Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy.
Thymidine kinase is involved in nucleic acid synthesis and is, therefore, considered to be an important proliferation tumor marker. For this reason, we monitored this marker in the course of colorectal cancer chemotherapy. We examined thymidine kinase (TK) levels in 30 patients with colorectal cancer who underwent adjuvant or palliative chemotherapy (CHT schemes). The condition for being included in the study was a minimum of 3 cycles of chemotherapy. TK was always assessed with radio-receptor analysis, before and after every chemotherapy cycle, together with other tumor markers. From the monitored tumor markers, only TK changed typically in the course of chemotherapy. In adjuvant chemotherapy, it was mostly low at the beginning of the cycle and its values usually increased considerably at the end. On the other hand, in palliative chemotherapy the dynamics of TK varied mainly depending on the effect of the therapy. Other tumor markers showed nonstandard behavior and minimal correlation with TK changes. Thymidine kinase seems to be a suitable parameter for monitoring the effect of adjuvant and palliative chemotherapy in colorectal cancer.


Plants with neurotoxic potential in undernourished subjects.
The consumption by humans of plants with potential to induce neurological disorders is widespread, but overt disease surfaces only when the subject's toxic threshold is exceeded. Excessive intake arising from food dependency in the setting of hunger, chronic undernutrition, vitamin deficiency, inadequate detoxication, or other individual susceptibility, can trigger acute encephalopathy (lychee, ackee fruits), sub-acute spastic paraparesis (grasspea, cassava root/leaves) or ataxic neuropathy (cassava root flour). While these disorders are very rarely encountered in high-income countries, they are not only common among impoverished populations but also often occur as outbreaks that impact a significant proportion of an affected community. Unfamiliarity with the adverse effects of plant toxins has sometimes led to the mistaken attribution of nutritional neurotoxic disease to a neurotropic viral or synthetic pesticidal etiology. The combination of human population growth, food and water insecurity, poverty and, with climate change, increased dependency on environmentally tolerant plants with neurotoxic potential, predictably may result in an increased prevalence of nutritional neurotoxic disorders, especially in certain parts of Africa and Asia.


Object-level image segmentation using low level cues.
This paper considers the problem of automatically segmenting an image into a small number of regions that correspond to objects conveying semantics or high-level structure. Although such object-level segmentation usually requires additional high-level knowledge or learning process, we explore what low level cues can produce for this purpose. Our idea is to construct a feature vector for each pixel, which elaborately integrates spectral attributes, color Gaussian mixture models, and geodesic distance, such that it encodes global color and spatial cues as well as global structure information. Then, we formulate the Potts variational model in terms of the feature vectors to provide a variational image segmentation algorithm that is performed in the feature space. We also propose a heuristic approach to automatically select the number of segments. The use of feature attributes enables the Potts model to produce regions that are coherent in color and position, comply with global structures corresponding to objects or parts of objects and meanwhile maintain a smooth and accurate boundary. We demonstrate the effectiveness of our algorithm against the state-of-the-art with the data set from the famous Berkeley benchmark.


On the Capacity of Amplitude Modulated Soliton Communication over Long Haul Fibers.
The capacity limits of fiber-optic communication systems in the nonlinear regime are not yet well understood. In this paper, we study the capacity of amplitude modulated first-order soliton transmission, defined as the maximum of the so-called time-scaled mutual information. Such definition allows us to directly incorporate the dependence of soliton pulse width to its amplitude into capacity formulation. The commonly used memoryless channel model based on noncentral chi-squared distribution is initially considered. Applying a variance normalizing transform, this channel is approximated by a unit-variance additive white Gaussian noise (AWGN) model. Based on a numerical capacity analysis of the approximated AWGN channel, a general form of capacity-approaching input distributions is determined. These optimal distributions are discrete comprising a mass point at zero (off symbol) and a finite number of mass points almost uniformly distributed away from zero. Using this general form of input distributions, a novel closed-form approximation of the capacity is determined showing a good match to numerical results. Finally, mismatch capacity bounds are developed based on split-step simulations of the nonlinear Schro¨dinger equation considering both single soliton and soliton sequence transmissions. This relaxes the initial assumption of memoryless channel to show the impact of both inter-soliton interaction and Gordon-Haus effects. Our results show that the inter-soliton interaction effect becomes increasingly significant at higher soliton amplitudes and would be the dominant impairment compared to the timing jitter induced by the Gordon-Haus effect.


3D Bioprinting in Vascular Tissue Engineering and Tissue Vascularization of Cardiovascular Diseases.
In the 21st century, significant progress has been made in repairing damaged materials through material engineering. However, the creation of large-scale artificial materials still faces a major challenge in achieving proper vascularization. To address this issue, researchers have turned to biomaterials and three-dimensional (3D) bioprinting techniques, which allow for the combination of multiple biomaterials with improved mechanical and biological properties that mimic natural materials. Hydrogels, known for their ability to support living cells and biological components, have played a crucial role in this research. Among the recent developments, 3D bioprinting has emerged as a promising tool for constructing hybrid scaffolds. However, there are several challenges in the field of bioprinting, including the need for nanoscale biomimicry, the formulation of hydrogel blends, and the ongoing complexity of vascularizing biomaterials, which requires further research. On a positive note, 3D bioprinting offers a solution to the vascularization problem due to its precise spatial control, scalability, and reproducibility compared to traditional fabrication methods. This paper aims to examine the recent advancements in 3D bioprinting technology for creating blood vessels, vasculature, and vascularized materials. It provides a comprehensive overview of the progress made and discusses the limitations and challenges faced in current 3D bioprinting of vascularized tissues. Additionally, the paper highlights the future research directions focusing on the development of 3D bioprinting techniques and bioinks for creating functional materials.


Sugar Promotes Feeding in Flies via the Serine Protease Homolog scarface.
A balanced diet of macronutrients is critical for animal health. A lack of specific elements can have profound effects on behavior, reproduction, and lifespan. Here, we used Drosophila to understand how the brain responds to carbohydrate deprivation. We found that serine protease homologs (SPHs) are enriched among genes that are transcriptionally regulated in flies deprived of carbohydrates. Stimulation of neurons expressing one of these SPHs, Scarface (Scaf), or overexpression of scaf positively regulates feeding on nutritious sugars, whereas inhibition of these neurons or knockdown of scaf reduces feeding. This modulation of food intake occurs only in sated flies while hunger-induced feeding is unaffected. Furthermore, scaf expression correlates with the presence of sugar in the food. As Scaf and Scaf neurons promote feeding independent of the hunger state, and the levels of scaf are positively regulated by the presence of sugar, we conclude that scaf mediates the hedonic control of feeding.


Chk1 suppresses bypass of mitosis and tetraploidization in p53-deficient cancer cells.
Many cancer cells are unable to maintain a numerically stable chromosome complement. It is well established that aberrant cell division can generate progeny with increased ploidy, but the genetic factors required for maintenance of diploidy are not well understood. Using an isogenic model system derived by gene targeting, we examined the role of Chk1 in p53-proficient and -deficient cancer cells. Targeted inactivation of a single CHK1 allele in stably diploid cells caused an elevated frequency of mitotic bypass if p53 was naturally mutated or experimentally disrupted by homologous recombination. CHK1-haploinsufficient, p53-deficient cells frequently underwent sequential rounds of DNA synthesis without an intervening mitosis. These aberrant cell cycles resulted in whole-genome endoreduplication and tetraploidization. The unscheduled bypass of mitosis could be suppressed by targeted reversion of a p53 mutation or by exogenous expression of Cdk1. In contrast, the number of tetraploid cells was not increased in isogenic cell populations that harbor hypomorphic ATR mutations, suggesting that suppression of unscheduled mitotic bypass is a distinct function of Chk1. These results are consistent with a recently described role for Chk1 in promoting the expression of genes that promote cell cycle transitions and demonstrate how Chk1 might prevent tetraploidization during the cancer cell cycle.


[The effect of insulin on the catalytic efficacy of rat skeletal muscle hexokinase isoenzyme II].
The effect of insulin on the intracellular localization of rat skeletal muscle hexokinase isozyme II (hexokinase II) was studied in vivo. It was found that after injection of the hormone the glucose concentration in the muscle gradually increases in parallel with the hexokinase II redistribution between the cytosol and the mitochondrial fraction in the direction of the bound form of the enzyme. This effect of insulin is due to glucose, an indispensable participant of the complex formation between the enzyme and the mitochondrial membrane. It was shown that the effect of glucose as a hexokinase II adsorbing reagent is a highly specific one. The hexokinase II binding to mitochondria in the presence of glucose is accompanied by changes in some kinetic properties of the enzyme. A kinetic analysis of catalytic efficiency of the free and bound hexokinase II forms revealed that the catalytic efficiency of hexokinase II within the composition of the enzyme-membrane complex exceeds by two orders of magnitude that of the free enzyme. The data obtained are discussed in the framework of an adsorption mechanism of hexokinase activity regulation in the cell.


Appearance of SERS activity in single silver nanoparticles by laser-induced reshaping.
We report simultaneous plasmonic scattering and Raman spectroscopic observations of single citrate capped silver nanoparticles (AgNPs) which exhibit surface enhanced Raman scattering (SERS) upon meeting specific conditions induced by laser (532 nm) exposure. We show that nanoparticles which are not initially SERS active become SERS active by laser-induced reshaping/reorientation. A set-up developed for these observations enabled in situ high speed time-lapse characterization using plasmonic and Raman spectroscopies in conjunction with dark-field microscopy (DFM). Changes in the AgNPs were confirmed by monitoring plasmonic scattering spectra and DFM images. Time-lapse observations have shown that laser-induced changes in the plasmonic properties of AgNPs resulted in the appearance of SERS. Spectral matching between plasmon resonance and downward molecular vibronic transitions for molecules adsorbed on the surface of plasmonic nanomaterials is attributed to the nanoparticle SERS. We have further shown that the release of silver ions by silver nanoparticles can be the probable reason for their plasmonic changes. Gold nanoparticles inert to such mild (850 μW, 532 nm) laser-induced changes do not exhibit the appearance of SERS.


