Evaluation and Identification of Resistance Lines and QTLs of Maize to Seedborne Fusarium verticillioides.
Internal fungal contamination in cereal grains may affect plant growth and result in health concerns for humans and animals. Fusarium verticillioides is a seedborne fungus that can systemically infect maize. However, few efforts had been devoted to studying the genetics of maize resistance to seedborne F. verticillioides. In this study, we developed a disease evaluation method to identify resistance to seedborne F. verticillioides in maize, by which a set of 121 diverse maize inbred lines were evaluated. A 160 F10-generation recombinant inbred line (RIL) population derived from a cross of the resistant (BT-1) and susceptible (N6) inbred line was further used to identify major quantitative trait loci (QTLs) for seedborne F. verticillioides resistance. Eighteen inbred lines with a high resistance to seedborne F. verticillioides were characterized and could be used as potential germplasm resources for genetic improvement of maize resistance. Six QTLs with high heritability across multiple environments were detected on chromosomes 3, 4, 6, and 10, among which was a major QTL, qISFR4-1. Located on chromosome 4 at the interval of 12922609-13418025, qISFR4-1 could explain 16.63% of the total phenotypic variance. Distinct expression profiles of eight candidate genes in qISFR4-1 between BT-1 and N6 inbred lines suggested their pivotal regulatory roles in seedborne F. verticillioides resistance. Taken together, these results will improve our understanding of the resistant mechanisms of seedborne F. verticillioides and would provide valuable germplasm resources for disease resistance breeding in maize.


[Interferon alpha-2b in the complex therapy of patients with pulmonary tuberculosis concurrent with bronchoobstructive syndrome].
Interferon alpha-2b was tested for its effect on therapeutic effectiveness in pulmonary tuberculosis patients with bronchoobstructive syndrome and signs of secondary immunodeficiency. The patients were randomized to 2 groups. The study group (n=35) received rectal interferon alpha-2b, 3 million IU, on chemotherapy days (twice weekly). The total duration of a course of immunochemothery was 4 months or more. The control group (n=35) did not take the immunomodulator. The use of interferon contributed to the normalization of T-cell immunological parameters in 60.6% of the patients and functional parameters in 35.7% and could achieve closure of decay cavities (the only cavity or one of the cavities) in 90.6% of cases (in the control group, these were in 33.3, 20, and 64.3%, respectively).


Controlled vitamin C restriction and physical performance in volunteers.
A double-blind study on the effects of vitamin C restriction on physical performance was executed with 12 healthy men. During seven weeks of low vitamin C intake six subjects were on a daily diet of regular food products, providing 20% of the Dutch Recommended Dietary Allowances (RDA) for vitamin C (Dutch RDA is 50 mg/day). Other vitamins were supplemented at twice the RDA level. After three weeks of low vitamin intake an additional vitamin C dose of 15 mg/day was provided, resulting in a total intake of 25 mg/day (50% of the Dutch RDA). Six control subjects consumed the same diet supplemented with twice the RDA for all vitamins. In the restriction group blood vitamin C levels decreased significantly (p less than 0.01). Vitamin C restriction had no harmful effects on health, aerobic power (VO2-max), and onset of blood lactate accumulation (OBLA). However, an increased heart rate at OBLA level was observed during the period of low vitamin C intake (p less than 0.05), possibly by interference with either catecholamine or carnitine metabolism. These results suggest that short-term marginal vitamin C deficiency does not affect physical performance in single bouts of intensive exercise.


Coping styles among Japanese women with breast cancer.
In order to investigate changes in coping styles before and after diagnosis of cancer, and the relationship between coping styles and emotional states among Japanese women, we conducted a study using the Profile of Mood States (POMS) and Dealing With Illness-Coping Inventory. Coping methods such as active-cognitive, active-behavioral and avoidance were found to be more frequently used after the women were diagnosed with cancer than before (p < 0.001). There were also positive correlations between active-reliance behavior and tension-anxiety and depression, between cognitive-passive behavior and depression and lack-of-vigor, between passive-resignation behavior and anger-hostility and confusion, and between avoidance-solitary behavior and anger-hostility, fatigue, depression, lack-of-vigor and confusion. In conclusion, a diagnosis of cancer causes a patient to use more frequently avoidance behavior as well as active coping styles, and these passive/avoidance coping styles are often correlated with negative emotions. These results imply that patients with breast cancer need support considering the relationship between passive/avoidance coping styles and negative emotions.


Exploring patient reactions to pen-tablet computers: a report from CaReNet.
We wanted to study patient receptivity to using pen-tablet computers for collecting data in a practice-based research network. We analyzed exit interviews and field notes collected by trained research assistants as part of a larger Colorado Research Network (CaReNet) study comparing pen-tablet and paper-pencil methods to collect data for the Primary Care Network Survey (PRINS). A total of 168 patients completed a patient exit interview after completion of the pen-tablet-based survey instrument. Analyses of these brief interviews and field notes indicated that patients had favorable reactions to using pen-tablet computers. The most common barriers were related to glitches in the technology; the voice recognition software was the most problematic, with patients (as well as clinicians) finding this feature to be frustrating. Patients were able and willing to use pen-tablet computers for completing forms within busy primary care offices. Increasing patient involvement in practice-based research may be even more practicable through the use of this novel technology, which can allow patient-directed data collection at a single point in time as well as longitudinally.


Use of pluripotent stem cells for reproductive medicine: are we there yet?
In recent years, pluripotent stem cells have demonstrated to be exciting tools to understand embryonic development, cell lineage specification, tissue generation and repair, and various other biological processes. In addition, the identification and isolation of germ line stem cells has given more insight into germ cell biology at the molecular level and into the underlying causes of infertility which was not possible earlier. The recent derivation of in vitro derived sperm and oocytes from pluripotent stem cells in the mouse model represents a major breakthrough in the field and substantiates the critical relevance of stem cells as a potential alternative resource for treating infertility. Although the past years have yielded compelling information in understanding germ cell development via in vitro stem cell assays, extended investigative research is necessary in order to derive fully functional 'artificial gametes' in a safe way for future therapeutic applications.


Health locus of control and participation in physical activity.
Abstract The purpose of this study was to determine the physical activity participation patterns of college students when defined by their Health Locus of Control orientation. One thousand thirty-three college-aged students completed the Wellness Activity Profile, a questionnaire that yielded data on Health Locus of Control and self-reported frequency of participation in physical activities. Discriminant analyses indicated that the combination of physical activities associated with internally and externally oriented students were different for both males and females. Participation in high caloric expenditure activities was more frequent among internal subjects (Male: bicycling, volleyball, other individual sports, and snorkel/scuba diving; Female: basketball, weight training, tennis, fast walking/jogging/running, and judo/karate), while low caloric expenditure activities were associated with an external orientation (Male: baseball/softball, sailing, fishing, golf, and other recreational sports; Female: track and field jumping and fishing).


Using modified nucleotides to map the DNA determinants of the Tus-TerB complex, the protein-DNA interaction associated with termination of replication in Escherichia coli.
A series of modified nucleotides was used to map the hydrogen-bonding and hydrophobic sites of the TerB DNA required for Tus interaction. Each of four consensus guanine residues in the TerB-binding site was replaced by 7-deazaguanine, 2-aminopurine, or inosine nucleobase analogues, and each thymine by a uracil analogue. The observable equilibrium dissociation constant for the Tus protein-TerB DNA complex was measured at pH 7.5, 25 degrees C, and 150 mM potassium glutamate using a competition binding method. Substitutions made at position 10 with a 7-deazaguanine, 2-aminopurine, or inosine analogue had a large effect on the stability of the complex, approximately +3 kcal/mol in each case. Substitutions made at positions 13 and 17 had a varied response. For uracil substitutions, potential hydrophobic sites were identified at six positions in the TerB DNA. The energetic penalty for the removal of a single methyl group ranged between +1 and +2 kcal/mol. Rate dissociation measurements agree with these results. Overall, major and minor groove determinants are required for binding. An unusual result was that the conserved nucleotide at position 6 did not significantly affect in vitro binding of the complex.


Surface roughness rather than surface chemistry essentially affects insect adhesion.
The attachment ability of ladybird beetles Coccinella septempunctata was systematically investigated on eight types of surface, each with different chemical and topographical properties. The results of traction force tests clearly demonstrated that chemical surface properties, such as static/dynamic de-wettability of water and oil caused by specific chemical compositions, had no significant effect on the attachment of the beetles. Surface roughness was found to be the dominant factor, strongly affecting the attachment ability of the beetles.


Physiological response of soybean leaves to uniconazole under waterlogging stress at R1 stage.
Waterlogging is a major limiting factor in global crop production and seriously endangers growth and yield improvement in low-lying, rainfed regions. Soybean is an important economic crop affected by waterlogging stress. The current study investigates the effects of waterlogging stress on the leaf physiology and yield of two soybean varieties (Kenfeng 14, waterlogging-tolerant and Kenfeng 16, waterlogging-sensitive) and the mitigation effect of uniconazole (S3307) in promoting growth and productivity under waterlogging conditions. The results showed that waterlogging stress increased antioxidant enzyme activity and decreased the contents of non-enzymatic antioxidants such as AsA and GSH. Furthermore, the content of MDA and H2O2 increased significantly, indicating oxidative stress and O2-· production rate also improved, and the increase in the waterlogging-sensitive variety Kenfeng 16 was greater than that of the waterlogging-tolerant variety Kenfeng 14. Spraying S3307, however, increased the activities of antioxidants such as SOD, POD, CAT, and APX. GR, MDHAR, and DHAR increased the content of non-enzymatic antioxidants, effectively inhibited the increase of MDA, H2O2 content, and O2-· production rate, and alleviated the loss of yield factors caused by waterlogging stress. The waterlogging-tolerant variety Kenfeng 14 recovered better than the waterlogging-sensitive variety Kenfeng 16. In summary, S3307 ameliorated the effects of waterlogging stress on the physiological characteristics of soybean leaves and improved yield as a result of improved antioxidant defense mechanisms that impeded lipid peroxidation. Thus, S3307 could decelerate the damages caused by waterlogging stress to some extent.


