Escherichia coli poly(A)-binding proteins that interact with components of degradosomes or impede RNA decay mediated by polynucleotide phosphorylase and RNase E.
The multifunctional ribonuclease RNase E and the 3'-exonuclease polynucleotide phosphorylase (PNPase) are major components of an Escherichia coli ribonucleolytic "machine" that has been termed the RNA degradosome. Previous work has shown that poly(A) additions to the 3' ends of RNA substrates affect RNA degradation by both of these enzymes. To better understand the mechanism(s) by which poly(A) tails can modulate ribonuclease action, we used selective binding in 1 m salt to identify E. coli proteins that interact at high affinity with poly(A) tracts. We report here that CspE, a member of a family of RNA-binding "cold shock" proteins, and S1, an essential component of the 30 S ribosomal subunit, are poly(A)-binding proteins that interact functionally and physically, respectively, with degradosome ribonucleases. We show that purified CspE impedes poly(A)-mediated 3' to 5' exonucleolytic decay by PNPase by interfering with its digestion through the poly(A) tail and also inhibits both internal cleavage and poly(A) tail removal by RNase E. The ribosomal protein S1, which is known to interact with sequences at the 5' ends of mRNA molecules during the initiation of translation, can bind to both RNase E and PNPase, but in contrast to CspE, did not affect the ribonucleolytic actions of these enzymes. Our findings raise the prospect that E. coli proteins that bind to poly(A) tails may link the functions of degradosomes and ribosomes.


Body Temperature Monitoring for Regular COVID-19 Prevention Based on Human Daily Activity Recognition.
Existing wearable systems that use G-sensors to identify daily activities have been widely applied for medical, sports and military applications, while body temperature as an obvious physical characteristic that has rarely been considered in the system design and relative applications of HAR. In the context of the normalization of COVID-19, the prevention and control of the epidemic has become a top priority. Temperature monitoring plays an important role in the preliminary screening of the population for fever. Therefore, this paper proposes a wearable device embedded with inertial and temperature sensors that is used to apply human behavior recognition (HAR) to body surface temperature detection for body temperature monitoring and adjustment by evaluating recognition algorithms. The sensing system consists of an STM 32-based microcontroller, a 6-axis (accelerometer and gyroscope) sensor, and a temperature sensor to capture the original data from 10 individual participants under 4 different daily activity scenarios. Then, the collected raw data are pre-processed by signal standardization, data stacking and resampling. For HAR, several machine learning (ML) and deep learning (DL) algorithms are implemented to classify the activities. To compare the performance of different classifiers on the seven-dimensional dataset with temperature sensing signals, evaluation metrics and the algorithm running time are considered, and random forest (RF) is found to be the best-performing classifier with 88.78% recognition accuracy, which is higher than the case of the absence of temperature data (<78%). In addition, the experimental results show that participants' body surface temperature in dynamic activities was lower compared to sitting, which can be associated with the possible missing fever population due to temperature deviations in COVID-19 prevention. According to different individual activities, epidemic prevention workers are supposed to infer the corresponding standard normal body temperature of a patient by referring to the specific values of the mean expectation and variance in the normal distribution curve provided in this paper.


Alpha-fetoprotein and acetylcholinesterase are not predictive of fetal junctional epidermolysis bullosa, Herlitz variant.
Junctional epidermolysis bullosa, Herlitz variant (junctional EB-Herlitz) is a lethal autosomal recessive skin disorder currently amenable to prenatal diagnosis only by direct analysis of fetal skin. However, elevated levels of alpha-fetoprotein, as well as the presence of acetylcholinesterase in amniotic fluid, have been associated with other severe fetal genodermatoses. Fetal skin samplings were performed in ten pregnancies at risk for fetal junctional EB-Herlitz, with three fetuses affected on the basis of electron microscopic detection of blisters within the lamina lucida and abnormal hemidesmosomes. In neither affected nor unaffected pregnancies were maternal serum or amniotic fluid alpha-fetoprotein levels elevated. Moreover, alpha-fetoprotein levels in both maternal serum and amniotic fluid were not statistically different comparing affected and unaffected fetuses. Acetylcholinesterase was not present in the amniotic fluid samples of the three affected pregnancies. Unlike other severe fetal genodermatoses, neither alpha-fetoprotein nor acetylcholinesterase was predictive of junctional EB-Herlitz.


Effectiveness of a large-scale home visiting programme (PIM) on early child development in Brazil: quasi-experimental study nested in a birth cohort.
A large-scale parenting programme with weekly home visits (Primeira Infância Melhor (PIM)) has been implemented in the south of Brazil for nearly two decades, but lacks evaluation of its effects on early childhood development (ECD). This quasi-experimental study aimed to assess the effects of PIM in real-life settings within a population-based birth cohort study. Data from the 2015 Pelotas Birth Cohort Study and the state programme information system were linked to identify study children who received PIM. Propensity score matching was used to create a comparable control group (using one-to-one matching) to estimate the effect of PIM on ECD measured at age 4 years. First, the impact of any enrolment in PIM was evaluated; then the intervention group was stratified according to whether enrolment occurred during pregnancy or after birth. Double adjustment was applied in linear regression to analyse child development scores, and Poisson regression for delayed development (below the 10th percentile of whole cohort). Effect modification due to family income was explored. There was no evidence that any enrolment in PIM (601 pairs) by age 4 years was associated with child development. However, PIM starting during pregnancy (estimated for 121 pairs) predicted higher development scores (0.27 SD; 95% CI 0.02 to 0.52), and 71% lower prevalence of delayed development (prevalence ratio=0.29; 95% CI 0.13 to 0.69), compared with the control group. There was strong statistical evidence (p=0.003, test of interaction) that the effect of PIM starting in pregnancy was larger than when starting after birth (480 pairs). The effect of PIM starting during pregnancy was found to be restricted to poorer families. In a real-life setting, PIM was effective only when starting during pregnancy and only for poorer families. A higher-quality programme might be more effective with a broader population.


Add on Exenatide Treatment is Beneficial in Poorly Controlled Obese Type 2 Diabetics under Intensive Insulin Regimens.
Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10.44 years, body mass index 41.1±6.8 kg/m2, HbA1c 9.9±1.5%), under high dose (94.1±39.6 unit) intensive insulin. Exenatide twice daily was added for a mean follow-up period of 11.22±7.01 (3-30) months. Intensive insulin regimens were continued in 7 patients while the others were switched to basal insulin during the follow-up. Results: During the follow-up, mean HbA1c levels of the patients significantly improved (p=0.019), along with the significant decrease in body mass index and the total insulin need (p<0.001 for both). Baseline insulin dosages were significantly higher in the intensive regimen group (p=0.013) while other demographical and clinical characteristics were similar. No significant difference was present between the groups regarding the alterations of HbA1c, body mass index and the reduction in total insulin dosages. Conclusion: Add on exenatide appears to be a rational treatment modality in uncontrolled obese patients with type 2 diabetes mellitus despite intensive insulin regimens. Further prospective randomized studies with longer follow-up periods are recommended.


Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H.
Although the importance of CD4+ T cell responses to human cytomegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4+ CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HCMV isolates revealed that the gB and gH epitope sequences recognized by human CD4+ T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4+ CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse peptide-sensitized Patr-DR7+ cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class II lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.


Artificial neural network approach to predict surgical site infection after free-flap reconstruction in patients receiving surgery for head and neck cancer.
The aim of this study was to develop an effective surgical site infection (SSI) prediction model in patients receiving free-flap reconstruction after surgery for head and neck cancer using artificial neural network (ANN), and to compare its predictive power with that of conventional logistic regression (LR). There were 1,836 patients with 1,854 free-flap reconstructions and 438 postoperative SSIs in the dataset for analysis. They were randomly assigned tin ratio of 7:3 into a training set and a test set. Based on comprehensive characteristics of patients and diseases in the absence or presence of operative data, prediction of SSI was performed at two time points (pre-operatively and post-operatively) with a feed-forward ANN and the LR models. In addition to the calculated accuracy, sensitivity, and specificity, the predictive performance of ANN and LR were assessed based on area under the curve (AUC) measures of receiver operator characteristic curves and Brier score. ANN had a significantly higher AUC (0.892) of post-operative prediction and AUC (0.808) of pre-operative prediction than LR (both P<0.0001). In addition, there was significant higher AUC of post-operative prediction than pre-operative prediction by ANN (p<0.0001). With the highest AUC and the lowest Brier score (0.090), the post-operative prediction by ANN had the highest overall predictive performance. The post-operative prediction by ANN had the highest overall performance in predicting SSI after free-flap reconstruction in patients receiving surgery for head and neck cancer.


[Production of immunoregulatory cytokines in autoimimune damage of the ovaries in mammals].
Several ovarian disorders in women are associated with autoimmune factors. In this study it was investigated a level of cytokines--TNF-alpha and IFNs in ovarian homogenate and blood serum at ovarian autoimmune damage of mammals. Experimental immune ovarian failure was induced in CBA mice by either immunization with allogenic ovarian extracts or administration of xenogenic anti-ovarian antibodies. Both models were accompanied with abnormalities in production of immunoregulatory cytokines. These data confirm the importance of definition of proinflammatory cytokine level for disclosing immune mechanisms which lay in a pathogenesis autoimmune ovarian diseases of female reproductive organs.


Mouse models of autoimmune diseases.
Significant progress has been made in past decades in our understanding of the basic mechanisms underlying autoimmune diseases. Nevertheless, many questions remain unanswered, in particular regarding the mechanisms at very early stages of these diseases. Reliable animal models are of crucial importance in basic research and may help us to understand central disease pathways. They are also indispensable for pre-clinical drug testing. Here we present and discuss two mouse models of rheumatoid arthritis and multiple sclerosis, respectively. In experimental studies using the models of collagen-induced arthritis and experimental autoimmune encephalomyelitis, the efficacy of new biological agents has been tested, which paved the way for clinical trials. A further interesting field where mouse models may provide valuable informations, is the identification of susceptibility genes for autoimmune diseases. Overall, in some instances studies with inbred strains may have an advantage over human studies, because environmental factors may easily be controlled and the genetic differences between different mouse strains are better characterized.