[The peritoneal environment: physiopathogenesis of endometriosis].
In this report an hypothetical model of the pathophysiology of endometriosis is reviewed based on recent literature, focusing a variety of factors within the specific environment confined by peritoneum, whose alteration has repercussion among endometriotic and immune response cells relationships. At this point vasoactive substances, cytokines (interleukines and growth factors), and menstrual cycle hormones may act as soluble mediators that are able to induce several effects over cellular proliferation, growth and differentiation; and expression of new antigenic epitopes and cell adhesion molecules. This interactions are evident through inflammatory and immune responses, wound repair, fibrosis and pelvic adhesion formation, producing an adequate peritoneal environment for the initiation, maintenance, and progression of endometriotic implants. These finally leads to endometriosis-associated symptoms as pelvic pain, dysmenorrhea, dyspareunia and infertility.


Social patterning of childhood overweight in the French national ELFE cohort.
An inverse social gradient in early childhood overweight has been consistently described in high-income countries; however, less is known about the role of migration status. We studied the social patterning of overweight in preschool children according to the mother's socio-economic and migration background. For 9250 children of the French ELFE birth cohort with body mass index collected at age 3.5 years, we used nested logistic regression to investigate the association of overweight status in children with maternal educational level, occupation, household income and migration status. Overall, 8.3% (95%CI [7.7-9.0]) of children were classified as overweight. The odds of overweight was increased for children from immigrant mothers (OR 2.22 [95% CI 1.75-2.78]) and descendants of immigrant mothers (OR 1.35 [1.04-2.78]) versus non-immigrant mothers. The highest odds of overweight was also observed in children whose mothers had low education, were unemployed or students, or were from households in the lowest income quintile. Our findings confirm that socio-economic disadvantage and migration status are risk factors for childhood overweight. However, the social patterning of overweight did not apply uniformly to all variables. These new and comprehensive insights should inform future public health interventions aimed at tackling social inequalities in childhood overweight.


Effect of maternity-care practices on breastfeeding.
Our goal was to assess the impact of "Baby-Friendly" hospital practices and other maternity-care practices experienced by mothers on breastfeeding duration. This analysis of the Infant Feeding Practices Study II focused on mothers who initiated breastfeeding and intended prenatally to breastfeed for >2 months, with complete data on all variables (n = 1907). Predictor variables included indicators of 6 "Baby-Friendly" practices (breastfeeding initiation within 1 hour of birth, giving only breast milk, rooming in, breastfeeding on demand, no pacifiers, fostering breastfeeding support groups) along with several other maternity-care practices. The main outcome measure was breastfeeding termination before 6 weeks. Only 8.1% of the mothers experienced all 6 "Baby-Friendly" practices. The practices most consistently associated with breastfeeding beyond 6 weeks were initiation within 1 hour of birth, giving only breast milk, and not using pacifiers. Bringing the infant to the room for feeding at night if not rooming in and not giving pain medications to the mother during delivery were also protective against early breastfeeding termination. Compared with the mothers who experienced all 6 "Baby-Friendly" practices, mothers who experienced none were approximately 13 times more likely to stop breastfeeding early. Additional practices decreased the risk for early termination. Increased "Baby-Friendly" hospital practices, along with several other maternity-care practices, improve the chances of breastfeeding beyond 6 weeks. The need to work with hospitals to implement these practices continues to exist, as illustrated by the small proportion of mothers who reported experiencing all 6 of the "Baby-Friendly" hospital practices measured in this study.


Efficient sequential search of genetic systems for diagnosis of twin zygosity.
Conventionally, the zygosity of twins into monozygotic (MZ) and dizygotic (DZ) is determined by utilizing several blood groups or other genetic markers. Existence of many blood groups or other genetic markers raises the crucial problem of choosing minimum number of blood groups and applying them in a sequence with minimum cost offering maximum effectiveness in classifying the twins by zygosity. In this note, a statistical approach to this problem is made and a solution provided. The efficient sequential search procedure utilizing the gene frequency of four blood groups from the German population of Nordrhein-Westfalen province and applying the results to a twin set of 72 pairs (32 MZ and 40 DZ) of the same population indicates that efficient sequences with 3 and 4 blood groups are AB0----P----Rh and AB0----P----Rh----MNSs, respectively. Further, it is understood that the efficient sequence for zygosity determination will be differing from population to population. As gene frequencies of blood systems differ in the various populations, this will effect the probability that a DZ twin pairs is concordant for a specific marker. Moreover, the relative cost may also turn out to be a decisive factor in the determination of the best sequence. Hence, indiscriminate use of several conventional blood group systems in the determination of zygosity of twins from a particular population should be discontinued. The formulae developed in this note are quite general and the procedure explained can easily be generalized to other situations.


Evolutionary Game Model of Group Choice Dilemmas on Hypergraphs.
We introduce an evolutionary game on hypergraphs in which decisions between a risky alternative and a safe one are taken in social groups of different sizes. The model naturally reproduces choice shifts, namely the differences between the preference of individual decision makers and the consensual choice of a group, that have been empirically observed in choice dilemmas. In particular, a deviation from the Nash equilibrium toward the risky strategy occurs when the dynamics takes place on heterogeneous hypergraphs. These results can explain the emergence of irrational herding and radical behaviors in social groups.


Efficacy of Lactobacillus-supplemented triple therapy for H. pylori eradication: A meta-analysis of randomized controlled trials.
To assess the effect of Lactobacillus supplementation on Helicobacter pylori eradication rates and side effects of the triple therapy. PubMed, Embase, Web of Science and Cochrane Library were searched for articles published up to July, 2019. Review Manager 5.3 and Stata 12.0 were used for statistical analyses. The initial database search resulted in 852 articles. Through exclusion and screening, 11 randomized controlled trials involving a total of 724 patients were finally included in this meta-analysis. The H. pylori elimination rate in the Lactobacillus supplement group was significantly higher than that in the control group (RR 1.16, 95% CI 1.08-1.25, P<0.0001). Subgroup analysis showed that the eradication rates were significantly enhanced in both adults and children group, and no significant difference was detected between Asia and Europe group. In addition, sub-analysis based on duration of Lactobacillus supplementation showed the pooled RRs in the long-term and short-term groups were 1.17 (95%CI 1.06-1.30) and 1.16 (95% CI 1.04-1.30), respectively. Regarding the Lactobacillus strains, the pooled RR was 1.33 (95% CI 1.10-1.62) in the L. casei group, 1.18 (95% CI 1.03-1.34) in the L. reuteri group while 1.02 (95% CI 0.87-1.21) in the Lactobacillus GG group. As for the total side effects, Lactobacillus supplementation significantly reduced the incidence of taste disturbance (RR = 0.36, 95% CI 0.17-0.74, P = 0.005). Lactobacillus supplementation during the treatment of Helicobacter pylori infection can effectively improve the eradication rates, and reduce the incidence of therapy-related taste disturbance.


[Microflora of theintestines of persons in contact with aminoglycosides and penicillin].
A total of 90 persons being in contact with aminoglycosides and penicillin were examined. It was found that such a contact resulted in dysbacteriosis of the intestine. The culture of Coli bacteria isolated from the persons had a low fermentative activity and lost their mobility. Bificol, a biological preparation proved to be promising in the treatment of persons with dysfunction of the intestine against the background of dysbacteriosis.


Clusterin immunoexpression is associated with early stage endometrial carcinomas.
Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184-15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression.


This racket is not mine: The influence of the tool-use on peripersonal space.
The aim of the present study was to test whether the peripersonal space (PPS), defined as the portion of the space immediately surrounding the body, is modulated by the long-term motor experience with a specific tool in a sportsmen population. To this end, we evaluated, by means of a multisensory integration paradigm, how tennis players and novices to the sport of tennis perceived the PPS while holding a tennis racket. Going deeply, in the case of the athletes, we tested the effect of their personal racket, i.e., the one they regularly use during their sport activities, compared to a common one. When handling one of these objects or nothing, participants were requested to verbally respond to a tactile stimulus administered at the right wrist while hearing a task-irrelevant sound emitted by a speaker positioned either near to the hand (Near) or far from it (Far). Reaction time to a tactile stimulus associated with the Far sound were higher than those associated with the Near sound when tennis players and novices held the common racket, whereas this difference disappeared when the athletes handled the personal tennis racket. These results suggest that the tool daily used during sport activity is stably embodied in the peripersonal space of tennis players.


The Korean version of the neuropsychiatric inventory: a scoring tool for neuropsychiatric disturbance in dementia patients.
The Neuropsychiatric Inventory (NPI) is a standardized, validated, and reliable tool to assess neuropsychiatric derangements in dementia patients. The aim of this study is to develop the Korean version of the NPI (K-NPI) and to test its reliability and usefulness in dementia patients. The subjects were 49 normal controls and 92 patients with Alzheimer's disease (43), vascular dementia (32), frontotemporal lobar degeneration (11), and other causes (6). Their caregivers familiar with the subjects' everyday behavior were interviewed with the K-NPI. In a subgroup (29/141) of the caregivers, the K-NPI was repeated for test-retest reliability, average of 23.1 days after the initial test. Prevalence rates of 12 behavioral domains in dementia patients were comparable to those of the original NPI; apathy was the most common and hallucination was the least common behavior. Total K-NPI scores correlated positively with dementia severity assessed with the Korean Mini-Mental State Examination. Test-retest reliabilities of frequencies and severities of all subscales were significantly high. Depression, anxiety, apathy, irritability, night-time behavior, and eating change were identified at very low rates in normal controls and were significantly less than those in dementia patients (p<0.001). The K-NPI, whose reliability and competency are comparable to those of the original version, may be a reliable and useful tool for measuring neuropsychiatric disturbances in Korean dementia patients.


