In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network.
A genome-scale metabolic model of the Gram-positive, facultative anaerobic opportunistic pathogen Staphylococcus aureus N315 was constructed based on current genomic data, literature, and physiological information. The model comprises 774 metabolic processes representing approximately 23% of all protein-coding regions. The model was extensively validated against experimental observations and it correctly predicted main physiological properties of the wild-type strain, such as aerobic and anaerobic respiration and fermentation. Due to the frequent involvement of S. aureus in hospital-acquired bacterial infections combined with its increasing antibiotic resistance, we also investigated the clinically relevant phenotype of small colony variants and found that the model predictions agreed with recent findings of proteome analyses. This indicates that the model is useful in assisting future experiments to elucidate the interrelationship of bacterial metabolism and resistance. To help directing future studies for novel chemotherapeutic targets, we conducted a large-scale in silico gene deletion study that identified 158 essential intracellular reactions. A more detailed analysis showed that the biosynthesis of glycans and lipids is rather rigid with respect to circumventing gene deletions, which should make these areas particularly interesting for antibiotic development. The combination of this stoichiometric model with transcriptomic and proteomic data should allow a new quality in the analysis of clinically relevant organisms and a more rationalized system-level search for novel drug targets.


[Trends of urban haze in Jiangsu Province China over the past 33 years].
Based on the surface meteorological data of Jiangsu Province during 1980-2012, climatic characteristics and trends of the weather phenomenon of haze were analyzed. The result indicates that during 1980-2012, the haze day increased, and the severe and moderate haze days significantly increased. In the northern and coastal cities, haze days had a significant increase. Haze is often appeared in the fall and winter, and is rare in the summer, it also occurs inland, and is less in the coast. The haze happens more frequently in June since the straw burning during.summer harvest time. The haze day was evenly distributed during the 80's, and increased during the 90's over southern and southwestern Jiangsu Province, middle and northern Jiangsu haze days had a growing after 2000, especially after 2010. The continuous, regional, and regional-continuous haze days were in an increasing trend. As the urban built-up area has been expanded each year, industrial emissions, coal consumption, and car ownership increase every year, resulting in regional temperature increase and relative humidity decrease, resulting in urban heat island and dry island effects. Thence the haze formation and maintenance conditions increased, which led to the increasing of haze days, and the continuous, regional and regional- continuous haze days were significantly increased.


Host gill attachment causes blood-feeding by the salmon louse (Lepeophtheirus salmonis) chalimus larvae and alters parasite development and transcriptome.
Blood-feeding is a common strategy among parasitizing arthropods, including the ectoparasitic salmon louse (Lepeophtheirus salmonis), feeding off its salmon host's skin and blood. Blood is rich in nutrients, among these iron and heme. These are essential molecules for the louse, yet their oxidative properties render them toxic to cells if not handled appropriately. Blood-feeding might therefore alter parasite gene expression. We infected Atlantic salmon with salmon louse copepodids and sampled the lice in two different experiments at day 10 and 18 post-infestation. Parasite development and presence of host blood in their intestines were determined. Lice of similar instar age sampled from body parts with differential access to blood, namely from gills versus lice from skin epidermis, were analysed for gene expression by RNA-sequencing in samples taken at day 10 for both experiments and at day 18 for one of the experiments. We found that lice started feeding on blood when becoming mobile preadults if sitting on the fish body; however, they may initiate blood-feeding at the chalimus I stage if attached to gills. Lice attached to gills develop at a slower rate. By differential expression analysis, we found 355 transcripts elevated in lice sampled from gills and 202 transcripts elevated in lice sampled from skin consistent in all samplings. Genes annotated with "peptidase activity" were among the ones elevated in lice sampled from gills, while in the other group genes annotated with "phosphorylation" and "phosphatase" were pervasive. Transcripts elevated in lice sampled from gills were often genes relatively highly expressed in the louse intestine compared with other tissues, while this was not the case for transcripts elevated in lice sampled from skin. In both groups, more than half of the transcripts were from genes more highly expressed after attachment. Gill settlement results in an alteration in gene expression and a premature onset of blood-feeding likely causes the parasite to develop at a slower pace.


Costal blood supply in free flap grafting.
The principal nourishment to the rib in a free flap is derived from the nutrient artery that pierces the costal head and terminates in the medullary cavity. A question surrounds the adequacy of the periosteal vessels in providing nourishment to the entire bone. A study of the blood supply and bony metabolism in the osseous portion of four free flaps of rib and attached pleura used to reconstruct the laryngotrachea in four dogs was undertaken. A microvascular anastomosis was attached to the anterior intercostal artery. An intact anastomosis was demonstrated in all four animals with fill of the most distal arborization in the bone in three. Technetium Tc 99m scanning, tetracycline labeling, and light microscopy revealed healthy metabolizing bone. The airway in all four animals was widely patent.


Simultaneously deleting ADH2 and THI3 genes of Saccharomyces cerevisiae for reducing the yield of acetaldehyde and fusel alcohols.
The reduced yields of acetaldehyde and fusel alcohols through fermentation by Saccharomyces cerevisiae is of significance for the improvement of the flavor and health of alcoholic beverages. In this study, the ADH2 (encode alcohol dehydrogenase) and THI3 (encode decarboxylase) genes of the industrial diploid strain S. cerevisiae XF1 were deleted. Results showed that single-gene-deletion mutants by separate gene deletion of ADH2 or THI3 led to a reduced production of the acetaldehyde or fusel alcohols, respectively. In the meantime, the double-gene-deletion mutant S. cerevisiae XF1-AT was constructed by deleting the ADH2 and THI3 simultaneously. An equivalent level of the ethanol production by the S. cerevisiae XF1-AT could be achieved but with the yields of acetaldehyde, isoamyl alcohol and iso-butanol reduced by 42.09%, 15.65% and 20.16%, respectively. In addition, there was no interaction between the ADH2 deletion and THI3 deletion in reducing the production of acetaldehyde and fusel alcohols. The engineered S. cerevisiae XF1-AT provided a new strategy to alcoholic beverages brewing industry for reducing the production of acetaldehyde as well as the fusel alcohols.


IL-33 neutralization suppresses lupus disease in lupus-prone mice.
IL-33 is a new member of the IL-1 family that plays a role in inflammation. In this study, we evaluated the potential of IL-33 inhibition as a treatment for systemic lupus erythematosus (SLE) using the lupus-prone model MRL/lpr mice and the underlying mechanisms of action. We treated mice with anti-mouse IL-33 antibody (anti-IL-33Ab) via intraperitoneal injection every other day from week 14 until week 20 for 6 weeks. A control group received the same amount of IgG control. Renal damage and mouse survival were compared. Cytokines, antibodies, immune complex, Tregs, myeloid-derived suppressor cells (MDSCs), and Th17 cells were also analyzed. Correlations between serum IL-33 and SLE disease activity index in human SLE were also investigated. MRL/lpr mice treated with anti-IL-33Ab showed reduced proteinuria and reduced serum anti-dsDNA levels. Nephritis, immune complex deposits, and the circulating antibodies and immune complex besides the mortality were significantly reduced by anti-IL-33Ab. Anti-IL-33Ab remarkably increased Tregs and MDSCs and reduced the Th17 cells and IL-1β, IL-6, and IL-17 levels in MRL/lpr mice. These results suggest that IL-33 inhibition may inhibit SLE via expansion of Tregs and MDSCs and inhibition of Th17 cells and proinflammatory responses, indicating that blockade of IL-33 has a protective effect on SLE.


Measuring adverse childhood experiences with latent class trajectories.
Adverse childhood experiences (ACEs) are associated with several negative health and behavioral outcomes during adolescence, but most of the extant research has employed ACEs scores at one or two time points. Studies have not assessed whether latent class ACEs trajectories affect adolescent problem behaviors and conditions. We used longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS, n = 3444) to assess ACEs at several time points and empirically developed latent class trajectories. We then examined the sociodemographic characteristics of youth who belonged to each trajectory group. We next evaluated whether the ACEs trajectories during childhood were associated with delinquent behavior, substance use, and symptoms of anxiety or depression. Finally, we explored whether closeness to mother buffered the impact of ACEs on these outcomes. Eight types of ACEs were captured in the FFCWS data. ACE scores were assessed at year one, three, five, and nine, along with the outcomes during year 15. Trajectories were estimated with a semiparametric latent class models. The analysis revealed three latent trajectories during childhood: a low/none ACEs group, a medium exposure group, and a high exposure group. Adolescents in the high exposure group manifested a heightened risk of involvement in delinquent behaviors and substance use. They also reported more symptoms of anxiety and depression than their peers in the low/none and medium exposure groups. Repeated exposure to ACEs during childhood can have serious negative repercussions in the lives of adolescents, but maternal closeness may buffer their effects. Scholars should continue to examine the dynamics of ACEs exposure during childhood by using empirical approaches appropriate for identifying age-graded trajectories.


Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.
Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.


Insulin resistance indexes in women with premature ovarian insufficiency - a pilot study.
Premature ovarian insufficiency (POI) is associated with hypoestrogenism and an increased risk of metabolic disorders. In many clinics, a variety of insulin resistance (IR) tests are used during routine clinical assessments. To date, there is no clear opinion about which of these tests should be applied in women with premature ovarian insufficiency (POI). Therefore, our preliminarily aim was to compare the most frequently used insulin resistance indexes in the clinical assessment of a group of POI women and a control group. Our retrospective study included 98 women with karyotypically normal spontaneous POI aged 18-39 years and a control group of 78 healthy women. Each patient was given an oral glucose tolerance test (OGTT) to evaluate their insulin release and insulin resistance. In addition, each woman's insulin resistance (IR) was evaluated us-ing the homeostasis model assessment for insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), the fasting glucose-to-insulin ratio (FGIR), and Matsuda and McAuley indexes. The two groups' glucose levels were compared at 0, 60 and 120 min of the OGTT. At 0 and 60 min of the OGTT, the insulin levels of the POI women were significantly higher than those of the control group. The number of women in whom IR was detected using the various kits was comparable between the two groups. In conclusion, only the OGTT evaluation revealed a significant difference in insulin concentrations between the two study groups. The indexes most commonly used to detect IR did not detect differences in IR between the POI women and the members of the healthy control group. QUICKI detected significantly more women with IR within both study groups than other tests did.