Peptide-Conjugated Silver Nanoparticles for the Colorimetric Detection of the Oncoprotein Mdm2 in Human Serum.
Invited for this month's cover are the collaborating groups of Prof. Gilles Bruylants and Prof. Ivan Jabin, Université libre de Bruxelles, Belgium. The cover picture shows the principle of a colorimetric sensor, based on peptide-conjugated silver nanoparticles, for the detection of the cancer biomarker Mdm2. The particles were functionalized via a recently developed strategy based on the use of calixarene diazonium salts. The calixarene-based coating provides an unprecedented stability to the silver nanoparticles, enabling their use as colorimetric reporters for in vitro diagnostics. The cover was designed by I. Jabin. More information can be found in the Research Article by I. Jabin, G. Bruylants, and co-workers.


A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function.
Next-generation sequencing has facilitated the diagnosis of neurodevelopmental disorders with variable and non-specific clinical findings. Recently, a homozygous missense p.(Asp37Tyr) variant in TRAPPC2L, a core subunit of TRAPP complexes which function as tethering factors during membrane trafficking, was reported in two unrelated individuals with neurodevelopmental delay, post-infectious encephalopathy-associated developmental arrest, tetraplegia and accompanying rhabdomyolysis. We performed whole genome sequencing on members of an Ashkenazi Jewish pedigree to identify the underlying genetic aetiology of global developmental delay/intellectual disability in three affected siblings. To assess the effect of the identified TRAPPC2L variant, we performed biochemical and cell biological functional studies on the TRAPPC2L protein. A rare homozygous predicted deleterious missense variant, p.(Ala2Gly), in TRAPPC2L was identified in the affected siblings and it segregated with the neurodevelopmental phenotype within the family. Using a yeast two-hybrid assay and in vitro binding, we demonstrate that the p.(Ala2Gly) variant, but not the p.(Asp37Tyr) variant, disrupted the interaction between TRAPPC2L and another core TRAPP protein, TRAPPC6a. Size exclusion chromatography suggested that this variant affects the assembly of TRAPP complexes. Employing two different membrane trafficking assays using fibroblasts from one of the affected siblings, we found a delay in traffic into and out of the Golgi. Similar to the p.(Asp37Tyr) variant, the p.(Ala2Gly) variant resulted in an increase in the levels of active RAB11. Our data fill in a gap in the knowledge of TRAPP architecture with TRAPPC2L interacting with TRAPPC6a, positioning it as a putative adaptor for other TRAPP subunits. Collectively, our findings support the pathogenicity of the TRAPPC2L p.(Ala2Gly) variant.


A Self-Assembled Matrix System for Cell-Bioengineering Applications in Different Dimensions, Scales, and Geometries.
Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation-mediated self-assembling mechanism, a biomatrix system optimal for 2D human mesenchymal stromal cell (hMSC) culture and osteogenesis is identified. Its utility for hMSC bioengineering is further demonstrated in coating porous bioactive glass scaffolds and nanoparticle synthesis for esiRNA delivery to knock down the SOX-9 gene with high delivery efficiency. The self-assembled injectable system is further utilized for 3D cell culture, segregated co-culture of hMSC with human umbilical vein endothelial cells (HUVEC) as an angiogenesis model, and 3D bioprinting. Most interestingly, the coating of bioactive glass with the self-assembled biomatrix not only supports the proliferation and osteogenesis of hMSC in the 3D scaffold but also induces the amorphous bioactive glass (BG) scaffold surface to form new apatite crystals resembling bone-shaped plate structures. Thus, the self-assembled biomatrix system can be utilized in various dimensions, scales, and geometries for many different bioengineering applications.


Applying behavior change models to understand spiritual mechanisms underlying change in substance abuse treatment.
Despite increasing attention directed to conceptual and methodological issues surrounding spirituality and despite the centrality of "spiritual transformation" in the recovery literature, there is little systematic evidence to support the role of spiritual change as a necessary condition for substance abuse behavior change. As an explicit conceptualization of mechanisms underlying behavior change is fundamental to effective interventions, this article: 1) briefly reviews relevant behavior change theories to identify key variables underlying change; 2) presents an integrative conceptual framework articulating linkages between program components, behavior change processes, spiritual change mechanisms and substance abuse outcomes; and 3) presents a discussion of how the mechanisms identified in our model can be seen in commonly used substance abuse interventions. Overall, we argue that spiritual transformation at an individual level takes place in a social context involving peer influence, role modeling, and social reinforcement.


Aluminum phagocytosis in quadriceps muscle following vaccination in children: relationship to macrophagic myofasciitis.
Macrophagic myofasciitis (MMF) is a rare, seemingly emerging entity among adult patients in France. We encountered two children with the first two cases of MMF in North America. A 5-year-old male with chronic intestinal pseudo-obstruction required nighttime parenteral nutrition. Abnormal pupillary reflexes and urinary retention suggested a diffuse dysautonomia, which prompted a neurological diagnostic work-up. A 3-year-old child had developmental delay and hypotonia. Both children received age-appropriate immunizations. Quadriceps muscle biopsy from each child showed the typical patchy, cohesive centripetal infiltration of alpha-1-antitrypsin+, alpha-1-antichymotrypsin+, CD68+, PAS+, CD1a-, S-100-, factor XIII- granular macrophages with adjacent myofiber atrophy, dilated blood vessels, and mild endomysial and perimysial fibrosis. No myonecrosis was observed and no discrete granulomas were seen. A single aluminum peak was demonstrated on energy dispersive X-ray microanalysis. The etiology of the clinical symptoms in these cases and in cases reported as MMF remains intriguing. Despite numerous stains to demonstrate organisms, most infectious causes leading to macrophage activation were ruled out. These cases are being reported to increase awareness of this condition and to encourage a systematic epidemiologic and clinicopathologic study in North America.


Scanning Rate Extension of Conventional DSCs through Indirect Measurements.
In this work, a method is presented which allows the determination of calorimetric information, and thus, information about the precipitation and dissolution behavior of aluminum alloys during heating rates that could not be previously measured. Differential scanning calorimetry (DSC) is an established method for in-situ recording of dissolution and precipitation reactions in various aluminum alloys. Diverse types of DSC devices are suitable for different ranges of scanning rates. A combination of the various available commercial devices enables heating and cooling rates from 10-4 to 5 Ks-1 to be covered. However, in some manufacturing steps of aluminum alloys, heating rates up to several 100 Ks-1 are important. Currently, conventional DSC cannot achieve these high heating rates and they are still too slow for the chip-sensor based fast scanning calorimetry. In order to fill the gap, an indirect measurement method has been developed, which allows the determination of qualitative information, regarding the precipitation state, at various points of any heat treatment. Different rapid heat treatments were carried out on samples of an alloy EN AW-6082 in a quenching dilatometer and terminated at defined temperatures. Subsequent reheating of the samples in the DSC enables analysis of the precipitation state of the heat-treated samples. This method allows for previously un-measurable heat treatments to get information about the occurring precipitation and dissolution reactions during short-term heat treatments.


[Seroprevalence of Lyme borreliosis in workers from Cordoba, Colombia].
Establishing the seroprevalence of Lyme disease in workers from Cordoba. Representative serum samples (152) were taken from the cities of Montería, Cereté, Lorica and Cotorra in the Córdoba department in Colombia. Borrelia burgdorferi antibodies were detected by ELISA and confirmed by western blot anti-Borrelia blot assay. RPR (rapid plasma regain) test for Treponema pallidum (syphilis) and ELISA for leptospirosis IgM were carried out to discard cross-reactivity. A total of 152 serum samples were tested; 30 (20 %) were positive by ELISA. The 30 positive sera were RPR negative. Seven sera were confirmed by western blot; seroprevalence was 4.6 %. Reactivity against p41, p58, p75, OspA, p30, OspC, p17, VLsE and p83/100 were detected. Our results revealed antigenic evidence of Borrelia in the rural area of Cordoba. Identifying clinical, ecological and serological cases, linked to searching for Borrelia burgdorferi in infected tick vectors must be carried out in rural parts of Colombia.


Biological system responses to zearalenone mycotoxin exposure by integrated metabolomic studies.
This study aims to investigate the effect of zearalenone supplementation on rat metabolism. Rats received biweekly intragastric administration of zearalenone mycotoxin (3 mg/kg body weight) for 2 weeks. Urine and plasma samples after zearalenone administration were analyzed by NMR-based metabolomics. Zearalenone exposure significantly elevated the plasma levels of glucose, lactate, N-acetyl glycoprotein, O-acetyl glycoprotein, and propionate but reduced the plasma levels of tyrosine, branched-chain amino acids, and choline metabolites. Zearalenone supplementation decreased the urine levels of butyrate, lactate, and nicotinate. However, it increased the urine levels of allantoin, choline, and N-methylnicotinamide at 0-8 h after the last zearalenone administration and those of 1-methylhistidine, acetoacetate, acetone, and indoxyl sulfate at 8-24 h after the last zearalenone administration. These results suggest that zearalenone exposure can cause oxidative stress and change common systemic metabolic processes, including cell membrane metabolism, protein biosynthesis, glycolysis, and gut microbiota metabolism.


