Genomic organization, transcription, splicing and gene regulation in Leishmania.
The parasitic protozoan Leishmania is the aetiological agent of a spectrum of clinical diseases, ranging from disfiguring skin lesions to life-threatening visceral infection, and is a serious health problem in tropical and subtropical areas world-wide. Leishmania parasites undergo a dramatic transformation as they move between the different environments of an extracellular insect stage and an intracellular form in the vertebrate host. In an attempt to develop new strategies for the treatment of leishmaniasis, the techniques of molecular genetics have been utilised to elucidate the mechanisms which direct and control this cyclical differentiation. This review discusses current knowledge concerning the organization and regulation of the Leishmania nuclear genome and includes a discussion of chromosomal organization, genomic arrangement, transcription, transcript processing by trans-splicing and polyadenylation, and post-transcriptional regulation. The salient features as well as the supporting evidence for each topic are briefly reviewed.


Causes of bloody stools in neonates: a case series report.
Bloody stools in a neonate may stand for a spectrum of conditions ranging from benign to life-threatening. It is critical to detect the cases that have significant underlying pathology, especially those which require urgent surgical intervention. Previous studies always focused on one particular disease related to bloody stools in neonates, or the study only involved a small number of cases. This study aimed to investigate the common causes of bloody stools in neonates. This retrospective cohort study included the neonates admitted to our institution due to "bloody stools" over a 5-year period. We compared the differences among patients' characteristics, feeding choice, underlying diseases, and operation rate between preterm and term neonates. A total of 300 patients were included, accounting for 1.1% of the total neonatal admissions. The overall rate of exclusive breastfeeding was 28.0%. The most common underlying causes for bloody stools were: cow's milk protein allergy (CMPA, 53.3%), swallowed blood syndrome (10.0%), viral enteritis (9.7%), necrotizing enterocolitis (NEC) > stage II (8.3%), non-specific enteritis (7.3%), and anal fissure (5.0%). The median [interquartile range (IQR)] onset age for bloody stools for all infants was 12 [3-22] days after birth. Preterm neonates had a lower rate of exclusive breastfeeding (P=0.844), higher incidence of NEC > stage II (P=0.014), later bloody stools onset age (P<0.001), and longer length of hospital stay than term neonates (P<0.001). For neonates with NEC, those with bottle-fed had an earlier onset age for bloody stools than those with breast-fed (P=0.027). Only 1.7% (n=5) required surgery (2 stage III NEC, 1 post-NEC stricture, and 2 volvuli). Survival at hospital discharge was 100%. Bloody stools in neonates is generally a benign, self-limiting disorder, not related to surgical conditions. The overall operation rate among neonates with bloody stools was only 1.7%. CMPA and NEC were the most common underlying non-surgical and surgical diseases, respectively, for neonates with bloody stools. Feeding choice is related to bloody stools in neonates, policies and strategies to support breastfeeding should be strengthened in the future.


Hexacoordinate oxy-globin models Fe(Por)(NH3)(O2) react with NO to form only the nitrato analogs Fe(Por)(NH3)(η1-ONO2), even at ~100 K.
The oxy-globin models Fe(Por)(NH(3))(O(2)), prepared by sequential reactions of O(2) ((18)O(2)) and NH(3) with thin porous layers of Fe(II)(Por), react with NO ((15)NO) at 80-100 K to form only the low-spin nitrato complexes Fe(Por)(NH(3))(η(1)-ONO(2)), thus implying that peroxynitrite intermediates, if formed, must undergo very facile isomerization to the nitrato analog.


Locating previously unknown patterns in data-mining results: a dual data- and knowledge-mining method.
Data mining can be utilized to automate analysis of substantial amounts of data produced in many organizations. However, data mining produces large numbers of rules and patterns, many of which are not useful. Existing methods for pruning uninteresting patterns have only begun to automate the knowledge acquisition step (which is required for subjective measures of interestingness), hence leaving a serious bottleneck. In this paper we propose a method for automatically acquiring knowledge to shorten the pattern list by locating the novel and interesting ones. The dual-mining method is based on automatically comparing the strength of patterns mined from a database with the strength of equivalent patterns mined from a relevant knowledgebase. When these two estimates of pattern strength do not match, a high "surprise score" is assigned to the pattern, identifying the pattern as potentially interesting. The surprise score captures the degree of novelty or interestingness of the mined pattern. In addition, we show how to compute p values for each surprise score, thus filtering out noise and attaching statistical significance. We have implemented the dual-mining method using scripts written in Perl and R. We applied the method to a large patient database and a biomedical literature citation knowledgebase. The system estimated association scores for 50,000 patterns, composed of disease entities and lab results, by querying the database and the knowledgebase. It then computed the surprise scores by comparing the pairs of association scores. Finally, the system estimated statistical significance of the scores. The dual-mining method eliminates more than 90% of patterns with strong associations, thus identifying them as uninteresting. We found that the pruning of patterns using the surprise score matched the biomedical evidence in the 100 cases that were examined by hand. The method automates the acquisition of knowledge, thus reducing dependence on the knowledge elicited from human expert, which is usually a rate-limiting step.


Crystal structures of penicillin-binding protein 6 from Escherichia coli.
Penicillin-binding protein 6 (PBP6) is one of the two main DD-carboxypeptidases in Escherichia coli, which are implicated in maturation of bacterial cell wall and formation of cell shape. Here, we report the first X-ray crystal structures of PBP6, capturing its apo state (2.1 A), an acyl-enzyme intermediate with the antibiotic ampicillin (1.8 A), and for the first time for a PBP, a preacylation complex (a "Michaelis complex", determined at 1.8 A) with a peptidoglycan substrate fragment containing the full pentapeptide, NAM-(L-Ala-D-isoGlu-L-Lys-D-Ala-D-Ala). These structures illuminate the molecular interactions essential for ligand recognition and catalysis by DD-carboxypeptidases, and suggest a coupling of conformational flexibility of active site loops to the reaction coordinate. The substrate fragment complex structure, in particular, provides templates for models of cell wall recognition by PBPs, as well as substantiating evidence for the molecular mimicry by beta-lactam antibiotics of the peptidoglycan acyl-D-Ala-D-Ala moiety.


Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study.
To evaluate the association between consumption of ultra-processed foods and all cause mortality. Prospective cohort study. Seguimiento Universidad de Navarra (SUN) cohort of university graduates, Spain 1999-2018. 19 899 participants (12 113 women and 7786 men) aged 20-91 years followed-up every two years between December 1999 and February 2014 for food and drink consumption, classified according to the degree of processing by the NOVA classification, and evaluated through a validated 136 item food frequency questionnaire. Association between consumption of energy adjusted ultra-processed foods categorised into quarters (low, low-medium, medium-high, and high consumption) and all cause mortality, using multivariable Cox proportional hazard models. 335 deaths occurred during 200 432 persons years of follow-up. Participants in the highest quarter (high consumption) of ultra-processed foods consumption had a higher hazard for all cause mortality compared with those in the lowest quarter (multivariable adjusted hazard ratio 1.62, 95% confidence interval 1.13 to 2.33) with a significant dose-response relation (P for linear trend=0.005). For each additional serving of ultra-processed foods, all cause mortality relatively increased by 18% (adjusted hazard ratio 1.18, 95% confidence interval 1.05 to 1.33). A higher consumption of ultra-processed foods (>4 servings daily) was independently associated with a 62% relatively increased hazard for all cause mortality. For each additional serving of ultra-processed food, all cause mortality increased by 18%. ClinicalTrials.gov NCT02669602.


Quantities and associations of lead, zinc, cadmium, manganese, chromium, nickel, vanadium, and copper in fresh Mississippi delta alluvium and New Orleans alluvial soils.
The topic of this study is the effect of anthropogenic metals on the geochemical quality of urban soils. This is accomplished by comparing the metal contents and associations between two alluvial soils of the lower Mississippi River Delta, freshly deposited alluvial parent materials and alluvial soils collected from a nearby urban environment. Fresh alluvium samples (n = 97) were collected from the Bonnet Carré Spillway. The urban alluvial soil samples (n = 4026) were collected from New Orleans and stratified by census tracts (n = 286). The Spillway samples tend to have less Pb and Zn than generally noted for the baseline of natural soils. Except for Mn and V, Spillway alluvium contains significantly less metal than urban soils. For Spillway samples, the median metal content (in microg g(-1)) is 4.7 Pb, 11.1 Zn, 0.7 Cd, 164 Mn, 0.8 Cr, 3.9 Ni, 3.2 V, and 3.9 Cu. For urban soils, the median metal content (in microg g(-1)) is 120 Pb, 130 Zn, 3.2 Cd, 138 Mn, 2.1 Cr, 9.8 Ni, 3.8 V, and 12.7 Cu. Metal associations also differ between Spillway alluvium and urban alluvial soils. Fresh alluvium correlation coefficients between individual metals vary from 0.87 to 0.99 (P < 10(-13)) except for Cr which ranges from 0.57 to 0.68 (P < 10(-7)). The urban soil correlation coefficients for metals and the index value are 0.40-0.98. In urban soils, Pb, Zn, Cr, and Cu are dominant metals and highly associated, with a correlation coefficient ranging from 0.83 to 0.98 (P < 10(-25)). Their strong association justifies the use of GIS to map the integrated soil metal index (sum of the medians of metals by census tract) of New Orleans. Although also positively correlated (0.40-0.68, P < 10(-10)), Cd, Mn, Ni and V differ in their distribution in the city compared to Pb, Zn, Cr and Cu. Overall, significantly higher metal values occur in the inner city and lower values occur in outlying areas. The human health impact of the mixture of metals is not well understood. This study provides empirical data about the mixture and distribution of metals in New Orleans alluvial soils. Given common technical development, especially of traffic flows in cities, similar patterns of soil metals are expected for all US cities and probably international cities as well. Primary prevention of urban metal accumulations is necessary to enhance and sustain the development of urban culture.