In vivo study of photosensitizer pharmacokinetics by fluorescence transillumination imaging.
The possibility of in vivo investigation of the pharmacokinetics of photosensitizers by means of fluorescence transillumination imaging is demonstrated. An animal is scanned in the transilluminative configuration by a single source and detector pair. Transillumination is chosen as an alternative approach to reflection imaging. In comparison with the traditional back-reflection technique, transillumination is preferable for photosensitizer detection due to its higher sensitivity to deep-seated fluorophores. The experiments are performed on transplantable mouse cervical carcinomas using three drugs: photosens, alasens, and fotoditazin. For quantitative evaluation of the photosensitizer concentration in tumor tissue the fluorescence signal is calibrated using tissue phantoms. We show that the kinetics of photosensitizer tumor uptake obtained by transillumination imaging in vivo agree with data of standard ex vivo methods. The described approach enables rapid and cost-effective study of newly developed photosensitizers in small animals.


Dietary zinc and iron intake and risk of depression: A meta-analysis.
The associations between dietary zinc and iron intake and risk of depression remain controversial. Thus, we carried out a meta-analysis to evaluate these associations. A systematic search was performed in PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases for relevant studies up to January 2017. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. A total of 9 studies for dietary zinc intake and 3 studies for dietary iron intake were finally included in present meta-analysis. The pooled RRs with 95% CIs of depression for the highest versus lowest dietary zinc and iron intake were 0.67 (95% CI: 0.58-0.76) and 0.57 (95% CI: 0.34-0.95), respectively. In subgroup analysis by study design, the inverse association between dietary zinc intake and risk of depression remained significant in the cohort studies and cross-sectional studies. The pooled RRs (95% CIs) for depression did not substantially change in the influence analysis and subgroup analysis by adjustment for body mass index (BMI). The present meta-analysis indicates inverse associations between dietary zinc and iron intake and risk of depression.


The role of brushite and octacalcium phosphate in apatite formation.
Studies of apatite mineral formation are complicated by the possibility of forming several calcium phosphate phases. The least soluble, hydroxyapatite (HAP), is preferentially formed under neutral or basic conditions. In more acidic solutions phases such as dicalcium phosphate dihydrate (Brushite, DCPD) and octacalcium phosphate (OCP) are often found. Even under ideal HAP precipitation conditions the precipitates are generally nonstoichiometric, suggesting the formation of calcium-deficient apatites. Both DCPD and OCP have been implicated as possible precursors to the formation of apatite. This may occur by the initial precipitation of DCPD and/or OCP followed by transformation to a more apatitic phase. Although DCPD and OCP are often detected during in vitro crystallization, in vivo studies of bone formation rarely show the presence of these acidic calcium phosphate phases. In the latter case the situation is more complicated, since a large number of ions and molecules are present that can be incorporated into the crystal lattice or adsorbed at the crystallite surfaces. In biological apatite, DCPD and OCP are usually detected only during pathological calcification where the pH is often relatively low. In normal in vivo calcifications these phases have not been found, suggesting the involvement of other precursors or the formation of an initial amorphous calcium phosphate phase (ACP) followed by transformation to apatite.


Topological Control on Silicates' Dissolution Kinetics.
Like many others, silicate solids dissolve when placed in contact with water. In a given aqueous environment, the dissolution rate depends on the composition and the structure of the solid and can span several orders of magnitude. Although the kinetics of dissolution depends on the complexities of both the dissolving solid and the solvent, a clear understanding of which structural descriptors of the solid control its dissolution rate is lacking. By pioneering dissolution experiments and atomistic simulations, we correlate the dissolution rates-ranging over 4 orders of magnitude-of a selection of silicate glasses and crystals to the number of chemical topological constraints acting between the atoms of the dissolving solid. The number of such constraints serves as an indicator of the effective activation energy, which arises from steric effects, and prevents the network from reorganizing locally to accommodate intermediate units forming over the course of the dissolution.


Design of an autofocus capsule endoscope system and the corresponding 3D reconstruction algorithm.
A traditional capsule endoscope can only take 2D images, and most of the images are not clear enough to be used for diagnosing. A 3D capsule endoscope can help doctors make a quicker and more accurate diagnosis. However, blurred images negatively affect reconstruction accuracy. A compact, autofocus capsule endoscope system is designed in this study. Using a liquid lens, the system can be electronically controlled to autofocus, and without any moving elements. The depth of field of the system is in the 3-100 mm range and its field of view is about 110°. The images captured by this optical system are much clearer than those taken by a traditional capsule endoscope. A 3D reconstruction algorithm is presented to adapt to the zooming function of our proposed system. Simulations and experiments have shown that more feature points can be correctly matched and a higher reconstruction accuracy can be achieved by this strategy.


Effects of downregulating oct-4 transcript by RNA interference on early development of porcine embryos.
The objective of this study was to investigate the role of the POU family transcription factor, Oct-4, in the early development of porcine embryos. We attempted Oct-4 downregulation of porcine early embryos by RNA interference, and evaluated Oct-4 suppression of developmental competencies and gene transcripts in porcine embryos. Injection of specific siRNA resulted in a distinct decrease in Oct-4 mRNA and protein expression in porcine embryos until at least the morula stage. Although the porcine embryos injected with Oct-4 siRNA were able to develop to the morula stage, these embryos failed to form blastocysts. Gene transcripts of caudal-like transcription factor (Cdx2) and fibroblast growth factor 4 (Fgf4), which were involved in segregation of the trophectderm and functionalization of the inner cell mass, were unchanged by Oct-4 siRNA injection. Our results indicated that Oct-4 is an important factor for porcine embryos and, in particular, for the regulation of porcine blastocyst formation.


Thorium-induced neurobehavioural and neurochemical alterations in Swiss mice.
Thorium ((232)Th), a heavy metal radionuclide that targets the liver and skeleton, has been shown to accumulate in the central nervous system at low levels. The present study was aimed to investigate neurobehavioural and neurochemical changes in mice treated with (232)Th at sub-lethal doses. Swiss albino mice were administered intraperitoneally with thorium nitrate. The chelation-based therapeutic effect of calcium diethylenetriamine pentaacetate (Ca-DTPA) was tested on the (232)Th-treated mice. (232)Th localisation was determined in brain regions by the Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method. Achetylcholine esterase (AChE) activity in different brain regions was evaluated to assess the cholinergic function of mice CNS. Oxidative damage was evaluated by assessing the activities of antioxidant enzymes (i.e., superoxide dismutase and catalase) and the level of lipid peroxidation. The neurobehavioural alteration in the treated mice was studied by the shuttle box method. (232)Th accumulation found in different brain regions followed the order: Cerebellum (Cbl) > cortex (Ctx) > hippocampus (Hp) > striatum (Str). However, removal of (232)Th by Ca-DTPA was significant from brain regions like Cbl, Ctx and Str but not from Hp. A significant increase in lipid peroxidation and acetylcholine esterase (AChE) activity was observed in the treated mice but activities of superoxide dismutase and catalase was found substantially decreased. (232)Th treatment impaired the learning and memory-based neurobehaviour of the mice. Furthermore, our data suggest that Ca-DTPA injection in (232)Th-treated animals failed to improve the neurobehaviour of the treated mice, perhaps because Ca-DTPA could not decorporate (232)Th or mitigate (232)Th-mediated neurochemical changes effectively from/in hippocampus, a brain region implicated in learning and memory response. Administration of (232)Th in mice caused neurobehavioural alteration and impairment of cholinergic function, which might be the consequence(s) of oxidative stress induction in different brain regions.


Crystallization of biological macromolecules using agarose gel.
Gellified media prevent convection and crystal sedimentation, and provide an attractive growth environment for optimising biological crystals. Agarose gels are particularly easy to use and they are compatible with most of the common crystallization methods. They also offer new possibilities like counter-diffusion techniques. This paper gives a brief overview of their general properties and presents an application of a counter-diffusion setup combining agarose gel and capillaries to the crystallization of proteins and protein / nucleic acid complexes.


Analysis of activation-induced conformational changes in p47phox using tryptophan fluorescence spectroscopy.
Activation of the neutrophil NADPH oxidase requires translocation of cytosolic proteins p47(phox), p67(phox), and Rac to the plasma membrane or phagosomal membrane, where they assemble with membrane-bound flavocytochrome b. During this process, it appears that p47(phox) undergoes conformational changes, resulting in the exposure of binding sites involved in assembly and activation of the oxidase. In the present study, we have directly evaluated activation-induced conformational changes in p47(phox) using tryptophan fluorescence and circular dichroism spectroscopy. Treatment of p47(phox) with amphiphilic agents known to activate the NADPH oxidase (SDS and arachidonic acid) caused a dose-dependent quenching in the intrinsic tryptophan fluorescence of p47(phox), whereas treatment with a number of other amphiphilic agents that failed to activate the oxidase had no effect on p47(phox) fluorescence. In addition, the concentration range of activating agents required to induce changes in fluorescence correlated with the concentration range of these agents that induced maximal NADPH oxidase activity in a cell-free assay system. We next determined if activation by phosphorylation caused the same type of conformational changes in p47(phox). Protein kinase C phosphorylation of p47(phox) in vitro resulted in comparable quenching of fluorescence, which also correlated directly with NADPH oxidase activity. Finally, the circular dichroism (CD) spectrum of p47(phox) was significantly changed by the addition of SDS, whereas treatment with a non-activating detergent had no effect on the CD spectrum. These results support the conclusion that activation by amphiphilic agents results in changes in the secondary structure of p47(phox). Thus, our studies provide direct evidence linking conformational changes in p47(phox) to the NADPH oxidase activation/assembly process and also further support the hypothesis that amphiphile-mediated activation of the NADPH oxidase induces changes in p47(phox) that are similar to those mediated by phosphorylation in vivo.


