Mortality risk factors and validation of severity scoring systems in critically ill patients with acute renal failure.
Risk stratification and prediction of outcome in acute renal failure patients in the intensive care unit are important determinants for improvement of patient care and design of clinical trials. In order to identify mortality risks factors and validate general and specific predictive models for acute renal failure (ARF) patients in the intensive care unit (ICU), 324 patients were prospectively evaluated. Multivariate analysis by logistic regression was utilized for identification of mortality risk factors. Discrimination and calibration were used to evaluate the performance of the following models at referral to nephrologist and at initiation of renal replacement therapy: APACHE II, SAPS II, LODS, and ATN-ISI. Organ failure was assessed by SOFA and OSF. The hospital mortality rate was 85%. The identified mortality risk factors were: age > or = 65 yr, BUN > or = 70 mg/dL, ARF of septic origin, and previous hypertension. Serum creatinine > or = 3.5 mg/dL, systolic blood pressure > or = 100 mm Hg, and normal consciousness were associated with mortality risk reduction. Performance of all prognostic models was disappointing with unsatisfactory calibration and underestimation of mortality on the day of referral to the nephrologist and at initiation of renal replacement therapy. Cross-validation of prognostic models for ARF resulted in poor performance of all studied scores. Therefore, a specific model is still warranted for the design of clinical trials, comparison of studies, and for prediction of outcome in ARF patients, especially in the ICU.


Calreticulin as a marker and therapeutic target for cancer.
Calreticulin (CRT) is a multifunctional protein found within the endoplasmic reticulum (ER). In addition, CRT participates in the formation and development of tumors and promotes the proliferation and migration of tumor cells. When a malignant tumor occurs in the human body, cancer cells that die from immunogenic cell death (ICD) expose CRT on their surface, and CRT that is transferred to the cell surface represents an "eat me" signal, which promotes dendritic cells to phagocytose the tumor cells, thereby increasing the sensitivity of tumors to anticancer immunotherapy. Expression of CRT in tumor tissues is higher than in normal tissues and is associated with disease progression in many malignant tumors. Thus, the dysfunctional production of CRT can promote tumorigenesis because it disturbs not only the balance of healthy cells but also the body's immune surveillance. CRT may be a diagnostic marker and a therapeutic target for cancer, which is discussed extensively in this review.


Detection of Human cytomegalovirus UL55 Gene and IE/E Protein Expression in Colorectal Cancer Patients in Egypt.
A possible relation between Human cytomegalovirus (HCMV) and colorectal cancer (CRC) has been widely explored with an unclear role yet speculated. The study aimed at detecting HCMV UL55 gene, immediate early and early (IE/E) proteins in colorectal tumor tissues and adjacent non neoplastic tissues (ANNT). Also, it aimed to correlate HCMV presence with CRC clinicopathological features. A prospective study of 50 HCMV seropositive patients with resectable CRC were enrolled in the study. Demographic, clinical, and radiological findings were recorded. Pathological assessment was done. Paired CRC tumorous and ANNT were examined for HCMV UL55 by PCR and for IE/ E proteins by immunohistochemistry (IHC). 70% of CRC patients enrolled were females and 36% were elderly (> 60y). Adenocarcinoma was the prevalent histopathological type (92%) with Grade 2, higher stages, and nodal involvement accounting for (64%, 64% and 56%) respectively. HCMV detection was significantly higher in tumoral tissue versus ANNT by PCR and IHC (P < 0.001, P < 0.008) respectively. Moderate agreement was found between the two techniques (κ = 0.572, P < 0.001). Univariate analysis identified HCMV presence to be significantly higher in elderly patients, in tumors with higher stage and with nodal involvement (P = 0.041, P = 0.008, P = 0.018 respectively). In multivariate analysis, the latter two retained significance (P = 0.010, P = 0.008). CRC tumor tissues are more infected by HCMV than ANNT. A significant association of HCMV presence with a higher CRC tumor stage and nodal involvement in an age-dependent manner was detected. HCMV oncomodulatory and a disease progression role is suspected.


Dyotropic rearrangement of bridgehead substituents in closed dithienylethenes; conjugated verses non-conjugated analogues.
Type I dyotropic rearrangement reactions of halogen and methyl substituents at the bridgehead position of diarylethenes and dihydroarylethenes have been studied through density functional theory at B3LYP/6-31+G(d) level. The calculations have been performed to explore the dyotropic rearrangement as a possible factor for the elusive nature of halogenated dithienylethenes (closed). The dyotropic rearrangement process in closed dithienylethenes is then compared with the dihydro analogues. Moreover, the effect of hetero atom and conjugation is also explored through quantum mechanical calculations.


Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice.
CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to tape-stripped mouse skin by evaluating the production of cytokines and Ig isotypes. Confocal laser scanning microscopy revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Co-administration of CpG-ODN and OVA to the disrupted skin elicited an antigen-specific Th1-predominant immune response and enhanced the production of Th1-type cytokines, IL-12 and IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. Cytokine production was supported by the expression of mRNA in the draining lymph node. In terms of antigen-specific antibody production, the level of IgG2a which is regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed. Furthermore, administration of CpG-ODN via the skin drastically attenuated the production of IgE in mice undergoing IgE-type immune response. Administration of CpG-ODN through the skin may shift the immune response from Th2 to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases like AD, which is characterized by Th2-dominated inflammation.


'Candidatus Phytoplasma hispanicum', a novel taxon associated with Mexican periwinkle virescence disease of Catharanthus roseus.
Mexican periwinkle virescence (MPV) phytoplasma was originally discovered in diseased plants of Madagascar periwinkle (Catharanthus roseus) in Yucatán, Mexico. On the basis of results from RFLP analysis of PCR-amplified 16S rRNA gene sequences, strain MPV was previously classified as the first known member of phytoplasma group 16SrXIII, and a new subgroup (16SrXIII-A) was established to accommodate MPV phytoplasma. Phylogenetic analysis of 16S rRNA gene sequences indicated that strain MPV represents a lineage distinct from previously described 'CandidatusPhytoplasma' species. Nucleotide sequence alignments revealed that strain MPV shared less than 97.5 % 16S rRNA gene sequence similarity with all previously described 'Ca.Phytoplasma' species. Based on unique properties of the DNA, we propose recognition of Mexican periwinkle virescence phytoplasma strain MPV as representative of a novel taxon, 'CandidatusPhytoplasma hispanicum'.


Antigenic phenotype of pigment cell lesions: a study of melanoma, its precursor lesions and heterogeneity in metastatic melanoma.
Expression of surface antigens on cells comprising malignant, dysplastic, and benign pigment cell lesions has been evaluated in situ using an avidin-biotin immunohistologic technique. We have demonstrated expression of HLA-DR, beta 2-microglobulin, and 2 melanoma-associated antigens (MAA) in a range of benign and malignant lesion, and have confirmed the close association of HLA-DR and MAA on malignant lesions. In addition, 5 subcutaneous lesions removed at the same time from one individual were evaluated. Clinical and histologic appearance differed among lesions although the antigenic patterns were similar.


[Chronic Tropheryma whipplei infection: an important differential diagnosis of refractory polyarthritis].
Refractory arthritis is a common problem in routine rheumatology practice, and can be a diagnostic challenge. In these cases, chronic Tropheryma whipplei (T. whipplei) infection is an important differential diagnosis that should be considered. Based on five clinical cases, this case-based review describes the diagnostic and therapeutic principles in the management of chronic T. whipplei infection. Whipple's disease is a multisystemic infectious disease caused by the bacterium T. whipplei. The disease typically manifests with arthralgia, weight loss and diarrhoea. Joint involvement often develops years before gastrointestinal symptoms occur. In addition to systemic manifestations ("classic Whipple's disease"), T. whipplei can also lead to localized joint infections without gastrointestinal involvement. Articular manifestations of systemic and localized T. whipplei infections are commonly misdiagnosed as a sign of various forms of autoimmmune arthritis. Whipple's disease and localized T. whipplei joint infection should be considered in the diagnostic work-up of refractory arthritis. Synovial fluid analysis by means of specific polymerase chain reaction-based testing for T. whipplei is diagnostically ground-breaking.


Prevalence and determinants of disability among adults in Malaysia: results from the National Health and Morbidity Survey (NHMS) 2015.
Reliable national data on disability which is internationally comparable is needed in Malaysia. This study aims to examine the prevalence of disability among adults in Malaysia and its determinants, particularly the socioeconomic factors and comorbidities. This study was based on the disability module, which is part of the National Health and Morbidity Survey 2015. This survey was implemented using a multi-stage stratified sampling design. A locally validated Washington Group questionnaire was used to collect data on disability. Based on the definition of having at least one domain scored "a lot of difficulty or unable to do at all" or at least "some difficulty" scored in two domains, the prevalence of disability among adults in Malaysia was 11.8% (95% CI: 11.15, 12.53). Logistic regression analysis performed showed that population at risk of having disability in Malaysia were those of older people, ethnic minority, low level of education, single, obese, physically inactive and having mental health problems. Among older people, disability was significantly higher among those with no formal education, having mental health problems and physically inactive. The prevalence of disability among adults in Malaysia is comparable to WHO estimates and most developing countries. Planning for healthcare services should consider at-risk population, particularly older people and those from disadvantaged background to ensure equity healthcare.