Bilateral orbital roof fracture.
Bilateral orbital roof fractures are rare events usually associated with high-energy impact trauma. The clinical picture is often multiple because of involvement of cranial, cerebral, and facial injuries. The primary diagnostic and therapeutic approaches aim to safeguard the cerebral state and to intercept the consequences of severe orbital trauma. The latter may present dramatic events and determine permanent ocular bulb or optic nerve damage, even vision impairment and blindness. Immediate intraorbital decompression decreases the pressure exerting directly or indirectly on the optic nerve. Surgical decompression of the orbit was performed in a young man showing almost complete blindness after bilateral orbital roof fracture. The final result showed good recovery of vision and functional motility of the bulbs.


Gradients of precipitation and ant abundance may contribute to the altitudinal range limit of subsocial spiders: insights from a transplant experiment.
Species range boundaries often form along environmental gradients that dictate the success of the phenotypes present in each habitat. Sociality may allow colonization of environments where related species with a solitary lifestyle cannot persist. Social spiders in the genus Anelosimus appear restricted to low- and mid-elevation moist environments in the tropics, while subsocial spiders, common at higher elevations and latitudes, appear to be absent from the lowland tropical rainforest. Here, we seek factors that may simultaneously prevent subsocial Anelosimus species from colonizing the lowland rainforest while favouring species with large social groups in this habitat. To this end, we transplanted small groups of a subsocial species, which contain the offspring of a single female, from cloud forest habitat in the centre of its natural range to lower montane rainforest on the range margin and to lowland rainforest outside of the species range. Groups transplanted at the range margin and below their range limit were less likely to disperse and experienced increased mortality. This was correlated with greater rainfall intensity and ant abundance. We show that protection from rainfall enhances the performance of small groups of spiders in the lowland rainforest, and suggest that predation or disturbance by ants may influence the geographical range limits of this species.


[Effect of oral administration of guanxin II decoction on coronary blood flow and cardiac systolic/diastolic function in healthy males].
To observe the effects of oral administration of guanxin II decoction (GX II) on cardiovascular function, especially on the dynamics of coronary blood flow in healthy males. Changes of heart rate, diastolic pressure, systolic pressure, left ventricular ejection fraction (LVEF), E peak, A peak, E/A value of mitral flow, diastolic peak velocity (Vmax) and diastolic flow velocity time integrals (VTI) of left anterior descending coronary artery (LAD) in 11 healthy male subjects were measured before and after oral administration of GX II, using non-invasive echocardiogram. Compared with those before GX II administration, the changes after administration in heart rate, systolic pressure, diastolic pressure, LVEF, E peak, A peak and E/A value, were insignificantly different (P>0.05), but the Vmax and VTI significantly increased at 30 min, 60 min, 90 min and 120 min after GX II administration (P<0.05). To increase the coronary blood flow is possibly one of the mechanisms of GX II in treating coronary heart disease and angina pectoris.


A comprehensive particulate matter monitoring system and dosimetry-based ambient particulate matter standards.
A numerical particulate matter (PM) measurement model is developed to characterize and evaluate PM sampling methods. Simulations are conducted using the model to evaluate currently widely used PM samplers, including Federal Reference Method (FRM) samplers. The simulations show that current PM samplers are very vulnerable to both changes in measurement target (i.e., natural variability of particle size distribution) and the sampler's design, manufacturing, and operating conditions, potentially resulting in significant errors in the monitoring data. The numerical model is used in conjunction with two types of commercially available PM monitoring devices to form a Comprehensive Particulate Matter Monitoring System (CPMMS). The first type of device can be any mass-based PM monitor with a well-defined sampling efficiency curve. The second type of device is one capable of measuring particle size distribution with a reasonably good relative accuracy between size categories but not necessarily accurate in measuring absolute mass concentrations. This study shows that CPMMS can produce much higher quality PM monitoring data than the current PM samplers under the same conditions. In addition, unlike past and current PM monitoring data such as total suspended particulates, coarse PM (PM10), fine PM (PM2.5), etc., the CPMMS monitoring data will survive changes in PM regulatory definition. A new concept, dosimetry-based PM metrics and standards, is proposed to define ambient PM level based on the deposition fraction of particles in the human respiratory tract. The dosimetry-based PM metrics is more meaningful because it correlates the ambient PM level with the portion that can be deposited in the respiratory tract without an arbitrary cutoff particle diameter. CPMMS makes dosimetry-based PM metrics and standards feasible.


Cow's milk allergy.
To highlight the most recent insights on cow's milk allergy (CMA), its treatment, and management. CMA is one of the most common food allergies among children. Burdened by the risk for fatal reaction, CMA may imply also a severe impairment of health-related quality of life at individual and family level as well as well as individual and societal costs. The updated Diagnosis and Rationale for Action against Cow's Milk Allergy series is going to provide a series of manuscripts that will offer a comprehensive state-of-the-art specifically on CMA, including international evidence-based recommendations. The current results from randomized clinical trials highlight that oral immunotherapy may be effective by itself in providing desensitization. Preliminary data suggest that biologicals such as omalizumab may be able to increase the threshold of reactivity to milk or several foods (if multiple food allergies) without requiring allergen exposure. Breastfeeding is the first choice for infants with CMA. Extensively hydrolyzed formula and amino-acid formula are valid alternatives and may be particularly helpful when eliminating multiple foods, with severe complex gastrointestinal food allergies, eosinophilic esophagitis, severe eczema, or symptoms while exclusively breastfeeding. Heed is needed to ensure the formula is nutritionally sufficient. Due to a high degree of cross-reactivity with cow's milk proteins and risk for allergic reactions, goats' milk or other mammals' milk should not be used. The adoption and implementation of evidence-based recommendations may guide a proper diagnostics and management and awaited advances in knowledge will allow the development of a personalized treatment tailored on the specific CMA patient's profile.


Hypergammaglobulinaemic purpura presenting as reticulate purpura.
Hypergammaglobulinaemic purpura, first described by Waldenstrom, is a rare skin disease. The essential features are the presence of purpura with polyclonal hypergammaglobulinaemia. We describe a case of hypergammaglobulinaemic purpura occurring in a Chinese man with reticulate purpura and haemorrhagic blisters.


HIV in female sex workers in five border provinces of Vietnam.
To determine the prevalence of HIV and associated risk factors among female sex workers (FSWs) in border provinces of Vietnam. 911 FSWs in five border provinces of Vietnam (Lai Chau, Quang Tri, Dong Thap, An Giang, and Kien Giang) were enrolled in a cross sectional study. Subjects were interviewed using a standardised questionnaire about selected sociodemographic and behavioural characteristics, history of STIs, and information about their cohabiting partners (husbands or live-in partners). Serological tests were done for HIV and syphilis (TPHA+RPR) and urine tests (PCR) for chlamydia and gonorrhoea. Associations between HIV and selected features of FSWs and their partners were examined using univariate and multivariate logistic regression analysis. Overall, the prevalence of HIV among FSWs in the five provinces of Vietnam was 4.5%. The prevalence of HIV was higher in the southern border regions (4.0%-7.0%) than the northern (2%) and central (1%) regions. In multivariate analysis between HIV and selected features of FSWs, income < or =$33/month (OR 2.36, p = 0.04), age of first sex < or =15 (OR = 5.48, p = 0.005), and > or =9 clients per week (OR 2.80, p = 0.018) were associated with HIV infection. Positive syphilis serology achieved a borderline significant association with HIV (OR 2.30, p = 0.095). Having a regular non-paying partner (OR = 0.35, p = 0.060) was a borderline protective factor for HIV. Interventions to limit HIV transmission among FSWs in Vietnam should be implemented early and focus on young poor populations in these border areas.


Optically induced deexcitation of rare-Earth ions in a semiconductor matrix.
We report on verification of the proposed energy transfer mechanism responsible for photoluminescence of rare earth (RE) ions in semiconductors. Using two-color spectroscopy in the visible and the midinfrared regions (with a free-electron laser) we demonstrate reversal of the most important step in the excitation process. In that way, formation of the intermediate state bridging atomic states of the RE ion core and extended orbitals of a semiconducting host is explicitly confirmed and its characteristic energy spectroscopically determined. The study is performed for InP:Yb. It is argued, however, that the conclusions are valid for all semiconductor:RE systems, including the notorious Si:Er.


Prospective study on renal outcome of IgA nephropathy superimposed on diabetic glomerulosclerosis in type 2 diabetic patients.
In order to examine the clinical outcome of IgA nephropathy (IgAN) superimposed on diabetic glomerulosclerosis in type 2 patients we studied 36 Chinese patients (26 men, 10 women), who were recruited for renal biopsy when they had proteinuria of more than 1 g/day. Twenty-seven had isolated diabetic glomerulosclerosis and nine had IgAN superimposed on diabetic glomerulosclerosis (combined). Renal function was assessed by serial serum creatinine, 24-h urine protein and creatinine measurements. Patient survival rate, incidence of end-stage renal disease (ESRD), blood pressure, and glycaemic control status were determined. The age at the time of renal biopsy was younger for the combined group when compared with the diabetic glomerulosclerosis group (44+/-3.6 vs 58+/-2.1 years, P=0.006). The duration of diabetes was, however, similar for the two groups (8.0+/-2.3 vs 6.7+/-1.2 years, P=NS). After a mean follow-up of 31.6+/-15.3 months, 15 patients (one in the combined group and 14 in the diabetic glomerulosclerosis group) developed ESRD. Nine patients (all in the diabetic glomerulosclerosis group) died during follow-up. With similar glycaemic and blood pressure control, the two groups had comparable rate of decline of creatinine clearance (CrCl) (-0.73+/-0.26 vs -0.73+/- 0.18 ml/min/1.73 m(2)/month, P=NS), final serum creatinine (363+/-134 vs 426+/-52 micromol/l, P=NS) and proteinuria levels (4.3+/-0.9 vs 4.4+/-0.6 g/day, P=NS), as well as CrCl (44.1+/-19.0 vs 33.4+/-6.9 ml/min/ 1.73 m(2), P=NS). It is concluded that the superimposed IgAN does not significantly alter the medium-term clinical outcome of patients with diabetic glomerulosclerosis.