Unraveling RubisCO Form I and Form II Regulation in an Uncultured Organism from a Deep-Sea Hydrothermal Vent via Metagenomic and Mutagenesis Studies.
Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the first major step of carbon fixation in the Calvin-Benson-Bassham (CBB) cycle. This autotrophic CO2 fixation cycle accounts for almost all the assimilated carbon on Earth. Due to the primary role that RubisCO plays in autotrophic carbon fixation, it is important to understand how its gene expression is regulated and the enzyme is activated. Since the majority of all microorganisms are currently not culturable, we used a metagenomic approach to identify genes and enzymes associated with RubisCO expression. The investigated metagenomic DNA fragment originates from the deep-sea hydrothermal vent field Nibelungen at 8°18' S along the Mid-Atlantic Ridge. It is 13,046 bp and resembles genes from Thiomicrospira crunogena. The fragment encodes nine open reading frames (ORFs) which include two types of RubisCO, form I (CbbL/S) and form II (CbbM), two LysR transcriptional regulators (LysR1 and LysR2), two von Willebrand factor type A (CbbO-m and CbbO-1), and two AAA+ ATPases (CbbQ-m and CbbQ-1), expected to function as RubisCO activating enzymes. In silico analyses uncovered several putative LysR binding sites and promoter structures. Functions of some of these DNA motifs were experimentally confirmed. For example, according to mobility shift assays LysR1's binding ability to the intergenic region of lysR1 and cbbL appears to be intensified when CbbL or LysR2 are present. Binding of LysR2 upstream of cbbM appears to be intensified if CbbM is present. Our study suggests that CbbQ-m and CbbO-m activate CbbL and that LysR1 and LysR2 proteins promote CbbQ-m/CbbO-m expression. CbbO-1 seems to activate CbbM and CbbM itself appears to contribute to intensifying LysR's binding ability and thus its own transcriptional regulation. CbbM furthermore appears to impair cbbL expression. A model summarizes the findings and predicts putative interactions of the different proteins influencing RubisCO gene regulation and expression.


Medicinal chemistry and biomedical applications of bismuth-based compounds and nanoparticles.
Bismuth as a relatively non-toxic and inexpensive metal with exceptional properties has numerous biomedical applications. Bismuth-based compounds are used extensively as medicines for the treatment of gastrointestinal disorders including dyspepsia, gastric ulcers and H. pylori infections. Recently, its medicinal application was further extended to potential treatments of viral infection, multidrug resistant microbial infections, cancer and also imaging, drug delivery and biosensing. In this review we have highlighted the unique chemistry and biological chemistry of bismuth-209 as a prelude to sections covering the unique antibacterial activity of bismuth including a description of research undertaken to date to elucidate key molecular mechanisms of action against H. pylori, the development of novel compounds to treat infection from microbes beyond H. pylori and the significant role bismuth compounds can play as resistance breakers. Furthermore we have provided an account of the potential therapeutic application of bismuth-213 in targeted alpha therapy as well as a summary of the biomedical applications of bismuth-based nanoparticles and composites. Ultimately this review aims to provide the state of the art, highlight the untapped biomedical potential of bismuth and encourage original contributions to this exciting and important field.


Construction of a chromosome map for the phage group II Staphylococcus aureus Ps55.
The genome size and a partial physical and genetic map have been defined for the phage group II Staphylococcus aureus Ps55. The genome size was estimated to be 2,771 kb by pulsed-field gel electrophoresis (PFGE) using the restriction enzymes SmaI, CspI, and SgrAI. The Ps55 chromosome map was constructed by transduction of auxotrophic and cryptic transposon insertions, with known genetic and physical locations in S. aureus NCTC 8325, into the Ps55 background. PFGE and DNA hybridization analysis were used to detect the location of the transposon in Ps55. Ps55 restriction fragments were then ordered on the basis of genetic conservation between the two strains. Cloned DNA probes containing the lactose operon (lac) and genes encoding staphylococcal protein A (spa), gamma hemolysin (hlg), and coagulase (coa) were also located on the map by PFGE and hybridization analysis. This methodology enabled a direct comparison of chromosomal organization between NCTC 8325 and Ps55 strains. The chromosome size, gene order, and some of the restriction sites are conserved between the two phage group strains.


Active and passive distraction in children undergoing wound dressings.
The aim of this study was to test how distraction influences pain, distress and anxiety in children during wound care. Sixty participants aged 5-12 years were randomized to three groups: serious gaming, the use of lollipops and a control group. Self-reported pain, distress, anxiety and observed pain behaviour were recorded in conjunction with wound care. Serious gaming, an active distraction, reduced the observed pain behaviour and self-reported distress compared with the other groups. A sense of control and engagement in the distraction, together, may be the explanation for the different pain behaviours when children use serious gaming.


National field evaluation of a defined substrate method for the simultaneous enumeration of total coliforms and Escherichia coli from drinking water: comparison with the standard multiple tube fermentation method.
A defined substrate method was developed to simultaneously enumerate total coliforms and Escherichia coli from drinking waters without the need for confirmatory or completed tests. It is a new method based on technology that uses a hydrolyzable substrate as a specific indicator-nutrient for the target microbes. No equipment other than a 35 degrees C incubator and long-wavelength (366-nm) light is necessary. To perform the test, one only has to add water to the powdered ingredients in a tube or flask. If total coliforms are present in the water sample, the solution will change from its normal colorless state (no target microbes present) to yellow. The specific presence of E. coli will cause the same tube to fluoresce under a longwave (366-nm) UV lamp. The test, called Autoanalysis Colilert (AC), was compared with Standard Methods for the Examination of Water and Wastewater 10-tube multiple tube fermentation (MTF) in a national evaluation. Five utilities, representing six U.S. Environmental Protection Agency regions, participated. All water samples came from distribution systems. Split samples from a wide variety of water sources were analyzed for the MPN-versus-MPN comparison. A total of 1,086 tubes were positive by MTF, and 1,279 were positive by AC. There was no statistical difference between MTF and AC. Species identifications from positive tubes confirmed the sensitivity of the AC. A national evaluation of the AC test showed that it: (i) was as sensitive as Standard Methods MTF, (ii) specifically enumerated 1 total coliform per 100 ml, in a maximum of 24 h, (iii) simultaneously enumerated 1 E. coli per 100 ml in the same analysis, (iv) was not subject to false-positive or false-negative results by heterotrophic bacteria, (v) did not require confirmatory tests, (vi) grew injured coliforms, (vii) was easy to inoculate, and (viii) was very easy to interpret.


[Assessment of olfactory disturbances in the patients with rhinosinusitis and polypi nasi treated by endoscopic sinus surgery].
One of the most common symptoms of chronic rhinosinusitis with polyps is smell deterioration. Polypectomy and mechanical restoration of patency of the nose not always and not to the same degree leads to the sense of smell improvement. THE AIM OF STUDY was to assess the sense of smell and nasal patency in patients with chronic rhinosinusitis with polyps treated endoscopically during the healing period and the process of functional normalization of the nasal mucosa. 30 patients suffering from chronic rhinosinusitis with polyps treated endoscopically were included in the study. Nasal resistance (anterior rhinomanometry), smell (smell threshold and identification tests) and rhinoscopic findings were assessed and analyzed 1, 3, 6 and 12 months postoperatively. The most conspicuous decrease of mean nasal resistance was observed in the first control examination (1 month postoperatively) and then further slight improvement continued until sixth postoperative month. Restoration of the patency of the nose yielded only inconsiderable improvement of smell in first postoperative month. Significant improvement of smell could be detected as late as in third and sixth month after the operation. In the twelfth postoperative month slight deterioration of the mean results of smell and nasal patency tests was noted. At the same time control endoscopic examination revealed recurrent polyposis in 26.6% of patients whereas the improvement in mean smell test result in comparison to preoperative results was observed in over 66.6% of patients. The smell improvement in patients with rhinosinusitis with polyps after endoscopic surgery occurs later than the nasal patency improvement what may be attributed to the process of healing and functional normalization of the nasal mucosa. On average after a year in some patients first clinical symptoms of recurrent disease emerges. Taking in to the consideration chronic and complex nature of the disease it seems reasonable to assess nasal resistance and smell during longer follow up period.


FMRI language mapping in children: a panel of language tasks using visual and auditory stimulation without reading or metalinguistic requirements.
In the context of presurgical mapping or investigation of neurological and developmental disorders in children, language fMRI raises the issue of the design of a tasks panel achievable by young disordered children. Most language tasks shown to be efficient with healthy children require metalinguistic or reading abilities, therefore adding attentional, cognitive and academic constraints that may be problematic in this context. This study experimented a panel of four language tasks that did not require high attentional skills, reading, or metalinguistic abilities. Two reference tasks involving auditory stimulation (words generation from category, "category"; auditory responsive naming, "definition") were compared with two new tasks involving visual stimulation. These later were designed to tap spontaneous phonological production, in which the names of pictures to be named involve a phonological difference (e.g. in French poule/boule/moule; "phon-diff") or change of segmentation (e.g. in French car/car-te/car-t-on; "phon-seg"). Eighteen healthy children participated (mean age: 12.7+/-3 years). Data processing involved normalizing the data via a matched pairs pediatric template, and inter-task and region of interest analyses with laterality assessment. The reference tasks predominantly activated the left frontal and temporal core language regions, respectively. The new tasks activated these two regions simultaneously, more strongly for the phon-seg task. The union and intersection of all tasks provided more sensitive or specific maps. The study demonstrates that both reference and new tasks highlight core language regions in children, and that the latter are useful for the mapping of spontaneous phonological processing. The use of several different tasks may improve the sensitivity and specificity of fMRI.