Frequency of memory cytotoxic T lymphocytes to equine infectious anemia virus proteins in blood from carrier horses.
Horses with equine infectious anemia virus (EIAV) have episodes of viremia and disease; however, most eventually become inapparent carriers. A possible mechanism of control is cytotoxic T lymphocytes (CTL). To evaluate CTL in inapparent carriers with low viral loads, peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous EIAV-infected PBMC and human IL-2 to detect memory CTL (CTLm). In initial studies, three carriers had CTLm and one of these had low-level effector CTL (CTLe). The CTLm were restricted by equine lymphocyte alloantigen-A (ELA-A) locus encoded MHC class I molecules on autologous equine kidney (EK) target cells. In addition, EK cells did not express MHC class II molecules. The CTLm frequency in PBMC from five inapparent carriers infected for 22 to 50 months was determined by limiting dilution analysis. PBMC were diluted, stimulated, and tested on EK cell targets infected with EIAV and recombinant vaccinia viruses expressing EIAV Env or Gag/Pr proteins. All five carriers had CTLm to EIAV-infected targets, while four had CTLm to targets expressing Env and four had CTLm to targets expressing Gag/Pr proteins. The CTLm frequency range was 60 to 468 per 10(6) PBMC to EIAV-infected targets, 4 to 286 to Env-expressing targets, and 25 to 190 to Gag/Pr-expressing targets. These results should facilitate the identification of epitopes recognized by predominant CTLm from horses controlling a lentivirus infection.


Loaded cartilage T2 mapping in patients with hip dysplasia.
To evaluate the change in cartilage T2 values with loading in patients with hip dysplasia. Fifteen patients with hip dysplasia and nine asymptomatic healthy volunteers were evaluated between April 2008 and February 2009. All subjects provided written informed consent before participation in this prospective, institutional review board-approved study. Midcoronal T2 mapping of hips was performed under unloaded and loaded conditions (with 50% body weight) at 3.0-T magnetic resonance (MR) imaging. Loading was achieved with a mechanical loading system. T2 values under unloaded conditions and the change in T2 values at the weight-bearing area of the acetabular and femoral cartilage with loading were compared between normal and dysplastic hips. The change in T2 with loading was correlated with the patient's age and body mass index as well as with the center-edge angle determined on conventional radiographs. The decrease in cartilage T2 at the outer superficial zones of the acetabular cartilage with loading was significantly greater in patients with hip dysplasia than in healthy volunteers: The mean T2 change with loading was -7.6% +/- 10.6 (+/-standard deviation) for dysplastic hips and 1.2% +/- 10.9 for normal hips (P = .04). Among patients with hip dysplasia, there was a positive correlation between the center-edge angle on anteroposterior radiographs and T2 changes with loading at the outer deep zones of the acetabular cartilage. Cartilage T2 mapping with loading during MR imaging enabled the detection of site-specific changes in cartilage T2 in dysplastic hips.


In vitro metabolism of the vitamin D analog, 22-oxacalcitriol, using cultured osteosarcoma, hepatoma, and keratinocyte cell lines.
Using four cultured cell models representing liver, keratinocyte, and osteoblast, we have demonstrated that the vitamin D analog, 22-oxacalcitriol is degraded into a variety of hydroxylated and side chain truncated metabolites. Four of these metabolic products have been rigorously identified by high pressure liquid chromatography, diode array spectrophotometry, and gas chromatography-mass spectrometry analysis as 24-hydroxylated and 26-hydroxylated derivatives as well as the cleaved molecules, hexanor-1alpha,20-dihydroxyvitamin D3 and hexanor-20-oxo-1alpha-hydroxyvitamin D3. Comparison with chemically synthesized standards has revealed the stereochemistry of the biological products. Although differences exist in the amounts of products formed with the different cell types, it is apparent that 22-oxacalcitriol is subject to metabolism by both vitamin D-inducible and noninducible enzymes. Time course studies suggest that the truncated 20-alcohol is derived from a side chain hydroxylated molecule via a hemiacetal intermediate and the 20-oxo derivative is likely formed from the 20-alcohol. Biological activity measurements of the metabolites identified in our studies are consistent with the view that these are catabolites and that the biological activity of 22-oxacalcitriol is due to the parent compound. These results are also consistent with recent findings of others that the biliary excretory form of 22-oxacalcitriol is a glucuronide ester of the truncated 20-alcohol.


Managed care contracts. A primer on how to analyze contracts and avoid the traps: Part 2.
Because many business entities are attempting to increase their control over medical practice, physicians must take extreme care in reading proposed amendments to managed care contracts. Beware of vague language concerning utilization review; contracts that require you to passively accept future contract modifications; innocuous language that may endow the medical director with excessive authority; and unacceptable regulations concerning medical, financial, and administrative records. The author suggests counterproposals that are fair to both business entities and participating physicians. He further recommends maintaining an ongoing discussion between both parties in order to further chances for success.


Minimally invasive resection and vertebroplasty for an osteolytic C-1 metastasis of malignant meningioma: case report.
Malignant meningiomas are a rare but aggressive subset of intracranial meningiomas leading to a very limited life expectancy. The occurrence of spinal metastases in these tumors is an even rarer event. The described patient had an intracranial malignant meningioma and developed a symptomatic osteolytic contrast-enhancing lesion in the left C-1 lateral mass suspicious for metastasis. The authors performed a minimally invasive posterior resection of the lesion with vertebroplasty of C-1. Histopathology verified metastasis of the malignant meningioma. The surgical procedure resulted in prompt and permanent pain reduction until the patient died 18 months later. Given the very limited life expectancy in this case, the authors did not consider occipitocervical fusion because of their desire to preserve the range of motion of the head. Therefore, they suggest minimally invasive tumor resection and vertebroplasty in selected palliative tumor patients.


Lactobacillus plantarum strain YU from fermented foods activates Th1 and protective immune responses.
Lactic acid bacteria (LAB) are known to have effects on immune function. From 203 strains of LAB isolated from fermented foods, we selected a beneficial strain, Lactobacillus plantarum strain YU (LpYU), which has high interleukin (IL)-12-inducing activity in mouse peritoneal macrophages. This activity of LpYU was partially mediated by Toll-like receptor (TLR) 2, but not TLR4 or TLR9. Oral administration of LpYU to ovalbumin (OVA)-immunized mice caused suppression of serum OVA-specific immunoglobulin E (IgE) levels, enhancing interferon (IFN)-γ production from spleen cells in response to OVA. Furthermore, LpYU enhanced natural killer cell activity in spleen cells and the production of IgA from Peyer's patch cells. Because activation of Th1 immune responses and IgA production induce antiviral effects, we evaluated the inhibitory effects of LpYU against the influenza A virus (A/NWS/33, H1N1) (IFV). Oral administration of LpYU suppressed viral proliferation in the lungs and in bronchoalveolar lavage fluids (BALFs). Both levels of IFV-specific secretory IgA in BALF and feces and titers of IFV-specific neutralizing antibody in BALFs and sera were increased. These results indicate that LpYU has a protective effect against IFV replication. We conclude that this strain has a beneficial effect in activating Th1 immune responses and preventing viral infection.


Effect of uphill walking with varying grade and speed during load carriage on muscle activity.
Indian soldiers, while guarding the mountainous border areas, often carry loads in steep uphill gradients. This activity may predispose the risk of muscle injury. The present study aimed to examine the effects of an increasing load, speed and gradient during incremental uphill treadmill walking on different muscles. Twelve infantry soldiers walked on a treadmill at two speeds (2.5 and 4 km/h) with no load, and carrying 10.7, 17 and 21.4 kg loads at 0, 5, 10, 15, 20, 25% gradients. Electromyographic responses of erector spinae (>240%) and vastus medialis (>240%) were mostly affected, followed by soleus (>125%) and gastrocnemius medialis (>100%) at maximum speed, load and gradient combination compared to 0% gradient. Carrying 10.7 kg at 15% gradient and above was found to be highly strenuous and fatiguing with the risk of muscle injury. Uphill load carriage in slower speed is recommended for the maintenance of combat fitness of the individual at higher gradients. Practitioner Summary: The present article has evaluated the stress encountered by soldiers during load carriage at incremental uphill gradients while walking at different speeds by recording the muscular activities. Load carriage in steep uphill gradients is highly strenuous and may lead to muscle injury thus compromising the combat fitness.


Site-directed mutagenesis of the Anabaena sp. strain PCC 7120 nitrogenase active site to increase photobiological hydrogen production.
Cyanobacteria use sunlight and water to produce hydrogen gas (H₂), which is potentially useful as a clean and renewable biofuel. Photobiological H₂ arises primarily as an inevitable by-product of N₂ fixation by nitrogenase, an oxygen-labile enzyme typically containing an iron-molybdenum cofactor (FeMo-co) active site. In Anabaena sp. strain 7120, the enzyme is localized to the microaerobic environment of heterocysts, a highly differentiated subset of the filamentous cells. In an effort to increase H₂ production by this strain, six nitrogenase amino acid residues predicted to reside within 5 Å of the FeMo-co were mutated in an attempt to direct electron flow selectively toward proton reduction in the presence of N₂. Most of the 49 variants examined were deficient in N₂-fixing growth and exhibited decreases in their in vivo rates of acetylene reduction. Of greater interest, several variants examined under an N₂ atmosphere significantly increased their in vivo rates of H₂ production, approximating rates equivalent to those under an Ar atmosphere, and accumulated high levels of H₂ compared to the reference strains. These results demonstrate the feasibility of engineering cyanobacterial strains for enhanced photobiological production of H₂ in an aerobic, nitrogen-containing environment.