Expression of ADAMTS-7 in myocardial dystrophy associated with white muscle disease in lambs.
The aim of the present study was to investigate the role of ADAMTS-7 gene in the pathogenesis of myocardial dystrophy associated with white muscle disease (WMD) in lambs. A total of 217 cardiac tissue samples from lambs with WMD were used in the study. Histopathological sections of the samples were stained with hematoxylin-eosin (HE) and examined using Western-blot, real-time PCR (RT-PCR) and immunohistochemistry for ADAMTS-7 gene expression, and the findings were statistically evaluated. Histopathological examinations revealed fibrosis associated with hyalinization, necrosis and granular calcifications in cardiomyocytes. Western blot and RT-PCR showed a statistically significant upregulation of ADAMTS-7 (p<0.05) (p<0.05). Immunohistochemical analyses showed that immunopositive cell numbers significantly high for ADAMTS-7 (p<0.05). The study has revealed that ADAMTS-7 gene is significantly expressed in myocardial dystrophy associated with WMD in addition to its role in the pathogenesis of this disease.


Managed long-term care: care integration through care coordination.
The New York State managed long-term care demonstration program combines traditional home, community, and institutional long-term care services with other benefits integral to maximizing overall well-being for a frail elderly population. A distinguishing feature of the model is the responsibility to coordinate both covered and noncovered services. This article, a case study of VNS CHOICE, a managed long-term care plan that serves 2,500 New York City residents, describes the program's operating structure, service delivery model, and care management strategies. By providing a capitated Medicaid long-term care benefit, VNS CHOICE can utilize a broad array of services, offer significant flexibility to care management staff, and support member and family involvement in care planning. Its broad care coordination responsibility allows it to achieve integrated care without integrated financing.


Effects of recombinant tumor necrosis factor-alpha on cultured microvascular endothelial cells derived from human dermis.
We investigated the effects of recombinant human tumor necrosis factor-alpha (TNF) on cell proliferation and on expression of MHC class II antigens and intercellular adhesion molecule ICAM-1 in human dermal microvascular endothelial cells (HDMEC) derived from human foreskin. Second-passage HDMEC were treated with 0.1-10,000 U/ml TNF for up to 6 d, and cell growth was assessed by cell counts and a recently developed fluorogenic assay using 4-methylumbelliferyl heptanoate as a substrate. APAAP immunocytochemistry was performed using monoclonal antibodies against HLA-DR, HLA-DQ, and ICAM-1. TNF did not markedly inhibit the growth of HDMEC but induced expression of HLA-DR (1,000 U/ml and more) and of ICAM-1 (1 U/ml and more). Combination with interferon-gamma led to synergistic ICAM-1 induction. These results demonstrate a profound effect of TNF on the activation of dermal microvascular endothelial cells and suggest a major role of TNF in the mediation of leucocyte adhesion to endothelial cells of the skin microvasculature with possible implications for the initiation and maintenance of inflammatory skin processes.


Gaming Behaviors and the Association with Sleep Duration, Social Jetlag, and Difficulties Falling Asleep among Norwegian Adolescents.
The relationship between gaming and sleep is mostly informed by studies of addictive gaming behavior, thus limiting our understanding of sleep in the context of nonproblematic engaged gaming. The present study investigated whether addicted, problem, and engaged gaming behavior was associated with sleep duration, social jetlag, and difficulties falling asleep. The sample consisted of 13- and 16-year-old Norwegian adolescents (n = 3228) participating in the Health Behavior in School-Aged Children (HBSC) survey in 2018. Participants were categorized into addicted, problem, engaged, and normal/non-gaming behavior groups according to which GAS-7 criteria they fulfilled. Robust generalized linear mixed models with a random intercept for class ID were used to examine the association between the sleep variables and gaming behavior. Addicted gaming behavior was unfavorably associated with all sleep parameters. The findings for engaged gaming and problem gaming behavior were somewhat mixed. Engaged gamers slept less on weekends, less on weekdays for those aged 16, and experienced greater social jetlag compared to the normal/non-gaming group. Problem gamers experienced greater social jetlag and had higher odds of experiencing difficulties falling asleep. Overall, the results suggest that all types of gaming behaviors might harm sleep health, but to a greater extent for the addicted gamers.


A comparison of alternative strategies for choosing control populations in observational studies.
Various approaches have been used to select control groups in observational studies: (1) from within the intervention area; (2) from a convenience sample, or randomly chosen areas; (3) from areas matched on area-level characteristics; and (4) nationally. The consequences of the decision are rarely assessed but, as we show, it can have complex impacts on confounding at both the area and individual levels. We began by reanalyzing data collected for an evaluation of a rapid response service on rates of unplanned hospital admission. Balance on observed individual-level variables was better with external than local controls, after matching. Further, when important prognostic variables were omitted from the matching algorithm, imbalances on those variables were also minimized using external controls. Treatment effects varied markedly depending on the choice of control area, but in the case study the variation was minimal after adjusting for the characteristics of areas. We used simulations to assess relative bias and means-squared error, as this could not be done in the case study. A particular feature of the simulations was unexplained variation in the outcome between areas. We found that the likely impact of unexplained variation for hospital admissions dwarfed the benefits of better balance on individual-level variables, leading us to prefer local controls in this instance. In other scenarios, in which there was less unexplained variation in the outcome between areas, bias and mean-squared error were optimized using external controls. We identify some general considerations relevant to the choice of control population in observational studies.


Cerebellar liponeurocytoma--a case report.
Cerebellar liponeurocytomas have been included in the 2000 classification of tumours of the central nervous system, under the heading of glioneuronal tumours. The tumour has two populations of cells- one composed of cells with morphology of neurocytes and the other are lipidised cells which look like mature fat cells. The tumour occurs in adults and has a good prognosis. Less than fifteen cases have been reported in world literature. We report a case of this rare tumour entity in a 32 years old female patient.


Sentinel lymph node mapping in early stage of endometrial and cervical cancers.
The sentinel lymph node (SLN) is defined as the first chain node in the lymphatic basin that receives primary lymphatic flow. If the SLN is negative for metastatic disease, then other nodes are expected to be disease-free. SLN techniques have been extensively applied in the staging and treatment of many tumors, including melanoma, breast and vulvar cancers. This study aims to evaluate our technique in SLN mapping in early stage endometrial and cervical cancers. We scheduled a cross-sectional pilot study for patients undergoing staging surgery for endometrial and cervical cancer from November 2012 to February 2014 in Beheshti and Sadoughi Hospitals. Our SLN mapping technique included 1 h preoperative or intraoperative injection of 4 ml of 1% methylene blue dye in the tumor site. At the time of surgery, blue lymph nodes were removed and labeled as SLNs. Then systematic lymph node dissection was completed, and all of the nodes were sent for pathologic examination concerning metastatic involvement. All of the sentinel nodes were first stained with hematoxylin and eosin and examined. Those negative in this study were then stained with immunohistochemistry using anti-keratin antibody. Descriptive statistics, sensitivity, negative predictive values (NPV), false negative (FN) and detection rates were calculated. Twenty-three patients including 62% endometrial and 38% cervical cancers enrolled in the study. Median of SLN count in the endometrial and cervical cancers was 3 and 2, respectively. Among endometrial and cervical cancers, detection rate of metastatic disease was 80% and 87.5%, respectively. The FN rate for this technique was 0 and the sensitivity and NPV are 100% for both endometrial and cervical cancers. Considering the lower risk of metastases in early stage of both endometrial and cervical cancers, SLN technique allows for confident and accurate staging of cancer.


KNOWLEDGE OF CERUMEN AND EFFECT OF EAR SELF-CLEANING AMONG HEALTH WORKERS IN A TERTIARY HOSPITAL.
Ear wax lubricates, cleans and protects the external auditory canal while ear self-cleaning can lead to ear infections, trauma and perforation of the tympanic membrane. An erroneous understanding of these facts can lead to wrong practices with grievous consequences. To assess the knowledge on ear wax and the effects of ear self-cleaning among health workers in Nigeria. A cross-sectional study was done on health workers in a tertiary hospital in Nigeria with administration of structured questionnaire. Knowledge of the participants on the effect of ear self-cleaning were classified as poor, fair or good based on the calculation of their knowledge score. Out of 150 respondents, 10.7% of them had good knowledge of ear wax and the health effects of self-ear cleaning while 51.3% had poor knowledge. There was strong association between knowledge score and occupation (x2=24.113, P=0.007), while there was no association between knowledge score and practice of ear self-cleaning. Most respondents had poor knowledge of the function of ear wax and the damage to the auditory canal associated with ear self-cleaning. There is thus, the need for public enlightenment on the complications of the practice.


Nasotracheal intubation for head and neck surgery.
Nasotracheal intubation offers the head and neck surgeon more scope for surgical manoeuvre in operations of the mouth, pharynx, larynx and also the neck. Concern over the complications of using this route of intubation and lack of training may be limiting its use. A thorough knowledge of the anatomy, benefits of using nasal vasoconstrictors and attention to technique are prerequisites to maintaining the skill. This article reviews each of these topics and aims to encourage the appropriate use of nasotracheal intubation in current practice.


Differential gene expression in apoptotic 32Dcl3 cells: induction of metallothionein.
Growth factor deprivation induced cell death of the hematopoietic cell line 32Dcl3 is widely used as a model system to study apoptotic signalling pathways. Here we show that the onset of cell death after IL-3 withdrawal can be strongly delayed by either cycloheximide or actinomycin D, indicating that de novo protein synthesis is required. Subtractive cDNA library hybridization was used to identify genes upregulated in apoptotic 32Dcl3 cells. Here we present data showing metallothionein-I (MT-I) mRNA transiently upregulated by a factor of three- to 20-fold. Increased levels of total MT-I+II protein after IL-3 withdrawal were demonstrated. An induction of MT-I RNA as well as of MT-I+II total protein was also observed in serum deprived NIH3T3 fibroblasts. Testing the effect of different inducers of apoptosis on 32Dcl3 cells we found that only IL-3 withdrawal and ethanol treatment led to an upregulation of MT-I mRNA level. Since MTs are believed to play a role in the metabolism of zinc, we tested the effect of zinc on induced cell death. When 32Dcl3 cells are treated with zinc (50-300 microM) in the absence of IL-3, loss of viability as well as degradation of the cellular DNA were delayed, indicating that zinc represses apoptosis. On the other hand zinc pre-treatment induced MT expression and accelerated the onset of apoptosis. Our data, therefore, suggest that MT exerts a proapoptotic function.