Analysis of constitutive heterochromatin of Aotus (Cebidae, Primates) by restriction enzyme and fluorochrome bands.
The current classification of genus Aotus includes nine species, four of which occur above the Amazon River and five below it. The position of several of these taxa as a valid species has been questioned. Recently, we described the chromosomal constitution of a population in the state of Rondonia, Brazil, whose karyotype typically presented a considerable accumulation of constitutive heterochromatin. To best characterize these heterochromatins, in this work we subjected the metaphases of these animals to banding using AluI, HaeIII, HinfI, RsaI, DdeI, MboI and MspI restriction enzymes and CMA3 and DAPI fluorochromes. The banded metaphases were also submitted to sequential C-banding. RsaI, DdeI and MboI enzymes showed, in all chromosomes, a banding pattern of C type, similar to that obtained using barium hydroxide. This banding was also seen with AluI, HinfI and MspI, but with reduction or elimination of the C-bands in the chromosome pairs 1, 3-7 and 9. MspI also reduced the C-band of pairs 11, 16-21 and 23. HaeIII induced intermediate bands between G and C. Considering the data of the different bands produced, it was possible to characterize at least three distinct types of constitutive heterochromatin in Aotus from Rondonia: (a) centromeric bands, (b) bands of the heterochromatic short arms and (c) interstitial bands.


Ecological stoichiometry and homeostasis characteristics of plant-litter-soil system with vegetation restoration of the karst desertification control.
It is of great significance to clarify the ecologically chemical stoichiometric characteristics of plant-litter-soil in vegetation restoration process for elucidating the nutrient cycling law and soil nutrient management of karst ecosystem. The carbon (C), nitrogen (N) and phosphorus (P) contents of leaves, litter and soil and their stoichiometry were determined in loquat (Eribotrya japonica) plantations in a karst plateau canyon after 3, 6, 10 and 15 years of restoration. The homeostasis characteristics of leaf N, P, and N:P with the change in soil nutrients during restoration were revealed. The results showed that leaf C, N, and P contents initially increased and then decreased with increasing years of restoration at the same sampling time. The contents of nutrients in soil and litter varied with increasing restoration years, with the highest values mostly appearing in May and July. This could be due to greater moisture in May and July, which helps with nutrient absorption and transformation. The leaf N:P ratio of loquat with different restoration years was 35.76-47.39, with an average of 40.06. Therefore, loquat leaves may experience P limitation in the growth process. The relationships between N, P and N:P in leaves and soil indexes could be simulated by a homeostasis model. Except for the weak sensitivity of loquat leaf N in 10 years, the other indexes and treatments had a certain homeostasis. Plants maintain homeostasis by regulating physiological responses in vivo in response to soil nutrient changes, indicating that loquat has good adaptability in karst desertification environments, but attention should focus on the management of soil P in the field as part of the vegetation restoration process. Therefore, in future research, we should combine the soil water and fertilizer conditions of different growing seasons in karst rocky desertification areas and provide scientific field management to ensure that the results of rocky desertification management can play a role in rural revitalization.


Utility of upright radiographs in traumatic thoracolumbar fracture management.
It is common practice to use a combination approach of computed tomography (CT) scan followed by upright radiographs when assessing traumatic thoracolumbar (TL) vertebral fractures. The purpose of this study was to determine the clinical utility of upright spine radiographs in the setting of traumatic TL fracture management. Our null hypothesis is that upright TL radiographs rarely change management of acute vertebral fractures. A retrospective study was performed on patients with an initial plan of non-operative management for a TL fracture between January 2014 and June 2020 at a single Level 1 trauma center. Patients were followed from time of initial consult to either conversion to surgery (operative) or last available outpatient follow up imaging (non-operative). Lateral kyphotic angle of the fractured vertebra and anterior vertebral body height% loss on initial CT, first upright radiograph, and endpoint upright radiograph imaging were measured. Measurements were compared between and within operative and non-operative groups using t-tests and Mann-Whitney U tests when appropriate. P-values ≤ 0.05 were considered statistically significant. The study included 70 patients with an average age of 54 years and 37 (52.9%) were women. Six (8.6%) of 70 patients had a change from non-operative to operative management based on upright radiographs. The mean (standard deviation) change in degrees of kyphosis from CT scan to first X-ray was 4.6 (7.0) in the non-operative group and 11.5 (8.1) in the operative group (P = 0.03). Delta degrees of kyphosis from CT scan to endpoint X-ray was 6.4 (9.0) and 16.2 (6.2) in the non-operative and operative groups, respectively (P = 0.01). In the operative group, mean degrees of kyphosis increased from 1.6 (7.6) in initial CT to 13.1 (8.9) in first X-ray (P = 0.02). First X-ray mean anterior body height% loss was 37.5 (17.6) and 53.2 (16.1) in the non-operative and operative groups, respectively (P = 0.04). Upright radiographs are useful in guiding traumatic vertebral fracture management decisions. Larger studies are needed to determine the degree of change in kyphosis between CT and first standing radiograph that is suggestive of operative management. Not applicable.


Musculoskeletal pain: prevalence, prevention, and differences among dental office personnel.
Data regarding the presence and specific region of musculoskeletal pain were collected as part of a study that surveyed more than 5,000 dental personnel, dentists, and dental auxiliaries. The magnitude of the overall study, which included all types of dental professionals, made possible identification of the prevalence of musculoskeletal pain and comparison of regions of pain among the different dental professionals.


Patterns and predictors of blood-brain barrier permeability derangements in acute ischemic stroke.
MRI permeability imaging is a promising approach to identify patients with acute ischemic stroke with an increased propensity for hemorrhagic transformation (HT). Permeability imaging provides direct visualization of blood-brain barrier derangements in ischemic fields. We retrospectively analyzed clinical and MRI data on patients with acute cerebral ischemia within the middle cerebral artery territory to identify the frequency, patterns, and predictors of permeability derangements and their association with HT types. A total of 179 permeability scans was obtained in 127 patients (59 men; mean age, 66.8 years). Among 179 image sets (82 pre-/no treatment and 97 posttreatment), permeability derangements were present in 29 images, frequently at the basal ganglia (n=23) and rarely at the juxta-cortical area (n=6). After adjusting for covariates, diastolic pressure (OR, 1.12, per 1-mm Hg increase; 95% CI, 1.02 to 1.22) and s-glucose (OR, 1.04, per 1-mg/dL increase; 95% CI, 1.01 to 1.07) were independently associated with pretreatment permeability derangements, whereas low-density lipoprotein cholesterol (OR, 0.97, per 1-mg/dL increase; 95% CI, 0.94 to 0.99), malignant MRI profile (OR, 24.84; 95% CI, 1.50 to 412.93), and time from onset to recanalization therapy (OR, 1.47, per 1-hour increase; 95% CI, 1.10 to 1.96) were independently associated with permeability derangements after recanalization therapy. Types of HT varied among the patients with permeability derangements (no HT, 4; hemorrhagic infarct type, 12; and parenchymal hematoma, 13) and transient derangements (without subsequent HT) and normalization of derangements (in the presence of HT) on permeability images was observed in several cases. Permeability derangements, a dynamic process associated with ischemic stroke pathophysiology and recanalization therapy, vary in pattern and evolution toward HT. Several prognostic and therapeutic predictors for HT are independently associated with pre- and posttreatment permeability derangements.


Efficient Noble-Metal-Free Catalysts Supported by Three-Dimensional Ordered Hierarchical Porous Carbon.
Development of heterogeneous catalysts has attracted increasing attention, owing to their remarkable catalytic performance and recyclability. Herein, we report well-developed heterogeneous catalysts with a three-dimensional ordered hierarchical structure, constructed from nickel or cobalt nanoparticles embedded in porous carbon. The obtained catalysts were fully characterized by several techniques. On account of the uniform distribution of metal nanoparticles in the porous carbon matrix and large diffusion channels that allow for effective mass transport, the catalysts exhibited superior catalytic performance for styrene epoxidation reaction. In particular, the catalysts showed good catalytic activity, high selectivity and excellent recyclability toward the styrene epoxidation. Thus, this facile approach developed allows for fabricating advanced heterogeneous catalysts with high catalytic activities for useful practical applications.


Honest and faked responses on the Attitudes Toward Disabled Persons Scale--Form A.
This study was completed by Dr Speakman while he was Associated Professor and Chairman of the Department of Rehabilitation in the Faculty of Medicine at the University of Zimbabwe. At that time Andrew Tembo was a physical therapy student and Sarah Hendry was an occupational therapy student. In recent years there has been increased interest in the attitudes held towards disabled persons by physiotherapy students and physiotherapists. Research on this topic has been conducted in Canada, Australia, the USA, and South Africa. In every one of these studies the instrument used to measure attitudes was one of the three forms of the Attitudes Toward Disabled Persons Scales (ATDPS). A major shortcoming of self-report scales such as the ATDPS is that they can often be faked. If the scales contain "transparent" statements, that is, statements to which the socially desirable answer is obvious or seems obvious, the subjects may be tempted to fake their responses. It is therefore important to determine if a self-report scale can be faked. Of the five studies that have been undertaken to determine if the ATDPS are fakeable, four have indicated that they are not, while one has demonstrated that they are. As it seems that the ATDPS will continue to be the instrument of choice in the measurement of attitudes toward disabled persons by physiotherapy students and physiotherapists, it is important that this question be resolved.