Critical Role of Autophagy in the Processing of Adenovirus Capsid-Incorporated Cancer-Specific Antigens.
Adenoviruses are highly immunogenic and are being examined as potential vectors for immunotherapy. Infection by oncolytic adenovirus is followed by massive autophagy in cancer cells. Here, we hypothesize that autophagy regulates the processing of adenoviral proteins for antigen presentation. To test this hypothesis, we first examined the presentation of viral antigens by infected cells using an antibody cocktail of viral capsid proteins. We found that viral antigens were processed by JNK-mediated autophagy, and that autophagy was required for their presentation. Consistent with these results, splenocytes isolated from virus-immunized mice were activated by infected cells in an MHC II-dependent manner. We then hypothesize that this mechanism can be utilized to generate an efficient cancer vaccine. To this end, we constructed an oncolytic virus encompassing an EGFRvIII cancer-specific epitope in the adenoviral fiber. Infection of cancer cells with this fiber-modified adenovirus resulted in recognition of infected cancer cells by a specific anti-EGFRvIII antibody. However, inhibition of autophagy drastically decreased the capability of the specific antibody to detect the cancer-related epitope in infected cells. Our data suggest that combination of adenoviruses with autophagy inducers may enhance the processing and presentation of cancer-specific antigens incorporated into capsid proteins.


Pituitary responsiveness to luteinizing-hormone-releasing hormone in different reproductive disorders. A review.
As a result of the use of synthetic luteinizing-hormone-releasing hormone (LHRH) (and its analogs), significant advances in modern clinical practice are being realized. We studied the use of LHRH as a test for pituitary reserve for gonadotropin secretion in different reproductive disorders. Synthetic LHRH was used as a diagnostic test for discriminating pituitary from hypothalamic disorders. After appropriate LHRH priming of the pituitary, LHRH was used to document hypothalamic dysfunction in patients with Kallmann's syndrome who had normal gonadotropin responsiveness to LHRH. The gonadotropin responsiveness to 100 micrograms of LHRH was impaired or absent in patients with panhypopituitarism, craniopharyngiomas, hemochromatosis and acromegaly accompanied by abnormal lactation. In women with gonadal dysgenesis, the absence of gonadal steroid feedback exacerbated the pituitary responsiveness to LHRH. Women with hyperprolactinemia are also known to have a blunted gonadotropin response to endogenous and exogenous LHRH. An experimental rat model was developed in our laboratory to study the site of prolactin action on gonadotropin secretion. LHRH challenge tests during perphenazine-induced hyperprolactinemia in rats indicated that prolactin may decrease pituitary sensitivity to LHRH. Additional experiments indicated that the increased progesterone produced in these hyperprolactinemic (pseudopregnant) rats was probably responsible for the decreased pituitary responsiveness to LHRH. Further studies will be necessary to determine whether prolactin, which can alter ovarian steroidogenesis in vitro, interferes with ovulation directly in addition to affecting the hypothalamic-pituitary axis.


Spontaneous miscarriage driven by maternal genetic mutation at position of PAI-1-844G/A: shed light on a race-specific genetic polymorphism.
Association between a genetic polymorphism and disease, either positively or negatively, within a population may not necessarily predict association in other race-ethnic populations. The aim of this study was to genotype well recognized thrombophilia associated polymorphisms as common risk factors for miscarriage and investigate their benefit to use as risk factors in southwest region of Iran females (Khuzestan) in the Arabs ethnic minority group with spontaneous miscarriage. We developed a Reverse Dot Blot Assay for the genotyping of four polymorphisms. There were significant differences in the genotype distribution and allelic frequencies of the MTHFR 1298 A > C, MTHFR 677 C > T, Factor V Leiden 1691 G > A, PAI-1-844G > A polymorphisms between the case and control groups. The MTHFR 1298 A > C, MTHFR 677 C > T and Factor V Leiden 1691 G > A polymorphisms were significantly associated with spontaneous miscarriage risk. Unlike some other race-ethnic populations, PAI-1-844G > A polymorphism was associated with risk of developing unplanned miscarriage in Iranian Arabs ethnic minority group females.


The preparation and drug-release behaviour of CTA/EC and PMS/EC composite microcapsules.
A cellulose triacetate (CTA) and three different molecular weights of poly(alpha-methyl styrene) (PMS) were used as co-wall materials to prepare composite microcapsules with ethylcellulose (EC). A non-solvent-addition phase-separation method was used. The core material was theophylline (TH) and the solvent-non-solvent pair was dichloromethane-n-hexane, and the drug-release rates of the microcapsules prepared from these two types of co-wall materials were compared. The effects of their phase-separation range on the properties of the microcapsules, such as particle size, release rate and the morphology of the microcapsules are also discussed. The release rate of microcapsules was also affected by the compatibility of the co-wall materials and the EC. The dissolution studies indicated that the drug-release time of CTA/EC and PMS/EC composite microcapsules was sustained to 10 and 3.5 times, respectively, in comparison with that for pure EC microcapsules.


Nanocomplexation of thrombin with cationic amylose derivative for improved stability and hemostatic efficacy.
As a topical hemostatic agent, thrombin has wide application for many surgical treatments. However, native thrombin always suffers from its physical and chemical instabilities. In this work, a nanocomplexation strategy was developed for modifying the stability and hemostatic efficacy of thrombin, in which a water-soluble cationic amylose derivative containing poly(l-lysine) dendrons was prepared by a click reaction and then used to complex thrombin in an aqueous system. For resultant thrombin nanocomplexes, their morphology and particle size distribution were investigated. Their stabilities were studied in terms of activity retention percentages under different storage time, pH values, and illumination time. In addition, their ability to achieve in vitro fibrinogen and blood coagulation were evaluated. Via a rat hepatic hemorrhage model and a rat iliac artery hemorrhage model, these thrombin nanocomplexes were confirmed to have good tissue biocompatibility and in vivo hemostatic effectiveness.


The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis.
To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc). SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease-modifying therapy.


Disappearance of epidermal growth factor receptor is essential in the fusion of the nasal epithelium.
Abstract Epidermal growth factor (EGF) and receptor (-R) signaling pathway is required for epithelial cell growth and differentiation such as the degeneration of the medial edge epithelial cells during the fusion process of secondary palate formation. As epithelial fusion takes place during primary palate formation, we investigated the involvement of the EGF-R in fusion of the medial (MNP) and lateral (LNP) nasal prominences of the mouse embryo was examined. Immunoreactivity of EGF-R was investigated in embryonic day 10 embryos (32-37 somite stages). The EGF-R immunoreactivity was observed in the nasal epithelia of the presumptive fusion area before fusion. It became undetectable just prior to the fusion and faintly reappeared at the time of the fusion. In contrast, the non-fusing epithelial cells of the nasal groove maintained the immunoreactivity throughout these stages. In order to elucidate whether the EGF/EGF-R signaling pathway was involved in nasal epithelial fusion, EGF solution was injected into the exocoelum of explanted mouse embryos, and the embryos were cultured for 18-24 h by whole embryo culture (WEC). This exogenous EGF inhibited fusion of nasal prominences in 66.7-81.5% of the embryos. Treatment with EGF for 4-14 h showed that exogenous EGF disturbed the EGF-R disappearance and normal alteration of epithelial cell morphology in the fusion area. These results suggest that temporal disappearance of the EGF/EGF-R signaling from presumptive fusion of the nasal prominences is required for morphological change of the epithelial cells leading to the fusion of MNP and LNP.


Imaging Biomarkers and Prevalence of Complex Aortic Plaque in Cryptogenic Stroke: A Systematic Review.
Complex aortic plaque (CAP) is a potential embolic source in patients with cryptogenic stroke (CS). We review CAP imaging criteria for transesophageal echocardiogram (TEE), computed tomography angiography (CTA), and magnetic resonance imaging and calculate CAP prevalence in patients with acute CS. PubMed and EMBASE databases were searched up to December 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Two independent reviewers extracted data on study design, imaging techniques, CAP criteria, and prevalence. The Cochrane Collaboration tool and Guideline for Reporting Reliability and Agreement Studies were used to assess risk of bias and reporting completeness, respectively. From 2293 studies, 45 were reviewed for CAP imaging biomarker criteria in patients with acute CS (N=37 TEE; N=9 CTA; N=6 magnetic resonance imaging). Most studies (74%) used ≥4 mm plaque thickness as the imaging criterion for CAP although ≥1 mm (N=1, CTA), ≥5 mm (N=5, TEE), and ≥6 mm (N=2, CTA) were also reported. Additional features included mobility, ulceration, thrombus, protrusions, and assessment of plaque composition. From 23 prospective studies, CAP was detected in 960 of 2778 patients with CS (0.32 [95% CI, 0.24-0.41], I2=94%). By modality, prevalence estimates were 0.29 (95% CI, 0.20-0.40; I2=95%) for TEE; 0.23 (95% CI, 0.15-0.34; I2=87%) for CTA and 0.22 (95% CI, 0.06-0.54; I2=92%) for magnetic resonance imaging. TEE was commonly used to assess CAP in patients with CS. The most common CAP imaging biomarker was ≥4 mm plaque thickness. CAP was observed in one-third of patients with acute CS. However, high study heterogeneity suggests a need for reproducible imaging methods.