Photoreceptors in primitive chordates: fine structure, hyperpolarizing receptor potentials, and evolution.
Two species of primitive chordates have hyperpolarizing photoreceptor potentials, as vertebrates do. In Salpa the photoreceptive membrane is composed of microvilli, whereas in Amaroucium it is modified from cilia. There appears to be no functional correlation between fine structure of photoreceptive membrane and polarity of response to light.


The Formation and Displacement of Ordered DNA Triplexes in Self-Assembled Three-Dimensional DNA Crystals.
Reconfigurable structures engineered through DNA hybridization and self-assembly offer both structural and dynamic applications in nanotechnology. Here, we have demonstrated that strand displacement of triplex-forming oligonucleotides (TFOs) can be translated to a robust macroscopic DNA crystal by coloring the crystals with covalently attached fluorescent dyes. We show that three different types of triplex strand displacement are feasible within the DNA crystals and the bound TFOs can be removed and/or replaced by (a) changing the pH from 5 to 7, (b) the addition of the Watson-Crick complement to a TFO containing a short toehold, and (c) the addition of a longer TFO that uses the duplex edge as a toehold. We have also proved by X-ray diffraction that the structure of the crystals remains as designed in the presence of the TFOs.


Mesh cage reconstruction with autologous cancellous graft in anterior cervical discectomy and fusion.
Retrospective case series. To present the technique and results of anterior cervical discectomy and fusion (ACDF) by using mesh cage reconstruction with autologous cancellous bone graft. Since the initial ACDF description by Bailey and Badgley, a variety of grafting techniques have been proposed. The primary disadvantage of autologous bone grafting is donor site pain when compared with allograft. However, autologous bone graft still remains the standard and cancellous bone retrieval through a cortical window minimizes subperiosteal stripping. This may improve donor site morbidity while providing the advantages of autologous bone graft. Thirty-seven patients who had undergone ACDF with cancellous bone graft by using mesh cages and anterior plating with at least 6 months follow-up were reviewed. All patients had autologous cancellous bone graft harvested through a cortical window with limited subperiosteal striping. Bone graft was then packed into and around a titanium mesh cage that furnishes structural support. The principal diagnosis was radiculopathy in 30 patients, myeloradiculopathy in 2 patients, instability in 3 patients, and kyphosis in 2 patients. Sixty-four levels were fused: one 4-level fusion, eight 3-level fusions, eight 2-level fusions, and twenty 1-level fusions. All patients demonstrated improved neurologic function and resolution of preoperative pain postoperatively. The donor site for cancellous bone was the iliac crest in 33 patients and the manubrium in 4 patients. Perioperative donor site pain was absent in 35 of 38 patients by 6 weeks with resolution of donor site pain by 3 months in all patients. At most recent follow-up, no patients had donor site pain, no instrumentation failure, and no wound complications. Sixty-three of 64 (98.4%) of cervical segments fused. One pseudoarthrosis occurred in an attempted 4-level fusion, which fused after a second operation. Autologous bone grafting with mesh cage reconstruction is an acceptable alternative to autologous tricortical structural graft or allograft with reduced donor site pain and excellent biologic arthrodesis.


Adoption of an Internet-based patient education programme in psychiatric hospitals.
Internet-based patient support systems are widely assumed to predict a future trend in patient education. Coherent information is still lacking on how patient education is adopted in psychiatric hospitals and how information technology is used in it. Our aim was to describe nurses' adoption of an Internet-based patient education programme and the variables explaining it. The study was based on Rogers' model of the diffusion of innovation. The Internet-based patient education sessions were carried out by nurses on nine acute psychiatric inpatient wards in two Finnish hospitals. They were evaluated with reports and analysed statistically. Out of 100 nurses, 83 adopted the programme during the study period. The nurses fell into Rogers' groups, late majority (72%), laggards (17%), early majority (7%), early adopters (3%) and innovators (1%). Three groups were formed according to their activity: laggards, late majority, adopters (including early majority, early adopters, innovators). There was a statistical difference between the nurses' programme adoption between the two hospitals (P= 0.045): more laggards (65% vs. 35%) and adopters (73% vs. 27%) in the same hospital. The findings help to provide insight into the contexts and settings when adopting information technology programmes in the area of mental health care.


The gut virome in inflammatory bowel disease pathogenesis: From metagenomics to novel therapeutic approaches.
The association of intestinal dysbiosis with the pathogenesis of inflammatory bowel disease has been well established. Besides bacteria, microbiota comprises yeasts, archaea, protists and viruses, neglected actors in inflammatory bowel disease-associated microbiota. In the past, a great limitation in studying microbiota composition was the low sensitivity of sequencing technologies and that few computational approaches were sufficient to thoroughly analyse the whole microbiome. However, new cutting-edge technologies in nucleic acid sequencing, -omics analysis and the innovative statistics and bioinformatics pipelines made possible more sensitive and accurate metagenomics, ultimately identifying novel players in intestinal inflammation, including prokaryotic and eukaryotic viruses, that together form the gut virome. The discovery of peculiar inflammatory bowel disease-associated microbial strains will not only shed new light on inflammatory bowel disease aetiogenesis, they may also support the development of novel therapeutic strategies not merely treating symptoms, but precisely counteracting the primary cause of chronic intestinal inflammation.


Impairment of cardiac neuronal function in childhood dilated cardiomyopathy: an 123I-MIBG scintigraphic study.
Abnormalities of norepinephrine uptake have been found to reflect impairment of cardiac adrenergic neuronal function in adults with heart failure. To our knowledge, no data on childhood dilated cardiomyopathy (DCM) are available. The aim of this study was to assess the cardiac neuronal function using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in children with idiopathic DCM. We studied 26 patients (mean age, 44+/-50 mo) with DCM and left ventricular dysfunction and 12 control subjects (mean age, 49+/-65 mo) with normal left ventricular function. All subjects underwent planar cardiac imaging after intravenous injection of 20-75 MBq 123I-MIBG. A static anterior view was acquired 4 h after injection. The heart-to-mediastinum count ratio was measured as described previously. On the basis of a reduction of the heart-to-mediastinum count ratio, cardiac neuronal uptake of 123I-MIBG was significantly decreased in patients with DCM compared with cardiac uptake in control subjects (172%+/-34% versus 277%+/-14%; P<0.0001). A significant correlation was found between left ventricular ejection fraction and 123I-MIBG cardiac uptake in patients with DCM (y = 2.5x + 113.3; r = 0.80; P<0.0001). Cardiac adrenergic neuronal function is impaired in children with idiopathic DCM. 1231-MIBG cardiac scintigraphy is a useful tool to assess cardiac neuronal function in childhood DCM.


DNA damage and reticular stress in cytotoxicity and oncotic cell death of MCF-7 cells treated with fluopsin C.
Fluopsin C is an antibiotic compound derived from secondary metabolism of different microorganisms, which possesses antitumor, antibacterial, and antifungal activity. Related to fluopsin C antiproliferative activity, the aim of this study was to examine the following parameters: cytotoxicity, genotoxicity, cell cycle arrest, cell death induction (apoptosis), mitochondrial membrane potential (MMP), colony formation, and mRNA expression of genes involved in adaptive stress responses and cellular death utilizing a monolayer. In addition, a three-dimensional cell culture was used to evaluate the effects on growth of tumor spheroids. Fluopsin C was cytotoxic (1) producing cell division arrest in the G1 phase, (2) elevating expression of mRNA of the CDKN1A gene and (3) decrease in expression of mRNA H2AFX gene. Further, fluopsin C enhanced DNA damage as evidenced by increased expression of mRNA of GADD45A and GPX1 genes, indicating that reactive oxygen species (ROS) may be involved in the observed genotoxic response. Reticulum stress was also detected as noted from activation of the ribonuclease inositol-requiring protein 1 (IRE1) pathway, since a rise in mRNA expression of the ERN1 and TRAF2 genes was observed. During the cell death process, an increase in mRNA expression of the BBC3 gene was noted, indicating participation of this antibiotic in oncotic (ischemic) cell death. Data thus demonstrated for the first time that fluopsin C interferes with the volume of tumor spheroids, in order to attenuate their growth. Our findings show that fluopsin C modulates essential molecular processes in response to stress and cell death.


Carbamylated erythropoietin ameliorates the metabolic stress induced in vivo by severe chronic hypoxia.
Ischemia and chronic hypoxia (CH) trigger a variety of adverse effects arising from metabolic stress that injures cells. In response to reduced O2, hypoxia-inducible factor 1alpha (HIF-1alpha) activates erythropoietin (Epo) as well as many other target genes that counteract the effects of O2 deficiency. Epo produced by the kidney stimulates erythrocyte production, leading to decreased HIF-1alpha production by improved tissue O2 delivery. However, Epo is produced by many other tissues, and it is currently unclear to what extent, if any, locally produced Epo modulates HIF-1alpha expression. Derivatives of Epo that possess tissue-protective activities but do not stimulate erythropoiesis [e.g., carbamylated Epo (CEpo)] are useful tools with which to determine whether exogenous Epo modulates HIF-1alpha in the absence of changes in hemoglobin concentration. We compared the effects of CH (6.5% O2 for 10 days) with or without CEpo administered by daily s.c. injection (10 microg/kg of body weight). CEpo administration did not alter the survival rate, weight loss, or increased hemoglobin concentration associated with CH. Therefore, CEpo does not directly suppress HIF-mediated erythropoiesis. CEpo does, however, prevent CH-induced neuronal increases of HIF-1alpha and Epo receptor-associated immunoreactivity (a measure of stress) while reducing the apoptotic index. In contrast, the myocardium did not exhibit increased HIF-1alpha expression during CH, although CEpo did reduce the apoptotic index. These observations therefore demonstrate that CEpo administration reduces the metabolic stress caused by severe CH, resulting in improved cellular survival independent of erythrocyte production.