Neuroprotective activity of fructose-1,6-bisphosphate following transient forebrain ischemia in the Mongolian gerbil.
We examined the protective activity of fructose-1,6-bisphosphate (FBP) on mortality and delayed hippocampal cell death induced by transient cerebral ischemia in the Mongolian gerbil. Forebrain ischemia was produced by bilaterally occluding the common carotid arteries for 15 min using microaneurysm clips; then the blood supply to the brain was restored. The number of survivors was counted for 8 days, and the histopathological damage in the CA1 region of the hippocampus was scored according to the semiquantitative scale of Rudolphi and colleagues. When injected 15 min before the ischemic insult, FBP (100 and 333 mg/kg, i.v.) significantly reduced the rate of mortality during the 8-day observation period. Equivalent doses of fructose and fructose monophosphate did not improve survival, and neither did low doses (33 mg/kg) of FBP. FBP also produced a significant degree of protection against the CA1 pyramidal cell loss in comparison with its vehicle (distilled water). Conversely, when we administered the compound, at the same dose, 15 min after the release of the arterial occlusion, we observed neither a significant reduction of mortality nor significant protection against hippocampal CA1 pyramidal cell loss. These results suggest that FBP possesses salutary properties against the damages induced by transient cerebral ischemia, although they are evident only when the compound is administered before the resolution of the ischemic injury.


Identifying Molecular Changes in Early Cervical Cancer Samples of Patients That Developed Metastasis.
Cervical cancer is one of the most common cancers in women worldwide. Patients diagnosed with early-stage cervical cancer have a good prognosis, however, 10-20% suffer from local or distant recurrent disease after primary treatment. Treatment options for recurrent cervical cancer are limited. Therefore, it is crucial to identify factors that can predict patients with an increased risk of recurrence to optimize treatment to prevent the recurrence of cervical cancer. We aimed to identify biomarkers in early-stage primary cervical cancer which recurred after surgery. Formalin-Fixed, Paraffin-Embedded surgical specimens of 34 patients with early-stage cervical cancer (FIGO 2009 stage 1B1) and 7 healthy controls were analyzed. Targeted gene expression profiling using the PanCancer IO 360 panel of NanoString Technology was performed. The findings were confirmed by performing immunohistochemistry stainings. Various genes, namely GLS, CD36, WNT5a, HRAS, DDB2, PIK3R2, and CDH2 were found to be differentially highly expressed in primary cervical cancer samples of patients who developed distant recurrence. In addition, The relative infiltration score of CD8+ T cells, CD80+CD86+ macrophages, CD163+MRC1+ macrophages, and FOXP3+IL2RA+ regulatory T cells were significantly higher in this group of samples. In contrast, no significant differences in gene expression and relative immune infiltration were found in samples of patients who developed local recurrence. The infiltration of CD8 and FOXP3 cells were validated by immunohistochemistry using all samples included in the study. We identified molecular alterations in primary cervical cancer samples from patients who developed recurrent disease. These findings can be utilized towards developing a molecular signature for the early detection of patients with a high risk to develop metastasis.


Validation of a Rapid, Robust, Inexpensive Screening Method for Detecting the HLA-B*58:01 Allele in the Prevention of Allopurinol-Induced Severe Cutaneous Adverse Reactions.
The HLA B*58:01 allele has been worldwide reported as a pharmacogenetic susceptibility to allopurinol-induced severe cutaneous adverse reactions (SCARs). To prevent these life-threatening conditions, the American College of Rheumatology hingly recommended that the HLA-B*58:01 be screened prior to the initiation of allopurinol therapy. Therefore, we developed a rapid, robust, inexpensive screening method using SYBR® Green real time PCR to detect the HLA-B*58:01 allele. A total of 119 samples were tested. The assay has a sensitivity of 100% (95% CI: 69.15%-100%), a specificity of 100% (95% CI: 96.67%-100%), a positive predictive value of 100% (95% CI: 69.15%-100%) and a negative predictive value of 100% (95% CI: 96.67%-100%). HLA-B*58:01 genotyping results showed 100% agreement with those obtained from Luminex SSO/SBT/SSP. The lowest limit of detection of this method is 0.8 ng/μL of DNA. The unit cost of the test is only $3.8 USD. This novel screening test using SYBR® real time PCR would be appropriate to identify individuals with the HLA-B*58:01 allele for the prevention of allopurinol-induced SCARs.


[Role of oxygen free radicals in ischemic reperfusion lesions to the myocardium].
Free oxygen radicals are highly active oxygen compounds contributing to several pathological states. A possible source of free oxygen radicals during reversible ischemic heart disease and mechanisms of their toxicity to the myocardium are discussed. Despite controversial results of clinical trials with the use of antioxidants in reducing an area of necrosis in the experimental myocardial infarction, it seems that free oxygen radicals play an important role in ischemic-reperfusion heart disease. Some promising results with the use of antioxidants (significant decrease in dyskinesis of ischemic left ventricular muscle and reduction of cardiac arrhythmias incidence) may be of clinical importance.


Modeling of alcohol use mediates the effect of family history of alcoholism on adolescent alcohol expectancies.
The relative impact of biological family history of alcoholism and exposure to abusive parental drinking on alcohol effect expectancies of adolescent offspring were investigated in the present study. Exposure to familial models of alcohol abuse and biological family history were both predictive of positive alcohol effect expectancies of adolescent offspring. Degree of exposure to an alcohol-abusing family member mediated the relationship between biological family history of alcoholism and adolescent alcohol outcome expectancies. These results support prior findings of expectancy differences between youths with and without a family background of alcoholism and provide evidence supporting the significance of family modeling influences in the development of adolescents' alcohol expectancies.


Pathways of substance P stimulation of canine tracheal ciliary beat frequency.
Substance P (SP), an inflammatory neuropeptide, may be released by intraepithelial nerves in response to an irritant or inflammatory stimulus. To investigate the neural and humoral pathways mediating the response of tracheal ciliary beat frequency (CBF) to topically applied SP, CBF was measured on the ventral midtracheal surface of anesthetized beagles by using heterodyne-mode correlation analysis laser light scattering. In the first study, aerosolized SP, delivered to the lungs of eight beagle dogs, stimulated CBF in a dose-dependent manner from a baseline of 4.9 +/- 0.4 Hz to a maximum of 14.9 +/- 1.5 Hz at dose of 10(-7) M. In the second study, the tracheal lumen was isolated from the bronchial airways by inflating the cuff of an endotracheal tube near the carina. Intravenous hexamethonium bromide (2 mg/kg), ipratropium bromide (0.5 micrograms/kg), and indomethacin (2 mg/kg) were used as blocking agents to inhibit the nicotinic, muscarinic, and cyclooxygenase pathways, respectively. Aerosolized 10(-9), 10(-8), or 10(-7) M SP was delivered sequentially to the tracheal lumen for 3 min at 30-min intervals. SP caused two distinct CBF stimulatory episodes at 4 min (mean time of the maximal response) and at 18 min (mean time of the maximal response) after onset of delivery and returned to baseline after 25 min. SP stimulated CBF from the baseline of 5.1 +/- 0.4 Hz to a maximum of 14.2 +/- 2.5 Hz during the first episode (P less than 0.01) and to 10.4 +/- 0.6 Hz during the second episode (P less than 0.01) at dose of 10(-8) M. These responses were inhibited by all the blocking agents. These data suggest that SP stimulates CBF via a cyclooxygenase-dependent parasympathetic reflex.


Medical education in Poland.
Both undergraduate and postgraduate medical education in Poland are currently undergoing a significant reform, based on new national educational standards, arising from European Union recommendations. This article describes the previous system and the new approach to medical curriculum, draws a picture of the current situation and discusses the impact of this educational change on the quality of future graduates.


Image-based biomechanical modeling for coronary atherosclerotic plaque progression and vulnerability prediction.
Atherosclerotic plaque progression and rupture play an important role in cardiovascular disease development and the final drastic events such as heart attack and stroke. Medical imaging and image-based computational modeling methods advanced considerably in recent years to quantify plaque morphology and biomechanical conditions and gain a better understanding of plaque evolution and rupture process. This article first briefly reviewed clinical imaging techniques for coronary thin-cap fibroatheroma (TCFA) plaques used in image-based computational modeling. This was followed by a summary of different types of biomechanical models for coronary plaques. Plaque progression and vulnerability prediction studies based on image-based computational modeling were reviewed and compared. Much progress has been made and a reasonable high prediction accuracy has been achieved. However, there are still some inconsistencies in existing literature on the impact of biomechanical and morphological factors on future plaque behavior, and it is very difficult to perform direct comparison analysis as differences like image modality, biomechanical factors selection, predictive models, and progression/vulnerability measures exist among these studies. Encouraging data and model sharing across the research community would partially resolve these differences, and possibly lead to clearer assertive conclusions. In vivo image-based computational modeling could be used as a powerful tool for quantitative assessment of coronary plaque vulnerability for potential clinical applications.


MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High Phosphorus.
Vascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or high-phosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and high-calcium and -phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.


Cancer and inflammation: an old intuition with rapidly evolving new concepts.
Recent scientific advances have contributed much to the dissection of the complex molecular and cellular pathways involved in the connection between cancer and inflammation. The evidence for this connection in humans is based on the association between infection or chronic sterile inflammation and cancer. The decreased incidence of tumors in individuals who have used nonsteroidal anti-inflammatory drugs is supportive of a role for inflammation in cancer susceptibility. The increased incidence of tumors in overweight patients points to a role for adipose tissue inflammation and energy metabolism in cancer. Energy metabolism, obesity, and genetic instability are regulated in part by the relationship of the organism with commensal bacteria that affect inflammation with both local and systemic effects. Different aspects of inflammation appear to regulate all phases of malignant disease, including susceptibility, initiation, progression, dissemination, morbidity, and mortality.