Daylength mediated control of seasonal growth patterns in perennial trees.
Daylength is a key regulator of seasonal growth patterns in perennial trees in temperate regions. Cessation of growth is induced by short day signal in these trees before the advent of winter and constitutes a major adaptive developmental program. In this review, we report on the recent progress made in identifying the molecular mechanisms that underlie the daylength mediated control of seasonal growth in perennial trees. A major finding that has emerged from the analysis of this process is that the regulation of growth cessation in perennial trees and flowering time by daylength in annuals such as Arabidopsis thaliana involves identical signalling components.


A novel non-competitive amperometric immunosensor by using thiourea-glutaraldehyde-modified gold electrode for immunoglobulin M detection.
A novel non-competitive amperometric immunosensor based on a self-assembled monolayer (SAM) of thiourea modified by a polymeric Schiff's base of glutaraldehyde on gold electrode has been developed for determination of IgM. Alkaline phosphatase (ALP)-conjugated monoclonal anti-mouse immunoglobulin M (IgM) antibody was selectively bound to IgM molecules onto the surface of the electrode. Electrochemical response arising from the catalytic reaction of alkaline phosphatase enzyme. Its reaction with various phosphates such as p-aminophenyl phosphate and p-nitrophenyl phosphatase (p-NPP) generates the electrochemically active products p-aminophenol (p-AP) and p-nitrophenol (p-NP), respectively.


Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of randomized, controlled trials.
Anemia affects almost all patients with chronic kidney disease (CKD), reduces quality of life, and is a risk factor for early death. Higher hemoglobin (Hb) targets have been widely advocated because of data from observational studies showing that higher Hb is associated with improved survival and quality of life, but higher Hb targets may cause access thrombosis and hypertension and are costly. This study aimed to evaluate the benefits and harms of different Hb targets in CKD on the basis of randomized trial evidence. A comprehensive search of the Cochrane Trials Registry, Medline, Embase, and reference lists was performed. Two independent reviewers assessed studies for inclusion criteria and extracted data on all-cause mortality, cardiovascular disease, strokes, hypertension, seizures, hyperkalemia, access thrombosis, and quality of life. Analysis was by a random-effects model, and results are expressed as relative risk (RR) or weighted mean difference with 95% confidence intervals (CI). Nineteen relevant trials were identified. Twelve trials (638 patients) compared use of erythropoietin versus no erythropoietin treatment, and seven trials (2058 patients) compared higher versus lower Hb targets. Compared with Hb values of >130 g/L or more in the CKD population with cardiovascular disease, Hb values of <120 g/L were associated with lower all-cause mortality (RR, 0.84; 95% CI, 0.71 to 1.00). Hb values of 100 g/L or less reduced the risk of hypertension (RR, 0.50; 95% CI, 0.33 to 0.76) but increased the risk of seizures (RR, 5.25; 95% CI, 1.13 to 24.34). From the available trial evidence, in CKD patients with cardiovascular disease, the benefits associated with higher Hb targets (reduced seizures) are outweighed by the harms (increased risk of hypertension and death). There is insufficient data to guide decisions in patients without cardiovascular disease or in the predialysis population.


Naphthalene cytotoxicity of differentiating Clara cells in neonatal mice.
Selective Clara cell injury produced by many bioactivated lung toxicants is thought to result from high levels of activating enzymes found in differentiated Clara cells. A recent study found an elevated susceptibility to the Clara cell toxicant 4-ipomeanol in neonatal rabbits when Clara cell P450 activity is low. To determine whether differentiating Clara cells in another species (mouse) are more susceptible to injury by a different bioactivated Clara cell toxicant (naphthalene), adult, 14-day postnatal (DPN) and 7DPN male mice were given a single intraperitoneal dose (25, 50, or 100 mg/kg) of naphthalene and killed 24 hr later. Epithelial damage, as assessed by quantitative histopathology, included cellular swelling, vacuolization, and exfoliation. In 7DPN mice, bronchiolar epithelium was severely injured at the lowest dose of naphthalene tested, 25 mg/kg. Bronchiolar epithelium in 14DPN mice was moderately injured at 25 mg/kg; injury severity was greatest at 50 and 100 mg/kg. Minimal bronchiolar epithelial injury occurred in adult mice at 50 mg/kg and moderate injury at 100 mg/kg. In proximal bronchi, epithelium of 7DPN mice showed signs of injury only at 100 mg/kg. Bronchial epithelium of adult mice was not injured at any dose. Isolated distal airways from 7DPN and 14DPN mice were more sensitive to naphthalene exposure than isolated distal airways from adult mice. Despite the low levels of P450 activity, differentiating Clara cells in neonatal mice are more susceptible to injury by the bioactivated cytotoxicant naphthalene than are differentiated Clara cells in adult mice.


Drosophila mixed lineage kinase/slipper, a missing biochemical link in Drosophila JNK signaling.
Mixed lineage kinases (MLKs) belong to the family of mitogen activated protein kinase kinase kinase (MAPKKK) and cause neuronal cell death mediated through c-Jun, N-terminal kinase (JNK) pathway. Recently, genetic studies in Drosophila revealed the presence of an MLK termed slipper (slpr). However, its biochemical features like physiological substrate, role in different MAPK pathways and developmental and tissue-specific expression pattern were not reported. Here, we report cDNA cloning, expression analysis and biochemical characterization of a Drosophila mixed lineage kinase (dMLK) that is also known as slipper. The protein structure analysis of dMLK/slipper revealed, in addition to the conserved domains, a stretch of glutamine in the amino terminus and an asparagine-threonine stretch at the carboxy-terminus. In situ hybridization and reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that dMLK is expressed in early embryonic stages, adult brain and thorax. Ectopic expression of dMLK either in Drosophila S2 or in mammalian HEK293 cells leads to activation of JNK, p38 and extracellular signal regulated kinase (ERK) pathways. Further, dMLK directly phosphorylates Hep, dMKK4 and also their mammalian counterparts, MKK7 and SEK1, in an in vitro kinase assay. Taken together, our results provide for the first time a comprehensive expression profile and new biochemical insight of dMLK/slipper.


Three dimensional vascular ultrasound imaging.
Intravascular ultrasound (IVUS) is a new catheter-based system that produces two-dimensional (2D) images of vascular structures. Existing systems produce real-time, cross-sectional "slices" of vessels using 5.0 French (Fr) (30 MHz) and 8.0 Fr (20 MHz) IVUS catheters containing ultrasound transducers at the tip. Computerized, three-dimensional (3D) reconstruction of these 2D images using a personal computer- (PC) based image analysis system is described. A set (n = 90) of longitudinally aligned, consecutive images is sampled from a 5.0 cm vessel segment, and computerized processing creates rendered 3D images. By adjusting image density threshold and viewing angle, the morphology, location, and spatial distribution of arterial pathology can be seen. Refinements in computer hardware and software have reduced processing time and improved image resolution to the point where 3D IVUS imaging is a clinically applicable tool. Possible applications include diagnosis of complex arterial pathology, guidance of intraluminal instruments, and assessment of the effects of endovascular interventions.


Gray matter network measures are associated with cognitive decline in mild cognitive impairment.
Gray matter networks are disrupted in Alzheimer's disease and related to cognitive impairment. However, it is still unclear whether these disruptions are associated with cognitive decline over time. Here, we studied this question in a large sample of patients with mild cognitive impairment with extensive longitudinal neuropsychological assessments. Gray matter networks were extracted from baseline structural magnetic resonance imaging, and we tested associations of network measures and cognitive decline in Mini-Mental State Examination and 5 cognitive domains (i.e., memory, attention, executive function, visuospatial, and language). Disrupted network properties were cross-sectionally related to worse cognitive impairment. Longitudinally, lower small-world coefficient values were associated with a steeper decline in almost all domains. Lower betweenness centrality values correlated with a faster decline in Mini-Mental State Examination and memory, and at a regional level, these associations were specific for the precuneus, medial frontal, and temporal cortex. Furthermore, network measures showed additive value over established biomarkers in predicting cognitive decline. Our results suggest that gray matter network measures might have use in identifying patients who will show fast disease progression.


Is previous respiratory disease a risk factor for lung cancer?
Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously. Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma. The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case-control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking. Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20-1.48 and OR, 1.50; 95% CI, 1.21-1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33-4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis "only." Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter. Findings from this large international case-control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer.


Health promotion in the workplace: assessing stress and lifestyle with an intranet tool.
Chronic noncommunicable conditions, particularly cardiovascular and metabolic diseases, are the major causes of death and morbidity in both industrialized and low- to middle-income countries. Recent epidemiological investigations suggest that management of lifestyle factors, such as stress and lack of physical activity, could have an important value in cardiometabolic conditions, while information technology tools could play a significant facilitatory role. The objective of our study was to verify the feasibility of using a private website, directed to the workers of a major Italian company, to describe their health profile and lifestyle and work habits using an ad hoc self-administered questionnaire. We administered anonymous multiple choice Web-based questionnaires to 945 participants (683 completed the task) as part of an ongoing health promotion program in a multinational company. Qualitative and quantitative data were synthesized with nonlinear principal component analysis to construct indicators (ie, variables) for stress, control, and lifestyle domains. Considering in addition absenteeism, the Calinski-Harabasz statistic and cluster analysis jointly differentiated seven clusters, which displayed different distributions of standardized classification variables. The final step consisted in assessing the relationship of the resulting seven subject typologies with personal data, illnesses, and metabolic syndrome status, carried out for the most part with descriptive methods. Statistical analyses singled out two not-overlapping domains of stress and control, as well as three not-overlapping domains of physical activity, smoking, and alcohol habits. The centroids of the seven clusters generated by the procedure were significantly (P < .001) different considering all possible 21 comparisons between couples of groups. Percentage distributions of variables describing personal information (gender, age group, work category, illness status, or metabolic syndrome) within participant typologies show some noteworthy findings: females, workers aged 35-44 years, junior white collar workers, and respondents reporting illness were more prevalent in the stress group than in the overall studied population; preclinical metabolic syndrome status was more prevalent in the group with higher alcohol consumption. Absentees reported more illness. The present Intranet-based study shows the potential of applying diverse statistical techniques to deal jointly with qualitative and quantitative self-reported data. The resulting formal description of subject typologies and their relationship with personal characteristics might provide a convenient tool for supporting health promotion in the work environment.