Three-dimensional lanthanide(III)-copper(II) compounds based on an unsymmetrical 2-pyridylphosphonate ligand: an experimental and theoretical study.
Based on an unsymmetrical 2-pyridylphosphonate ligand, two types of Ln(III)-Cu(II) compounds with three-dimensional structures were obtained under hydrothermal conditions, namely, Ln(2)Cu(3)(C(5)H(4)NPO(3))(6).4H(2)O (1.Ln; Ln=La, Ce, Pr, Nd) and Ln(2)Cu(3)(C(5)H(4)NPO(3))(6) (2.Ln; Ln=Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho). Compounds 1.Ln are isostructural and crystallize in chiral cubic space group I2(1)3. In these structures, each Ln ion is nine-coordinate and has a tricapped triprismatic geometry, while each Cu center is six-coordinate with an octahedral environment. The {LnO(9)} polyhedra and {CuN(2)O(4)} octahedra are connected by edge sharing to form an inorganic open framework structure with a 3-connected 10-gon (10,3) topology in which the Ln and Cu atoms are alternately linked by the phosphonate oxygen atoms. Compounds 2.Ln are isostructural and crystallize in trigonal space group R3. In these structures, the {LnO(6)} octahedra are triply bridged by the {CPO(3)} tetrahedra by corner sharing to form an infinite chain along the c axis. Each chain is connected to its six equivalents through corner sharing of {CPO(3)} tetrahedra and {CuN(2)O(2)} planes to form a three-dimensional framework structure in which the Ln and Cu atoms are linked purely by O-P-O units. The formation of these two types of structures is rationalized by quantum chemical calculations, which showed that both the lanthanide contraction and the electron configuration of Cu(II) play important roles. When Cu(II) was replaced by Zn(II), only the first type of compounds resulted. The magnetic properties of complexes 1.Ln and 2.Ln were investigated. The nature of Ln(III)-Cu(II) (Ln=Ce, Pr, Nd) interactions is illustrated by comparison with their Ln(III)-Zn(II) analogues.


Superiority of traditional village diet and lifestyle in minimizing cardiovascular disease risk in Papua New Guineans.
In the traditional society of Papua New Guinea (PNG) atherosclerotic cardiovascular diseases (CVD) are rare. However, among the urban population reports of cases of atheroma-related CVD are increasing. The purpose of this study was therefore to compare the CVD risk factors in a homogeneous population of the Southern Highlands Province living in both rural and urban areas differing only in their diet and lifestyle. A total of 221 Samberigi people over the age of 25 years were selected for the survey. These included 123 individuals from remote villages of Samberigi and 98 of their relatives who had lived in Port Moresby city continuously for a minimum of 5 years. The anthropometric measurements, blood lipid, blood glucose and glycosylated haemoglobin (HbA1c) levels were measured and compared. The rural diets were mainly of vegetarian type, limited in variety and low in fat and protein content. In the urban subjects, the typical meal comprised refined foods with high fat and protein content. The urban men and women had significantly (p < 0.05) greater body weight, body mass index (BMI), and waist and hip circumferences than their rural counterparts. In Port Moresby, 57% of the men and 67% of the women were overweight or obese compared to 28% of their rural counterparts. Similarly, the mean plasma total cholesterol, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), fasting blood glucose and HbA1c were significantly higher in the urban group. However, no significant differences were demonstrated for waist to hip ratio, LDLC/HDLC ratio and lipoprotein (a) levels between the two groups. The total cholesterol, LDLC and HbA1c were positively associated with age and BMI in both rural and urban locations. In conclusion, there were significant increases in CVD risk factors in the urban population compared to the rural residents. This was predominantly due to the adoption of a western lifestyle and diet as people moved from rural villages to the city of Port Moresby.


Waardenburg Syndrome type 1: A case report.
Waardenburg Syndrome (WS) is a rare hereditary disorder that is characterized by the clinical manifestations of oculocutaneous anomalies of pigmentation, congenital deafness, dystopia canthorum, and broad nasal root. It demonstrates both genetically and clinically heterogenous characteristics. In this article, we report an 11-month-old boy with WS1, one of four clinicat types of WS. He exhibited white forelock, hypopigmented macules and patches, heterochromia irides, and dystopia canthorum.


Inhibition of collagenolytic cathepsins by beta-lactoglobulin in milk and its suppressive effect on bone resorption.
It is well known that the collagenolytic cathepsins play an important role in the degradation of bone matrix. Therefore, the purpose of this study was to clarify the prevention effect of bone resorption by milk components. Using double-layer reverse zymography, we found a 20 kDa protein in milk which inhibited cysteine proteases. This inhibitory protein was identified as beta-lactoglobulin B. The inhibitory activity of beta-lactoglobulin B against cathepsin K was stronger than that of beta-lactoglobulin A. Beta-lactoglobulin B specifically inhibited papain type cysteine proteases such as cathepsins K and L, but not serine proteases, aspartic proteases or metallo proteases. Beta-lactoglobulin B inhibited cathepsin K non-competitively and the Ki value was 10(-5) M. The formation of osteoclastic pits in the culture system was effectively inhibited by 10(-4)-10(-5) M beta-lactoglobulin B in vitro. Furthermore, we demonstrated that beta-lactoglobulin B inhibited degradation of type I-collagen by collagenolytic cathepsins. Using the everted-sac method in rat small intestines, it was found that beta-lactoglobulin was more easily absorbed from the intestines of young rats (5 wk-old) than from those of older rats (more than 20 wk-old). The digested products of beta-lactoglobulin B with lysyl-endopeptidase showed a similar inhibitory activity against cathepsin K to the intact beta-lactoglobulin B did. Therefore, peroral intake of beta-lactoglobulin in milk and its digested peptides are expected to help protect osteoclastic bone resorption via inhibition of collagenolytic cathepsins K and L.


Heat Tolerance in Curraleiro Pe-Duro, Pantaneiro and Nelore Cattle Using Thermographic Images.
The objective of this study was to compare physiological and thermographic responses to heat stress in three breeds of cattle. Fifteen animals of each of the Nelore, Pantaneiro and Curraleiro Pe-Duro breeds, of approximately two years of age, were evaluated. Heart and respiratory rates, rectal and surface temperature of animals as well as soil temperature were recorded at 8:30 and 15:30 on six days. Variance, correlation, principal factors and canonical analyses were carried out. There were significant differences in the rectal temperature, heart and respiratory rate between breeds (p < 0.001). Nelore and Pantaneiro breeds had the highest rectal temperatures and the lowest respiratory rate (p < 0.001). Breed was also significant for surface temperatures (p < 0.05) showing that this factor significantly affected the response of the animal to heat tolerance in different ways. The Curraleiro Pe-Duro breed had the lowest surface temperatures independent of the period evaluated, with fewer animals that suffered with the climatic conditions, so this may be considered the best adapted when heat challenged under the experimental conditions. Thermography data showed a good correlation with the physiological indexes, and body area, neck and rump were the main points.


Heterogeneity of so-called neuroendocrine lung tumors.
The diagnosis of neuroendocrine (NE) lung tumor is dependent on a number of observations: organoid structure, dense core granules, and various molecular components, including chromogranin A, neurosecretory enolase, synaptophysin, neural cell adhesion molecules, and others. None of these is specific for lung tumors. The Kulchitsky cell, which has these characteristics, forms a carcinoid, which exemplifies the NE tumor. It is euploid, has few mitoses, no necrosis and a 5- to 10-year survival of over 90%. When carcinoids show malignant characteristics, i.e., increased mitoses and necrosis, they have been labeled atypical and have a survival of 50%. Because all other non-small cell lung tumors, especially large cell tumors, may show one or more of these things because of the inherent heterogeneity of lung tumors, the term NE has been applied to them without real evidence that this affects survival with or without chemotherapy. This is expensive and without clinical significance.


Bilateral cardiac sympathetic denervation for refractory arrhythmia in an individual with catecholaminergic polymorphic ventricular tachycardia associated with T-cell-mediated ganglionitis.
The individual in our case was troubled with difficult to control arrhythmia in the context of RYR2-mutation positive catecholaminergic polymorphic ventricular tachycardia (CPVT) despite medication. Recurrent implantable cardioverter defibrillator (ICD) shocks occurred for ventricular tachycardia (VT) and ventricular fibrillation (VF) as well as inappropriate shocks as a result of rapidly conducted atrial fibrillation (AF). Catheter ablation was effective in controlling these episodes of AF. Despite left cardiac sympathetic denervation, episodes of ventricular arrhythmia and subsequent ICD shocks persisted. Contralateral sympathetic cardiac denervation was subsequently undertaken, with histology suggesting T-cell mediated ganglionitis. 18 months on, there have been no further episodes of ventricular arrhythmia.


Phylogenetic analysis of isolates of Pasteurella pneumotropica from laboratory animals based on the gyrB gene sequence.
Phylogenetic analysis using the gyrB sequence was performed to investigate the genetic relevance among 49 isolates of P. pneumotropica. In the phylogeny, the isolates were clearly classified into three groups as follows: group A for the isolates of biotype Jawetz derived from mice, group B for the isolates of biotype Jawetz derived from rats, and group C for the isolates of biotype Heyl. These results suggest that the gyrB sequence of P. pneumotropica differs between the isolates of two biotypes, and also between the isolates derived from mice and rats in the biotype Jawetz.


Effects of Gelatin Hydrolysates Addition on Technological Properties and Lipid Oxidation of Cooked Sausage.
This study investigated the impacts of gelatin hydrolysate addition on the technological properties and lipid oxidation stability of cooked sausage. Gelatin hydrolysate was prepared from pork and duck skin gelatin, through stepwise hydrolysis using collagenase and pepsin. The cooked sausages were formulated without gelatin (control) or with 1% pork skin gelatin, 1% duck skin gelatin, 1% pork skin gelatin hydrolysate, and 1% duck skin gelatin hydrolysate. The pH, color characteristics, protein solubility, cooking loss, and textural properties of cooked sausages were evaluated, and the 2-thiobarbituric acid reactive substances (TBARS) value was measured weekly to determine lipid oxidation stability during 4 wk of refrigerated storage. Enzymatic hydrolysis of gelatin decreased protein content and CIE L* but increased redness and yellowness (p<0.05). When 1% gelatin or gelatin hydrolysate was incorporated in cooked sausage, however, little to no impacts on pH value, moisture content, protein content, color characteristics, protein solubility, and cooking loss were found (p>0.05). The addition of 1% duck skin gelatin hydrolysate increased the cohesiveness and chewiness of cooked sausages. The inclusion of 1% duck skin gelatin accelerated lipid oxidation of cooked sausages during refrigerated storage (p<0.05), whereas duck skin gelatin hydrolysate caused a lower TBARS value in cooked sausage compared to duck skin gelatin. The results show comparable effects of gelatin and gelatin hydrolysate addition on the technological properties of cooked sausages; however, the oxidative stability of raw materials for gelatin extraction should be evaluated clearly in further studies.