Optimisation of secondary electrospray ionisation (SESI) for the trace determination of gas-phase volatile organic compounds.
An electrospray ionisation triple quadrupole mass spectrometer (Varian 1200 L) was modified to accept nitrogen samples containing low concentrations of volatile organic compounds. Six candidate probe compounds, methyl decanoate, octan-3-one, 2-ethylhexanoic acid, 1,4-diaminobutane, dimethyl methylphosphonate, and 2,3-butanediol, at concentrations below 50 ppb(v) were generated with permeation tubes in a test atmosphere generator. The concept of using a set of molecular probes to evaluate gas-phase electrospray ionisation of volatile analytes was assessed and the feasibility of adopting a unified ionisation approach for gas and liquid contamination of exobiotic environments established. 450 experiments were run in a five-replicate, fifteen-level, three-factor, central-composite-design with exponential dilution for each of the six probe compounds studied. The three factors studied were ionisation voltage, drying-gas flow and nebulising-gas flow. Parametric modelling by regression analysis enabled the differences in the ionisation behaviours of the probe compounds to be described by the optimisation models. Regression coefficients were in the range 0.91 to 0.99, indicating satisfactory levels of precision in the optimisation models. A wide range in ionisation efficiency was observed, with different optimised conditions required for the probe compounds. It was evident that no one factor appeared to dominate the response and the different factors produced different effects on the responses for the different molecules. 1,4-Butanediamine and dimethyl methylphosphonate required significantly lower ionisation voltages (1.2 kV) than the other four, which achieved optimised sensitivity towards the maximum voltage used in this design (5 to 6 kV). Drying-gas flow rates were found to be more important than nebulising-gas flow rates. However, variations in the constant term B(0) in the optimisation models indicated that other factors, not included in this study, were also likely to be involved in the ionisation process. Electrolyte-flow rate and ionisation temperature were proposed for follow up studies. Exponential dilution data indicated sensitive and analytically useful responses in the target range of 5 to 50 ppb(v) for all six compounds. Significantly, responses were seen at concentrations significantly below 5 ppb(v), with sub ppt(v) responses observed for 1,4-butanediamine, 2-ethylhexanoic acid, dimethylmethylphosphonate, and 1,3-butanediol. Responses in the ppt(v) to ppb(v) range were observed for the remaining two compounds. The observations from this study demonstrated the utility of adopting a set of probe compounds to evaluate electrospray ionisation performance for volatile organic compound based assays; indicated the existence of multiple ionisation mechanisms; and revealed potential sensitivity at the parts per quadrillion level ppq(v).


Phenolic glycosides from Exostema mexicanum leaves.
Phytochemical investigation of the leaves of Exostema mexicanum led to the isolation of two novel acylated flavonol glycosides 6, 7 and three glycosides 1-4 structurally belonging to the group of 4-phenylcoumarins. One of them, 5-O-beta-D-glucopyranosyl-4'-hydroxy-7-methoxy-4-phenylcoumarin (2), turned out to be new. Furthermore, the 4-phenylcoumarin aglycone 3'-hydroxy-4',5,7-trimethoxy-4-phenylcoumarin (5) was obtained. The in vitro cytotoxicity of 3-5 against the cell line ECV-304 was evaluated; the aglycone 5 was highly cytotoxic, whereas the glycosidic compounds 3 and 4 were inactive.


Metagenomic study of the gut microbiota associated with cow milk consumption in Chinese peri-/postmenopausal women.
Cow milk consumption (CMC) and alterations of gut bacterial composition are proposed to be closely related to human health and disease. Our research aims to investigate the changes in human gut microbial composition in Chinese peri-/postmenopausal women with different CMC habits. A total of 517 subjects were recruited and questionnaires about their CMC status were collected; 394 subjects were included in the final analyses. Fecal samples were used for studying gut bacterial composition. All the subjects were divided into a control group (n = 248) and a CMC group (n = 146) according to their CMC status. Non-parametric tests and LEfSe at different taxonomic levels were used to reveal differentially abundant taxa and functional categories across different CMC groups. Relative abundance (RA) of one phylum (p_Actinobacteria), three genera (g_Bifidobacterium, g_Anaerostipes, and g_Bacteroides), and 28 species diversified significantly across groups. Specifically, taxa g_Anaerostipes (p < 0.01), g_Bacteroides (p < 0.05), s_Anaerostipes_hadrus (p < 0.01), and s_Bifidobacterium_pseudocatenulatum (p < 0.01) were positively correlated with CMC levels, but p_Actinobacteria (p < 0.01) and g_Bifidobacterium (p < 0.01) were negatively associated with CMC levels. KEGG module analysis revealed 48 gut microbiome functional modules significantly (p < 0.05) associated with CMC, including Vibrio cholerae pathogenicity signature, cholera toxins (p = 9.52e-04), and cephamycin C biosynthesis module (p = 0.0057), among others. In conclusion, CMC was associated with changes in gut microbiome patterns including beta diversity and richness of some gut microbiota. The alterations of certain bacteria including g_Anaerostipes and s_Bifidobacterium_pseudocatenulatum in the CMC group should be important for human health. This study further supports the biological value of habitual cow milk consumption.


Enhanced diazinon susceptibility in pyrethroid-resistant horn flies (Diptera: Muscidae): potential for insecticide resistance management.
Dose-mortality data from 40 horn fly, Haematobia irritans (L.), populations revealed that susceptibility to permethrin and diazinon was negatively correlated (i.e., as susceptibility to permethrin decreased, toxicity of diazinon increased). Permethrin-resistant horn fly populations exposed for 18 wk to cattle tagged with ear tags impregnated with 20% (AI) diazinon resulted in a 2- to 6-fold reduction in this resistance. These populations also had LC50s for diazinon that were two to five times lower than those of populations susceptible to permethrin. Frequency of homozygous permethrin-resistant individuals decreased as much as 57% after exposure to diazinon during this period.


1,5-Anhydroglucitol Predicts Mortality in Patients with HBV-Related Acute-on-chronic Liver Failure.
1,5-Anhydroglucitol (1,5AG) activity has been reported in chronic liver disease. Hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) patients have a high mortality. We aimed to discover the relationship between serum 1,5AG and the prognosis of HBV-ACLF. Serum 1,5AG levels were determined in 333 patients with HBV-ACLF, 300 without diabetes were allocated to derivation (n=206) and validation cohorts (n=94), and 33 were recruited to evaluate 1,5AG in those with diabetes. Forty patients with chronic hepatitis B, 40 with liver cirrhosis, and 40 healthy people were controls in the validation cohort. In the derivation and validation cohorts, serum 1,5AG levels were significantly lower in nonsurvivors than in survivors. The AUC of 1,5AG for 28-day mortality was 0.811. In patients with diabetes, serum 1,5AG levels were also significantly lower in nonsurvivors than in survivors. In multivariate Cox regression analysis, serum 1,5AG levels were independently associated with 28-day mortality. A novel predictive model (ACTIG) based on 1,5AG, age, TB, cholesterol, and INR was derived to predict mortality. In ACTIG, the AUC for 28-day mortality was 0.914, which was superior to some prognostic score models. ACTIG was also comparable to those prognostic score models in predicting 6-month mortality. In mice with D-galactosamine/lipopolysaccharide-induced liver failure, 1,5AG levels were significantly reduced in serum and significantly increased in urine and liver tissue. Serum 1,5AG levels are a promising predictor of short-term mortality in HBV-ACLF patients. The 1,5AG distribution changed in mice with D-galactosamine/ lipopolysaccharide-induced liver failure.


Cost-utility analysis of prophylactic treatment with oral ganciclovir for cytomegalovirus retinitis.
Cytomegalovirus (CMV) retinitis is a relatively common opportunistic infection in late-stage HIV disease, causing significant morbidity and mortality. Prophylactic use of oral ganciclovir has recently been shown to decrease the incidence of CMV retinitis but is relatively expensive and may not be very well tolerated by many patients. We performed a decision analysis to assess the cost-effectiveness of prophylactic oral ganciclovir therapy. A decision analysis using a Markov approach compared absence of prophylaxis and prophylaxis with oral ganciclovir. Estimates of effectiveness of prophylaxis and costs of illness were obtained from published literature. Drug costs were based on national average wholesale prices. All health care costs were based on 1996 U.S. dollars. Sensitivity analyses were done over ranges of estimates of cost and effectiveness. Using our baseline estimates of cost and effectiveness, use of oral ganciclovir prophylaxis in patients with CD4 counts <50 cells/mm3 would be associated with average lifetime health care costs of $104,746, compared with $90,985 for no prophylaxis. Using oral ganciclovir, the average quality-adjusted life-years (QALYs) would be 2.05, and the CMV retinitis-free life-years would be 1.64, compared with 1.87 and 1.27, respectively, for no prophylaxis. The incremental cost-utility of oral ganciclovir is $76,676 per year of life saved and $37,542 per year of additional CMV retinitis-free life. Oral ganciclovir would become more cost-effective relative to no prophylaxis if the probability of CMV retinitis while taking oral ganciclovir declined. Oral ganciclovir would be less cost-effective if the cost of treating CMV retinitis declines, if our estimates of quality of life are low, or if the overall incidence of CMV retinitis declines. Oral ganciclovir is a less cost-effective approach than several other interventions used for HIV-disease prophylaxis. It would potentially become cost-effective if it is possible to target oral ganciclovir prophylaxis to patients who are most likely to benefit.