[Isolation of human serum lipoproteins using a sedimentation method and the determination of their lipid composition].
A method for separation of human blood serum lipoproteins into 3 fractions (low- and high-density lipoproteins, subfractions 2 and 3) is described in detail. The method may be used to rapidly obtain information on the status of lipid metabolism in humans and animals. The results of lipid composition analysis of individual lipoprotein fractions are presented. These data were obtained in a series of experiments and EC-1052 computer-processed with the use of a COM applied program pack. Basing on the results of investigation of individual fractions' lipid composition, the authors make a conclusion on the characteristic features of each fraction, which in future may be helpful in the diagnosis of pathologic process and in detection of lipid metabolism disorders in the body.


Disappearance of the common bile duct signal caused by oral negative contrast agent on MR cholangiopancreatography.
We report a case in which the signal of the common bile duct disappeared owing to reflux of oral negative contrast agent on MR cholangiopancreatography (MRCP). The patient had previously undergone endoscopic sphincterotomy; after endoscopic sphincterotomy, it is known that patients develop reflux of the duodenal contents into the bile duct. Radiologists should be aware that MRCP of patients who have the possibility of bile counterflow may be hindered by oral negative contrast agents.


Glucose lowering and pancreato-protective effects of Abrus Precatorius (L.) leaf extract in normoglycemic and STZ/Nicotinamide - Induced diabetic rats.
Abrus precatorius (L.) leaves are used as folk medicine by the local communities in the western region of Ghana to treat diabetes mellitus; however, this health claim remains unverified scientifically. The study investigated glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) in normoglycemic and STZ/nicotinamide (NIC)-induced diabetic rats. after preparation of APLE, it was subjected to phytochemical screening, proximate composition and elemental assessments by using standard methods. Oral glucose tolerance test (OGTT) and maltose, lactose and sucrose oral challenge were assessed in normoglycemic rats post-APLE. Morphological characteristics of glucose response curve (time of glucose peak and shape of glucose response curve) were determined. Subsequently, diabetes mellitus was experimentally established in normoglycaemic adult Sprague-Dawley rats (weighing 150-250 g) of both sexes by sequential injection of Streptozotocin (STZ, 60 mg/kg ip)-reconstituted in sodium citrate buffer and NIC (110 mg/kg ip)-reconstituted in normal saline (1:1 v/v) for 16 weeks. Except control rats (normal saline 5 ml/kg ip; baseline fasting blood glucose [FBG] of 6.48 mmol/L), rats having FBG (stable at 11.1 mmol/L or ≥ 250 mg/dL) 3 days post-STZ/NIC injection were randomly re-assigned to one of the following groups: model (STZ/NIC-induced diabetic rats), APLE (100, 200 and 400 mg/kg respectively po) and metformin (300 mg/kg po) and treated daily for 28 days. Bodyweight and FBG were measured on weekly basis. FBG was measured by using standard glucometers. On day 28, rats were sacrificed under chloroform anesthesia, blood collected via cardiac puncture; kidney, liver and pancreas surgically harvested. While the pancreas was processed, sectioned and H&E-stained for histological examination, fresh kidney and liver were homogenized for assessment of total anti-oxidant capacity. Median cross-sectional area of pancreatic islets of Langerhans was determined for each group by using Amscope. Cumulatively, APLE (100, 200 and 400 mg/kg respectively) dose-dependently decreased the initial FBG by 55.22, 76.15 and 77.77% respectively compared to model (-1.04%) and metformin (72.29%) groups. APLE treatment recovered damaged pancreatic β-cells and also increased median cross-sectional area (x106 μm2) of pancreatic islets compared to that of model group. APLE significantly (P < 0.05) increased total anti-oxidant capacity (5.21 ± 0.02 AscAE μg/mL) of plasma, kidney and liver compared to model (4.06 ± 0.04 AscAE μg/mL) and metformin (4.87 ± 0.03 AscAE μg/mL) groups. APLE has demonstrated glucose lowering and pancreato-protective effects in rats and arrested the characteristic loss in bodyweight associated with diabetes mellitus. This finding preliminarily confirms folk use of APLE as an anti-diabetic herbal medicine, whiles providing a rationale for further translational studies on APLE.


Co-infection with HIV associated with reduced vulnerability to symptoms of depression during antiviral treatment for hepatitis C.
In this prospective study, we examined new-onset major depressive disorder (MDD) and the differential expression of depressive symptoms in a sample of 132 HCV mono-infected and 40 HIV/HCV co-infected patients initiating pegylated interferon-based treatment, including protease inhibitor therapy. The semi-structured clinical interview (SCID-I) was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Of the total sample, 60 patients (34.9%) developed SCID-I defined MDD during antiviral treatment. The proportion of HCV mono- and HIV/HCV patients developing MDD during treatment was not significantly different (37.9% vs. 25%; p=0.185). In both groups, there was a significant increase in HAMD total score from baseline to week 4, and a significant decrease between week 24 and 6 months post-treatment cessation. The greatest increase was observed in the symptoms of the neurovegetative syndrome. HCV mono-infected patients reported higher scores than co-infected patients, particularly impaired activity and somatic symptoms, but the differences were only significant at week 12. The finding that co-infected patients appear less vulnerable to the development of depressive symptoms during HCV treatment than HCV mono-infected patients warrants further exploration, including a thorough analysis of the biological and psychosocial factors associated with this emergence.


Intrauterine growth restriction is not associated with decreased exercise capacity in adolescents with congenital heart disease.
Multiple studies demonstrate the association of intrauterine growth restriction (IUGR) with impaired aerobic fitness in adolescents and adults. To our knowledge, there are no studies including individuals with the history of both IUGR and congenital heart disease (CHD). Thus, we sought to evaluate the impact of IUGR on exercise capacity in adolescents with CHD. We conducted a retrospective chart review of patients <18 years of age who underwent cardiopulmonary exercise testing (CPET) between August 1, 2003 and July 1, 2016. Individuals with birth weight <10th percentile for gestational age were defined as IUGR. Patients with IUGR were matched with non-IUGR patients by cardiac diagnosis and age at CPET. We excluded patients >18 years of age at time of CPET, those without a documented birth weight, gestational age, or Race. A total of 282 patients were included with CHD present in 86 IUGR cases and 86 controls. There was no difference in percent predicted exercise duration (IUGR: 65.2% ± 31.2, non-IUGR: 67.4% ± 27.2; P = .67). Resting heart rate, chronotropic index, percent-predicted peak oxygen consumption, and pulmonary function were similar between groups. Regression analyses confirmed that IUGR was not independently associated with difference in percent-predicted exercise duration. Intrauterine growth restriction is not associated with the differences in the measurements of exercise capacity in adolescents with CHD. These findings contrast earlier studies, showing decreased fitness in individuals with low birth weight but without CHD. To our knowledge, this is the first study to examine the impact of IUGR on exercise capacity in patients with CHD.


Pupillary response to percutaneous auricular vagus nerve stimulation in alcohol withdrawal syndrome: a pilot trial.
Autonomic symptoms in alcohol-withdrawal syndrome (AWS) are associated with a sympathetic driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge. 30 patients suffering from alcohol use disorder, undergoing AWS, stable on medication, were recruited in this open-label, single-arm pilot trial with repeated measure design. Peripheral VNS (monophasic volt impulses of 1ms, alternating polarity, frequency 1 Hz, amplitude 4mV) was administered at the left cymba conchae for 72 hours, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as dependent variable in a repeated measures ANOVA (rmANOVA). A repeated measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F2,116 = 27.97, p < .001, ηp2 > .14). Tukey-adjusted post-hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol-craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27). Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind.


The mouse primed lymphocyte typing (mPLT)test. II. Detection of variant H-2 K and D molecules in the typing analysis of the class I-associated lymphocyte-stimulating (LS) determinants, using the B10.W lines.
The mouse primed lymphocyte typing (mPTL) assay, based on the sequential reactivation of specific immunocompetent, alloantigen-reactive T blast cells in secondary mixed leucocyte culture (MLC), has been utilized to define the major histocompatibility complex (MHC) Class I-associated lymphocyte-stimulating (LS) determinants. The test panel of secondary stimulating cells has been expanded to include 25 B10.W lines (mouse strains carrying MHC regions derived from wild mice), thus permitting examination of more than thirty 'independently derived' MHC haplotypes. Data obtained using mPLT cells generated in primary MLC between H-2 K- and/or DL-disparate strain combinations indicate that each allelic Class I product expresses a unique set of LS determinants recognized by alloreactive T lymphocytes. In addition, we have observed that Class I products, which are apparently serologically identical but which are encoded for by genes of independently derived haplotypes, can express mutually distinct LS determinants. These data suggest that T lymphocytes possess the capacity to distinguish between Class I antigens that are serologically similar (or even identical) and support the concept that LS determinants recognized by T cells are distinct from the majority of specificities recognized by B cells. This concept has marked importance in interpretation of data in the human system, for which there is now an attempt to correlate serology and PLT.


Isolation of capsid protein dimers from the tick-borne encephalitis flavivirus and in vitro assembly of capsid-like particles.
Flaviviruses have a spherical capsid that is composed of multiple copies of a single capsid protein and, in contrast to the viral envelope, apparently does not have an icosahedral structure. So far, attempts to isolate distinct particulate capsids and soluble forms of the capsid protein from purified virions as well as to assemble capsid-like particles in vitro have been largely unsuccessful. Here we describe the isolation of nucleocapsids from tick-borne encephalitis (TBE) virus and their disintegration into a capsid protein dimer by high-salt treatment. Purified capsid protein dimers could be assembled in vitro into capsid-like particles when combined with in vitro transcribed viral RNA. Particulate structures could also be obtained when single-stranded DNA oligonucleotides were used. These data suggest that the dimeric capsid protein functions as a basic building block in the assembly process of flaviviruses.