Traffic patterns and childhood cancer incidence rates in California, United States.
Some studies have suggested that residential proximity to high traffic areas is associated with increased risk of childhood cancer, although the epidemiologic evidence to date has been mixed. This study takes advantage of available information on population-based cancer reporting and various spatially assigned indices of traffic in a sufficiently large and heterogeneous area to obtain reasonably stable estimates of risk associations. The time period 1988-1994 included a total of 7143 newly diagnosed cases of childhood cancer and 46 million child-years of observation in California. Rate ratios, estimated via Poisson regression (with adjustment for age, sex, and race/ethnicity), were computed for estimated traffic level as measured by spatial information on neighborhood vehicle density, road density, and traffic density. Compared to area air monitoring data, traffic density estimates were the most strongly correlated with measures of benzene and 1,3-butadiene. Rate ratios at the 90th percentile of traffic density (neighborhoods with over 320,700 vehicle miles traveled per day per square mile) were 1.08 (95% Cl 0.98-1.20) for all cancers in children, 1.15 (95% CI 0.97-1.37) for the leukemias, and 1.14 (95% CI 0.90-1.45) for the gliomas. There was also little or no evidence for rate differences in areas characterized by high vehicle or road density. These data suggest that childhood cancer rates are not higher in high traffic neighborhoods, but future studies which can better refine timing and measures of exposure are needed to more directly address the question of etiologic risks.


Amelioration of ischemia/reperfusion-induced myocardial infarction by the 2-alkynyladenosine derivative 2-octynyladenosine (YT-146).
The present study was aimed at determining whether the novel adenosine A2-agonist YT-146 may have cardioprotective effects against ischemia-reperfusion injury. Anesthetized open-chest dogs underwent 90-min occlusion of the left anterior descending artery and subsequent 300-min reperfusion. The animals were randomly assigned to receive vehicle, 3, or 10 microg/kg YT-146 or ischemic preconditioning (4 episodes of 5 min occlusion followed by 5 min of reperfusion). Blood pressure, heart rate, and regional myocardial blood flow throughout the experiment were measured, as was the myocardial infarct size after reperfusion. The infarct size of the vehicle-treated dog was 56.2% +/- 2.7% (n = 5), whereas that of 3 or 10 microg/kg YT-146-treated dog was smaller (ie, 29.5% +/- 8.7% or 20.2% +/- 7.0%, respectively; n = 5). The infarct size of the dog treated with 10 microg/kg YT-146 was reduced to a degree similar to that of the ischemic preconditioning (19.2% +/- 6.3%, n = 5). YT-146 at both doses elicited a dose-dependent increase in acute hyperemic coronary flow immediately after reperfusion. The cardioprotective effect may be attributed to the limitation of the infarct size, probably via A2-receptor-mediated coronary artery dilatation during the early period of reperfusion.


Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes which limit the binding of stress hormones to their receptors.
A mechanism of action for Panax ginseng (PG) and Eleutherococcus senticosus (ES) is proposed which explains how they could produce the paradoxical effect of sometimes increasing and sometimes decreasing the stress response. The mechanism suggests that this biphasic effect results from increased occupancy of positive and negative feedback stress hormone receptors by their natural ligands due to inhibition of specific enzymes which function to limit receptor occupancy. Specifically, it is suggested that PG inhibits 11-beta hydroxysteroid dehydrogenase one and ES inhibits catechol- O -methyl transferase, both of which reside in close proximity to stress hormone receptors and catalyse the degradation of stress hormones into inactive compounds. In addition, it is suggested that the increased energy said to result from PG and ES may be a consequence of their increasing the occupancy of stress hormone receptors which function to redistribute the body's energy reserves from regeneration to activity.


Small changes in ambient temperature affect alternative splicing in Arabidopsis thaliana.
Alternative splicing (AS) gives rise to multiple mRNA isoforms from the same gene, providing possibilities to regulate gene expression beyond the level of transcription. In a recent paper in Nucleic Acids Research we used a high resolution RT-PCR based panel to study changes in AS patterns in plants with altered levels of an hnRNP-like RNA-binding protein in Arabidopsis thaliana. Furthermore, we detected significant changes in AS patterns between different Arabidopsis ecotypes. Here we investigated how small changes in ambient temperature affect AS. We found significant changes in AS for 12 of 28 investigated events (43%) upon transfer of Arabidopsis plants from 20°C to 16°C and for 6 of the 28 investigated events (21%) upon transfer from 20°C to 24°C.


Contextual influences on animal decision-making: Significance for behavior-based wildlife conservation and management.
Survival and successful reproduction require animals to make critical decisions amidst a naturally dynamic environmental and social background (i.e. "context"). However, human activities have pervasively, and rapidly, extended contextual variation into evolutionarily novel territory, potentially rendering evolved animal decision-making mechanisms and strategies maladaptive. We suggest that explicitly focusing on animal decision-making (ADM), by integrating and applying findings from studies of sensory ecology, cognitive psychology, behavioral economics and eco-evolutionary strategies, may enhance our understanding of, and our ability to predict how, human-driven changes in the environment and population demography will influence animal populations. Fundamentally, the decisions animals make involve evolved mechanisms, and behaviors emerge from the combined action of sensory integration, cognitive mechanisms and strategic rules of thumb, and any of these processes may have a disproportionate influence on behavior. Although there is extensive literature exploring ADM, it generally reflects a canalized, discipline-specific approach that lacks a unified conceptual framework. As a result, there has been limited application of ADM theory and research findings into predictive models that can enhance management outcomes, even though it is likely that the relative resilience of species to rapid environmental change is fundamentally a result of how ADM is linked to contextual variation. Here, we focus on how context influences ADM, and highlight ideas and results that may be most applicable to conservation biology.


Nutritional requirements and antibiotic resistance patterns of Helicobacter species in chemically defined media.
The growth of the gastric pathogen Helicobacter pylori in the absence of serum remains challenging, and nutritional requirements have only partially been defined, while almost nothing is known about nutritional requirements of other Helicobacter spp. Although previous data showed that H. pylori grows in the chemically defined medium F-12, but not in other tissue culture media examined, the specific components responsible for growth were not entirely understood. Here we describe the optimization of amino acids, metals, and sodium chloride for H. pylori. Iron, zinc, and magnesium were critical for growth; copper was not required. Optimization of sodium chloride was further beneficial. Nutritional requirements and antibiotic resistance patterns of several other Helicobacter spp. revealed that all except H. felis grew in serum-free, unsupplemented F-12. All Helicobacter spp. were resistant to at least six antimicrobial agents when cultured in the presence of serum. However, in the absence of serum, H. pylori, H. mustelae, and H. muridarum became sensitive to polymyxin B and/or trimethoprim. Much of the data were obtained using a convenient ATP assay to quantify growth. H. pylori has surprisingly few absolute requirements for growth: 9 amino acids, sodium and potassium chloride, thiamine, iron, zinc, magnesium, hypoxanthine, and pyruvate. These data suggest that H. pylori and other Helicobacter spp. are not as fastidious as previously thought. The data also suggest that chemically defined media described herein could yield the growth of a wide range of Helicobacter spp., allowing a more detailed characterization of Helicobacter physiology and interactions with host cells.


The offset of the tibial shaft from the tibial plateau in Chinese people.
Long-stem tibial components are available for complex primary and revision total knee arthroplasties. Most of the stems' designs are based on anatomic data from Western populations. We conducted a morphologic study to determine the relationship of the tibial shaft to the tibial plateau in Chinese people. We included knees from fifty Chinese individuals (twenty-five females and twenty-five males) in this study. On magnetic resonance imaging scans of the tibial plateau and the proximal part of the tibial shaft of each lower limb, the distance between the axis of the tibial shaft and the center of the tibial plateau was measured and was defined as the offset of the tibial shaft from the tibial plateau at three resection levels: the first just distal to the subchondral bone of the medial tibial plateau, the second 5 mm distal to it, and the third 10 mm distal to it. The dimensions of the tibial plateau were measured as well. At the first, second, and third resection levels, the mean tibial shaft offsets (and standard deviations) from the center of the tibial plateau were, respectively, 7.23 + or - 2.44 mm (3.40 + or - 1.94 mm of mediolateral offset and 6.22 + or - 2.05 mm of anteroposterior offset), 6.33 + or - 2.26 mm (3.14 + or - 2.04 mm of mediolateral offset and 5.24 + or - 1.96 mm of anteroposterior offset), and 4.75 + or - 2.07 mm (2.68 + or - 1.91 mm of mediolateral offset and 3.46 + or - 2.03 mm of anteroposterior offset). At each resection level, the mean offset in the male group was significantly larger than that in the female group. There is a large variation in the offset of the tibial shaft from the tibial plateau in Chinese people. The axis of the tibial shaft is located anterolateral to the center of the tibial plateau in this population. The use of an anterolaterally offset tibial keel or stem seems more suitable for Chinese patients undergoing primary or revision total knee arthroplasty.