Development and evolution of a variable left-right asymmetry in nematodes: the handedness of P11/P12 migration.
In Caenorhabditis elegans, two lateral blast cells called P11/12L and P11/12R are symmetric left-right homologs at hatching, migrate subsequently in opposite anteroposterior directions during the first larval stage, and adopt two different fates, thus breaking the symmetry between them. Our results show that, unlike most other cell fate decisions in C. elegans, the orientation of P11/12L/R migration is highly biased, but not fixed. The handedness of their migration is linked to whole body handedness and is randomized in lin-12/Notch mutants and by ablation of the Y cell. Migration handedness is independent of P11 and P12 fate determination, previously shown to require the LIN-44/Wnt and the LIN-3/EGF pathways (L. I. Jiang and P. W. Sternberg, 1998, Development 125, 2337-2347). We further show that several changes in P11/12L/R asymmetry have occurred during nematode evolution: loss of asymmetry or reversals in orientation of migration. Strikingly, for most species studied, handedness of migration is highly biased but not fixed. Thus, whereas the final cell fate pattern of P11/12 is invariant, the developmental route leading to it is subject both to developmental indeterminacy and to evolutionary variations.


Becoming a tobacco-free campus: A survey of student attitudes, opinions and behaviors.
The effectiveness of tobacco-free campus policies in preventing and mitigating tobacco use relies on students' perceptions, opinions, and adherence to clean-air restrictions. The purpose of this study was to gather data regarding student attitudes, opinions and tobacco use behaviors, one year following implementation of the tobacco-free campus initiative. Data were gathered using an anonymous, online survey of graduate and undergraduate students at a public university, one year following implementation of a tobacco-free campus policy. Survey items included tobacco use behaviors, nicotine dependence, opinions towards the policy, challenges in policy adherence among tobacco users, and awareness of tobacco cessation resources for students. Analysis primarily included descriptive statistics. Of 108 respondents, only 18 were habitual tobacco users with most using: cigarettes, cigars or cigarillos (38%), vaping (17.8%), hookah (11.9%), and smokeless tobacco (11.9%). Several reported multiple use. Common motives for tobacco use were relaxation and mood regulation. Tobacco users rated a moderate level of difficulty in adhering to the policy. Only half of the total respondents were aware of cessation resources, specifically peer counseling. Most tobacco users (71%) believed that they could quit without assistance. Preliminary data show 21.8% prevalence of tobacco use within the sample. Information on student opinions and behaviors, including lower risk perception, dual use, and lack of awareness of cessation resources can inform more effective prevention and mitigation strategies, in addition to the tobaccofree campus policy. Further research is needed to monitor policy adherence and changes in student tobacco behaviors.


Forceplate and accelerometer measures for evaluating the effect of muscle fatigue on postural control during one-legged stance.
The control of balance is vital in many sporting activities as well as in activities of daily life. In order to treat deficiencies properly valid and reliable methods are needed to evaluate different aspects of stability. Muscle fatigue has been proposed to cause a change in postural control strategy, and the use of different tools and variables might therefore elucidate these changes. The aims of the present study were: to investigate if forceplate and accelerometer measurements about postural control during one-legged stance indicate changes in postural control strategy after fatiguing exercise; and to investigate the correlation between forceplate and accelerometer measurements obtained before and after fatiguing exercise. The study used an experimental design. Twenty-three healthy women (mean age 26.8 years; range 20-34 years) were studied. Forceplate and accelerometer data were obtained simultaneously and consisted of measures of centre of pressure movements and horizontal trunk acceleration in medio-lateral and antero-posterior directions. The calf muscles of the right leg were fatigued by repeated heel rises. The average amplitude of centre of pressure movements and trunk acceleration increased, whereas the average velocity of centre of pressure movements decreased during fatigue. These changes indicate a change of movement strategy. Moderate correlation between trunk acceleration and centre of pressure movements was seen, confirming the link between the variables, but indicating that different aspects of the ability to control balance were measured. Calf muscle fatigue has a short-lasting effect on body balance, with measurements indicating a change in postural control strategy. Different tools and variables are needed to identify different balance control strategies. The procedures used in the present study may be modified to identify subjects with inadequate capacity to choose between balance control strategies; they are also applicable in clinical settings outside a laboratory environment.


Metabolomics of cereals under biotic stress: current knowledge and techniques.
Prone to attacks by pathogens and pests, plants employ intricate chemical defense mechanisms consisting of metabolic adaptations. However, many plant attackers are manipulating the host metabolism to counteract defense responses and to induce favorable nutritional conditions. Advances in analytical chemistry have allowed the generation of extensive metabolic profiles during plant-pathogen and pest interactions. Thereby, metabolic processes were found to be highly specific for given tissues, species, and plant-pathogen/pest interactions. The clusters of identified compounds not only serve as base in the quest of novel defense compounds, but also as markers for the characterization of the plants' defensive state. The latter is especially useful in agronomic applications where meaningful markers are essential for crop protection. Cereals such as maize make use of their metabolic arsenal during both local and systemic defense responses, and the chemical response is highly adapted to specific attackers. Here, we summarize highlights and recent findings of metabolic patterns of cereals under pathogen and pest attack.


Skin tears: introducing best practice.
In an Essity-sponsored symposium, three key opinion leaders discussed the importance of developing, sharing and applying best practice in skin tear management. Camila Fronzo summarises the key points presented at the EWMA and Journées Cicatrisations conference 2021 This conference report offers an introduction to the symposium 'Skin integrity: introducing best practice in skin tears', held in October as part of the joint European Wound Management Association (EWMA) and Journées Cicatrisations virtual conference 2021. The first speaker, Karen Campbell, listed the individual and mediating factors that could affect skin tear development. She then summarised the three types of skin tears, and mentioned the dos and don'ts when treating these wounds. The next speaker, Wendy White, highlighted the importance of creating awareness, changing perceptions and implementing change around skin tear management. She shared the results on staff education from a recent quality improvement project, aimed at improving skin integrity and reducing skin tears in an aged care facility in Western Australia. The third and final speaker, Sitthichai Rees, presented further findings from the same project, focusing on the effects on skin tear incidence. His call to action can be followed by any health professional managing skin tears.


Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes.
The cell cycle events accompanying TGF-beta1-induced growth arrest of normal mouse resting B lymphocytes stimulated by LPS were investigated. We showed that TGF-beta1 prevents the retinoblastoma protein (pRb) phosphorylation and induces growth arrest in mid- to late G1. To explore the molecular basis of the effect of TGF-beta1, we analyzed the in vitro kinase activities of cyclin/cyclin-dependent kinase (cdk) complexes involved in the progression through G1 phase and in the G1/S transition, by using the glutathione S-transferase-pRb fusion protein as a substrate. Cdk2-associated kinase activity was strongly induced in mitogen-treated B cells. It was dramatically inhibited by TGF-beta1 as were the cyclin E- and cyclin A-dependent kinase activities. TGF-beta1 treatment had no significant effect on the expression of two G1/S phase proteins, cyclin E and cdk2. In contrast, the appearance of cyclin A, occuring in late G1 phase, was almost totally inhibited by TGF-beta1. We also showed that expression of the cdk inhibitor protein p27Kip1 decreased as cells progressed through the G1 phase. An accumulation of p27 was found in TGF-beta1-treated cells, showing that TGF-beta1 prevented LPS-induced decline of p27. Finally we found that the lack of kinase activity associated with cyclin E/cdk2 complexes was correlated with increased amounts of cdk2- and cyclin E-bound p27. Overall, these results suggest that both cyclin A and cdk2 may be active participants in the TGF-beta1-induced cell cycle arrest in normal mouse B cells and indicate the involvement of p27 in this mechanism.


Characteristics of sexual assault in women with a major psychiatric diagnosis.
In a previous study of women who had been sexually assaulted, we reported a 26% prevalence of a major psychiatric diagnosis. The purpose of this study was to better characterize sexual assaults in women with a major psychiatric diagnosis. All female patients >or=15 years old with a complaint of sexual assault underwent a standardized history and physical examination by an upper-level resident in obstetrics and gynecology. Data were abstracted and verified. A psychiatric diagnosis was determined by history and by use of computer-linked medical records. Chi-square or Fisher exact test was used for categoric analysis. Of the 819 women who were examined, 211 women (26%) had a major psychiatric diagnosis. In these 211 women, the prevalence of solely mood, thought, or substance use disorders were 26%, 14%, and 16%, respectively, whereas 44% had >or=2 diagnoses. Having a psychiatric diagnosis was associated with increasing age (P =.001), homelessness (P =.001), and incarceration (P =.001). In comparison with women with no psychiatric diagnosis, sexual assaults in these 211 women occurred more frequently outdoors (P =.007), by a stranger (P <.001), or by >or=2 assailants (P =.02). Being assaulted with a weapon (P =.04) and being hit (P =.01) were more prevalent in assaults against women with a psychiatric diagnosis, as was anal contact (P =.03), contact to >or=2 body orifices (P =.001), and body trauma (P =.01). Sexual assaults in women with a major psychiatric diagnosis are common. These assaults are more violent and result in body trauma more frequently than do sexual assaults in women without a psychiatric diagnosis. Prevention and treatment strategies should target this vulnerable population.


Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
1. The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance. 2. Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed. Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens. Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design. Excreta were quantitatively collected during the last 3 days for AME determination. 3. The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively. The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively. The quality characteristics of wheat samples were in the expected range. 4. There were differences (P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples. The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples. Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples. 5. The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics. 6. The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05). The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05). 7. Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers. There was no relationship between growth performance of broilers and AMEn of the wheat samples.