Volcanic related methylmercury poisoning as the possible driver of the end-Devonian Mass Extinction.
The end-Devonian global Hangenberg event (359 Ma) is among the most devastating mass extinction events in Earth's history, albeit not one of the "Big Five". This extinction is linked to worldwide anoxia caused by global climatic changes. These changes could have been driven by astronomical forcing and volcanic cataclysm, but ultimate causes of the extinction still remain unclear. Here we report anomalously high mercury (Hg) concentration in marine deposits encompassing the Hangenberg event from Italy and Austria (Carnic Alps). The Hangenberg event recorded in the sections investigated can be here interpreted as caused by extensive volcanic activity of large igneous provinces (LIPs), arc volcanism and/or hydrothermal activity. Our results (very large Hg anomalies) imply volcanism as a most possible cause of the Hangenberg event, similar to other first order mass extinctions during the Phanerozoic. For the first time we show that apart from anoxia, proximate kill mechanism of aquatic life during the event could have been methylmercury formed by biomethylation of a volcanically derived, huge concentration of inorganic Hg supplied to the ocean. Methylmercury as a much more toxic Hg form, potentially could have had a devastating impact on end-Devonian biodiversity, causing the extinction of many pelagic species.


The elastase-inhibitor eglin has no effect in an ovine model of endotoxemia.
Small doses of endotoxin have been shown to induce pulmonary microvascular injury in sheep, possibly by the action of granulocytes. Eglin, a potent inhibitor of neutrophil elastase, was tested in an ovine model of endotoxemia. The experiment was performed in 12 unanesthetized chronically instrumented sheep with a lung lymph preparation. Endotoxin (S. abort. equii) was infused at 24 ng/(kg x h) with application of 20 mg/kg eglin 1 h before endotoxin in the treatment group and followed by 5 mg/(kg x h). No significant improvement due to the treatment was seen for either cardiovascular status (pulmonary and systemic vascular resistance) or permeability changes in the lung (lymph flow and lymph/plasma protein ratio), although sufficient eglin concentrations were achieved in plasma and lymph. The lack of an effect of eglin might be because higher concentrations are needed to block elastase-like activity of ovine granulocytes or because of a minor role for neutrophil elastase in this shock model.


The Myxococcus xanthus two-component system CorSR regulates expression of a gene cluster involved in maintaining copper tolerance during growth and development.
Myxococcus xanthus is a soil-dwelling member of the δ-Proteobacteria that exhibits a complex developmental cycle upon starvation. Development comprises aggregation and differentiation into environmentally resistant myxospores in an environment that includes fluctuations in metal ion concentrations. While copper is essential for M. xanthus cells because several housekeeping enzymes use it as a cofactor, high copper concentrations are toxic. These opposing effects force cells to maintain a tight copper homeostasis. A plethora of paralogous genes involved in copper detoxification, all of which are differentially regulated, have been reported in M. xanthus. The use of in-frame deletion mutants and fusions with the reporter gene lacZ has allowed the identification of a two-component system, CorSR, that modulates the expression of an operon termed curA consisting of nine genes whose expression slowly increases after metal addition, reaching a plateau. Transcriptional regulation of this operon is complex because transcription can be initiated at different promoters and by different types of regulators. These genes confer copper tolerance during growth and development. Copper induces carotenoid production in a ΔcorSR mutant at lower concentrations than with the wild-type strain due to lack of expression of a gene product resembling subunit III of cbb3-type cytochrome c oxidase. This data may explain why copper induces carotenoid biosynthesis at suboptimal rather than optimal growth conditions in wild-type strains.


Manifestations of insulin-dependent diabetes mellitus in the periodontium of young Brazilian patients. A 10-year follow-up study.
Eight female and 3 male patients from a group of 30 patients studied 10 years earlier and who had received no periodontal treatment during this period, in order to evaluate the progression of untreated periodontal disease in patients with insulin-dependent diabetes mellitus, were evaluated in terms of plaque accumulation, gingival inflammation, probing depth, and alveolar bone loss. The total number of dental surfaces that presented clinically detectable plaque deposits increased significantly (29% to 43%; P < 0.01; chi 2 = 46.36). Site-specific comparisons for plaque index between studies showed a significant variation (P < 0.01) in the upper arch only for palatal surfaces and in the lower arch for the buccal and lingual surfaces. The total dental surfaces with inflamed surrounding gingiva increased from 11% to 33% in this study (P < 0.01; chi 2 = 175.78). Site-specific comparison for gingival index showed a significant variation for all upper surfaces, while such difference for the lower arch was significant only for the buccal and lingual surfaces. The arithmetic means for the probing depth for the upper buccal, upper palatal, lower buccal, and lower lingual surfaces increased significantly (P < 0.01). The arithmetic means of alveolar bone loss also increased significantly for the upper posterior and lower regions (P < 0.01) and for the upper anterior and lower anterior regions (P < 0.05). The correlation between age and probing depth was significant only for the upper palatal region (P < 0.01). The correlation between age and bone loss was significant only for the upper posterior region (P < 0.05). The results of this follow-up study suggest that despite little variation in plaque accumulation, gingival inflammation, probing depth, and bone loss increased after a 10-year interval in patients who had received no periodontal treatment during this period.


10 Gb/s operation of photonic crystal silicon optical modulators.
We report the first experimental demonstration of 10 Gb/s modulation in a photonic crystal silicon optical modulator. The device consists of a 200 μm-long SiO2-clad photonic crystal waveguide, with an embedded p-n junction, incorporated into an asymmetric Mach-Zehnder interferometer. The device is integrated on a SOI chip and fabricated by CMOS-compatible processes. With the bias voltage set at 0 V, we measure a V(π)L < 0.056 V∙cm. Optical modulation is demonstrated by electrically driving the device with a 2(31) - 1 bit non-return-to-zero pseudo-random bit sequence signal. An open eye pattern is observed at bitrates of 10 Gb/s and 2 Gb/s, with and without pre-emphasis of the drive signal, respectively.


Endovascular Approach to Glomus Jugulare Tumors.
Paragangliomas are benign neuroendocrine tumors derived from the glomus cells of the vegetative nervous system. Typically, they are located in the region of the jugular bulb and middle ear. The optimal management is controversial and can include surgical excision, stereotactic radiosurgery and embolization. We report the endovascular approach to three patients harboring glomus jugulare paragangliomas. In all cases incomplete occlusion of the lesions was achieved and recanalization in the follow-up period was revealed. Two patients presented no clinical improvement and the remaining one experienced a transient withdrawal of tinnitus. It is technically difficult to achieve complete obliteration of glomus jugulare tumors with the use of embolization and the subtotal occlusion poses a high risk of revascularization and is not beneficial in terms of alleviating clinical symptoms.


Real-world study of patients with locally advanced HNSCC in the community oncology setting.
There is a need to understand the current treatment landscape for LA HNSCC in the real-world setting. This retrospective study assessed real-world outcomes and treatment patterns of 1,158 adult patients diagnosed with locally advanced (stage III-IVB) HNSCC initiating chemoradiotherapy (CRT) within the period January 2015 to December 2017 in a large network of US community oncology practices. Structured data were abstracted from electronic health records. Demographic, clinical and treatment characteristics were analyzed descriptively overall and stratified by index treatment (cisplatin + radiotherapy [RT], cisplatin + other chemotherapy + RT, or cetuximab + RT). Time to next treatment (TTNT) and overall survival (OS) were measured using the Kaplan-Meier method, and median duration of treatment was assessed. OS was compared across treatment cohorts using multinomial logistic regression with inverse probability treatment weighting. To identify covariates associated with OS, a multivariable adjusted Cox proportional hazard model was used. This study examined 22,782 records, of which 2124 had stage III to stage IVB and no other cancers, and 1158 met all eligibility criteria. Among the treatment cohorts analyzed (cisplatin + RT, cisplatin + other chemotherapy + RT, or cetuximab + RT), cisplatin + RT was the most common concurrent chemotherapy (65.8%). Among 1158 patients, 838 (72.4%) did not initiate subsequent treatment and 139 (12.0%) died. The median TTNT and median OS were only reached by the cetuximab + RT cohort. Among patients with oropharynx primary tumor location, patients with human papilloma virus (HPV) positive status had the longest time on treatment and highest survival at 60 months. Covariates associated with improved survival were never/former tobacco use, HPV positive status, and overweight or obese body mass index. Covariates associated with poorer survival were age of 60+ years, primary tumor location of hypopharynx or oral cavity and Eastern Cooperative Oncology Group performance status score of 2+. These data describe real-world treatment patterns in locally advanced head and neck squamous cell cancer and sets the baseline to assess outcomes for future studies on the community oncology population.


Clinicians' perceptions of women's experiences of endometriosis and of psychosocial care for endometriosis.
Endometriosis is a complex, chronic condition with known psychological and social implications for women. Little is known about clinicians' perceptions of the psychosocial aspects of endometriosis and associated care. To describe clinicians' perceptions of women's experiences of living with endometriosis and of the provision of psychosocial care for endometriosis. A qualitative approach was taken using semi-structured interviews with eight gynaecologists and four general practitioners who provide care to women with endometriosis in Victoria, conducted by telephone and in person from June to December 2014. Clinicians' perceptions of women's experiences of endometriosis were consistent with those reported by women, particularly when discussing potential infertility. However, less comprehensive descriptions of the effects of endometriosis on women's work and social life and intimate relationships were observed. Some clinicians asserted that endometriosis is caused by poor mental health. General practitioners positioned themselves as best placed to provide psychosocial care to women with endometriosis; gynaecologists suggested various potential providers but rarely themselves. Most clinicians assessed themselves as not being adequately trained to understand and provide care for the psychosocial aspects of endometriosis; half of the gynaecologists did not believe it was necessary for them to do so. The findings of this research demonstrate clinicians' need for further support in the provision of psychosocial care for women with endometriosis, potentially through expanded clinical guidelines and professional development opportunities.