The electronic couplings in electron transfer and excitation energy transfer.
The transport of charge via electrons and the transport of excitation energy via excitons are two processes of fundamental importance in diverse areas of research. Characterization of electron transfer (ET) and excitation energy transfer (EET) rates are essential for a full understanding of, for instance, biological systems (such as respiration and photosynthesis) and opto-electronic devices (which interconvert electric and light energy). In this Account, we examine one of the parameters, the electronic coupling factor, for which reliable values are critical in determining transfer rates. Although ET and EET are different processes, many strategies for calculating the couplings share common themes. We emphasize the similarities in basic assumptions between the computational methods for the ET and EET couplings, examine the differences, and summarize the properties, advantages, and limits of the different computational methods. The electronic coupling factor is an off-diagonal Hamiltonian matrix element between the initial and final diabatic states in the transport processes. ET coupling is essentially the interaction of the two molecular orbitals (MOs) where the electron occupancy is changed. Singlet excitation energy transfer (SEET), however, contains a Frster dipole-dipole coupling as its most important constituent. Triplet excitation energy transfer (TEET) involves an exchange of two electrons of different spin and energy; thus, it is like an overlap interaction of two pairs of MOs. Strategies for calculating ET and EET couplings can be classified as (1) energy-gap-based approaches, (2) direct calculation of the off-diagonal matrix elements, or (3) use of an additional operator to describe the extent of charge or excitation localization and to calculate the coupling value. Some of the difficulties in calculating the couplings were recently resolved. Methods were developed to remove the nondynamical correlation problem from the highly precise coupled cluster models for ET coupling. It is now possible to obtain reliable ET couplings from entry-level excited-state Hamiltonians. A scheme to calculate the EET coupling in a general class of systems, regardless of the contributing terms, was also developed. In the past, empirically derived parameters were heavily invoked in model description of charge and excitation energy drifts in a solid-state device. Recent advances, including the methods described in this Account, permit the first-principle quantum mechanical characterization of one class of the parameters in such descriptions, enhancing the predictive power and allowing a deeper understanding of the systems involved.


Two new sesquiterpene glucosides from the leaves of Nicotiana tabacum.
Two new sesquiterpene glycosides, 11R,12-dihydroxy-6(7)-spirovetiven-8-one-9-O-beta-D-glucopyranoside (1) and rishitin M1-13-O-beta-D-glucopyranoside (2), have been isolated from the leaves of Nicotiana tabacum. Their structures were established by spectroscopic methods including (1)H, (13)C, and 2D NMR. The absolute configuration of the side chain in compound 1 was determined as R by NOESY and NOE difference spectra.


Sleep patterns and total mortality: a 12-year follow-up study in Japan.
A population-based cohort study was conducted to assess the relationship between total mortality and self-reported sleep patterns as regards not only to sleep duration but also subjective sleep quality. A total of 5,322 inhabitants in Gifu Prefecture, Japan, completed a self-administered questionnaire on health status and lifestyles including habitual sleep patterns, and were followed-up for an average of 11.9 years. Relative risks were computed by using Cox proportional hazards models. Both longer and shorter sleep, compared to 7-8 hour-sleep, was related to significantly increased risk of total mortality in males (relative risk [RR] for > or = 10 hours = 1.94, and RR for < 7 hour = 1.90), but not in females. Females complaining of poor awakening state experienced a higher mortality risk compared to those who woke up normally (RR: 1.97). Males who usually fell asleep easily showed a marginally lower mortality risk compared to those who fell asleep normally (RR: 0.70). Female users of sleeping pills were at an elevated risk (RR: 1.89). These findings were almost unchanged after adjustment for sleep duration and other confounders. Poor self-reported quality of sleep seemed to be associated with an increased risk of mortality independently of sleep duration.


Rice husk-based pyrogenic carbonaceous material efficiently promoted peroxymonosulfate activation toward the non-radical pathway for the degradation of pharmaceuticals in water.
Pristine pyrogenic carbonaceous material (BRH) obtained from rice husk and modified with FeCl3 (BRH-FeCl3) were prepared and explored as carbocatalysts for the activation of peroxymonosulfate (PMS) to degrade a model pharmaceutical (acetaminophen, ACE) in water. The BRH-FeCl3/PMS system removed the pharmaceutical faster than the BRH/PMS. This is explained because in BRH-FeCl3, compared to BRH, the modification (iron played a role as a structuring agent mainly) increased the average pore diameter and the presence of functional groups such as -COO-, -Si-O-, or oxygen vacancies, which allowed to remove the pollutant through an adsorption process and significant carbocatalytic degradation. BRH-FeCl3 was reusable during four cycles and had a higher efficiency for activating PMS than another inorganic peroxide (peroxydisulfate, PDS). The effects of BRH-FeCl3 and PMS concentrations were evaluated and optimized through an experimental design, maximizing the ACE degradation. In the optimized system, a non-radical pathway (i.e., the action of singlet oxygen, from the interaction of PMS with defects and/or -COO-/-Si-O- moieties on the BRH-FeCl3) was found. The BRH-FeCl3/PMS system generated only one primary degradation product that was more susceptible to biodegradation and less active against living organisms than ACE. Also, the BRH-FeCl3/PMS system induced partial removals of chemical oxygen demand and dissolved organic carbon. Furthermore, the carbocatalytic system eliminated ACE in a wide pH range and in simulated urine, having a low-moderate electric energy consumption, indicating the feasibility of the carbocatalytic process to treat water polluted with pharmaceuticals.


Comparison of Vestibular Depth Relapse and Wound Healing After Reconstructive Preprosthetic Surgery Using Cryopreserved Amniotic Membrane and Acellular Dermal Matrix - A Comparative Study.
The significance of membranes as wound dressing in oral surgeries has been reported by previous studies. The aim of the present split-mouth randomized clinical study was to assess and compare the wound dressing properties of acellular dermal matrix (ADM) and cryopreserved human amniotic membrane (AM) after reconstructive preprosthetic oral surgery. Twenty-eight patients with complete mandibular edentulism and resorbed alveolar bone were included. After taking mandibular impression, a clear acrylic splint with increased labial flange height was created. In each participant, labial vestibular depth was elevated using the Clark's technique. Subsequently, half of the exposed periosteum was covered with ADM while the other half was covered with cryopreserved human AM. Vestibule depth and relapse in the two sides were measured immediately after vestibuloplasty and at the end of the 1st week, 2nd week, 1st month, and 3rd months with graduations of 0.1 mm. Furthermore, after 3 and 7 days, samples were collected from graft material, and the macrophage population was analyzed by flow cytometry. There was no significant difference in the relapse of vestibule depth between the two grafts at different time intervals. However, the frequency of wound-infiltrating macrophages (CD68+ cells) was significantly higher in areas covered by ADM after 3 and 7 days. ADM is as effective as cryopreserved AM in terms of maintaining the postoperative vestibular depth. On the other hand, our results suggested that the onset of healing phase in ADM-covered areas occurs faster compared to the periosteum covered with cryopreserved human AM. This clinical trial showed significantly faster postoperative healing onset when ADM was used than when cryopreserved human AM was applied on the periosteum.


Regulation of expression of the ethanol dehydrogenase gene (adhE) in Escherichia coli by catabolite repressor activator protein Cra.
The adhE gene encodes ethanol dehydrogenase and is located at min 27.9 of the Escherichia coli chromosome. Expression of adhE is about 10-fold higher in cells grown anaerobically than in cells grown aerobically and is dependent on both transcriptional and posttranscriptional factors. In this study, a trans-regulatory element repressing adhE expression was characterized by genetic and biochemical approaches. A mutation downregulating adhE expression was mapped at min 2 of the chromosome. DNA sequence analysis revealed a missense mutation in the cra gene, formerly known as fruR. The cra gene encodes a catabolite repressor-activator protein (Cra) involved in the modulation of carbon flow in E. coli. The mutant protein (Cra*) sustained an Arg148-->His substitution causing 1.5- and 3-fold stronger repression of adhE transcription under anaerobic and aerobic conditions, respectively. By contrast, cra null mutants displayed 1.5- and 4-fold increased adhE transcription under those conditions. Disruption of the cra gene did not abolish the anaerobic activation of the adhE gene but diminished it twofold. Cra and Cra* were purified as fusion proteins tagged with an N-terminal 6xHis element. In vitro, both fusion proteins showed binding to the adhE promoter region and to the control fruB promoter region, which is a known Cra target. However, only 6xHis-tagged Cra, and not 6xHis-Cra*, was displaced from the DNA target by the effector, fructose-1-phosphate (F1P), suggesting that the mutant protein is locked in a promoter-binding conformation and is no longer responsive to F1P. We suggest that Cra helps to tighten the control of adhE transcription under aerobic conditions by its repression.