Regulated protein degradation controls PKA function and cell-type differentiation in Dictyostelium.
Cullins function as scaffolds that, along with F-box/WD40-repeat-containing proteins, mediate the ubiquitination of proteins to target them for degradation by the proteasome. We have identified a cullin CulA that is required at several stages during Dictyostelium development. culA null cells are defective in inducing cell-type-specific gene expression and exhibit defects during aggregation, including reduced chemotaxis. PKA is an important regulator of Dictyostelium development. The levels of intracellular cAMP and PKA activity are controlled by the rate of synthesis of cAMP and its degradation by the cAMP-specific phosphodiesterase RegA. We show that overexpression of the PKA catalytic subunit (PKAcat) rescues many of the culA null defects and those of cells lacking FbxA/ChtA, a previously described F-box/WD40-repeat-containing protein, suggesting CulA and FbxA proteins are involved in regulating PKA function. Whereas RegA protein levels drop as the multicellular organism forms in the wild-type strain, they remain high in culA null and fbxA null cells. Although PKA can suppress the culA and fbxA null developmental phenotypes, it does not suppress the altered RegA degradation, suggesting that PKA lies downstream of RegA, CulA, and FbxA. Finally, we show that CulA, FbxA, and RegA are found in a complex in vivo, and formation of this complex is dependent on the MAP kinase ERK2, which is also required for PKA function. We propose that CulA and FbxA regulate multicellular development by targeting RegA for degradation via a pathway that requires ERK2 function, leading to an increase in cAMP and PKA activity.


Definitive Radiotherapy for Primary Squamous Cell Carcinoma of the Vagina: Are High-Dose External Beam Radiotherapy and High-Dose-Rate Brachytherapy Boost the Best Treatment? Experience of Two Italian Institutes.
We assessed the clinical outcome and survival of 70 patients with primary vaginal squamous cell carcinoma undergoing radiotherapy (RT) at the Divisions of Radiotherapy, University of Pisa and ASST Cremona between January 1995 and June 2016. 58 patients received external beam RT (EBRT) to the entire vagina, para-vaginal area and pelvic nodes (total dose: 45-50.4 Gy). 29 patients (41.4%) received concomitant weekly cisplatin 40 mg/m2. 35 patients received an additional (15-36 Gy) high-dose-rate (HDR) brachytherapy (BT) boost and 13 received an additional (9-25 Gy) EBRT boost to the primary tumor site. 12 women exclusively received HDR-BT up to a total dose of (30-58 Gy). Median overall survival (OS) was 85 months. A total RT dose of > 60 Gy was significantly associated with a better OS (p = 0.015). There was a trend for a better OS for patients aged < 70 years and for those undergoing EBRT to the entire vagina and pelvis plus BT boost. The most common grade 1-2 acute toxicities were diarrhea (24.1%) and cystitis (20.7%); grade 3 cystitis only occurred in 2 patients (3.4%). EBRT followed by BT boost seems to be the best treatment for vaginal carcinoma. The total dose of RT should be > 60 Gy.


Path to the Interpeduncular Fossa: Anatomical Comparison of Endoscopic-Assisted versus Standard Subtemporal Approach.
Objective The aim of this study was to assess the assumed advantage of endoscopic assistance to the standard subtemporal approach. The idea was to measure qualitatively and quantitatively visibility versus operability. Design We performed eight subtemporal dissections on four cadaver heads. Our dissections integrated an operating microscope, endoscope, and neuronavigation. Comparison was made between visibility and operability afforded by the microscope alone or by the microscope-endoscope combination. Visibility was recorded as complete or incomplete and was quantified for key structures using linear measurements taken by the navigation system. Operability was determined by whichever maneuvers could be safely and comfortably accomplished in the space afforded. Results From our survey, the structures whose visibility most benefitted from the addition of the endoscope include: contralateral third nerve, posterior perforated substance, mammillary bodies, and contralateral superior cerebellar artery. With regard to quantitative evaluation, we found increased visibility of both basilar artery and posterior cerebral artery. With regard to the operability, no objective advantage was afforded by the addition of the endoscope. Subjectively, the maneuvers were easier to perform while using the endoscope. Conclusion Using the endoscope as an assistance tool during conducting classical subtemporal approach can help in overcome a lot of the classical subtemporal approach limitations.


Recall of Intensive Care Unit Stay in Critical Illness Survivors in Southeast Iran.
In survivors of critical illness, recall of an intensive care unit stay plays an important role in the development of post-intensive care unit syndrome, which includes psychological impairment after intensive care unit discharge. To investigate memories of the intensive care unit among survivors in southeast Iran. In this descriptive study, the intensive care unit memory tool was used to assess patients' memories of intensive care units. All participants (N = 100) had 1 or more factual memories (89%), memories of feelings (66%), or delusional memories (34%) from the intensive care unit. Patients who received mechanical ventilation were 4 times as likely to have delusional memories as those who did not receive mechanical ventilation. Unmarried patients were 4.8 times as likely as married patients to have memories of feelings from the intensive care unit. Steps should be taken to minimize distressing memories of an intensive care unit admission. Follow-up programs should take into account the psychological problems faced by intensive care unit survivors.


Modeling the epidemiological history of plague in Central Asia: palaeoclimatic forcing on a disease system over the past millennium.
Human cases of plague (Yersinia pestis) infection originate, ultimately, in the bacterium's wildlife host populations. The epidemiological dynamics of the wildlife reservoir therefore determine the abundance, distribution and evolution of the pathogen, which in turn shape the frequency, distribution and virulence of human cases. Earlier studies have shown clear evidence of climatic forcing on contemporary plague abundance in rodents and humans. We find that high-resolution palaeoclimatic indices correlate with plague prevalence and population density in a major plague host species, the great gerbil (Rhombomys opimus), over 1949-1995. Climate-driven models trained on these data predict independent data on human plague cases in early 20th-century Kazakhstan from 1904-1948, suggesting a consistent impact of climate on large-scale wildlife reservoir dynamics influencing human epidemics. Extending the models further back in time, we also find correspondence between their predictions and qualitative records of plague epidemics over the past 1500 years. Central Asian climate fluctuations appear to have had significant influences on regional human plague frequency in the first part of the 20th century, and probably over the past 1500 years. This first attempt at ecoepidemiological reconstruction of historical disease activity may shed some light on how long-term plague epidemiology interacts with human activity. As plague activity in Central Asia seems to have followed climate fluctuations over the past centuries, we may expect global warming to have an impact upon future plague epidemiology, probably sustaining or increasing plague activity in the region, at least in the rodent reservoirs, in the coming decades.See commentary: http://www.biomedcentral.com/1741-7007/8/108.


Biphasic Calcium Phosphate (BCP)-Immobilized Porous Poly (d,l-Lactic-co-Glycolic Acid) Microspheres Enhance Osteogenic Activities of Osteoblasts.
The purpose of this study was to evaluate the potential of porous poly (d,l-lactic-co-glycolic acid) (PLGA) microspheres (PMSs) immobilized on biphasic calcium phosphate nanoparticles (BCP NPs) (BCP-IM-PMSs) to enhance osteogenic activity. PMSs were fabricated using a fluidic device, and their surfaces were modified with l-lysine (aminated-PMSs), whereas the BCP NPs were modified with heparin⁻dopamine (Hep-DOPA) to obtain heparinized⁻BCP (Hep-BCP) NPs. BCP-IM-PMSs were fabricated via electrostatic interactions between the Hep-BCP NPs and aminated-PMSs. The fabricated BCP-IM-PMSs showed an interconnected pore structure. In vitro studies showed that MG-63 cells cultured on BCP-IM-PMSs had increased alkaline phosphatase activity, calcium content, and mRNA expression of osteocalcin (OCN) and osteopontin (OPN) compared with cells cultured on PMSs. These data suggest that BCP NP-immobilized PMSs have the potential to enhance osteogenic activity.


Developing a framework for interprofessional collaborative practice, cultural fluency, and ecological approaches to health.
This paper describes the development of a framework for reducing health disparities inclusive of interprofessional collaborative practice, cultural humility, and ecological approaches to health; the identification of common core competencies for students from various disciplines; and relevant assessment instruments to measure attainment of those competencies. The framework, associated logic model and initiatives, and core competencies were created through an iterative process involving multiple stakeholders. Using the framework as the outcome, a logic model was created to identify short, medium, and long-term activities and outcomes. Faculty were involved in the identification of core competencies and relevant validated assessment instruments. Future work will include mapping competencies across the curricula in a school of health at a liberal arts university and longitudinal assessment of students to evaluate attainment of competencies.


Cataract in retinopathy of prematurity - A review.
Preterm babies with retinopathy of prematurity (ROP) can become blind if they do not receive appropriate timely intervention. The presence of cataract in these individuals in addition to visual deprivation amblyopia, also delays proper screening, adequate treatment, and makes follow-up assessment difficult. Anatomical differences in these infants and amblyopia management, especially in unilateral cataract, are other important concerns, and hence, management of these cases with cataract and ROP is challenging. In this review, studies where ROP cases were associated with cataract, were evaluated with a focus on preterm individuals less than 6 months age. Preterm babies are at increased risk of developing cataract because of systemic factors. In addition, those with ROP may have cataract associated with retinal detachment or treatment received. The type of cataract, risk factors, and pathophysiology associated with each cause varies. This review highlights these different aspects of cataract in ROP including causes, pathophysiology, types of cataracts, and management. The management of these cases is critical in terms of the timing of cataract surgery and the challenges associated with surgery and posterior segment management for ROP. Anatomical differences, preoperative retina status, pupillary dilatation, neovascularization of iris in aggressive posterior ROP, fundus examination, amblyopia, and follow-up are various important aspects in the management of the same. The preoperative workup, intraoperative challenges, postoperative care, and rehabilitation in these individuals are discussed.