CXCR4 Antagonist Reduced the Incidence of Acute Rejection and Controlled Cardiac Allograft Vasculopathy in a Swine Heart Transplant Model Receiving a Mycophenolate-based Immunosuppressive Regimen.
CXC motif chemokine receptor 4 (CXCR4) blockade is pursued as an alternative to mesenchymal stem cell treatment in transplantation based on our previous report that burixafor, through CXCR4 antagonism, mobilizes immunomodulatory mesenchymal stem cells. Here, we explored the efficacy of combining mycophenolate mofetil (MMF)-based immunosuppressants with repetitive burixafor administration. Swine heterotopic cardiac allograft recipients received MMF and corticosteroids (control, n = 10) combined with burixafor as a 2-dose (burixafor2D, n = 7) or 2-dose plus booster injections (burixafor2D + B, n = 5) regimen. The efficacy endpoints were graft survival, freedom from first acute rejection, and the severity of intimal hyperplasia. Each specimen was sacrificed either at its first graft arrest or after 150 days. After 150 days, all specimens in the control group had died, but 28.5% of the burixafor2D group survived, and 60% of the burixafor2D + B group survived (P = 0.0088). Although the control group demonstrated acute rejection at a median of 33.5 days, the burixafor2D + B group survived without acute rejection for a median of 136 days (P = 0.0209). Burixafor administration significantly attenuated the incidence rate of acute rejection (P = 0.002) and the severity of intimal hyperplasia (P = 0.0097) at end point relative to the controls. These findings were associated with reduced cell infiltrates in the allografts, and modulation of C-reactive protein profiles in the circulation. The augmentation of conventional MMF plus corticosteroids with a CXCR4 antagonist is potentially effective in improving outcomes after heart transplantation in minipigs. Future studies are warranted into optimizing the therapeutic regimens for humans.


Ligament reconstruction using a semitendinosus tendon graft for proximal tibiofibular joint disorder: Case report.
We report our case of ligament reconstruction for treatment of proximal tibiofibular joint disorder using a semitendinosus tendon graft. A 21-year-old male college soccer player with no remarkable history of injury had been suffering from pain at the lateral aspect of the left knee when playing soccer. At another hospital, the patient was diagnosed with a lateral meniscus injury and cartilage injury of the external condyle of the tibia and underwent partial resection of the meniscus and bone drilling. However, his symptoms continued, and he was referred to our institution. Instability of the left proximal tibiofibular joint and pain were noted during weight-bearing dorsiflexion of the ankle. We diagnosed the case as a proximal tibiofibular joint disorder and surgically treated it by dissecting the proximal portion of the semitendinosus tendon, creating one transfibular and two transtibial tunnels, and then reconstructing the proximal tibiofibular ligament using the harvested semitendinosus tendon graft. The patient was allowed to run at postoperative 2 months, with no pain occurring while squatting at postoperative 3 months, subsequently resuming soccer at postoperative 8 months. The proximal tibiofibular joint disorder is a relatively rare pathology, and diagnosis and conservative treatment are often difficult. Although various surgical treatments are known, the clinical outcome of our case has been successful after reconstructing the anterior and posterior proximal tibiofibular ligaments using a semitendinosus tendon graft.


Association of Different Forms of Child Maltreatment With Peer Victimization in Mexican Children and Adolescents.
Objective: To examine the relationship between exposure to multiple forms of child abuse and neglect within the family context and peer victimization at school, accounting for the moderator effect of sex and educational level. Methods: Two thousand four hundred fifteen children and adolescents, aged 9 to 15 years, attending public schools in Mexico completed the Childhood Trauma Questionnaire-Short Form and a modified version of the Olweus' Bully/Victim Questionnaire. We used linear regression models to assess the association of five different forms of child abuse (emotional, physical, and sexual abuse, and emotional and physical negligence) with three forms of peer victimization (direct, indirect, and cyberbullying). Results: Direct forms of child abuse within the family (i.e., emotional, physical, and sexual abuse), but not neglect, were significantly and positively associated with a risk for peer victimization. In the fully adjusted models, emotional abuse was significantly associated with the three types of peer victimization: [indirect b = 0.48, t = 6.75, p < 0.001, direct (b = 0.47, t = 4.89, p < 0.001), and cyberbullying (b = 0.85, t = 5.45, p < 0. 001)]; while physical abuse was positive and significantly associated with direct victimization (b = 0.29, t = 3.28, p < 0.001). Boys suffering from sexual abuse within the family context showed higher levels of all subtypes of peer victimization. Students attending secondary school who suffered from sexual abuse showed higher levels of indirect victimization than did students attending primary schools. Conclusion: Child abuse within the family context seems to be associated with the risk of peer victimization. Preventive strategies to address bullying and promote resilience should take family factors into account. Interventions for high-risk families might be useful to prevent child multi-victimization.


Oxygen tension: dependent or independent variable in local control of blood flow?
We have looked at a fairly simple model of blood flow regulation at the microvascular level consisting of suffused microvascular preparations and isolated smooth muscles. When the O2 demand of the microvessel preparations was decreased by elevating suffusion solution PO2, changes in wall PO2 indicated that only the smallest microvessels could be controlled by a direct effect of oxygen. In vivo and in vitro studies of the oxygen sensitivity of smooth muscle indicated that even the smaller vessels were probably not directly controlled by oxygen availability during a free flow state, since measured perivascular PO2's did not fall to levels low enough to alter contractile performance of the vascular smooth muscle. Our data indicate that in any condition in which flow is interrupted for periods in excess of about 30 sec, one might anticipate vascular relaxation due to oxygen lack. It was judged resonable to extrapolate our findings to autoregulation of blood flow in resting skeletal muscle and to responses to modest exercise. Our data indicate that it is improbable that oxygen acts by a direct effect on the smooth muscle under these conditions. On the other hand, they suggest that a direct effect of oxygen might well be important in causing postocclusion hyperemia.


Therapeutic benefit of converting-enzyme inhibition in progressive renal disease.
Systemic hypertension is both the cause and the consequence of renal disease. Experimental studies suggest that the adverse effects of systemic hypertension on the progression of renal disease may depend upon the intraglomerular hemodynamic consequences. Systemic hypertension accompanied by afferent arteriolar vasoconstriction is associated with normal glomerular capillary pressure and relative protection against morphologic injury. In contrast, systemic hypertension with afferent arteriolar vasodilatation leads to glomerular hypertension and is associated with structural injury. Glomerular hypertension may be present even in the setting of normal systemic pressure, as in experimental diabetes. Therapeutic interventions that attenuate glomerular capillary hypertension slow the development of glomerular injury. Dietary protein restriction, which normalizes glomerular capillary filtration, perfusion, and pressure without lowering blood pressure, retards the development of glomerular sclerosis. Alternatively, selective reduction of glomerular capillary pressure with converting-enzyme inhibitor therapy is also protective against progressive renal injury. In contrast, antihypertensive therapy, which controls systemic hypertension but does not reduce glomerular capillary pressure, fails to protect remnant kidney rats from glomerular injury. These studies suggest that control of glomerular hypertension may be of special benefit to the patient with progressive renal disease.


Myxococcus-from single-cell polarity to complex multicellular patterns.
Myxococcus xanthus creates complex and dynamic multicellular patterns as it swarms. The cells have two polar gliding engines: pulling type IV pili at their leading pole and pushing slime secretory nozzles at their lagging pole. Evidence is presented that slime secretion is vital for cell survival and that the peptidoglycan/cytoskeleton serves as a template to keep both engines oriented in the same direction. Swarming requires that each cell periodically reverse its gliding direction. For the leading pole to become the trailing pole, old engines are inactivated at both ends while new engines are being created at both ends. Reversal is initiated by a small G-protein reversal switch; a pulse of frzE approximately P from a reversal clock triggers MglA to bind GTP. Mgl.GTP then recognizes the engines that are currently in use and inactivates both of them. Meanwhile, new engines appear as instructed by the template, and the cell starts to glide in the opposite direction.


Analysis of the publishing rate and the number of citations of general surgery dissertations.
A dissertation is a scientific document. However, if it is not published in a scientific journal, it will gain access to only a limited audience and thus will be unable to achieve its objective. Nevertheless, the rate of publishing in journals is not high among dissertations. In this study, we aimed to investigate the publishing rates of general surgery dissertations in journals and the total number of citations. All medical dissertations that have been prepared at general surgery departments of university hospitals and presented between the years 2006 and 2008 were analyzed. The authors checked whether the dissertations were published in a journal or not, by searching the dissertation in 4 different resources with the name of their authors. Two hundred and thirty-two dissertations were included. Half of those dissertations were experimental animal studies. Seventy dissertations were published in various journals. Fifty one (22%) of these were published in Science Citation Index Expanded journals, while 19 (8.1%) of them were published in Turkish non-Science Citation Index Expanded journals. There was no significant difference in terms of publishing rates between study types. The number of annual citations per article was 1.1. The writer of the dissertation was the first author in 35 (68,6%) articles. The publishing rates of dissertations in general surgery is low, with only 22% being published in Science Citation Index Expanded journals. The citation rate was also detected to be low in our study. Consequently, a dissertation should be considered as a scientific research study and planned as such, not as obligatory assignments. The publishing rates of dissertations should be increased, and authors should be led and encouraged to publish their dissertations.


Promotion of hepatocarcinogenesis in vivo and in vitro.
Various chemicals including phenobarbital (PB) have been shown to act as promoters in hepatocarcinogenesis in rodents. The effect of initiation and/or promotion of chemicals can be quantitatively measured by scoring the number and size of enzyme-altered islands (EAI). The effect of promotion is proportional to the period of treatment and is much greater when the promoter is given earlier after initiation. A unique aspect of hepatic promoters is their inhibitory action against carcinogenesis when given simultaneously with a carcinogen, reducing both the initiating and promoting activities of the carcinogen. With the aid of the promoting action of PB, carcinogenic activity of pure initiators is demonstrated. Promoting effect of PB was found at as low a dose as 5 ppm, which corresponds to 20 mg per 50 kg person per day, a dose several times less than the common therapeutic dose. In an attempt to analyze the mechanism of promotion and also to develop a model system for detecting environmental promoters in vitro, hepatic cells obtained from animals during carcinogenic treatment were transferred to a culture system. Cells comprising EAI after a certain critical stage gave rise to proliferative epithelial cell foci. Some hepatic promoters showed a growth enhancing effect on these foci while others did not, suggesting both the existence of direct action by some promoters on initiated cells and the presence of different promoter mechanisms. Chronic treatment with PB selectively induced gamma-glutamyl transpeptidase activity in "spontaneous" hepatomas of C3H mice, suggesting that PB may enhance the expression of altered gene functions of initiated cells.