Expression of the precore region of an avian hepatitis B virus is not required for viral replication.
The core-antigen-coding region of all hepadnaviruses is preceded by a short, in-phase open reading frame termed precore whose expression can give rise to core-antigen-related polypeptides. To explore the functional significance of precore expression in vivo, we introduced a frameshift mutation into this region of the duck hepatitis B virus (DHBV) genome and examined the phenotype of this mutant DNA by intrahepatic inoculation into newborn ducklings. Animals receiving mutant DNA developed DHBV infection, as judged by the presence in hepatocytes of characteristic viral replicative intermediates; molecular cloning and DNA sequencing confirmed that the original mutation was present in the progeny genomes. Infection could be efficiently transmitted to susceptible ducklings by percutaneous inoculation with serum from mutant-infected animals, indicating that infectious progeny virus was generated. These findings indicate that expression of the precore region of DHBV is not essential for genomic replication, core particle morphogenesis, or intrahepatic viral spread.


Guideline Discordance and Patient Cost Responsibility in Medicare Beneficiaries With Metastatic Breast Cancer.
Treatment for metastatic breast cancer (MBC) that is not concordant with the NCCN Guidelines for Breast Cancer has been associated with higher healthcare utilization and payer costs. However, a significant knowledge gap exists regarding the impact of guideline-discordant care on patient cost responsibility. This study examined this question among patients with MBC in the year postdiagnosis. This retrospective cohort study used data from the SEER-Medicare linked database from 2000 through 2013. Guideline discordance, defined by year-specific NCCN Guidelines, was assessed for first-line antineoplastic treatment and grouped into discrete categories. Patient cost responsibility (deductibles, coinsurance, copayments) in women with MBC were summed for all medical care received in the year postdiagnosis. The difference in patient cost responsibility by guideline discordance status was estimated using linear mixed-effect models. Of 3,709 patients with MBC surviving at least 1 year postdiagnosis, 17.6% (n=651) received guideline-discordant treatment. Median cost responsibility in the year postdiagnosis for patients receiving guideline-discordant treatment was $7,421 (interquartile range [IQR], $4,359-$12,983) versus $5,171 (IQR, $3,006-$8,483) for those receiving guideline-concordant care. In adjusted models, guideline-discordant treatment was significantly associated with $1,841 higher patient costs in the first year from index diagnosis date (95% CI, $1,280-$2,401) compared with guideline-concordant care. Patient cost responsibility differed by category of guideline discordance, with those receiving nonapproved bevacizumab having the highest cost responsibility (β=$3,330; 95% CI, $1,711-$4,948). Deviations from current treatment guidelines may have implications on patient healthcare cost responsibility. Additional research is needed to fully understand the mechanisms underlying how guideline deviation leads to greater costs for patients with MBC.


Dorsal spinal cord herniation at the thoracolumbar junction presenting with scalloping of ossification of the ligamentum flavum: case report.
Dorsal spinal cord herniation is reportedly a rare condition. Here, the authors report an unusual case of dorsal spinal cord herniation at the thoracolumbar junction presenting with scalloping of ossification of the ligamentum flavum (OLF). A 75-year-old woman with a 2-year history of bilateral leg dysesthesia presented with progressive gait ataxia. Neurological examination showed bilateral patellar tendon hyperreflexia with loss of vibratory sensation and proprioception in her bilateral lower extremities. CT myelography revealed a posterior kink and dorsal herniation of the spinal cord at T11-12, with OLF between T10-11 and T12-L1. In addition, scalloping of the OLF was observed at T11-12 at the site of the herniated spinal cord. This scalloping was first noted 9 years previously and had been gradually progressing. The patient underwent surgical repair of the spinal cord herniation. Subsequently, her spinal cord herniation and vibratory sensation and proprioception in both legs partly improved, but gait ataxia remained unchanged. Dorsal spinal cord herniation reportedly occurs under conditions of vulnerability of the dorsal dura mater. In this case, acquired vulnerability of the dorsal dura mater owing to previous epidural catheter placement into the thoracolumbar space may have resulted in dorsal spinal cord herniation.


[Visual evoked potentials in chessboard pattern reversion in children with optic neuritis].
Visual evoked potentials (VEP) to chess pattern reversion were studied in 17 children with optic neurites during the acute stage and in the course of convalescence 1-2 months and 1-3 years after the disease onset. Coarse VEP changes were detected in the patients during the acute stage of optic neuritis. A positive time course of VEP was followed up in late periods after the acute attack of the disease. Despite normalization of vision acuity, no complete restoration of VEP to small-cell chess patterns was seen. The findings evidence that studies of VEP to chess pattern reversion should be carried out to detect subclinical involvement of the optic nerve and to timely diagnose optic neuritis in children.


The effects of prior exposure on face processing in younger and older adults.
Older adults differ from their younger counterparts in the way they view faces. We assessed whether older adults can use past experience to mitigate these typical face-processing differences; that is, we examined whether there are age-related differences in the use of memory to support current processing. Eye movements of older and younger adults were monitored as they viewed faces that varied in the type/amount of prior exposure. Prior exposure was manipulated by including famous and novel faces, and by presenting faces up to five times. We expected that older adults may have difficulty quickly establishing new representations to aid in the processing of recently presented faces, but would be able to invoke face representations that have been stored in memory long ago to aid in the processing of famous faces. Indeed, younger adults displayed effects of recent exposure with a decrease in the total fixations to the faces and a gradual increase in the proportion of fixations to the eyes. These effects of recent exposure were largely absent in older adults. In contrast, the effect of fame, revealed by a subtle increase in fixations to the inner features of famous compared to non-famous faces, was similar for younger and older adults. Our results suggest that older adults' current processing can benefit from lifetime experience, however the full benefit of recent experience on face processing is not realized in older adults.


Normative MRI Data Increase the Sensitivity to Brain Volume Abnormalities in the Classification of Fetal Alcohol Spectrum Disorder.
To evaluate the use of a large MRI normative dataset to quantify structural brain anomalies that may improve diagnostic sensitivity for atypical brain volume in youth with fetal alcohol spectrum disorder (FASD). Participants included 48 children with prenatal alcohol exposure (PAE) and 43 controls, ages 8-17 years, from the longitudinal Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Recently published lifespan brain charts were used to quantify participants' (per)centile for brain volumes (cortical and subcortical gray matter and cortical white matter), providing an index of (dis)similarity to typically developing individuals of the same age and sex. Participants with PAE demonstrated lower mean centile scores compared with controls. Participants with PAE and scores ≤ 10th centile on at least one brain volume metric demonstrated significantly lower performance on measures of intellectual function and aspects of executive functioning compared with participants with PAE and "typical" volumes (>10th centile). Brain volume centiles explained a greater amount of variance in IQ and improved sensitivity to brain volume anomalies in FASD compared with the most commonly used diagnostic criterion of occipitofrontal circumference (OFC) ≤ 10th. Age- and sex-adjusted brain volumes based on a large normative dataset may be useful predictors of functional outcomes and may identify a greater number of individuals with FASD than the currently used criterion of OFC.


Strategies to create a regenerating environment for the injured spinal cord.
Spine cord injury (SCI) leads to devastating functional loss below the level of injury. Partially explained by the presence of a non-permissive environment, the injured spinal cord does not mount adequate regeneration to re-establish functional connections. Therefore, it is important to identify the cellular and molecular factors and their interactions that affect axonal regeneration within the changed environment. This review will discuss the current understanding of the neuronal and glial factors and the extracellular matrix in the spinal cord that inhibit axonal growth, and it will summarize some major approaches for facilitation of regeneration. The strategies are classified into the following categories: penetration of the blood-brain barrier; modulation of caspase activity to reduce apoptosis; stem cells and tissue implantation; administration of neurotrophic factors, including viral vector-mediated delivery; and modulation of the extracellular matrix. Although recent studies on genomic regulation and apoptosis have identified particularly important molecular targets, more is necessary to achieve long-term regeneration. A combination of the approaches targeting various aspects in the regenerating environment would be more effective than a single strategy. Overall, insights arising from the experimental results may eventually lead to better therapeutic intervention so as to lessen the functional disability and enhance the quality of life in patients with SCI.


[Determination of an expected plantar pressure threshold: dimensionless approach use to reduce the variability of the plantar pressures].
The aim of this study was to verify that the determination of walking velocities proportional to the leg lengths of the subjects together with the dimensionless expression of the results enable us to decrease the variability and to determine a plantar pressure threshold. Fifteen male subjects performed two walking tests on a treadmill at imposed velocities (V1 and V3) and similar velocities (V27 and V37). Similar velocities (Vsim =Nfr(g.Li)(0.5)) were determined from two fractions of the Froude number (Nfr), the gravitational acceleration (g) and the length of the lower limb (Li) of the subjects. An in-shoe plantar pressure measurement system allowed the pressure peaks to be recorded. The peak of pressure (p) was reported to the step length (a) and the weight of the subject (mg) for the dimensionless pressure peaks (Dim(P)=p.a2/mg) to be expressed. The coefficients of variability (CoV) and extends of the dimensionless pressure peaks (Epp) have been studied at the different imposed walking velocities. The CoV and Epp of the dimensionless pressure peaks recorded at V27 and V37 (similar velocities) are from 2 to 9% and 3 to 22% lower than those observed at V1 and V3, respectively. The analysis of the pressure peaks CoV and Epp shows that the method should allow a data bank usable to detect the effects of a disability on the plantar pressures to be elaborated. Indeed, our results enable us to define a plantar pressure pattern with a variability lower than those reported in most scientific articles.