Organophosphate exposures in the United States: a longitudinal analysis of incidents reported to poison centers.
The implementation of the Food Quality Protection Act of 1996 resulted in a decision by the U.S. Environmental Protection Agency to phase out and eliminate the use of organophosphate insecticides in residential environments. The phase-out and cancellation process began in the year 2000 and was complete in 2005. The purpose of this investigation was to utilize national Poison Control Center data to assess whether the risk mitigation decision had an impact on the number of incident cases involving organophosphates in the United States. Organophosphate exposure incident data were extracted from Annual Reports of the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) for the years 1995 to 2004. The number of organophosphate exposure incidents peaked at 20,135 in 1997, and declined in each subsequent year. A statistically significant decrease was observed in the average annual number of organophosphate exposure incidents when comparing data from the time periods before (1995-1999) and after (2000-2004) the commencement of the phase-out process. The decrease in organophosphate incident cases was observed for all age categories, as well as for the circumstances surrounding the exposure (unintentional and intentional exposure incidents). TESS data showed a significant decrease in incident cases involving organophosphates in association with the phase-out from residential uses. The results of this investigation are consistent with other studies that have reported that regulatory restriction of access to pesticide formulations may have a significant impact on the number of human exposure incidents.


Pilot study of sexual dysfunction following abdominal aortic aneurysm surgery.
The complication of sexual dysfunction as a quality of life (QoL) component after abdominal aortic aneurysm (AAA) surgery in men is poorly studied. To investigate the prevalence of sexual dysfunction and to highlight the importance of discussing this issue with patients undergoing AAA repair. The self-reported sexual dysfunction prevalence pre- and postoperatively, the effects on sexual QoL, and the postoperative Sexual Health Inventory for Men (SHIM) scores. Between April 1999 and July 2002, a questionnaire-based study, including the SHIM, was conducted on male patients 1-2 years after their elective open (EO) and rupture open (RO) or endovascular repair (EVAR) AAA repair. Demographics, risk factors for sexual dysfunction, sexual history, and postoperative sexual QoL data were obtained. Out of 142 alive male patients surveyed, 56 (40%) patients responded (26 EO, 21 EVAR, and 9 RO repair). The mean age was 69, 73, and 70 years, respectively, and 65%, 66%, and 66%, respectively, admitted to be sexually active postoperatively. The self-reported sexual dysfunction prevalence preoperatively was 27% (EO), 63% (EVAR), and 45% (RO); and postoperatively was 58%, 76%, and 67%, respectively. Detection using SHIM was higher at 70%, 95%, and 78%, respectively. There was a significantly greater increase in the postoperative prevalence of sexual dysfunction in the EO group than in the EVAR group (P < 0.05, chi(2)). The sexual QoL was worsened postoperatively in all groups: 53% (EO), 75% (EVAR), and 50% (RO); but only one-third of EO and EVAR patients, and none in RO patients, would seek treatment for their sexual dysfunction. There was a negative impact on the sexual QoL in all groups after surgery, and a significantly higher proportion of patients experienced deterioration in sexual QoL following EO surgical repair. Our results demonstrate the need for a prospective study.


Cbl PYXXM motifs activate the P85 subunit of phosphatidylinositol 3-kinase, Crk, atypical protein kinase C, and glucose transport during thiazolidinedione action in 3T3/L1 and human adipocytes.
The thiazolidinedione (TZD), rosiglitazone, has previously been found to tyrosine-phosphorylate Cbl and activate Cbl-dependent phosphatidylinositol (PI) 3-kinase and atypical protein kinase Cs (aPKCs) while stimulating glucose transport in 3T3/L1 adipocytes. Presently, the role of Cbl in rosiglitazone action was further assessed in both 3T3/L1 and human adipocytes by expressing Y371F and/or Y731F mutant forms of Cbl that nullified the functionality of canonical pYXXM motifs in Cbl. These mutants diminished the interaction of Cbl with the p85 subunit of PI 3-kinase and inhibited subsequent increases in Cbl-dependent PI 3-kinase activity, aPKC activity, and glucose transport. These mutants also inhibited the interaction of Cbl with Crk, which has been implicated in the activation of other PI 3-kinase-independent signaling factors that have been found to be required during activation of glucose transport by insulin and other agonists. We conclude that pYXXM motifs in Cbl serve to activate PI 3-kinase-dependent and possibly PI 3-kinase-independent pathways that are required for TZD-dependent glucose transport in adipocytes.


[Operative findings and therapeutic results in patients with primary hyperparathyroidism].
In the period from 1976 to September 1982 39 patients with the clinical diagnosis of primary hyperparathyroidism were operated on. Among then were 24 women and 14 men. The most frequent manifestation form is the renal one (n = 26). The proportion of patients with hypercalcaemic crisis was very large (n = 4). Topographically and anatomically the adenomas were most frequently found in the region of the right lower pole of the thyroid gland. 23 patients had a singular adenoma, 11 patients showed multiple adenomas and only 2 had a diffuse hyperplasia. In patients with persisting hyperparathyroidism before a repeated intervention an attempt of localization should be performed by a selective phlebography with taking of blood samples for the determination of PTH. The success of the operation is to be read off most clearly at the behaviour of the post-operative values of serum calcium. In 29 patients a normocalcaemia was achieved. 6 patients showed at first a hypocalcaemia, which however, was only temporary in 4 patients. 3 patients had a persisting hyperparathyroidism. In accordance with the literary data the formation of renal calculi clearly decreased after a successful operation.


Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles.
Excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5'-phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions.


Residual organic matter and microbial respiration in bottom ash: Effects on metal leaching and eco-toxicity.
A common assumption regarding the residual organic matter, in bottom ash, is that it does not represent a significant pool of organic carbon and, beyond metal-ion complexation process, it is of little consequence to evolution of ash/leachate chemistry. This article evaluates the effect of residual organic matter and associated microbial respiratory processes on leaching of toxic metals (i.e. arsenic, copper, chromium, molybdenum, nickel, lead, antimony and zinc), eco-toxicity of ash leachates. Microbial respiration was quantified with help of a respirometric test equipment OXITOP control system. The effect of microbial respiration on metal/residual organic matter leaching and eco-toxicity was quantified with the help of batch leaching tests and an eco-toxicity assay - Daphnia magna. In general, the microbial respiration process decreased the leachate pH and eco-toxicity, indicating modification of bioavailability of metal species. Furthermore, the leaching of critical metals, such as copper and chromium, decreased after the respiration in both ash types (fresh and weathered). It was concluded that microbial respiration, if harnessed properly, could enhance the stability of fresh bottom ash and may promote its reuse.


Cutaneous lymphangioma circumscriptum: frog spawn on the skin.
Lymphangiomas are congenital malformations of the lymphatic system that may involve the skin, subcutaneous tissues, and intestines. They account for 4% of all vascular tumors, but comprise 25% of benign vascular growths in children. They are hamartomatous in nature and may be grouped into cutaneous lymphangioma circumscriptum (CLC), cavernous lymphangiomas, and cystic hygromas. CLC appears localized to the dermis, although frequently extends deeper and laterally. It is important to distinguish CLC, a potentially recurrent disease, from an unusual type of metastatic carcinoma of the skin called carcinoma telangiectoides.


Clinical evaluation of ceramic implant abutments in anterior restorations.
The development of new high strength ceramic abutments can enhance the overall aesthetic outcome of an implant-supported prosthesis. This study was to compare the clinical application of alumina and zirconia ceramic implant abutments in the anterior region. Twenty-three consecutive patients requiring single-tooth implants in the anterior region were randomized to receive either an alumina ceramic abutment (CeraAdapt) or a zirconia ceramic abutment. All-ceramic (IPS-Empress 2) crowns were then fabricated and cemented over the abutments with composite cement. Peri-implant mucosal health and bone levels were evaluated by the gingival index and radiographs at 2-week and 1-year follow-up. Aesthetic outcomes as well as technical problems with the restorations were evaluated during the observation period from 12 to 48 months after functional loading. A total of 17 alumina ceramic abutments and 18 zirconia ceramic abutments were evaluated. No patients dropped out during the study period. Eighteen out of the 23 patients maintained good function throughout the study. The median observation period was 21 months. Ceramic crown loosening was found in two restorations at 1-week and 2-years respectively after insertion. One ceramic crown fractured at 1 week after insertion. At 1-year follow-up, mean marginal bone loss around implants was 1.2 +/- 0.5 mm and the peri-implant mucosa in relation to abutment or crown was healthy with a mean gingival score of 0.6 +/- 0.2. All patients were satisfied with the final aesthetic outcome. However, two alumina abutments fractured after two years of loading. In conclusion, both ceramic abutments have shown a favourable biological response and aesthetic outcome; however, zirconia abutments with their superior mechanical properties might be better for supporting single-tooth implant restorations in the aesthetic zone.


Impact of Selected Geriatric Syndromes on the Quality of Life in the Population Aged 60 and Older.
Geriatric syndromes represent a critical domain in the population more than 60 years old. Basic syndromes include frailty, sarcopenia, loss of body mass, and a mild cognitive disorder. These are significant problems which can affect the quality of life. In our study, the Rapid Geriatric Assessment (RGA) tool was used to assess the geriatric syndromes, and the WHOQOL-BREF was used to assess the quality of life to survey 498 respondents from a population aged 60 and older. In all the assessments, the distribution of variables was tested, a nonnormal distribution of variables was identified, and subsequently, nonparametric tests were performed to identify the differences between groups. The study showed that the domain of physical health and the psychological domain were most affected. The results have shown that individual geriatric syndromes affect certain domains of the quality of life of the population above 60 with various intensity.


[Rheumatology : what's new in 2022].
In rheumatology, this year has seen an expansion of knowledge about the treatment of rheumatoid arthritis, with the availability of results from randomized trials evaluating a new molecule targeting IL-6, and regarding the safety profile of tofacitinib compared to TNF-alpha inhibitors. Interesting data on the outcome of pregnancy in patients with spondylarthritis have also been published. New molecules and different treatment strategies have shown promising results in psoriatic arthritis and systemic lupus erythematosus. The utility of botulinum toxin A injections for Raynaud's phenomenon and the efficacy of transplantation of autologous adipose-derived regenerative cells for the treatment of hand dysfunctions have been questioned by 2 randomized controlled trials of patients with systemic sclerosis.