Absence of a cAMP-mediated antiabsorptive effect in an undifferentiated jejunal epithelium.
In the relatively undifferentiated jejunal mucosa occurring in piglet viral enteritis, we measured the response of transepithelial Na+ and Cl- fluxes in vitro to raised intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. At the acute 40-h stage of transmissible gastroenteritis (TGE), luminal membrane markers, sucrase and lactase, and a basolateral jejunal epithelial membrane marker Na+-K+-ATPase, were significantly decreased in activity, while a proliferative marker, thymidine kinase, was significantly enriched; these enzyme characteristics are typical of enterocytes isolated from crypts of other species. As expected, control piglet jejunum in short-circuited Ussing chambers after theophylline (10 mM) developed significant net secretory Na and Cl fluxes primarily due to significant antiabsorptive effects (delta JNa m----s = 3.48 +/- 0.52, delta JCl m----s = 2.59 +/- 0.28). Furosemide (10(-4) M), an inhibitor of electroneutral NaCl cotransport, produced antiabsorptive effects (delta JNa m----s = 2.53 +/- 0.31, delta JCl m----s = 2.58 +/- 0.28) in control jejunum that were not significantly different from those seen in response to theophylline. TGE jejunum, however, responded to theophylline not by an antiabsorptive effect but by significant electrogenic Cl- secretion (delta JCl s----m = 1.59 +/- 0.48); furosemide had no effect on ion fluxes in TGE tissue. Control and TGE jejunal mucosal homogenates did not differ in their basal or theophylline-stimulated levels of cAMP. We conclude that the relatively undifferentiated small intestine occurring in acute TGE does not generate either a cAMP-mediated antiabsorptive effect or a furosemide-mediated antiabsorptive effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Transvaginal laparoscopic appendectomy using innovative submucosal tunnels: a conducive modification for improving hybrid NOTES access and its critical appraisal.
Currently, transvaginal natural orifice transluminal endoscopic surgery (NOTES), the most minimally invasive option for laparoscopic surgery, suffers various technological restraints limiting its implementation. We discuss a simple modification for vaginal access to improve the existing hybrid NOTES technique. We retrospectively studied 18 women at our rural hospital in central India, who, under defined criteria, underwent transvaginal appendicectomy using innovative strategically designed submucosal tunnels. The procedure was successfully completed in all but the first three cases. None required additional abdominal trocar or analgesia beyond the first 6 h. The mean operative and hospitalisation times were 27.5 min and 18.5 h, respectively. We had no intraoperative complications and only one patient experienced postoperative self-limiting vaginal spotting. All patients were very pleased with the cosmetic results and sexual life as assessed by locally devised scales. On regular follow-up, all were progressing well. We recommend the method presented, as it is not only feasible and safe but has the potential to improve overall results. Clearly, a larger volume randomised trial would be optimal to confirm our conclusion.


Incidence of central line related/associated bloodstream infections in an acute hospital.
Bloodstream infection related to a central venous catheter in the intensive care unit is a substantial clinical and economic problem. The aim of the study was to examine the incidence of central line related bloodstream infections and central line associated bloodstream infections in Our Lady of Lourdes Hospital, Drogheda, during a six month period, using an active patient based prospective surveillance method. CLRBSI rate in ICU/HDU was 0.93/1000 central line days. There was no CLABSI identified in the studied time period. However, further interventions are needed, particularly with CVC care bundle. Also, the implementation of 2% chlorhexidin in 70% isopropylalcohol use for skin asepsis, which is recommended by the Irish national guidelines, would be beneficial.


Comparative patterns of hepatic drug metabolizing enzymes and their possible correlation with chromosomal aberrations in transplantable murine lymphoma: a time course study.
The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt. P-450), UDP-glucuronyl transferase (UDPGT), cytosolic glutathione-S-transferase (GSHT) activities, and major chromosomal aberrations were evaluated over various periods of time, following tumor transplantation in male Swiss Albino mice. Changes in the above markers were studied (1) to monitor the entire carcinogenic process and (2) to test the suitability of chemopreventive exposures in terms of phase and duration of tumor growth. The microsomal cyt. P-450 content and the UDPGT activity were significantly elevated (p < 0.01-0.001) from the early stages of tumor growth while the cytosolic GSHT activity reached its highest level (p < 0.01-0.001) only 10 days after tumor transplantation. During the later stages of tumor growth all the biotransforming enzyme activities showed a downhill trend, which was significantly lower than that of their normal counterparts (p < 0.01-0.001). The frequency of different chromosomal aberrations, which were of major structural, numerical, and physiological types, increased steadily throughout the entire length of the carcinogenic process (30 +/- 2 days).


A theoretical rationale why furan-side monoadduct is more favorable toward diadduct formation in 8-methoxypsoralen and thymine complexes.
The photoinduced mechanism of formation of mono- and diadducts between 8-MOP and thymine bases is studied using the ONIOM(MPWB1K/6-31 + G(d,p):B3LYP/6-31G(d,p):UFF) and B3LYP/6-31 + G(d,p) methods. The relevant cycloaddition displays favorable energy barriers and reaction energies in the triplet excited state, which involves the initial formation of a diradical followed by ring closure via singlet-triplet interaction. The monoadduct on the pyrone side is favored over the furan side when comparing reaction energies. The distinguishing feature in the formation of the monoadducts is that the furan-side adduct displays a better photostability, which is a relatively high-barrier exothermic reaction, and thus the energy balance of the monoadduct on the furan side toward final diadduct formation is favored.


Sensitivity of Neuropsychological Tests to Identify Cognitive Decline in Highly Educated Elderly Individuals: 12 Months Follow up.
Highly educated individuals have a lower risk of developing dementia and Alzheimer's disease (AD). A common assumption is that their "cognitive reserve" protects them from cognitive decline and postpones the clinical manifestation of dementia. These highly educated individuals usually obtain normal scores on cognitive screening tests, although at the same time they can experience subjective cognitive decline and difficulty in multiple cognitive domains. Although comprehensive neuropsychological evaluations usually identify subtle changes in cognition, they demand extensive resources and thus are expensive and difficult to obtain. Therefore, lack of sensitivity of screening tests on the one hand, along with difficulty to acquire a comprehensive neuropsychological evaluation on the other hand, impede identification of cognitive decline at its earliest stages in this special population. Accordingly, this study aims to identify which neuropsychological tests have the highest sensitivity to detect the earliest stages of cognitive decline among highly educated elderly [n = 27, ages 66-80 (mean = 72.6 SD = 4.54), mean education level = 17.14 (SD = 3.21 range: 12-24 years)]. Baseline scores and scores at one-year follow up were obtained. We also conducted MRI scans to characterize the relation between brain volume and cognitive performance. Results show significant reductions in RVALT, Semantic verbal Fluency, ROCF copy, and MoCA scores whereas PF, TMT, ROCF delay, digit span, and knowledge tests were not significant. The study stresses the importance of using sensitive neuropsychological tests to examine this special population and the need to create norms that combine an individual's education with age.


Progress of cell proliferation in striated muscle tissues during development of the mouse tongue.
The developmental stages of and places for the proliferation of tongue muscle cells have not yet been determined. To determine the stages of and places for proliferation between embryonic day (E) 9 and birth, we analyzed the expression of cyclin D1 mRNA and the immunolocalization for proliferating cell nuclear antigen (PCNA). The ratio of PCNA-positive nuclei to total nuclei (PCNA-labeling index) was obtained in the anterior, middle, and posterior regions. Cyclin D1 mRNA was highly expressed between E11 and E13, but decreased thereafter until birth. The distribution of PCNA-positive cell nuclei was consistent with that of myogenic cells in the occipital somites at E9. The PCNA-labeling index was highest at E11, then decreased until birth without a significant difference among the 3 regions. These findings suggest that some tongue muscle progenitor cells begin proliferation in the occipital somites at E9, and that the proliferation in the whole tongue region occurred most actively between E11 and E13, then decreased until birth without regional differences.


Gelation of Limulus lysate by synthetic dextran derivatives.
The Limulus test has been considered specific for the presence of bacterial endotoxins. To synthesize a simple model of endotoxin, palmitoyldextran phosphate was prepared by modification of dextran by palmitoylation and phosphorylation. The present studies indicated that a variety of polysaccharide derivatives, such as palmitoyldextran phosphate, palmitoyldextran, and dextran phosphate, give a positive Limulus test and show pyrogenic activity, except for low molecular dextran derivatives. On the other hand, polysaccharides, such as dextran, starch (soluble-, chitosan, xylan, and lentinan, were negative in these assays. The gelation reaction of Limulus lysate by modified dextran derivatives may depend on the molecular weight or modification of polysaccharides by palmitoylation and/or phosphorylation to a great extent.


[Ampulla fibrotuboscopy].
During a microsurgical operation the opportunity was taken to inspect the ampulla of the tube with a soft fibroscope in 68 patients. Several different normal and pathological appearances were found. Ampullary endoscopy gives much more precise information than salpingography and a very valuable prognosis because 14 normal pregnancies occurred where the tubes had been considered to be normal whereas no intra-uterine pregnancy occurred where the tubes were thought to be pathological. Instead, they re-obstructed or were the sites of ectopic pregnancies. This complementary examination carried out during operation seems to be a useful prognostic measure for patients undergoing ampullary surgery.