Coexpression of mammalian cytochrome P450 and reductase in Escherichia coli.
cDNAs for human cytochrome P450 2E1 and rat NADPH-cytochrome-P450 reductase were cloned separately and in tandem into bacterial expression vectors, and expression of the two proteins in Escherichia coli was monitored by immunoblotting, spectroscopy, and catalytic assays. The cDNAs were separated on the coexpression plasmid by 22 nucleotides, with the P450 cDNA preceding the reductase cDNA. P450 content in solubilized cell membranes, whether expressed alone or coexpressed with P450 reductase, was approximately 0.11 nmol/mg of protein, and approximately 0.8 nmol could be obtained per liter of culture. Reductase content was five- to sixfold greater than P450 content when coexpressed, but severalfold less than that obtained when expressed without the upstream P450 cDNA, indicating differences in both stability and translatability between the two proteins. Solubilized membranes from cells expressing both proteins catalyzed aniline hydroxylation, p-nitrophenol hydroxylation, and N-nitrosodimethylamine demethylation at rates equivalent to those obtained by combining P450 and reductase preparations; addition of purified reductase to these membranes did not augment the activity. However, in contrast to results obtained with P450 2E1 expressed in other heterologous systems, addition of rabbit liver cytochrome b5 to preparations catalyzing p-nitrophenol or N-nitrosodimethylamine oxidation did not increase turnover, and, although activity could be shown with unsolubilized membranes, oxidation of these substrates in vivo could not be demonstrated. Nonetheless, the ability to coexpress P450 and reductase in E. coli so as to generate a functional monooxygenase system in vitro enhances the utility of this organism for the expression and characterization of cloned P450 isoforms.


Understanding foot ulceration in patients with diabetes.
Foot ulceration is a complication that affects a significant proportion of the ever-increasing number of people with diabetes in the UK. Nurses caring for patients with diabetes are ideally placed to contribute to diabetic foot management through assessment, education and appropriate timely referral. This article examines how pathophysiological changes associated with diabetes and the demanding functional role of the foot predispose individuals to foot ulceration, how to assess and classify the diabetic foot and the principles of preventive and curative management.


SNAIL Transctiption factor in prostate cancer cells promotes neurite outgrowth.
Neurite outgrowth involves reciprocal signaling interactions between tumor cells and nerves where invading tumor cells have acquired the ability to respond to pro-invasive signals within the nerve environment. Neurite outgrowth could serve as a mechanism leading to invasion of cancer cells into the nerve sheath and subsequent metastasis. Snail transcription factor can promote migration and invasion of prostate cancer cells. We hypothesized that prostate cancer cell interaction with nerve cells will be mediated by Snail expression within prostate cancer cells. For this study we utilized various prostate cancer cell lines: C4-2 non-silencing (NS, control); C4-2 Snail shRNA, (stable Snail knockdown); LNCaP Neo (empty vector control) and LNCaP Snail (stably over-expressing Snail). Cancer cell adhesion and migration towards nerve cells (snF96.2 or NS20Y) was examined by co-culture assays. Conditioned media (CM) collected from C4-2 cells was cultured with nerve cells (PC-12 or NS20Y) for 48 h followed by qualitative or quantitative neurite outgrowth assay. Our results showed that cancer cells expressing high levels of Snail (LNCaP Snail/C4-2 NS) displayed significantly higher migration adherence to nerve cells, compared to cells with lower levels of Snail (LNCaP Neo/C4-2 Snail shRNA). Additionally, LNCaP Snail or C4-2 NS (Snail-high) CM led to a higher neurite outgrowth compared to the LNCaP Neo or C4-2 Snail shRNA (Snail-low). In conclusion, Snail promotes migration and adhesion to nerve cells, as well as neurite outgrowth via secretion of soluble factors. Therefore, targeting cancer cell interaction with nerves may contribute to halting prostate cancer progression/metastasis.


Transformation from non- to double-interpenetration in robust Cd(II) doubly-pillared-layered metal-organic frameworks.
Two known Cd(II) non-interpenetrated doubly-pillared metal organic frameworks are shown to undergo a change of degree of interpenetration upon loss of lattice solvent molecules to yield doubly-interpenetrated frameworks. The conversion is inferred from powder X-ray diffraction (PXRD) patterns and supported by additional evidence from single-crystal diffraction (SCD) data.


[Ultrasonographic examination of the hip joint region and bony pelvis in cattle].
Transcutaneous and transrectal ultrasonographic examination of the hip joint region and the pelvis was carried out in 7 cadavers, transcutaneous ultrasonography in 17 healthy young and adult cattle, and transrectal sonography was performed in 12 healthy cows in order to study the normal ultrasonographic appearance of these regions. 7.5 MHz linear-, 5.0 MHz and 3.5 MHz convex transducers and a 7.5 MHz rectal probe were used. The bone surfaces of the greater trochanter, the femoral neck and head, the acetabulum and the other pelvic bones were visualised as hyperechoic contours. The coxofemoral joint space was identified in all cadavers and live cattle. The joint pouch could not be visualised, neither in cadavers nor in live cattle. After experimental filling of the coxofemoral joint pouch by injection of 35-45 ml eosin-solution it appeared as a large anechoic zone between the articular surface and the echogenic joint capsule. The inner contours of the pelvic girdle, both iliosacral joint spaces, the abdominal aorta and the external iliac arteries were depicted clearly by transrectal ultrasonography. The practical application of diagnostic ultrasound in these regions is demonstrated in clinical patients suffering from a septic coxarthritis and a sequestration of a part of the tuber coxae following an open fracture. These results serve as reference data for ultrasonographic investigation of disorders of the hip joint and the pelvic region in cattle.


[THE ENVIRONMENT AND AUTOIMMUNE DISEASES].
The immune system carefully distinguishes between self and non-self-components. Therefore, any small deviation of this balanced function may result in an autoimmune activity and harm against self-antigens (autoantigens). The link between autoimmune diseases and various heredity and environmental factors has been discussed in numerous studies. The infectious factor is still considered to be the most important environmental factor leading to the development of autoimmune disease. Recent studies associated new environmental factors to autoimmunity, such as excessive salt consumption. In this paper, we summarize the relationship between environmental factors and autoimmune diseases covering innovations in this field.


The Association Between Handgrip Strength and Predialysis Serum Sodium Level in Patients With Chronic Kidney Disease Stage 5D.
Purpose: Handgrip strength (HGS) is a useful tool for the systematic assessment of muscle function related to nutritional status. Reduced HGS has been associated with adverse clinical outcomes in chronic kidney disease (CKD) stage 5D patients. In the same patients, predialysis low serum sodium (sNa) has been associated with malnutrition and mortality. Here, we investigated the role of predialysis sNa on muscle function in CKD-5D patients. Methods: We evaluated 45 patients on hemodialysis (HD) and 28 patients on peritoneal dialysis (PD) with HGS measurement, bioimpedance analysis, anthropometric measures, and malnutrition inflammation score (MIS). According to established diagnostic criteria, reduced HGS was defined as strength below 30 and 20 Kg in men and women, respectively. Predialysis sNa values were defined as the mean of all predialysis measurements during the preceding 6 months. Data analysis was performed separately for each of the HD and PD groups. Results: The proportions of reduced HGS did not differ between the HD (66%) and PD (54%) groups, respectively. Patients in the HD group as compared to those in the PD group had higher serum albumin and potassium and mid-arm muscle circumference and lower residual renal function (RRF) and residual urine volume. Multivariate logistic analysis, after controlling for muscle mass, nutritional biomarkers, MIS, fluid overload and RRF, showed that for every 1 mmol/l increase of sNa the odds of reduced HGS was decreased by 60% (OR = 0.40, 95% CI: 0.16-0.99) and 42% (OR = 0.58, 95% CI: 0.36-0.93) in HD and PD patients, respectively. However, stratified analysis indicated that lower sNa levels predicted reduced HGS in individuals with a background of malnutrition, inflammation, overhydration and less preserved RRF, representing unfavorable conditions strongly related to muscle wasting in the dialysis setting. Conclusions: Predialysis sNa is a strong and independent determinant of HGS, a reliable nutritional marker in CKD-5D stage patients. However, according to our findings, lower sNa levels appear to be a marker of underlying unfavorable conditions that are heavily associated with reduced HGS, rather than a causal determinant of reduced HGS. Whether optimizing sNa levels improves patient muscle performance requires further investigations.


Leukocyte antibodies and biologically active mediators in the pathogenesis of transfusion-related acute lung injury.
Transfusion-related acute lung injury (TRALI) is a clinical constellation of signs and symptoms associated with transfusion. In severe cases, the most prominent feature is acute onset of pulmonary edema. Two mechanisms have been advanced to explain pulmonary injury in this syndrome. One mechanism involves the presence of antibodies to white blood cells, usually in a transfused blood component. Interaction of antibodies, with white blood cells in the transfusion recipient, is hypothesized to cause cellular activation with release of cytokines resulting in pulmonary vascular endothelial damage and exudation of fluid across the pulmonary basement membrane. In the biologically active mediator mechanism, two events are hypothesized to cause TRALI. In the first event, polymorphonuclear cells become primed and pulmonary vascular endothelium becomes activated secondary to the production of biologically active mediators, as a result of physiologic stress. The second event is the infusion of biologically active mediators in a stored cellular blood product. The second event causes release of cellular activators with subsequent endothelial damage and exudation of fluid into the pulmonary alveoli.


Oxygen sensing with individual ZnO:Sb micro-wires: effects of temperature and light exposure on the sensitivity and stability.
Nanostructured ZnO has been widely investigated as a gas sensing material. Antimony is an important dopant for ZnO that catalyses its surface reactivity and thus strengthens its gas sensing capability. However, there are not enough studies on the gas sensing of antimony-doped ZnO single wires. We fabricated and characterized ZnO/ZnO:Sb core-shell micro-wires and demonstrated that individual wires are sensitive to oxygen gas flow. Temperature and light illumination strongly affect the oxygen gas sensitivity and stability of these individual wires. It was found that these micro- and nano-wire oxygen sensors at 200°C give the highest response to oxygen, yet a vanishingly small effect of light and temperature variations. The underlying physics and the interplay between these effects are discussed in terms of surface-adsorbed oxygen, oxygen vacancies and hydrogen doping.