[Autologous mesenchymal stem cell implantation promotes myocardial expressions of growth factors and improves cardiac function in failing rat hearts].
To explore the underlying mechanism of mesenchymal stem cells (MSCs) transfer induced cardiac function improvement in failing hearts. Congestive heart failure (CHF) was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization. Ten weeks later, cardiomyocyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats (all P<0.05 vs. sham). Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated (P<0.05 or P<0.01 vs. CHF), and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs (P<0.05 or P<0.01 vs. CHF). Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too. Autologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.


Orocephalometry and airway control in obese sleep-disordered breathers, obese normals, and matched controls undergoing general anesthesia.
Airway patency in conscious, normal humans is maintained by a complex orchestration of airway dilator muscles and reflex pathways yet is easily perturbed. Using patients at high risk for airway obstruction during anesthesia, as well as matched controls, this study sought (1) to determine if selected observations would contribute to our understanding of upper airway obstruction, and (2) to scientifically ground our clinical airway management interventions. The "at risk" patients tended to differ significantly from the controls with respect to a number of anthropometric and subjective measures which sought to describe the obstructive phenomena. At risk subjects were characterized as having a much greater incidence of induction and emergence obstruction, an abbreviated mental-hyoid distance, a flattened, compressed anterior-posterior craniofacial architecture, retrognanthism, relative macroglossia, and a narrower, bulky oropharynx. A theoretical model of airway obstruction was proposed characterizing the pharynx as a "collapsible tube" especially vulnerable in conditions such as sleep disordered breathing.


The effect of prenatal diagnosis on antibiotic therapy in neonates with hypoplastic left heart syndrome. Antibiotics in prenatally diagnosed patients with HLHS.
Hypoplastic left heart syndrome (HLHS) is a congenital heart anomaly that is diagnosed prenatally or postnatally. The prenatal diagnosis leads to limiting the rate of systemic complications in the preoperative period due to optimization of the early therapeutic management. The objective of the study is to determine the effect of prenatal diagnostic management of HLHS on the condition of newborns and the frequency of antibiotherapy employment prior to the first stage of surgical treatment. The study included 95 children with HLHS operated on in the years 2014-2016. The cohort was divided into two groups: newborns with a prenatally diagnosed heart defect (50 children - 52.6%) and neonates with the defect diagnosed after birth (45 children - 47.4%). The data of the patients were analyzed based on their medical records. The mean age of the children upon admission was 3.86 days in the group of patients with the prenatally diagnosed heart defect (PreHLHS) and 7.41 days in the group of newborns without the prenatal diagnosis (PostHLHS) (p = 0.001). In 60% of the PreHLHS group patients (30/50), at least one antibiotic was administered, while in the PostHLHS group, antibiotherapy was employed in 93.3% (42/45) cases (p = 0.001). Bacteriological tests demonstrated pathogen growth in 33 children (36% and 33.3%, respectively), what accounted for 34.7% of the entire cohort. On the average, the first antibiotic was introduced on the 6.55th day of life in the PreHLHS group and on the 2.73th day in the PostHLHS group (p = 0.005). The most profound differences in antibiotic employment involved aminoglycosides. The aforementioned type of antibiotic medications was administered to 6% of the children with the prenatal diagnosis and to 17.8% of the children diagnosed postnatally (p = 0.042). Preoperative antibiotherapy in children with HLHS was employed more frequently than it would be indicated by microbiology tests results. Antibiotics were observed to be introduced more commonly and earlier in the newborns with the postnatally diagnosed congenital heart defect.


Cannabaceae pollen in the atmosphere of Brianza, Northen Italy.
We have noted several patients suffering for rhinitis and/or asthma symptoms in the summer months without positive skin tests for pollens blossoming in the corresponding season. So we tried to determine the pollination pattern of pollens usually not tested, because no company produces the corrisponding extract. We determined airborne pollination by means of a volumetric pollen trap for five years from 2001 to 2005. We found, in addition to well-known aeroallergens, a significant percentage of Cannabaceae from the end of July to mid September with the highest concentration in 2004 (140 gr/m3). The potential allergenicity of Cannabis pollen was supported in the United States, where they found some patients with rhinitis or asthma during the pollen seasons and positive prick test for Cannabis, but the clinical significance of Cannabaceae pollen as an aeroallergen in Europe is still undefined.


Bacteria Detection: From Powerful SERS to Its Advanced Compatible Techniques.
The rapid, highly sensitive, and accurate detection of bacteria is the focus of various fields, especially food safety and public health. Surface-enhanced Raman spectroscopy (SERS), with the advantages of being fast, sensitive, and nondestructive, can be used to directly obtain molecular fingerprint information, as well as for the on-line qualitative analysis of multicomponent samples. It has therefore become an effective technique for bacterial detection. Within this progress report, advances in the detection of bacteria using SERS and other compatible techniques are discussed in order to summarize its development in recent years. First, the enhancement principle and mechanism of SERS technology are briefly overviewed. The second part is devoted to a label-free strategy for the detection of bacterial cells and bacterial metabolites. In this section, important considerations that must be made to improve bacterial SERS signals are discussed. Then, the label-based SERS strategy involves the design strategy of SERS tags, the immunomagnetic separation of SERS tags, and the capture of bacteria from solution and dye-labeled SERS primers. In the third part, several novel SERS compatible technologies and applications in clinical and food safety are introduced. In the final part, the results achieved are summarized and future perspectives are proposed.


Dynamic quantification of antigen molecules with flow cytometry.
Traditional methods for estimating the number of expressed molecules, based on the detection of target antigens bound with fluorescently labeled antibodies, assume that the antigen-antibody reaction reaches equilibrium. A calibration procedure is used to convert the intensity of the fluorescence signal to the number of target molecules. Along with the different limitations of every calibration system, this substantially limits the applicability of the traditional approaches especially in the case of low affinity antibodies. We address this problem here with studies in which we demonstrate a new approach to the antigen molecule quantification problem. Instead of using a static calibration system, we analyzed mean fluorescence values over time by flow cytometry during antibody-antigen binding. Experimental data obtained with an LSRII cytometer were fitted by a diffusion-reaction mathematical model using the Levenberg-Marquardt nonlinear least squares curve-fitting algorithm in order to obtain the number of target antigen molecules per cell. Results were compared with the Quanti-BRITE calibration system. We conclude that, instead of using experiment-specific calibration, the value of the binding rate constant for each particular antibody-antigen reaction can be used to quantify antigen molecules with flow cytometry. The radius of CD8 antibody molecule binding site was found, that allows recalculating the binding rate constant for other conditions (different sizes of reagent molecules, fluorescent label, medium viscosity and temperature). This approach is independent of specially prepared calibration beads, antibody reagents and the specific dye and can be applied to both low and high affinity antibodies, under both saturating and non-saturating binding conditions. The method was demonstrated on a human blood sample dataset investigating CD8α antigen on T cells in stable binding conditions.


Utilization of a high energy photon beam for whole body irradiation.
Use of a high energy linear accelerator (giving high dose rates) for whole body irradiation is recommended because (a) there is a shorter treatment time compared with other techniques using orthovoltage or 60Co irradiation; and (b) there is more comfort for the patient, who does not have to turn over to receive an acceptably uniform dose. Dosimetry indicates that the usual data is not applicable for such treatments given at large distances from the source. A method of dosage calculation at large distances was checked by using TLD dosimetry in a Rando phantom.


[Clinical randomized controlled trials of treatment of neck-back myofascial pain syndrome by acupuncture of Ashi-points combined with moxibustion of heat-sensitive points].
To observe the therapeutic effect of acupuncture of Ashi points in combination with moxibustion of heat-sensitive points for neck-back myofascial pain syndrome, so as to find a better combined therapy. A total of 62 eligible patients were randomly divided into treatment group (acupuncture of Ashi-points plus moxibustion of heat-sensitive points, n=32) and control group (acupuncture of Ashi-points plus TDP irradiation, n=30) by using single-blind method. Ashi-points were the tenderpoints or subcutaneous induration spots determined by digital pressure in the focus region, and the heat-sensitive points were the acupoints around the subcutaneous induration spots in the neck-back regions determined by patients' feeling (heat from the ignited moxa transmitting toward the deep muscle layer, extending toward the surrounding region of the Ashi-points, etc. and the distal part of the body) during moxibustion. Ashi-points were punctured with filiform needles and stimulated with reducing method by lifting, thrusting and twirling the acupuncture needle repeatedly till "Deqi", followed by retaining the needle for 30 min. Moxibustion was given to the patients for 10-90 min (when the patient began to feel heat penetrating into the deeper muscle layer to the termination of the heat transmission). TDP irradiation was given to the Ashi-points for 30 min in every session of treatment. The treatment was conducted once daily, 5 times a week, two weeks altogether. McGill pain questionnaire containing pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI) and "the criteria for assessing the therapeutic effect of back-myofascitis" recorded in "Standards for Diagnosis and Efficacy Evaluation of Clinical Conditions in Chinese Medicine" (published in 1994 in China) were used to evaluate the analgesic effect. Before the treatment, no significant differences were found between the treatment and control groups in PRI, VAS and PPI. After the treatment, PRI, VAS and PPI were all significantly lower in the treatment group than in the control group (P < 0.01). Of the 32 and 30 myofascitis patients in the treatment and control groups, 11 (34.4%) and 3 (10.0%) were cured, 20 (62.5%) and 25 (83.3%) experienced improvement in their symptoms, 1 (3.1%) and 2 (6.7%) had no apparent changes. The cure rate of the treatment group was significant bigger than that of the control group (P < 0.05). Acupuncture combined with moxibustion of Ashi-points can effectively relieve pain reaction in neck-back myofascial pain syndrome patients, which is significantly superior to that of acupuncture plus TDP irradiation therapy.