Behaviorally based clinical evaluation.
For the past two years this clinical evaluation tool has been revised biannually by the original committee. Feedback has been solicited from the entire faculty and incorporated into the subsequent revisions. In using the tool it is apparent that there are benefits for both students and faculty. Evaluation of the student is simplified because it is based on behaviorally described competencies. Because of this, consistency is further assured regardless of the number of evaluators. The faculty not only have a tool that is short and manageable enough to provide daily feedback but they also have the ease of using pass or fail for most of the evaluations. Students are better able to channel their energies and ultimately their behaviors to focus on necessary competencies to become an effective care giver. Students have the benefit of objective evaluation of their behaviors with an opportunity for daily feedback. The student is aware of expected performance levels prior to evaluation as well as the need for progress in those competencies. While the tool in its present format still has some shortcomings, the entire faculty have had the pleasure of knowing that as a group they have created a workable and discriminating evaluation tool.


Ineffectiveness of adenine arabinoside and adenine arabinoside 5'-monophosphate in simian varicella infection.
Adenine arabinoside and adenine arabinoside 5'-monophosphate (ara-AMP) have been evaluated for antiviral activity against simian varicella virus infection in monkeys. In a preliminary study for toxicity, intramuscular injection of ara-AMP at 15 mg/kg per day as a single injection for 5 days to two normal patas monkeys caused no detectable local reaction, no weight loss or changes in serum transaminase levels, and no hematological abnormalities. When this dose was given in the treatment of four simian varicella virus-infected patas monkeys, no effect was observed on the clinical course of infection, as compared with four infected monkeys which received phosphate-buffered saline. Treatment was begun 43 h after virus inoculation and was continued for 16 days. Toxicity of intravenously administered ara-AMP at 100 to 50 mg/kg per day for 5 days to pairs of uninfected patas monkeys was evident by hematological and hepatic histological alterations, as well as the death of one monkey in each pair. No gross evidence of toxicity occurred in two monkeys which received 20 mg of ara-AMP per kg per day. The antiviral efficacy of intravenous treatment was studied in groups of four African green monkeys which received adenine arabinoside at 15 mg/kg per day or ara-AMP at 18.4 mg/kg per day. Drug administration began 48 h after inoculation with simian varicella virus and continued for 10 days. The monkeys that received treatment did not respond to infection differently from four infected control monkeys similarly treated with phosphate-buffered saline.


The Superfund Basic Research Program--making a difference: past, present, and future.
Understanding exposure continues to be a paramount challenge and critical element in successfully managing Superfund sites. The Superfund Basic Research Program, administered by the National Institute of Environmental Health Sciences, an institute of the National Institutes of Health, is committed to providing the nation's decision makers with better tools to identify the routes and effects of exposure and develop innovative technologies to reduce exposures. In this article, we demonstrate how the program contributes to understanding the exposure disease link, highlight the cutting-edge and practical nature of this very fundamental research program and discuss its approach to addressing these problems. We also identify several broad themes that are likely to direct the program's future research endeavors.


Rheumatoid factors in leprosy and parasitic diseases.
Rheumatoid factors (RFs) occur with higher frequency and in higher titres in multibacillary forms of leprosy and several parasitic diseases than in healthy controls. The selection of controls is essential in studies of this kind. They should be individuals without signs of the disease under study living under similar socioeconomic conditions as the patients in the endemic country. In three studies where this matter was considered, RFs in lepromatous leprosy and Chagas' disease reacted more strongly with rabbit than human IgG, a feature generally considered to be quite restricted to rheumatoid arthritis. RFs interfere in various test systems, particularly in inducing false positive reactions for specific IgM antibodies in parasitic and other infectious diseases. Model experiments in rats, in vitro culture studies, and observations in humans indicate that RFs may have a protective role in trypanosome infections, malaria and schistosomiasis respectively.


Plasmacellular hyperplasia after allogeneic bone marrow transplantation.
B lymphoid cells with monotypic immunoglobulin (Ig) expression, i.e., a single Ig heavy chain isotype combined with a single light chain type, were observed in five of nine patients after allogeneic bone marrow transplantation. Three patients exhibited plasmacellular hyperplasia of lymph nodes and spleen; in one case the monotypic cells were immunoblasts in a lymph node, and one patient suffered from an immunoblastic lymphoma along the gastrointestinal tract. We present the clinical history and the detailed (immuno) histologic analysis of lymphoid tissue from three patients. In DNA analysis of lymph node using DNA probes specific for the JH-gene segment of Ig heavy chains and for light chains, bands indicative of single Ig gene rearrangements were not observed. Thus, the monotypic B lymphoid elements represent polyclonal B cell expansion.


Molecular characterization of podoviral bacteriophages virulent for Clostridium perfringens and their comparison with members of the Picovirinae.
Clostridium perfringens is a Gram-positive, spore-forming anaerobic bacterium responsible for human food-borne disease as well as non-food-borne human, animal and poultry diseases. Because bacteriophages or their gene products could be applied to control bacterial diseases in a species-specific manner, they are potential important alternatives to antibiotics. Consequently, poultry intestinal material, soil, sewage and poultry processing drainage water were screened for virulent bacteriophages that lysed C. perfringens. Two bacteriophages, designated ΦCPV4 and ΦZP2, were isolated in the Moscow Region of the Russian Federation while another closely related virus, named ΦCP7R, was isolated in the southeastern USA. The viruses were identified as members of the order Caudovirales in the family Podoviridae with short, non-contractile tails of the C1 morphotype. The genomes of the three bacteriophages were 17.972, 18.078 and 18.397 kbp respectively; encoding twenty-six to twenty-eight ORF's with inverted terminal repeats and an average GC content of 34.6%. Structural proteins identified by mass spectrometry in the purified ΦCP7R virion included a pre-neck/appendage with putative lyase activity, major head, tail, connector/upper collar, lower collar and a structural protein with putative lysozyme-peptidase activity. All three podoviral bacteriophage genomes encoded a predicted N-acetylmuramoyl-L-alanine amidase and a putative stage V sporulation protein. Each putative amidase contained a predicted bacterial SH3 domain at the C-terminal end of the protein, presumably involved with binding the C. perfringens cell wall. The predicted DNA polymerase type B protein sequences were closely related to other members of the Podoviridae including Bacillus phage Φ29. Whole-genome comparisons supported this relationship, but also indicated that the Russian and USA viruses may be unique members of the sub-family Picovirinae.


Genomic variation in neurons.
Neurons born during the fetal period have extreme longevity and survive until the death of the individual because the human brain has highly limited tissue regeneration. The brain is comprised of an enormous variety of neurons each exhibiting different morphological and physiological characteristics and recent studies have further reported variations in their genome including chromosomal abnormalities, copy number variations, and single nucleotide mutations. During the early stages of brain development, the increasing number of neurons generated at high speeds has been proposed to lead to chromosomal instability. Additionally, mutations in the neuronal genome can occur in the mature brain. This observed genomic mosaicism in the brain can be produced by multiple endogenous and environmental factors and careful analyses of these observed variations in the neuronal genome remain central for our understanding of the genetic basis of neurological disorders.


Vitamin E forms in Alzheimer's disease: a review of controversial and clinical experiences.
Vitamin E is a collective term for eight naturally occurring compounds, four tocopherols (alpha-, beta-, gamma-, and delta-) and four tocotrienols (alpha-, beta-, gamma-, and delta-). Although it is the major form of vitamin E in US diets, gamma-tocopherol receives little attention when compared to alpha-tocopherol, which is generally found in supplements and most studied for its effects on progression of cognitive impairment. Many clinical trials had been conducted with vitamin E and neurodegenerative disorders, with controversial results, including a recent study which disproves the benefit of vitamin E for Mild Cognitive Impairment and Alzheimer's Disease. This study examined the alpha-tocopherol supplement instead of gamma-tocopherol. Gamma-tocopherol has been found to be more effective in scavenging free radicals and nitrogen oxygen species that cause inflammation; both of these are components of neurodegenerative disorders. Secondly, the use of alpha-tocopherol supplements significantly reduces serum gamma-tocopherol, and this may have important biological effects. Therefore, any potential health benefits of alpha-tocopherol supplements may be offset by deleterious changes in the bioavailability of other forms of tocopherols and tocotrienols. This might account for the null effects of alpha tocopherol supplementation in Mild Cognitive Impairment and Alzheimer's Disease.


A novel compact broadband and radiation efficient antenna design for medical IoT healthcare system.
This paper investigates and develops a novel compact broadband and radiation efficient antenna design for the medical internet of things (M-IoT) healthcare system. The proposed antenna comprises of an umbrella-shaped metallic ground plane (UsMGP) and an improved radiator. A hybrid approach is employed to obtain the optimal results of antenna. The proposed solution is primarily based on the utilization of etching slots and a loaded stub on the ground plane and rectangular patch. The antenna consists of a simple rectangular patch, a 50 Ƹ microstrip feed line, and a portion of the ground plane printed on a relatively inexpensive flame retardant material (FR4) thick substrate with an overall compact dimension of 22 × 28 × 1.5 mm3. The proposed antenna offers compact, broadband and radiation efficient features. The antenna is carefully designed by employing the approximate calculation formulae extracted from the transmission line model. Besides, the parameters study of important variables involved in the antenna design and its influence on impedance matching performance are analyzed. The antenna shows high performance, including impedance bandwidth of 7.76 GHz with a range of 3.65Ƀ11.41 GHz results in 103% wider relative bandwidth at 10 dB return loss, 82% optimal radiation efficiency in the operating band, reasonable gain performance, stable monopole-shaped radiation patterns and strong current distribution across the antenna lattice. The suggested antenna is manufactured, and simulation experiments evaluate its performance. The findings indicate that the antenna is well suited for medical IoT healthcare systems applications.