[Advances in the studies of postmortem interval estimation by the levels of chemical components in human vitreous humor after death].
Estimation of postmortem interval (PMI) is one of the problems that need to be solved for forensic examination of the dead body. Accurate estimation of PMI has great values to criminal investigation and trial. The levels of chemical components in human vitreous humor are changed with time after death, which can help estimate the PMI. The levels of certain chemical components, such as potassium, magnesium, ammonia, urea, creatinine, uric acid, hypoxanthine, lactic acid and so on, in human vitreous humor will gradually increase with time after death, while others such as calcium, sodium, enzymes, glucose, vitamin C and so on will decrease. The updates and advances in those studies were reviewed in this article.


A set of X-ray test objects for image quality control in digital subtraction fluorography. I: Design considerations.
A set of X-ray test objects has been developed for quality control in digital subtraction fluorography (DSF). Factors which can be assessed include dynamic range, highlight overload and signal-to-noise ratio, low contrast sensitivity, unsharpness, and systematic misregistration. These test objects complement, both in design and calibration, those previously developed to evaluate the imaging performance of television fluoroscopy and small-format fluorography systems. In this article, the first of two, we describe the Leeds DSF test objects, paying particular attention to the reasoning behind their design.


[Fading spectrophotometric determination of heparin with brilliant cresyl blue].
A new fading spectrophotometric method for determining trace heparin is proposed in the present paper. In pH 3.0 Britton-Robinson (B-R) buffer solution, brilliant cresyl blue can react with heparin resulting in the decrease of absorbance of BCB at 592 nm. The conditions for the interaction were optimized, and the interferences of coexisting substances were investigated. Under the optimal conditions the reduction of the absorbance is proportional to the concentration of heparin in the range of 0.6-6.0 mg x L(-1) with the detection limit of 0.173 mg x L(-1). The molar absorptivity of the method was calculated to be 1.03 x 10(6) L x mol(-1) x cm(-1). The method has been applied to determine the heparin sodium injection solution with satisfactory results.


Supervised Quantum Learning without Measurements.
We propose a quantum machine learning algorithm for efficiently solving a class of problems encoded in quantum controlled unitary operations. The central physical mechanism of the protocol is the iteration of a quantum time-delayed equation that introduces feedback in the dynamics and eliminates the necessity of intermediate measurements. The performance of the quantum algorithm is analyzed by comparing the results obtained in numerical simulations with the outcome of classical machine learning methods for the same problem. The use of time-delayed equations enhances the toolbox of the field of quantum machine learning, which may enable unprecedented applications in quantum technologies.


Binding of phthalate plasticizers to human serum albumin in vitro: a multispectroscopic approach and molecular modeling.
As endocrine-disrupting chemicals, a few frequently used phthalate plasticizers were banned or restricted for use as additives in food in some countries. The interaction mechanisms between three phthalate plasticizers with human serum albumin (HSA) were studied by fluorescence (quenching, synchronous, and three-dimensional), UV-vis absorption, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy, in combination with molecular modeling under simulative physiological conditions, respectively. The results obtained from fluorescence quenching data revealed that the plasticizers-HSA interaction altered the conformational strcture of HSA. Meanwhile, the alterations of HSA secondary structure in the presence of phthalate plasticizers were investigated. The binding distances for the plasticizers-HSA system were provided by the efficiency of fluorescence resonance energy transfer. Furthermore, the thermodynamic analysis implied that hydrophobic forces were the main interaction for the plasticizers-HSA system, which agreed well with the results from the molecular modeling study.


Smoking and Radiolucent Periapical Lesions in Root Filled Teeth: Systematic Review and Meta-Analysis.
This systematic review and meta-analysis aimed to investigate the association between smoking habits and the prevalence of radiolucent periapical lesions (RPLs) in root-filled teeth (RFT). The Population, Intervention, Comparison, and Outcome (PICO) question was: in adult patients who have RFT, does the absence or presence of a smoking habit affect the prevalence of RPLs associated with RFT? Systematic MEDLINE/PubMed, Wiley Online Database, Web of Science, Scopus, and PRISMA protocol were used to evaluate and present the results. Studies comparing smokers with control non-smoker subjects, including RFT, and providing data on the prevalence of RFT with RPLs, were included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for certainty in the evidence. The risk of bias was assessed according to Cochrane Collaboration common scheme for bias and ROBINS-I tool. Cumulative meta-analysis was performed with a random effects model. PROSPERO registration code: CRD42020165279. Four studies reported data on inclusion criteria, representing data from 9257 root-filled teeth-4465 from non-smokers and 4792 from smoker patients. The meta-analysis provided an odds ratio indicating a significant association between smoking and higher prevalence of root filled teeth with radiolucent periapical lesions (OR = 1.16; 95% CI = 1.07-1.26; p = 0.0004). The certainty of the literature assessment was moderate per GRADE. The ROBINS-I tool classified three studies as low risk of bias, and the fourth as moderate risk of bias. Moderate, quality scientific evidence indicates a weak but significant relationship between smoking and the prevalence of RPLs in RFT. Smoking can be considered a negative prognostic factor for the outcome of root canal treatment. Endodontic providers should be aware of the relationship between smoking and persistent apical periodontitis, assessed as RPLs, in RFT.


Nutritional awareness of critically ill surgical high-dependency patients.
It has been recognized that malnutrition in hospital is a serious problem that may go undetected. There is growing evidence that early nutritional support in high-risk patients helps reduce postoperative complications; however, malnutrition is often diagnosed only once it is well established. This study showed that, both retrospectively and prospectively; there were no formal nutritional assessments of patients in a high-dependency unit (HDU), that time to feeding was generally within the recommended 5-7 day postoperative period, and that the most common form of supplementary feeding was total parenteral nutrition (TPN). Prospectively, the choice of supplementary feeding was dependent on the type of surgery and the individual patient's condition. Since this study was completed, a dietician has been allocated to the HDU and carries out formal nutritional assessments on a daily basis. Further research is required to assess the impact of the dietician on patient nutrition.


Prolidase activity in chronic wound and blister fluids.
We investigated prolidase activity in samples derived from wound fluid as well as blister fluid. Prolidase activity was elevated in fluid samples collected from wounds over the levels in sera collected from patients with chronic wounds (P < 0.05). Prolidase activity was also present in samples taken from blister diseases. However, prolidase activity in blister fluid was not higher than that in sera collected from patients with blister diseases. Our results indicate that prolidase may play a role in wound healing.


Interaction of mianserin and some hypotensive drugs in Wistar rats.
Mianserin is thought to exert little effect on the cardiovascular system. In fact its safety in comparison with tricyclic drugs is high. Various experiments gave varying results as for the influence of the drug on arterial blood pressure in people and animals. Therefore, a study was undertaken in Wistar rats to evaluate interactions of mianserin administered intraperitoneally as a single dose, and for 21 days with 3 hypotensive drugs showing different mechanism of action (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood pressure was measured with a LETICA apparatus. The results of the study revealed that administration of mianserin in normotensive rats leads to a short-term decrease in blood pressure and significantly enhanced the hypotensive effect of prazosine. Repeated doses of mianserin lead to a temporary increase in blood pressure after 2 weeks of administration. Single and repeated administration of mianserin did not change the hypotensive effect of propranolol and enalapril. Three-week therapy with mianserin significantly enhanced the hypotensive effect of prazosine.


Heparin alters the expression of different forms of immunoglobulin mu heavy chains and their associated proteins by pre-B cell lines and normal Ly-1 (CD5+) B cells.
Studies presented here show that heparin alters immunoglobulin expression by murine pre-B cell lines and normal Ly-1 (CD5+) B cells. Previous studies have shown that pre-B cell lines 70Z/3 and NFS-5.3 express mu heavy chains in the cytoplasm and a small amount on the cell surface. Both these cytoplasmic and surface mu are disulfide-linked to omega (lambda 5) surrogate light chains and are noncovalently associated with iota (Vpre-B) variable region-like proteins. We show that culturing 70Z/3 with heparin reduces the amount of the membrane-form mu (micron) on the cell surface. Culturing NFS-5.3 with heparin similarly decreases the membrane-form mu; however, it increases the surface level of a pentameric mu molecule containing secreted-form mu (microS) heavy chains, disulfide-linked omega (lambda 5) chains, and noncovalently associated proteins. Culturing peritoneal B cells with heparin also increases the production of the secreted-form microS, detectable in this case by the secretion of classical pentameric IgM. Similarly, injecting heparin intraperitoneally increases IgM secretion by peritoneal Ly-1 B cells. Thus heparin could influence pre-B cell and B cell differentiation and function.


Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment.
Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Aβ42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Aβ42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas.


[Treatment of burns in infants].
Because of the potential severity of their residual deformities, burn injuries in infants justify an early management in specialized centres when they cover more than 5% of body surface and in every case when hands, face, or external genitalia are concerned. Cooling with cold water is the first aid treatment to be performed as early as possible after the injury. The treatment in specialized centres must be both general and surgical. General treatment includes fluid and electrolyte therapy, temperature control, appropriate nutrition and pain suppression. Pain suppression is a major part of the treatment and morphine must be largely used. Surgical treatment starts as soon as the patient arrives in the centre and is eventually performed under general anesthesia: all the burned areas are covered with occlusive dressings. Infections are prevented by systematic cultures and adjusted antibiotic therapy. A vigorous rehabilitation program must be instituted as soon as possible: massages, compressive clothes, splints, physical therapy, plastic surgery. Primary prevention by sustained parental education is important in order to reduce the frequency of burn injuries in infants.


Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1.
Interleukin-10 (IL-10) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 (Th2) phenotype. Part of this process involves the prevention of the development of Th1 cells, which are a primary source of interferon gamma (IFNgamma), a potent activator of monocytes and an inhibitor of Th2 proliferation. Because monocytes and macrophages are important mediators of Th1-type responses, such as delayed-type hypersensitivity, we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells. Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFNgamma or IFNalpha. IL-10 preincubation resulted in the inhibition of gene expression for several IFN-induced genes, such as IP-10, ISG54, and intercellular adhesion molecule-1. The reduction in gene expression resulted from the ability of IL-10 to suppress IFN-induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFNalpha- and IFNgamma-inducible genes. This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1, a component of both IFNalpha- and IFNgamma-induced DNA binding complexes. Therefore, IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFNalpha and IFNgamma in monocytes by suppressing the tyrosine phosphorylation of STAT1. This may occur through the ability of IL-10 to induce expression of the gene, suppressor of cytokine signaling 3 (SOCS3).


Relationship between Helicobacter pylori infection and gastrointestinal microecology.
The prevalence of Helicobacter pylori (H. pylori) infection has exceeded 50% worldwide, and it is considered a high-risk factor for chronic gastritis, peptic ulcer, gastric adenocarcinoma, gastroesophageal reflux disease and functional dyspepsia. H. pylori drug resistance is a common problem worldwide. In recent years, the relationship between H. pylori infection and gastrointestinal microecology has received much attention. H. pylori infection changes the structure and composition of gastrointestinal microflora by regulating the gastrointestinal microecological environment, local pH value, cytokines and antimicrobial peptides, and immune response and then plays a crucial role in the occurrence and development of digestive system tumors, liver metabolism and extragastrointestinal diseases. The quadruple strategy of H. pylori eradication can also aggravate gastrointestinal microflora disorder. However, probiotics can reduce intestinal flora changes and imbalances through different mechanisms, thus enhancing the efficacy of H. pylori eradication therapy and reducing adverse reactions caused by eradication therapy. Therefore, this paper reviews the relationship between H. pylori infection and gastrointestinal microecology and its clinical application, providing a basis for clinical treatment.


The Effects of Nutritional Interventions on the Cognitive Development of Preschool-Age Children: A Systematic Review.
The developing human brain requires all essential nutrients to form and to maintain its structure. Infant and child cognitive development is dependent on adequate nutrition. Children who do not receive sufficient nutrition are at high risk of exhibiting impaired cognitive skills. This systematic review aimed to examine the effects of nutritional interventions on cognitive outcomes of preschool-age children. PubMed, PsycInfo, Academic Search Complete, and Cochrane Library electronic databases were searched to identify Randomized Controlled Trials (RCTs) published after the year 2000. Studies assessing the effects of food-based, single, and multiple micronutrient interventions on the cognition of nourished and undernourished children aged 2-6 years were deemed eligible. A total of 12 trials were identified. Eight out of the twelve studies found significant positive effects on cognitive outcomes. Iron and multiple-micronutrients supplementation yield improvements in the cognitive abilities of undernourished preschool-age children. Increased fish consumption was found to have a beneficial effect in the cognitive outcomes of nourished children. On the other hand, B-vitamin, iodized salt, and guava powder interventions failed to display significant results. Findings of this review highlight the importance of adequate nutrition during preschool years, and the crucial role sufficient nutrition plays in cognitive development.


Survival following orbital exenteration at a tertiary brazilian hospital.
to analyze the epidemiology, clinical features and survival rate of patients undergoing orbital exenteration (OE) in a tertiary referral hospital. we conducted a retrospective study of all patients undergoing OE at the Hospital das Clínicas, FMUSP between January 2007 and December 2012. We collected data records related to gender, age, origin, length of stay, duration of the disease, other treatments related to the disease, number of procedures outside of the face related to the disease, follow-up and histological diagnosis. we treated 37 patients in the study period. The average survival in one year was 70%, in two years, 66.1%, and 58.3% in three years. There was no significant difference in the one-year survival related to histological diagnosis (p=0.15), days of hospitalization (p=0.17), gender (p=0.43), origin (p=0.78), disease duration (p=0.27) or the number of operations for the tumor (p=0.31). Mortality was higher in elderly patients (p=0.02). The average years of life lost was 33.9 in patients under 60 years, 14.7 in patients in the 61-80 years range and 11.3 in patients over 80 years. the present series of cases is significant in terms of prevalence of orbital exenteration; on the other hand, it shows one of the lowest survival rates in the literature. This suggests an urgent need for improved health care conditions to prevent deforming, radical resections.


Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro.
Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation.


THE GORDON WILSON LECTURE: THE HEPATITIS C VIRUS: FROM HIPPOCRATES TO CURE.
The modern age of viral hepatitis began in the early 1960s with the serendipitous discovery of the Australia antigen, a protein that was later shown to represent the envelope of the hepatitis B virus leading to its designation as the hepatitis B surface antigen. This was the first marker for any hepatitis virus and became not only a diagnostic assay, but also a mandatory blood donor screening test and the basis for the first generation hepatitis B vaccine. Prospective studies of transfusion recipients then showed that hepatitis B virus accounted for only 25% of cases of post-transfusion hepatitis (PTH). Discovery of the hepatitis A virus in 1975 revealed that none of the non-B PTH cases were due to hepatitis A virus infection resulting in the designation of this predominant form of PTH as non-A, non-B hepatitis. Using pedigreed patient samples and the chimp model, it was shown even before the advent of molecular biology that the non-A, non-B agent was small and lipid enveloped suggesting it might be a flavivirus. This was confirmed when the agent was cloned by Houghton and colleagues at the Chiron Corporation in 1987 and renamed the hepatitis C virus (HCV). In 1990 a donor screening assay for HCV was introduced nationwide and by 1997 PTH had virtually disappeared with rates now mathematically estimated to be one case per 2 million transfusions, compared to a 30% incidence before 1970. Clinical and molecular studies of HCV have shown that it results in persistent infection in 75% to 85% of cases due to its high replication rate, its existence as a quasispecies with a high mutation rate and the ability of HCV proteins to blunt and ultimately exhaust the HCV immune response. Although HCV infection is clinically and histologically mild in most patients, it can lead to progressive fibrosis over the course of decades in 30% to 40% and culminate in cirrhosis and end-stage liver disease. HCV can also cause hepatocellular carcinoma, generally on the background of cirrhosis with an incidence of 1% to 3% per year in this setting. After 2 decades of difficult and prolonged treatments with interferon-based regimens that resulted in cure rates of less than 50%, successive generations of HCV specific direct-acting antivirals were introduced that now result in cure rates of 95% to 100% across all genotypes after only 8 to 12 weeks of nontoxic oral therapy. This unprecedented efficacy has led to speculation that HCV infection might be eradicated even in the absence of a vaccine, but there are many impediments to global eradication including ascertainment of silent carriers, access to medication, and high drug cost. Nonetheless, we are in a new era of HCV control and optimism abounds.


Stability and electronic properties of hybrid SnO bilayers: SnO/graphene and SnO/BN.
Van der Waals structures based on two-dimensional materials have been considered as promising structures for novel nanoscale electronic devices. Two-dimensional SnO films which display intrinsic p-type semiconducting properties were fabricated recently. In this paper, we consider vertically stacked heterostructures consisting of a SnO monolayer with graphene or a BN monolayer to investigate their stability, electronic and transport properties using density functional theory. The calculated results find that the properties of the constituent monolayers are retained in these SnO-based heterostructures, and a p-type Schottky barrier is formed in the SnO/graphene heterostructure. Additionally, the Schottky barrier can be effectively controlled with an external electric field, which is useful characteristic for the van der Waals heterostructure-based electronic devices. In the SnO/BN heterostructure, the electronic properties of SnO are least affected by the insulating monolayer suggesting that the BN monolayer would be an ideal substrate for SnO-based nanoscale devices.


A hyperventilation theory of job stress and musculoskeletal disorders.
There is evidence of a link between job stress and upper extremity work-related musculoskeletal disorders. However, the biobehavioral mechanisms by which psychosocial stress factors contribute to the development of musculoskeletal disorders are uncertain. Based on established principles of breathing and job stress and the relevant empirical literatures, a hyperventilation theory of job stress and work-related musculoskeletal disorders was developed. Hyperventilation (overbreathing) refers to a drop in arterial CO2 caused by ventilation that exceeds metabolic demands for O2. Excessive loss of CO2 (increase in rate of flow of CO2 from cells to longs) that results from hyperventilation produces a rise in blood pH (i.e., respiratory alkalosis). This disruption in the acid-base equilibrium triggers a chain of systemic physiological reactions that have adverse implications for musculoskeletal health, including increased muscle tension, muscle spasm, amplified response to catecholamines, and muscle ischemia and hypoxia. Hyperventilation is often characterized by a shift from a diaphragmatic to a thoracic breathing pattern, which imposes biomechanical stress on the neck/shoulder region due to the ancillary recruitment of sternocelidomastoid, scalene, and trapezius muscles in support of thoraci breathing. A hyperventilation theory provides an innovative framework for understanding how job stress contributes to pathophysiological processes that increase the risk of work-related musculoskeletal disorders. With respect to the control of these disorders, a hyperventilation theory has important implications for establishing effective work organization interventions and individual stress-management methods. In this regard, breathing is a biobehavioral metric for assessing whether psychosocial aspects of work organization are in balance with a worker's needs and resources. A hyperventilation theory also provides a unique rationale for coping with job stress and musculoskeletal discomfort through breathing training, light physical exercise, and rest breaks.