Ultrastructural localization of salivary mucins MUC5B and MUC7 in human labial glands.
As a result of their presence throughout the mouth in the submucosa or between muscle fibers, minor salivary glands secrete directly and continuously into the oral cavity, providing mucosal surfaces with highly glycosylated proteins that are active in bacterial aggregation and in oral tissue lubrication. In this study, we investigated the ultrastructural localization of the MUC5B and MUC7 mucins in human labial glands by means of a postembedding immunogold technique. Thin sections of normal human labial glands, obtained during surgery, were incubated with polyclonal antibodies to human salivary mucins MUC5B and MUC7, and then with gold-labeled secondary antibodies. Specific MUC5B reactivity was found in the secretory granules of mucous cells of all glands examined, and was associated with the luminal membrane of duct cells. MUC7 labeling was observed in the granules of both mucous and seromucous secretory cells of the glandular parenchyma. Quantitative analyses demonstrated that seromucous granules have higher immunogold labeling densities for MUC7 than mucous granules. Our immunohistochemical data extend the results of previous light microscopic studies of MUC5B and MUC7 localizations, pointing out the significant contribution of human labial glands in the secretion process of these two mucins.


Screening a Phage Display Library for Two Novel OmpU-Binding Peptides with Adhesion Antagonistic Activity against Vibrio mimicus.
Vibrio mimicus is a pathogen that causes ascites disease in fish. We have previously demonstrated that the outer membrane protein U (OmpU) is an important adhesin in V. mimicus. Here eight specific OmpU-binding phage clones, which presented three different OmpU-binding peptides (designated P1, P2, P3), were screened from a commercially available phage displayed 12-mer peptide library using rOmpU protein as target. Then, synthetic OmpU-binding peptides were measured for their adhesion antagonistic activity and binding affinity via adhesion inhibition test and non-competitive ELISA, respectively. The results showed that after co-incubated with the mixture of rOmpU and P3, visible green fluorescence could be observed on the epithelioma papulosum cyprinidi (EPC) cells surface; while the EPC cells co-incubated with the mixture of rOmpU and P1/P2 exhibited little green fluorescence. The average adhesion number of V. mimicus 04-14 isolate before and after treatment with peptide was 21.4 ± 1.5, 20.8 ± 0.8 (irrelevant peptide), 20.2 ± 0.5 (P3), 5.1 ± 0.7 (P1) and 3.4 ± 0.8 (P2), respectively. There was a significant decrease in the adhesive level of 04-14 isolate treated with P1/ P2 compared to the untreated isolate (p<0.01). The affinity constants of P1 and P2 were (6.17 ± 0.19) × 108 L/mol and (1.24 ± 0.56) × 109 L/mol, respectively. Furthermore, protective effects of P1 and P2 on grass carps challenged with V. mimicus were preliminary detected. It was found there was delayed death of fish in the groups treated with P1/P2, and the survival rate of challenged fish improved with the increase of the dose of adhesion antagonistic peptide. Taken together, two novel OmpU-binding peptides, which possessed adhesion antagonistic activity, high affinity and a certain degree of antibacterial activity against V. mimicus, were screened and identified.


SNP-based association study of kernel architecture in a worldwide collection of durum wheat germplasm.
Durum wheat, genetic resource with favorable alleles is considered as natural gene pool for wheat breeding. Kernel size and weight are important factors affecting grain yield in crops. Here, association analysis was performed to dissect the genetic constitution of kernel-related traits in 150 lines collected from 46 countries and regions using a set of EST-derived and genome-wide SNP markers with five consecutive years of data. Total 109 significant associations for eight kernel-related traits were detected under a mix linear model, generating 54 unique SNP markers distributed on 13 of 14 chromosomes. Of which, 19 marker-trait associations were identified in two or more environments, including one stable and pleiotropic SNP BE500291_5_A_37 on chromosome 5A correlated with six kernel traits. Although most of our SNP loci were overlapped with the previously known kernel weight QTLs, several novel loci for kernel traits in durum were reported. Correlation analysis implied that the moderate climatic variables during growth and development of durum are needed for the large grain size and high grain weight. Combined with our previous studies, we found that chromosome 5A might play an important role in durum growth and development.


Analysis of World Championship Swimmers Using a Performance Progression Model.
The primary aim was to create a performance progression model of elite competitors in the World Swimming Championships from 2006 to 2017 for all strokes and distances. Secondly, to identify the influence of annual ratios of progression, ages of peak performance and junior status on success in senior competitions. Data regarding the participants of senior and junior World Championships (WCs) between 2006 and 2017 were obtained from FINA. The final filtered database, after removing those swimmers who just participated in junior WCs, included 4076. Statistical models were used to examine differences between the top senior swimmers (the top 30% best performances; T30) and lower level swimmers (the bottom 70% performances; L70) for minimum age (MA), progress (P) and best junior time (BJ). In order to identify the variables that contribute to reach the T30 group, a logistic regression (LR), stepwise LR and decision tree were applied. To analyze the effect of each variable separately, a simple LR (gross odds ratio) was performed. Ratio probabilities (OR) and 95% confidence intervals were calculated for each variable. Swimmer's BJ and P were higher in the T30 group (p < 0.000). The decision tree showed the greatest explanatory capacity for BJ, followed by P. The MA had a very low explanatory capacity and was not significant in the LR. Swimmers with exceptional junior performance times, or have a high rate of progress are more likely to be successful at the senior WCs.


First clinical experience with the R Stent: a new highly flexible stainless steel tube intracoronary stent.
BACKGROUND: Coronary stents have been used with increasing frequency and in increasingly complex coronary disease. A new 316 LVM stainless steel coronary stent, the R Stent, has been designed to provide maximum flexibility for tracking and high radial strength post-deployment. PURPOSE: To assess the clinical feasibility of the R Stent in a tertiary referral population of patients with coronary heart disease. Specific objectives are to assess the R Stent's deployment success, angiographic and procedural success (<20% residual stenosis and >TIMI 2 flow), safety (absence of complications), and 30-day clinical success (angiographic/procedural success plus no major adverse coronary events). METHODS: Between April and November 1998, stent deployment was attempted in 27 patients with stable (46%) or unstable (54%) angina pectoris who qualified for percutaneous transluminal coronary angioplasty. Eighty per cent of patients had a pre-existing history of myocardial infarction, coronary bypass surgery or percutaneous transluminal coronary angioplasty, and several of the lesions were anatomically complex (totally occluded, n 32; thrombus present, n 32; heavily calcified, n 33; ostial, n 31; >20 mm long, n 39; angulation >45 degrees, n 37). Lesions in aortocoronary saphenous vein grafts were excluded. Adjunctive medical management included intraprocedural aspirin and heparin and post-procedural aspirin and ticlopidine. After deployment, patients were followed up in the hospital and at 30 days post procedure. RESULTS: Stent deployment was achieved in 32 of 33 attempts (26 of 27 patients). There was one deployment failure in a long, calcified ostial and proximal left coronary lesion. In the 26 successful deployments, TIMI 3 flow was achieved. One other patient experienced a painless increase in creatine kinase to 375 (CK-MB of 59) at 12 h without ECG changes. At 30 days, there were no deaths, no myocardial infarctions, no subacute thromboses, no repeat interventions, no bypass surgeries and no bleeding complications. Only the patient with post-procedural CK-MB elevation experience recurrence of CCS class 2 angina within the 30 days. CONCLUSION: The R Stent is a promising new device for the treatment of complex coronary heart disease. A larger, more broadly-based study is warranted.


Studies on yeast sulfite reductase. IV. Structure and steady-state kinetics.
Yeast NADPH-sulfite reductase (hydrogen sulfide:NADP+ oxidoreductase, EC 220.127.116.11) is a complex hemoflavoprotein. The Strokes radius was determined to be 80 A by gel filtration and the molecular weight was estimated to be 604,000. The minimal molecular weight calculated from flavin and heme content was 306,000, indicating that this enzyme contains two FAD, two FMN and two hemes per molecule. The enzyme consists of two types of subunit, alpha and beta, having molecular weights of 116,000 and 167,000, respectively. The subunit structure is suggested to be alpha 2 beta 2. The secondary structure, the amino acid composition and the isoelectric point were also investigated. The Km values for sulfite and NADPH were 17 microM and 10 microM, respectively. Sulfite and NADPH affected the reaction velocity to give parallel Lineweaver-Burk plots, indicating the involvement of the 'ping-pong' mechanism in the overall reaction. NADP+ inhibited the reaction competitively with NADPH and noncompetitively with sulfite. Inhibition by sulfide was partially noncompetitive with both substrates but very weak. These results are discussed and compared with sulfite reductase from Escherichia coli.


A comprehensive approach to percutaneous injury prevention during phlebotomy: results of a multicenter study, 1993-1995.
To examine a comprehensive approach for preventing percutaneous injuries associated with phlebotomy procedures. From 1993 through 1995, personnel at 10 university-affiliated hospitals enhanced surveillance and assessed underreporting of percutaneous injuries; selected, implemented, and evaluated the efficacy of phlebotomy devices with safety features (ie, engineered sharps injury prevention devices [ESIPDs]); and assessed healthcare worker satisfaction with ESIPDs. Investigators also evaluated the preventability of a subset of percutaneous injuries and conducted an audit of sharps disposal containers to quantify activation rates for devices with safety features. The three selected phlebotomy devices with safety features reduced percutaneous injury rates compared with conventional devices. Activation rates varied according to ease of use, healthcare worker preference for ESIPDs, perceived "patient adverse events," and device-specific training. Device-specific features and healthcare worker training and involvement in the selection of ESIPDs affect the activation rates for ESIPDs and therefore their efficacy. The implementation of ESIPDs is a useful measure in a comprehensive program to reduce percutaneous injuries associated with phlebotomy procedures.


Type 1 diabetes.
Type 1 diabetes accounts for only about 5-10% of all cases of diabetes; however, its incidence continues to increase worldwide and it has serious short-term and long-term implications. The disorder has a strong genetic component, inherited mainly through the HLA complex, but the factors that trigger onset of clinical disease remain largely unknown. Management of type 1 diabetes is best undertaken in the context of a multidisciplinary health team and requires continuing attention to many aspects, including insulin administration, blood glucose monitoring, meal planning, and screening for comorbid conditions and diabetes-related complications. These complications consist of microvascular and macrovascular disease, which account for the major morbidity and mortality associated with type 1 diabetes. Newer treatment approaches have facilitated improved outcomes in terms of both glycaemic control and reduced risks for development of complications. Nonetheless, major challenges remain in the development of approaches to the prevention and management of type 1 diabetes and its complications.