OGD/R-induced ferroptosis and pyroptosis in retinal pigment epithelium cells: Role of PLD1 and PLD2 modulation.
This study investigated the role of phospholipase D (PLD) in retinal ischemia-reperfusion (I/R) injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model commonly used in retinal I/R injury research. To create an in vitro cellular I/R model, pharmacological inhibitors and small interfering RNA (siRNA) were used to target PLD1 and PLD2 in retinal pigment epithelial (RPE) cells. Treatment with PLD inhibitors and siRNA reduced reactive oxygen species (ROS) and malondialdehyde (MDA) induced by OGD/R in RPE cells and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), indicating a reduction in oxidative damage and improvement in the antioxidant system. Next, we showed that inhibiting PLD1 or PLD2 reduced intracellular iron levels and lipid peroxidation, which are critical factors in ferroptosis. Additionally, PLD1 and PLD2 modulated the expression of proteins involved in the regulation of ferroptosis, including GPX4, SLC7A11, FTH1, and ACSL4. We also investigated the roles of PLD1 and PLD2 in preventing pyroptosis, another form of programmed cell death associated with inflammation. Our study found that OGD/R significantly increased the production of pro-inflammatory cytokines and activated caspase-1, NLRP3, ASC, cleaved-caspase 1 (C-caspase-1), and GSDMD-N in RPE cells, indicating pyroptosis induction. However, PLD1 and PLD2 inhibition or knockdown significantly inhibited the production of pro-inflammatory cytokines and activation of the NLRP3 inflammasome, Taken together, our findings support the hypothesis that the PLD signaling pathway plays a key role in OGD/R-induced ferroptosis and pyroptosis induction and may be a potential therapeutic target for preventing or treating retinal dysfunction and degeneration.


Chlamydial infection, plasma peroxidation and obesity in tubal infertility.
Genital tract infections and obesity are both sources of oxidative stress. Alterations in immune and antioxidant parameters may arise from this or from an indeterminate autoimmune mechanism. This study aimed to investigate the association of Chlamydial infection, obesity and oxidative response with tubal infertility in Nigerian women. It was a case-control study of 40 women with tubal infertility and 32 fertile women, respectively, recruited from the Infertility and Family Planning Clinics respectively, of the University College Hospital, Ibadan, Nigeria. Anthropometric indices were measured in each subject and endocervical swabs were taken to screen for current genital tract infection. Antioxidant, hormonal and immunologic analysis were performed on serum. None of the subjects had current genital tract infections. Chlamydia trachomatis IgG positivity was significantly higher in infertile than in fertile subjects [OR 4.33; 95%CI (0.078-0.681)]. No significant variations were observed in the anthropometric indices, antioxidant parameters and hormones between infertile and the fertile women. Body mass index correlated positively with oxidative stress in infertile subjects. Waist and hip circumferences correlated negatively with oestradiol in women with tubal infertility. Chlamydial infection is associated with tubal factor infertility, however, obesity seems to increase oxidative stress and reduce fertility potential in women with tubal factor infertility.


Minimally invasive surgery in infants with congenital diaphragmatic hernia: outcome and selection criteria.
The aim of the study was to determine clinical indications for performing minimally invasive surgery (MIS) with acceptable results by reviewing our experience in congenital diaphragmatic hernia (CDH) repair and comparing outcomes of MIS with open surgery. Medical records of patients who underwent CDH repair were reviewed retrospectively between January 2008 and December 2012, and outcomes were compared between MIS and open repair of CDH. From 2008 to 2012, 35 patients were operated on for CDH. Among these patients, 20 patients underwent open surgery, and 15 patients underwent MIS. Patients with delayed presentations (60.0% [9/15] in the MIS group vs. 20.0% [4/20] in the open surgery group; P = 0.015) and small diaphragmatic defect less than 3 cm (80.0% [12/15] in the MIS group vs. 0.0% [0/20] in the open surgery group; P < 0.001) were more frequently in the MIS group than the open surgery group. All 10 patients who also had other anomalies underwent open surgery (P = 0.002). Moreover, nine patients who needed a patch for repair underwent open surgery (P = 0.003). Patients in the MIS group showed earlier enteral feeding and shorter hospital stays. There was no recurrence in either group. CDH repair with MIS can be suggested as the treatment of choice for patients with a small sized diaphragmatic defect, in neonates with stable hemodynamics and without additional anomalies, or in infants with delayed presen tation of CDH, resulting in excellent outcomes.


Hyperspectral Near-Infrared Image Assessment of Surface-Acetylated Solid Wood.
Visualization of acetic anhydride flow and its heterogeneity within the wood block necessitates the development of a reliable and robust analytical method. Hyperspectral imaging has the potential to acquire a continuous spectrum of chemical analytes at different spectral channels in terms of pixels. The large set of chemical data (3-dimensional) can be expanded into relevant information in a multivariate fashion. We quantified gradients in acetylation degree over cross sections of Scots pine sapwood caused by a one-sided flow of acetic anhydride into wood blocks using near-infrared hyperspectral imaging. A principal component analysis (PCA) model was used to decompose the high-dimensional data into orthogonal components. Moreover, a partial least-squares (PLS) hyperspectral image regression model was developed to quantify heterogeneity in acetylation degree that was affected by the flow of acetic anhydride through wood blocks and into the tracheid cell walls. The model was validated and optimized with an external test data set and a prediction map using the root-mean-squared error of an individual predicted pixel. The model performance parameters are well suited, and prediction of the acetylation degree at the image level was complemented with confocal Raman imaging of selected areas on the microlevel. NIR image regression showed that the acetylation degree was determined not only by the time-dependent flow of the acetic anhydride through the wood macropores but also by the diffusion of the anhydride into the wood cell walls. Thereby, thin-walled earlywood sections were acetylated faster than the thick-walled latewood sections. Our results demonstrate the suitability of near-infrared imaging as a tool for quality control and process optimization at the industrial scale.


Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms.
In this study, we investigated the mechanisms by which temozolomide enhances radiation response in glioblastoma cells. Using a panel of four primary human glioblastoma cell lines with heterogeneous O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression, normal human astrocytes, and U87 xenografts, we investigated (a) the relationship of MGMT status with efficacy of temozolomide-based chemoradiation using a panel of in vitro and in vivo assays; (b) underlying mechanisms by which temozolomide enhances radiation effect in glioblastoma cells; and (c) strategies to overcome resistance to radiation + temozolomide. Temozolomide enhances radiation response most effectively in glioblastomas without detectable MGMT expression. On concurrent radiation + temozolomide administration in MGMT-negative glioblastomas, there seems to be decreased double-strand DNA (dsDNA) repair capacity and enhanced dsDNA damage compared either with radiation alone or with sequentially administered temozolomide. Our data suggest that O(6)-benzylguanine can enhance the antitumor effects of concurrent radiation + temozolomide in MGMT-positive cells by enhancing apoptosis and the degree of dsDNA damage. O(6)-Benzylguanine was most effective when administered concurrently with radiation + temozolomide and had less of an effect when administered with temozolomide in the absence of radiation or when administered sequentially with radiation. Our in vivo data using U87 xenografts confirmed our in vitro findings. The present study shows that temozolomide enhances radiation response most effectively in MGMT-negative glioblastomas by increasing the degree of radiation-induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of MGMT by the addition of O(6)-benzylguanine significantly enhances the antitumor effect of concurrent radiation + temozolomide. These are among the first data showing mechanisms of synergy between radiation and temozolomide and the effect of MGMT.


The short-chain fatty acid crotonate reduces invasive growth and immune escape of Candida albicans by regulating hyphal gene expression.
Microbes are exposed to nutritional and stress challenges in their environmental and host niches. To rise to these challenges, they regulate transcriptional programs that enable cellular adaptation. For instance, metabolite concentrations regulate post-translational modifications of chromatin, such as histone acetylation. In this way, metabolic signals are integrated with transcription. Over the last decade, several histone acylations have been discovered, including histone crotonylation. Their roles in microbial biology, environmental adaptation, and microbe-host interactions are incompletely defined. Here we show that the short-chain fatty acid crotonate, which is used to study histone crotonylation, changes cell morphology and immune interactions of Candida albicans. Crotonate reduces invasive hyphal morphogenesis of C. albicans within macrophages, thereby delaying macrophage killing and pathogen escape, as well as reducing inflammatory cytokine maturation. Crotonate's ability to reduce hyphal growth is environmentally contingent and pronounced within macrophages. Moreover, crotonate is a stronger hyphal inhibitor than butyrate under the conditions that we tested. Crotonate causes increased histone crotonylation in C. albicans under hyphal growth conditions and reduces transcription of hyphae-induced genes in a manner that involves the Nrg1 repressor pathway. Increasing histone acetylation by histone deacetylase inhibition partially rescues hyphal growth and gene transcription in the presence of crotonate. These results indicate that histone crotonylation might compete with acetylation in the regulation of hyphal morphogenesis. Based on our findings, we propose that diverse acylations of histones (and likely also non-histone proteins) enable C. albicans to respond to environmental signals, which in turn regulate its cell morphology and host-pathogen interactions.IMPORTANCEMacrophages curtail the proliferation of the pathogen Candida albicans within human body niches. Within macrophages, C. albicans adapts its metabolism and switches to invasive hyphal morphology. These adaptations enable fungal growth and immune escape by triggering macrophage lysis. Transcriptional programs regulate these metabolic and morphogenetic adaptations. Here we studied the roles of chromatin in these processes and implicate lysine crotonylation, a histone mark regulated by metabolism, in hyphal morphogenesis and macrophage interactions by C. albicans. We show that the short-chain fatty acid crotonate increases histone crotonylation, reduces hyphal formation within macrophages, and slows macrophage lysis and immune escape of C. albicans. Crotonate represses hyphal gene expression, and we propose that C. albicans uses diverse acylation marks to regulate its cell morphology in host environments. Hyphal formation is a virulence property of C. albicans. Therefore, a further importance of our study stems from identifying crotonate as a hyphal inhibitor.