Hydrolytic decarboxylation of carboxylic acids and the formation of protonated carbonic acid.
Acid-catalyzed decarboxylation reactions of carboxylic acids should avoid formation of protonated carbon dioxide, a very high energy species. A potential alternative route parallels ester hydrolysis, with addition of water to the carboxyl group followed by protonation of the unsaturated leaving group and formation of protonated carbonic acid, a species that had been predicted to be a viable reaction intermediate. The hydrolytic mechanism for the decarboxylation of pyrrole-2-carboxylic acid is consistent with observed (12)C/(13)C kinetic isotope effects (1.010 +/- 0.001 at H(0) = -0.01 and 1.043 +/- 0.001 at H(0) = -2.6), solvent kinetic isotope effects (k(H(2))(O)/k(D(2))(O) = 2 at H(0) = 0.9; k(H(2))(O)/k(D(2))(O) = 1 at H(0) = -2.9), and activation parameters [DeltaH() = 23.5 kcal.mol(-1) and DeltaS() = 5.5 cal.deg(-1).mol(-1) at H(0) = -2.9]. Thus, the specific route for a decarboxylation process is a consequence of the nature of the potential carbanion (or its conjugate acid), the acidity of the medium and avoidance of formation of protonated carbon dioxide.


Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport.
Vertebrate hemoglobin (Hb) and myoglobin (Mb) were among the first proteins whose structures and sequences were determined over 50 years ago. In the subsequent pregenomic period, numerous related proteins came to light in plants, invertebrates and bacteria, that shared the myoglobin fold, a signature sequence motif characteristic of a 3-on-3 α-helical sandwich. Concomitantly, eukaryote and bacterial globins with a truncated 2-on-2 α-helical fold were discovered. Genomic information over the last 20 years has dramatically expanded the list of known globins, demonstrating their existence in a limited number of archaeal genomes, a majority of bacterial genomes and an overwhelming majority of eukaryote genomes. In vertebrates, 6 additional globin types were identified, namely neuroglobin (Ngb), cytoglobin (Cygb), globin E (GbE), globin X (GbX), globin Y (GbY) and androglobin (Adgb). Furthermore, functions beyond the familiar oxygen transport and storage have been discovered within the vertebrate globin family, including NO metabolism, peroxidase activity, scavenging of free radicals, and signaling functions. The extension of the knowledge on globin functions suggests that the original roles of bacterial globins must have been enzymatic, involved in defense against NO toxicity, and perhaps also as sensors of O2, regulating taxis away or towards high O2 concentrations. In this review, we aimed to discuss the evolution and remarkable functional diversity of vertebrate globins with particular focus on the variety of non-canonical expression sites of mammalian globins and their according impressive variability of atypical functions.


Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase.
The opposing actions of glucagon and insulin on glucose metabolism within the liver are essential mechanisms for maintaining plasma glucose concentrations within narrow limits. Less well studied are the counterregulatory actions of glucagon on protein metabolism. In the present study, the effect of glucagon on amino acid-induced signaling through the mammalian target of rapamycin (mTOR), an important controller of the mRNA binding step in translation initiation, was examined using the perfused rat liver as an experimental model. The results show that amino acids enhance signaling through mTOR resulting in phosphorylation of eukaryotic initiation factor 4E-binding protein (4E-BP)1, the 70-kDa ribosomal protein (rp)S6 kinase, S6K1, and rpS6. In contrast, glucagon repressed both basal and amino acid-induced signaling through mTOR, as assessed by changes in the phosphorylation of 4E-BP1 and S6K1. The repression was associated with the activation of protein kinase A and enhanced phosphorylation of LKB1 and the AMP-activated protein kinase (AMPK). Surprisingly, the phosphorylation of two S6K1 substrates, rpS6 and eukaryotic initiation factor 4B, was not repressed but instead was increased by glucagon treatment, regardless of the amino acid concentration. The latter finding could be explained by the glucagon-induced phosphorylation of the ERK1 and the 90-kDa rpS6 kinase p90(rsk). Thus, glucagon represses phosphorylation of 4E-BP1 and S6K1 through the activation of a protein kinase A-LKB-AMPK-mTOR signaling pathway, while simultaneously enhancing phosphorylation of other downstream effectors of mTOR through the activation of the extracellular signal-regulated protein kinase 1-p90(rsk) signaling pathway. Amino acids also enhance AMPK phosphorylation, although to a lesser extent than glucagon and amino acids combined.


Subcellular localization and characterization of amylases in Arabidopsis leaf.
Amylolytic enzymes of Arabidopsis leaf tissue were partially purified and characterized. Endoamylase, starch phosphorylase, d-enzyme (transglycosylase), and possibly exoamylase were found in the chloroplasts. Endoamylase, fraction A2, found only in the chloroplast, was resolved from the exoamylases by chromatography on a Mono Q column and migrated with an R(F) of 0.44 on 7% polyacrylamide gel electrophoresis. Exoamylase fraction, A1, has an R(F) of 0.23 on the polyacrylamide gel. Viscometric analysis showed that A1 has a slope of 0.013, which is same as that of A3, the extrachloroplastic amylase. A1, however, can be distinguished from A3 by having much higher amylolytic activity in succinate buffer than acetate buffer, and having much less reactivity with amylose. A1 probably is also localized in the chloroplast, and contributes to the 30 to 40% higher amylolytic activity of the chloroplast preparation in succinate than acetate buffer at pH 6.0. The high activity of d-enzyme compared to the amylolytic activity in the chloroplast suggests that transglycosylation probably has an important role during starch degradation in Arabidopsis leaf. Extrachloroplastic amylase, A3, has an R(F) of 0.55 on 7% electrophoretic gel and constitutes 80% of the total leaf amylolytic activity. The results of substrate specificity studies, action pattern and viscometric analyses indicate that the extrachloroplastic amylases are exolytic.


The prognostic significance of early and late anaemia in acute coronary syndrome.
Anaemia in acute coronary syndrome (ACS) is a common and strong independent risk factor but it is unknown whether early anaemia is transient or whether it persists over the subsequent weeks. We also sought to evaluate whether late anaemia carries the similar prognostic significance as baseline anaemia. Another unknown is whether haemoglobin improves risk stratification over and above the GRACE score. Haemoglobin levels were prospectively measured in 448 consecutive patients presenting with ACS and at 7-weeks follow-up. Cardiovascular endpoints were defined as death or acute myocardial infarction (AMI) over a median duration of 30 months (range 1-50). The prevalence of anaemia on admission was 20% and this increased to 40% at 7-weeks follow-up. New anaemia occurred in 31% of patients. Baseline anaemia predicted CV endpoints independent of the admission GRACE (Global Registry of Acute Coronary Events) score [adjusted RR 2.54 (95% CI 1.73-3.71)]. Anaemia at 7-weeks follow-up was also a strong predictor of adverse outcomes [adjusted RR 1.67 (95% CI 1.04-2.69)]. Patients with persistent anaemia at 7 weeks were at an increased risk of death or AMI compared to those with persistently normal haemoglobin [unadjusted RR 3.58 (95% CI 2.04-6.29)]. In ACS, the prevalence of anaemia doubles from admission to 7-weeks follow-up (40%). Not only did baseline anaemia predict long-term prognosis independent of the admission GRACE score, but haemoglobin at 7-weeks post-ACS was also a simple independent predictor of adverse prognosis.


Pulmonary interstitial emphysema in adults: a clinicopathologic study of 53 lung explants.
Pulmonary interstitial emphysema (PIE) is an unusual condition wherein air dissects through alveolar walls into the adjacent interstitial tissues where it forms cystic spaces with an associated inflammatory reaction. It is well described in premature infants with respiratory distress syndrome and is observed in adults, usually in association with ventilator use. The fibrotic and inflammatory appearance may mimic normal anatomic structures as well as pathologic changes such as granulomatous disease, organizing pneumonia, fibroblast foci of usual interstitial pneumonia, or lymphangiectasia. The presence of interstitial emphysema has not been well characterized in the adult population. We retrospectively reviewed 53 consecutive explanted lungs for the histologic presence of PIE, of which 19 (36%) cases were found to be positive. PIE was seen most commonly in patients with usual interstitial pneumonia. Review of the medical record for each patient revealed no correlation between the presence of PIE and duration of disease. A correlation was seen between prior ventilation and/or biopsy. These findings may indicate that PIE is a result of medical intervention; however, in the remainder of cases the disease process itself may have been a contributing factor.


2,3,4,7,8-pentachlorodibenzofuran is a more potent cytochrome P4501A inducer than 2,3,7,8-tetrachlorodibenzo-p-dioxin in herring gull hepatocyte cultures.
Concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) on cytochrome P4501A (CYP1A) induction were determined in primary cultures of embryonic herring gull (Larus argentatus) hepatocytes exposed for 24 h. Based on the concentration that induced 50% of the maximal response (EC50), the relative potencies of TCDD and TCDF did not differ by more than 3.5-fold. However, also based on the EC50, PeCDF was 40-fold, 21-fold, and 9.8-fold more potent for inducing ethoxyresorufin-O-deethylase (EROD) activity, CYP1A4 mRNA expression, and CYP1A5 mRNA expression than TCDD, respectively. The relative CYP1A-inducing potencies of PeCDF and of other dioxin-like chemicals (DLCs) in herring gull hepatocytes (HEH RePs), along with data on concentrations of DLCs in Great Lakes herring gull eggs, were used to calculate World Health Organization toxic equivalent (WHO-TEQ) concentrations and herring gull embryonic hepatocyte toxic equivalent (HEH-TEQ) concentrations. The analysis indicated that, when using avian toxic equivalency factors (TEFs) recommended by the WHO, the relative contribution of TCDD (1.1-10.2%) to total WHO-TEQ concentration was higher than that of PeCDF (1.7-2.9%). These results differ from the relative contribution of TCDD and PeCDF when HEH RePs were used; PeCDF was a major contributor (36.5-52.9%) to total HEH-TEQ concentrations, whereas the contribution by TCDD (1.2-10.3%) was less than that of PeCDF. The WHO TEFs for avian species were largely derived from studies with the domestic chicken (Gallus gallus domesticus). The findings of the present study suggest that it is necessary to determine the relative potencies of DLCs in wild birds and to re-evaluate their relative contributions to the biochemical and toxic effects previously reported in herring gulls and other avian species.