Mitotic crossing-over by anticancer drugs in Saccharomyces cerevisiae strain D5.
Treatment with an anticancer drug causing mitotic crossing-over could lead to expression of recessive genes, previously masked in a heterozygote. Used clinically, such drugs might cause an increased risk of cancer in cases of familial tumours, such as Wilm's tumour or retinoblastoma. Potentially, novel forms of drug resistance could also be unmasked by such a recombinogenic event. We have estimated the extent of this potential problem in current clinical drugs by comparing a range of antitumour agents for ability to cause mitotic crossing-over in Saccharomyces cerevisiae strain D5. We have compared these data with ability to cause an increase in total aberrant colonies in the same experiments. Although many of the agents known to cause point mutation also have some ability for mitotic crossing-over, there are also point mutagens which have little recombinogenic potential. Conversely, some effective recombinogens appear to be either very specific or rather ineffective point mutagens. Although the most generally effective agents in the present experiments were alkylating agents, several other types of drug including DNA-cutting agents, topoisomerase inhibitors, other DNA-binding drugs and antimetabolites may stimulate mitotic crossing-over. None of the mitotic inhibitors or the DNA minor groove binding drugs tested caused recombinogenic events. It would seem that the ability to induce mitotic crossing-over is an important endpoint in its own right. Assays for this event might provide an important complement to other assays commonly required for registration of new pharmaceuticals.


The effect of dietary vitamin E deficiency on plasma zinc and copper concentrations.
Vitamin E and zinc have a number of functions in common, including membrane stabilisation, antioxidant function and modulation of prostaglandin metabolism. Previous studies have shown vitamin E malabsorption during zinc depletion and it appears that there is an interaction between the two nutrients. In this study we have investigated whether vitamin E deficiency affects zinc and copper concentrations in experimental animals. Male Wistar rats were maintained on a vitamin E deficient diet for either 6 or 10 months. At the end of the experimental period all animals had undetectable plasma vitamin E levels and increased red cell fragility. Plasma zinc concentrations were significantly reduced in all vitamin E deficient animals compared to control rats (p<0.002) and copper levels were reciprocally elevated (p<0.002). It appears likely that decreased zinc levels may represent redistribution of circulating zinc to tissues and cells as a secondary antioxidant, or for membrane stabilisation or prostaglandin synthesis.


Global health priorities for developing countries: some equity and ethical considerations.
Although the need to make health priorities equitable in addressing health disparities among populations of the world is widely acknowledged, there are presently no clearcut mechanisms for achieving this goal at the global level. This paper highlights some of the limitations associated with priority setting based exclusively on the interplay of burden of disease and cost-effectiveness analysis, and identifies occasions when equity considerations may favor conditions lacking immediate evidence on cost-effectiveness but associated with substantial burden in individuals and the society and for which optimal interventions are time bound. It also highlights the implications of overlooking conditions and issues that are deserving of high-priority status by global health actors and are in the longer-term interest of donor recipients. It concludes by exploring how representative mechanisms for societal preferences such as the periodic resolutions of the World Health Assembly backed by commitments of national governments provide a framework for making global health priorities more equitable.


Non-negligibly negative role of e-waste-derived pyrogenic carbon in the soil washing of copper and polybrominated diphenyl ethers.
The open incineration of electrical and electronic waste (e-waste) results in the accumulation of pyrogenic carbon in the soil. However, the effect of the e-waste-derived pyrogenic carbon (E-PyC) on the performance of soil washing at e-waste incineration sites remains unclear. In this study, the effectiveness of a citrate-surfactant mixed solution in removing copper (Cu) and decabromodiphenyl ether (BDE209) at two e-waste incineration sites was evaluated. The removal efficiencies of Cu (24.6-51.3%) and BDE209 (13.0-27.9%) were low in both soils and were not significantly improved by ultrasonic. Soil organic matter analysis, hydrogen peroxide and thermal pretreatment experiments, and microscale soil particle characterization demonstrated that the poor removal of soil Cu and BDE209 was due to steric effects of E-PyC on the release of the solid fraction of pollutants and the competitive sorption of the labile fraction of pollutants by E-PyC. Weathering of soil Cu weakened the influence of E-PyC but strengthened the negative impact of natural organic matter (NOM) on soil Cu removal by promoting complexation between NOM and Cu2+ ions. This study demonstrates that the negative effect of E-PyC on Cu and BDE209 removal by soil washing is non-negligible, which has implications for decontaminating e-waste incineration sites by soil washing.