An evaluation of the value of first thyroglobulin determination in the diagnostics of metastases immediately following differentiated thyroid carcinoma surgery.
Evaluation of the differential value of the first thyroglobulin (Tg) concentration, measured after thyroidectomy (Tx) but before thyroid remnant ablation, in patients with differentiated thyroid carcinoma (DTC) as a marker of either metastases or residual cancer (M). Data from 517 patients with DTC after Tx, with follow-up > 1.5 year were analysed retrospectively. Patients in whom either the course of the disease was unclear or interference in the Tg test was possible (a-TgAb [+], Tg recovery < 80%) were excluded from the study. Finally, the data from 247 patients were evaluated (age: 14-79 years; 223 women, 24 men). The results of TSH, thyroid radioiodine uptake (T(up24)), thyroid remnant volume (V) and Tg in patients with diagnosed M (group M1; n = 35) were compared with the same parameters in patients with remission > 1.5 year (group M0; n = 212). The area under the ROC curve was calculated. The clinical decision limit of Tg level to be suggestive of metastases was determined by means of efficiency curve. Groups M0 and M1 did not differ from each other with respect to TSH concentration (median 49.7 mIU/l vs 44.3; p = 0.16) or thyroid remnant volume (1.4 vs 1.1 ml; p = 0.79). However, they did differ with respect to T(up24) (7.6 vs 3.2%; p = 0.01) and Tg (4.5 vs 96.7 ng/ml; p = 0.000000). Area under ROC for Tg was 0.78 +/- 0.05 (mean +/- s.e.m.). The decision limit of Tg for suspected M was determined at 38.1 ng/ml, Tg sensitivity was 0.57 (95%CI 0.39-0.74) and specificity 0.96 (95%CI 0.92-0.98). First thyroglobulin concentration, determined after thyroidectomy but before other treatment, is higher in patients with metastatic DTC than in patients without such metastases. This indicates that Tg level may be used as an early marker of either residual or metastatic DTC (even if thyroid remnants are present).


[Association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia].
To assess the association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia. For 330 patients with primary azoospermia and 282 fertile male controls, single nucleotide polymorphisms (SNPs) of DICER rs3742330 and DROSHA rs10719 were determined with a restriction fragment length polymorphism (RFLP) method. For the SNP rs3742330, the frequency of A allele was higher among azoospermia patients compared with the controls (72.0% vs.64.4%, P=0.004), and so was the frequency of AA genotype (53.0% vs. 41.8%, P=0.027, OR=1.829, 95%CI: 1.071-3.124). On the other hand, the allelic and genotypic frequencies of rs10719 did not differ between the two groups (all P > 0.05). Polymorphisms of rs3742330 of the DICER gene, particularly the AA genotype, may be associated with azoospermia.


A keratinocyte's course of life.
An adequate permeability barrier function of the mammalian epidermis is guaranteed by the characteristic architecture of the stratum corneum. This uppermost layer consists of a highly organized extracellular lipid compartment which is tightly joined to the corneocytes. The generation of the extracellular lipid compartment and the transformation of the keratinocytes into corneocytes are the main features of epidermal differentiation. However, equally important is the continuous renewal of the stratum corneum, which is insured by a careful balance between the replenishment of new keratinocytes from the proliferating basal layer, and the well-orchestrated loss of the most superficial cells after the so-called 'epidermal programmed cell death'. In this overview, the complete life of keratinocytes is described, from the proliferative organization to the process of desquamation.


JUCHMME: a Java Utility for Class Hidden Markov Models and Extensions for biological sequence analysis.
JUCHMME is an open-source software package designed to fit arbitrary custom Hidden Markov Models (HMMs) with a discrete alphabet of symbols. We incorporate a large collection of standard algorithms for HMMs as well as a number of extensions and evaluate the software on various biological problems. Importantly, the JUCHMME toolkit includes several additional features that allow for easy building and evaluation of custom HMMs, which could be a useful resource for the research community. http://www.compgen.org/tools/juchmme, https://github.com/pbagos/juchmme. Supplementary data are available at Bioinformatics online.


Reply to Boyle's "Who is entitled to double effect?
I have only minor quibbles with Boyle's presentation of my version of the Doctrine of Double Effect (DDE) (Boyle, 1991). On my view, the extra morally problematic element in cases of direct intention is the subordination of a victim to purposes that he or she either rightfully rejects or (and this is something that I should now wish to add in light of Boyle's criticisms) cannot rightfully accept. In cases of indirect intention the victim is incidentally affected by an agent's strategy, but in cases of direct intention the victim is made part of the strategy. Boyle suggests at one point that this amounts to using the person.... But I do not think the "using" metaphor is always apt in these cases, although it is perhaps helpful in pointing to the objectionable element in direct intention, which in its perfectly general form can be put only more abstractly.... My only other concern with Boyle's exposition of my view involves his use of the expression "intentionally harming"....The discussion there tends to suggest, in contrast to what Boyle has said earlier, that I represent DDE as discriminating between cases of incidental and intentional harming. But this is precisely what I tried to avoid....


CD4+-T-cell responses generated during murine Salmonella enterica serovar Typhimurium infection are directed towards multiple epitopes within the natural antigen FliC.
The flagellar filament protein FliC is a natural antigen recognized by memory CD4+ T cells recovered from Salmonella enterica serovar Typhimurium-infected humans and mice. To further investigate T-cell responses to FliC, we derived FliC-specific CD4+-T-cell clones from mice of two different haplotypes following oral S. enterica serovar Typhimurium infection. Using C-terminal truncations of MalE-FliC recombinant fusion proteins, we mapped antigenic activity to four different regions of FliC; three of the four epitope-containing regions were present in both FliC and the alternate flagellin subunit FljB. We determined that two novel FliC epitopes were also present in flagellins from several gram-negative enteric bacterial species: E(k)-restricted FliC 80-94 (amino acids 80 to 94) and A(b)-restricted FliC 455-469. Further mapping confirmed the presence of two previously identified FliC epitopes: A(k)-restricted FliC 339-350 and A(b)-restricted FliC 428-442. Therefore, like the recognition site of the innate immune receptor Toll-like receptor 5, three of four FliC epitopes recognized by CD4+ T cells colocalize in the D0/D1 domains of FliC. Salmonella-infected macrophages and dendritic cells stimulated epitope-specific CD4+-T-cell proliferation; infected dendritic cells also activated T cells to produce gamma interferon. These data demonstrate that Salmonella infection generates murine CD4+-T-cell responses to multiple epitopes in the natural antigen FliC and that recognition of infected phagocytes by FliC-specific CD4+ T cells triggers effector functions known to be essential for protective immunity. Together, these data suggest that FliC-specific CD4+ T cells may contribute to cell-mediated host defenses against Salmonella.


Isolation of four new pterocarpans from Zygophyllum eurypterum (Syn. Z. atriplicoides) with enzyme-inhibition properties.
Four new pterocarpans, atricarpan A (=(-)-1,2-dihydroxy-4-(hydroxymethyl)-3,9-dimethoxypterocarpan; 1), atricarpan B (=(-)-2,3-ethylenedioxy)-1,4-dihydroxy-9-methoxypterocarpan; 2), atricarpan C (=(-)-1,9-dimethoxypterocarpan-3-carboxylic acid; 3), and atricarpan D (=(-)-2,9-dimethoxy-4-(5-oxohexyl)pterocarpan; 4) were isolated from the BuOH extract of the whole plant of Zygophyllum eurypterum. The structure elucidations of those compounds were based primarily on 1D- and 2D-NMR analysis, including COSY, HMBC, and HMQC correlations. Compounds 1-4 also inhibited butyrylcholinesterase (BChE; EC 18.104.22.168) enzyme in a concentration-dependent manner with IC(50) values between 12.5-65.0 microM. Similarly, compounds 1 and 4 inhibited lipoxygenase (LOX; EC 184.108.40.206) and acetylcholinesterase (AChE; EC 126.96.36.199) enzymes with IC50 values of 13.5 and 20.5 muM, respectively.


Reaction mechanism of uracil bromination by HBrO: a new way to generate the enol-keto form of 5-bromouracil.
Knowledge on the uracil bromination reaction is helpful for understanding the origin of the mutagenicity of 5-bromouracil (BrU). To get more details about this reaction, we explore the corresponding reaction mechanism by theoretical method. A total of seven pathways were studied for this purpose. The diketo form of BrU is observed as the main product in these pathways, which agrees well with experimental results. The most energy-favorable reaction pathway is found to be that Br and OH attacked the opposite sides of uracil. The reaction intermediate reported in the experiment is predicted to be reasonably stable. In the following step, a dehydration process occurs between H11 and O13-H14 when there are no explicit H(2)O taking part. However, when there are explicit water molecules in the environment, explicit H(2)O will lower the reaction barrier in the formation of reaction intermediates and the final product BrU. A proton-transfer process from C5 to O10 is facilitated by explicit H(2)O, which results in enol-keto form intermediate of this modified base (defined as BrU*). These results indicate a new way to generate the enol-keto form of BrU.


[The relation of workspace and installation space of epicyclic kinematics with six degrees of freedom].
The kinematics of a robotic device significantly determines its installation space when it comes to technical realisation. With regard to the deployment of robotic manipulators in surgery, manipulators with a preferably small installation space are needed. This study describes six versions of novel epicyclic kinematics with six degrees of freedom (DOF). At first, the kinematics functionality was analysed using Gruebler's formula. Subsequently, the quantitative determination of the relation of workspace and installation space was performed using Matlab algorithms. To qualitatively describe the shape of the workspace, the Matlab visualisation features were utilised. For comparison, the well-known Hexapod was used. The assessed kinematics had 6-DOF-functionality. It became apparent that one version of the epicyclic kinematics having two 3-DOF disk systems mounted in a parallel way featured a particularly good relation of workspace and installation space. Compared to the Hexapod, this is approximately four times better. The shape of the workspaces of all epicyclic kinematics assessed was convex and compact. It could be shown that a novel epicyclic kinematics has a notably advantageous relation of workspace and installation space. Apparently, it seems to be well suited for the deployment in robotic machines for surgical procedures.