Spatial propagation and localization of blood coagulation are regulated by intrinsic and protein C pathways, respectively.
Blood coagulation in vivo is a spatially nonuniform, multistage process: coagulation factors from plasma bind to tissue factor (TF)-expressing cells, become activated, dissociate, and diffuse into plasma to form enzymatic complexes on the membranes of activated platelets. We studied spatial regulation of coagulation using two approaches: 1), an in vitro experimental model of clot formation in a thin layer of plasma activated by a monolayer of TF-expressing cells; and 2), a computer simulation model. Clotting in factor VIII- and factor XI-deficient plasmas was initiated normally, but further clot elongation was impaired in factor VIII- and, at later stages, in factor XI-deficient plasma. The data indicated that clot elongation was regulated by factor Xa formation by intrinsic tenase, whereas factor IXa was formed by extrinsic tenase on activating cells and diffused into plasma, thus sustaining clot growth. Far from the activating cells, additional factor IXa was produced by factor XIa. Exogenously added TF had no effect on the clot growth rate, suggesting that plasma TF does not contribute significantly to the clot propagation process in a reaction-diffusion system without flow. Addition of thrombomodulin at 3-100 nM caused dose-dependent termination of clot elongation with a final clot size of 2-0.2 mm. These results identify roles of specific coagulation pathways at different stages of spatial clot formation (initiation, elongation, and termination) and provide a possible basis for their therapeutic targeting.


Crestal bone resorption around platform-switched dental implants with fine threaded neck after immediate and delayed loading.
Bone resorption and peri-implantitis are some of the most important problems of dental implantology. The implant macrodesign might decrease initial bone loss. The aim of this longitudinal study was to investigate crestal bone loss around screw type, tapered implants showing a fine threaded neck and platform switching design. In 32 patients of a dental practice, 147 maxillary implants with a diameter of 3.7 mm and 4.2 mm were placed and loaded according to clinical criteria. Immediate loading was exclusively performed in 3.7 mm diameter implants when adequate splinting and implant stability could be guaranteed (n=50). The remaining implants were loaded delayed. The bone level change was measured mesially and distally of the implant shoulder using follow-up X-rays and calculated per year in a linear mixed model. Bone resorption was low in all groups (3.7 immediate: -0.06 mm/year; 3.7 delayed: -0.16 mm/year; 4.2 delayed: -0.09 mm/year) after a mean follow-up period of 1.6 years (0.5-3.2 years). Based on the results of this study, it can be concluded that this implant macrodesign showed negligible bone resorption for all loading times. Immediate loading seems to be a reliable treatment option in the maxilla when clinical criteria are considered.


To Drill or Not to Drill: Management of Endodontic Emergencies and In-Process Patients during the COVID-19 Pandemic.
Dental professionals are at high risk of contracting coronavirus disease 2019 (COVID-19) infection because of their scope of practice with aerosol-generating procedures. Recommendation by the Centers for Disease Control and Prevention to suspend elective dental procedures and avoid aerosol-generating procedures posed significant challenges in the management of patients presenting with endodontic emergencies and uncertainty of outcomes for endodontic procedures initiated, but not completed, before shutdown. The purpose of this study was to evaluate the success of palliative care on endodontic emergencies during the COVID-19 pandemic and to evaluate the stability of teeth with long-term Ca(OH)2 placement because of delays in treatment completion. Patients presenting for endodontic emergencies during COVID-19 Shelter-in-Place orders received palliative care, including pharmacologic therapy and/or non-aerosol-generating procedural interventions. Part I of the study evaluated the effectiveness of palliative care, and need for aerosol-generating procedures or extractions was quantified. Part II of the study evaluated survivability and rate of adverse events for teeth that received partial or full root canal debridement and placement of calcium hydroxide before shutdown. Part I: Twenty-one patients presented with endodontic emergencies in 25 teeth during statewide shutdown. At a follow-up rate of 96%, 83% of endodontic emergencies required no further treatment or intervention after palliative care. Part II: Thirty-one teeth had received partial or full root canal debridement before statewide shutdown. Mean time to complete treatment was 13 weeks. At a recall rate of 100%, 77% of teeth did not experience any adverse events due to delays in treatment completion. The most common adverse event was a fractured provisional restoration (13%), followed by painful and/or infectious flare-up (6.4%), which were managed appropriately and therefore seemed successful. Only 1 tooth was fractured and nonrestorable (3%), leading to a failed outcome of tooth extraction. The remaining 4 outcome failures (13%) were due to patient unwillingness to undergo school-mandated COVID testing or patient unwillingness to continue treatment because of perceived risk of COVID infection. Palliative care for management of endodontic emergencies is a successful option when aerosol-generating procedures are restricted. This treatment approach may be considered in an effort to reduce risk of transmission of COVID-19 infection during subsequent shutdowns. Prolonged Ca(OH)2 medicament because of COVID-19 related delays in treatment completion appeared to have minimal effect on survival of teeth.


Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.
Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.


German S2e-Guideline "Knee Dislocation".
Knee dislocation is a devastating form of multiligament injury of the knee. Due to its high complexity, there is a large number of different diagnostic and treatment strategies. With the aim of providing evidence-based treatment recommendations, the S2e guideline on knee dislocation is aimed at all professional groups involved in diagnostics and therapy (orthopaedic and trauma surgeons, physiotherapists, outpatient/inpatient surgeons, sports physicians, etc.) as well as those affected (patients with knee dislocation) and service providers (health insurance companies, pension insurance companies). In addition to the presentation of conceptual differences between the injury entities, this includes the special features of diagnostic testing, options for conservative and surgical therapy as well as aspects of follow-up treatment - against the background of the interdisciplinary treatment approach to a severe knee injury.


Interaction between ryanodine and neomycin binding sites on Ca2+ release channel from skeletal muscle sarcoplasmic reticulum.
Neomycin is a potent inhibitor of skeletal muscle sarcoplasmic reticulum (SR) calcium release. To elucidate the mechanism of inhibition, the effects of neomycin on the binding of [3H]ryanodine to the Ca2+ release channel and on its channel activity when reconstituted into planar lipid bilayer were examined. Equilibrium binding of [3H]ryanodine was partially inhibited by neomycin. Inhibition was incomplete at high neomycin concentrations, indicating noncompetitive inhibition rather than direct competitive inhibition. Neomycin and [3H]ryanodine can bind to the channel simultaneously and, if [3H]ryanodine is bound first, the addition of neomycin will slow the dissociation of [3H]ryanodine from the high affinity site. Neomycin also slows the association of [3H]ryanodine with the high affinity binding site. The neomycin binding site, therefore, appears to be distinct from the ryanodine binding site. Dissociation of [3H]ryanodine from trypsin-treated membranes or from a solubilized 14 S complex is also slowed by neomycin. This complex is composed of polypeptides derived from the carboxyl terminus of the Ca2+ release channel after Arg-4475 (Callaway, C., Seryshev, A., Wang, J. P., Slavik, K., Needleman, D. H., Cantu, C., Wu, Y., Jayaraman, T., Marks, A. R., and Hamilton, S. L. (1994) J. Biol. Chem. 269, 15876-15884). The proteolytic 14 S complex isolated with ryanodine bound produces a channel upon reconstitution into planar lipid bilayers, and its activity is inhibited by neomycin. Our data are consistent with a model in which the ryanodine binding sites, the neomycin binding sites, and the channel-forming portion of the Ca2+ release channel are located between Arg-4475 and the carboxyl terminus.


Purification and Characterization of an Iminopeptidase from the Primary Leaf of Wheat (Triticum aestivum L.).
Iminopeptidase (EC 126.96.36.199) was substantially purified from the primary leaves of 7-day-old wheat seedlings (Triticum aestivum L.). The purification procedure consisted of five steps: acid precipitation, molecular exclusion chromatography on Sephacryl S-200, Ultrogel AcA 44, Sepharose 2B and ion-exchange chromatography on DEAE-cellulose. Iminopeptidase isolated in this manner was only active against the beta-naphthylamides of proline and hydroxyproline. For each substrate, the pH optimum was 7.4 and activity was sensitive to sulfhydryl group inhibitors. The iminopeptidase hydrolyzed the dipeptides Pro-Leu, Pro-Gly, Hyp-Gly, and Pro-Tyr. Iminopeptidase activity against the dipeptide Pro-Gly was higher than against Hyp-Gly. The molecular weight was estimated to be about 400,000. Evidence was obtained for the existence of endogenous inhibitors of iminopeptidase activity.


Diagnostic yield and safety of percutaneous CT-guided biopsy of retroperitoneal lesions and analysis of imaging features.
Computed tomography (CT)-guided biopsy is emerging as a preferred method for obtaining tissue samples from retroperitoneal lesions due to clear visualization of needle and vessels. To assess diagnostic yield and safety of CT-guided biopsy of retroperitoneal lesions and compare CT findings in different disease categories. This retrospective analytical study included 86 patients with retroperitoneal lesions who underwent CT-guided biopsy from December 2010 to March 2020. All procedures were performed with co-axial technique and multiple cores were obtained and subjected to histopathology. Additional tests like immunohistochemistry or microbiological analysis were done depending on clinical suspicion. Diagnostic yield calculation and comparison of imaging findings was done by one-way ANOVA, chi-square, and Fisher's exact tests. CT-guided biopsy was technically successful in all cases with a diagnostic yield of 91.9%. Minor complications in the form of small hematomas were seen in two patients. Major disease categories on final diagnosis were lymphoma, tuberculosis, and metastases. A variety of malignant and benign soft-tissue neoplasms were also noted less commonly. With help of immunohistochemistry, lymphoma subtype was established in 88.8% of cases. Addition of microbiological tests like the GeneXpert assay helped in the diagnosis of tuberculosis in some cases. A mass-like appearance and vascular encasement was common in metastatic group and lymphoma. Percutaneous CT-guided biopsy is a safe method for the sampling of retroperitoneal lesions with high diagnostic yield. Imaging findings are mostly overlapping; however, some features are more common in a particular disease condition.


Diffraction of a superfluid fermi gas by an atomic grating.
An atomic grating generated by a pulsed standing-wave laser field is proposed to manipulate the superfluid state in a quantum degenerate gas of fermionic atoms. We show that in the presence of atomic Cooper pairs, the density oscillations of the gas caused by the atomic grating exhibit a much longer coherence time than that in the normal Fermi gas. Our result indicates that the technique of a pulsed atomic grating is a potential candidate to detect the atomic superfluid state in a quantum degenerate Fermi gas.