Outcomes of pregnancies using donor sperm compared with those using partner sperm: systematic review and meta-analysis.
Registry data from the Human Fertilisation and Embryology Authority (HFEA) show an increase of 40% in IUI and 377% in IVF cases using donor sperm between 2006 and 2016. The objective of this study was to establish whether pregnancies conceived using donor sperm are at higher risk of obstetric and perinatal complications than those conceived with partner sperm. As more treatments are being carried out using donor sperm, attention is being given to obstetric and perinatal outcomes, as events in utero and at delivery have implications for long-term health. There is a need to know if there is any difference in the outcomes of pregnancies between those conceived using donor versus partner sperm in order to adequately inform and counsel couples. We performed a systematic review and meta-analysis of the outcomes of pregnancies conceived using donor sperm compared with partner sperm. Searches were performed in the OVID MEDLINE, OVID Embase, CENTRAL and CINAHL databases, including all studies published before 11 February 2019. The search strategy involved search terms for pregnancy, infant, donor sperm, heterologous artificial insemination, donor gametes, pregnancy outcomes and perinatal outcomes. Studies were included if they assessed pregnancies conceived by any method using, or infants born from, donor sperm compared with partner sperm and described early pregnancy, obstetric or perinatal outcomes. The Downs and Black tool was used for quality and bias assessment of studies. Of 3391 studies identified from the search, 37 studies were included in the review and 36 were included in the meta-analysis. For pregnancies conceived with donor sperm, versus partner sperm, there was an increase in the relative risk (RR) (95% CI) of combined hypertensive disorders of pregnancy: 1.44 (1.17-1.78), pre-eclampsia: 1.49 (1.05-2.09) and small for gestational age (SGA): 1.42 (1.17-1.79) but a reduced risk of ectopic pregnancy: 0.69 (0.48-0.98). There was no difference in the overall RR (95% CI) of miscarriage: 0.94 (0.80-1.11), gestational diabetes: 1.49 (0.62-3.59), pregnancy-induced hypertension (PIH): 1.24 (0.87-1.76), placental abruption: 0.65 (0.04-10.37), placenta praevia: 1.19 (0.64-2.21), preterm birth: 0.98 (0.88-1.08), low birth weight: 0.97 (0.82-1.15), high birthweight: 1.28 (0.94-1.73): large for gestational age (LGA): 1.01 (0.84-1.22), stillbirth: 1.23 (0.97-1.57), neonatal death: 0.79 (0.36-1.73) and congenital anomaly: 1.15 (0.86-1.53). The majority of our findings are reassuring, except for the mild increased risk of hypertensive disorders of pregnancy and SGA in pregnancies resulting from donor sperm. However, the evidence for this is limited and should be interpreted with caution because the evidence was based on observational studies which varied in their quality and risk of bias. Further high-quality population-based studies reporting obstetric outcomes in detail are required to confirm these findings.


Extended polyglutamine tracts cause aggregation and structural perturbation of an adjacent beta barrel protein.
Formation of fibrillar intranuclear inclusions and related neuropathologies of the CAG-repeat disorders are linked to the expansion of a polyglutamine tract. Despite considerable effort, the etiology of these devastating diseases remains unclear. Although polypeptides with glutamine tracts recapitulate many of the observed characteristics of the gene products with CAG repeats, such as in vitro and in vivo aggregation and toxicity in model organisms, extended polyglutamine segments have also been reported to structurally perturb proteins into which they are inserted. Additionally, the sequence context of a polyglutamine tract has recently been shown to modulate its propensity to aggregate. These findings raise the possibility that indirect influences of the repeat tract on adjacent protein domains are contributory to pathologies. Destabilization of an adjacent domain may lead to loss of function, as well as favoring non-native structures in the neighboring domain causing them to be prone to intermolecular association and consequent aggregation. To explore these phenomena, we have used chimeras of a well studied globular protein and exon 1 of huntingtin. We find that expansion of the polyglutamine segment beyond the pathological threshold (>35 glutamines) results in structural perturbation of the neighboring protein whether the huntingtin exon is N- or C-terminal. Elongation of the polyglutamine region also substantially increases the propensity of the chimera to aggregate, both in vitro and in vivo, and in vitro aggregation kinetics of a chimera with a 53-glutamine repeat follow a nucleation polymerization mechanism with a monomeric nucleus.


Structural Differences between Wild-Type and Double Mutant EGFR Modulated by Third-Generation Kinase Inhibitors.
Mutations in the EGFR kinase domain are implicated in non-small-cell lung cancer. Of particular interest is the drug-resistant double mutant (L858R/T790M, DM EGFR), which is not inhibited selectively by any approved kinase inhibitor. Here we apply bipartite tetracysteine display to demonstrate that DM and WT EGFR differ in structure outside the kinase domain. The structural difference is located within the cytoplasmic juxtamembrane segment (JM) that links the kinase domain with the extracellular and transmembrane regions and is essential for EGFR activation. We show further that third-generation DM EGFR-selective TKIs alter JM structure via allostery to restore the conformation found when WT EGFR is activated by the growth factors EGF and HB-EGF. This work suggests that the oncogenic activity of DM EGFR may extend beyond kinase activity per se to include kinase-independent activities. As JM structure may provide a biomarker for these kinase-independent functions, these insights could guide the development of allosteric, DM-selective inhibitors.


Thrombopoietin: from theory to reality.
Much is now known about the physiology of platelets and their role in primary hemostasis; however, until recently far less was understood about their immediate precursors, marrow megakaryocytes (MKs). With the cloning and characterization of thrombopoietin (TPO), the principle regulator of the growth and development of MKs, research has been rapid and broad-based. In several laboratories TPO was cloned based on it's binding to the product of the proto-oncogene c-mpl, at the time an orphan cytokine receptor, and was subsequently found to affect nearly all aspects of thrombopoiesis. Many of the molecular pathways that mediate TPO action have been explored. Like all other members of the hematopoietic cytokine receptor family upon hormone binding members of the JAK family of kinases are activated, which, in turn, phosphorylate the TPO receptor, generating docking sites for second messengers that affect multiple signaling pathways. Ultimately, cellular proliferative and anti-apoptotic mechanisms are initiated, increasing MK numbers, and a process termed endomitosis (EnM) begins, generating large, highly polyploid cells. The net result is the expansion of cells that give rise to mature platelets, a process that can be accentuated by the therapeutic administration of the hormone to thrombocytopenic patients.


Improvement of Freeze-Dried Survival of Lactiplantibacillus plantarum Based on Cell Membrane Regulation.
The cell membrane of Lactiplantibacillus plantarum is a key structure for cell survival. In this study, we aimed to improve the lyophilization resistance of L. plantarum by regulating the cell membrane structure. Unsaturated fatty acids or cell membrane-regulating substances were added during culturing to determine their effect on the composition of cell membrane fatty acids and the survival rate of the cells after freeze-drying. The results showed that Tween 80, β-carotene and melatonin increased the lyophilization survival rate of L. plantarum by 9.44, 14.53, and 18.34%, respectively. After adding a lyophilization protective agent at a concentration of 21.49% at a 1:1 ratio, a combination of Tween 80, melatonin, and β-carotene was added to regulate the cell membrane, which increased the lyophilization survival rate by 32.08-86.05%. This study proposes new research directions and ideas for improving the survival rate of probiotics for industrial production.


Landslide-dammed paleolake perturbs marine sedimentation and drives genetic change in anadromous fish.
Large bedrock landslides have been shown to modulate rates and processes of river activity by forming dams, forcing upstream aggradation of water and sediment, and generating catastrophic outburst floods. Less apparent is the effect of large landslide dams on river ecosystems and marine sedimentation. Combining analyses of 1-m resolution topographic data (acquired via airborne laser mapping) and field investigation, we present evidence for a large, landslide-dammed paleolake along the Eel River, CA. The landslide mass initiated from a high-relief, resistant outcrop which failed catastrophically, blocking the Eel River with an approximately 130-m-tall dam. Support for the resulting 55-km-long, 1.3-km(3) lake includes subtle shorelines cut into bounding terrain, deltas, and lacustrine sediments radiocarbon dated to 22.5 ka. The landslide provides an explanation for the recent genetic divergence of local anadromous (ocean-run) steelhead trout (Oncorhynchus mykiss) by blocking their migration route and causing gene flow between summer run and winter run reproductive ecotypes. Further, the dam arrested the prodigious flux of sediment down the Eel River; this cessation is recorded in marine sedimentary deposits as a 10-fold reduction in deposition rates of Eel-derived sediment and constitutes a rare example of a terrestrial event transmitted through the dispersal system and recorded offshore.


[Nonvariceal acute upper digestive tract hemorrhage--therapeutic approach].
Nonvariceal acute upper gastrointestinal hemorrhage continues to be a frequent cause for hospital admission, consumes considerable financial resources and belongs to diagnoses associated with significant morbidity and mortality. Despite the progress in endoscopic and intensive care therapies the mortality remained unchanged. It results from the increasing number of high risk patients, namely the older ones with significant comorbidity. The cornerstone of therapeutical success is considered to be the adequate hemodynamic and ventilatory stability, initiation of pharmacotherapy with proton pump inhibitors and eventually somatostatin, and in particular, the early endoscopy using modern methods of hemostasis. In case of two unsuccessful endoscopic sessions the surgical approach is justified.


Long-term compliance with endoscopic surveillance for familial adenomatous polyposis.
The study assessed compliance of patients with familial adenomatous polyposis (FAP) with endoscopic surveillance. In this nationwide, cross-sectional study, individuals from FAP families registered with the Netherlands Foundation for the Detection of Hereditary Tumours were invited to complete a questionnaire on endoscopic screening experiences. A total of 328 individuals were eligible for the study of whom 85 were at risk for FAP, 108 had an intact rectum after a colectomy with ileorectal anastomosis (IRA), and 135 had had a pouch following a proctocolectomy with ileoanal anastomosis (IPAA). Based on medical record data, 20% of the at-risk group and 26% of the IRA-group were found to be undercompliant with surveillance advice which was associated significantly with perceived self-efficacy, use of sedatives during surveillance, pain after surveillance and low perceived benefits of surveillance (P < 0.05). One in five individuals at risk for FAP and one in four with a retained rectum are undercompliant with screening advice. We recommend that sedatives should be patient-tailored for FAP individuals undergoing surveillance and that adequate pain medication be provided after endoscopy.