Sequential Azidation/Azolation of Prenylated Derivatives and a Click Reaction Enable Selective Labeling and Degradation of RAS Protein.
We propose the introduction of the azido and azo-functionalities into prenylated derivatives under mild conditions in a selective and efficient way. Upon protocol establishment and substrate scope determination, we apply this method to prenylated protein (citronellol-BSA) labeling, chemical pulldown, and enrichment. Eventually, we achieve the degradation of RAS on MCF-7 and HeLa cell lines by employing the well-designed probe von Hippel-Lindau derivatives C4 through the sequential azidation/azolation and click-reaction (SACR) pathway targeting the prenyl functionality attached to the Caax motif of the tested RAS protein. This method displays great potential in regulation of prenylated molecules.


[Endoscopic laser treatment of neoplasm and tubulovillous adenoma of the rectosigmoid. Initial experiences and review of the literature].
With laser it's possible to produce a radiation of definite wave length which is rich in energy. This energy is changed into heat during its impinge on tissue. Different effects (coagulation, vaporization) can be produced in dependence on wave length, the technical features of laser and the different interaction of laser light. In 8 patients with obstructive polypous carcinomas of rectosigmoid a complete passage-recovery could be achieved. The therapy was effective in 8 out of 11 patients with villous adenomas. One patient had a relapse into adenoma after half a year. With laser a distal rectostenosis at high degree could be widened at Morbus Crohn. Complications didn't appear. Indications of laser-therapy are explained. The laser-therapy is effective, not very risky but not cheap. Therefore it requires an application of overlapping subjects.


Development of bone-like composites via the polymer-induced liquid-precursor (PILP) process. Part 1: influence of polymer molecular weight.
Bone is an organic-inorganic composite consisting primarily of collagen fibrils and hydroxyapatite crystals intricately interlocked to provide skeletal and metabolic functions. Non-collagenous proteins (NCPs) are also present, and although only a minor component, the NCPs are thought to play an important role in modulating the mineralization process. During secondary bone formation, an interpenetrating structure is created by intrafibrillar mineralization of the collagen matrix. Many researchers have tried to develop bone-like collagen-hydroxyapatite (HA) composites via the conventional crystallization process of nucleation and growth. While those methods have been successful in inducing heterogeneous nucleation of HA on the surface of collagen scaffolds, they have failed to produce a composite with the interpenetrating nanostructured architecture of bone. Our group has shown that intrafibrillar mineralization of type I collagen can be achieved using a polymer-induced liquid-precursor (PILP) process. In this process, acidic polypeptides are included in the mineralization solution to mimic the function of the acidic NCPs, and in vitro studies have found that acidic peptides such as polyaspartate induce a liquid-phase amorphous mineral precursor. Using this PILP process, we have been able to prepare collagen-HA composites with the fundamental nanostructure of bone, wherein HA nanocrystals are embedded within the collagen fibrils. This study shows that through further optimization a very high degree of mineralization can be achieved, with compositions matching that of bone. Synthetic collagen sponges were mineralized with calcium phosphate while analyzing various parameters of the reaction, with the focus of this report on the molecular weight of the polymeric process-directing agent. In order to determine whether intrafibrillar mineralization was achieved, an in-depth characterization of the mineralized composites was performed, including wide-angle X-ray diffraction, electron microscopy and thermogravimetric analyses. The results of this work lead us closer to the development of bone-like collagen-HA composites that could become the next generation of synthetic bone grafts.


Managing recurrent urinary tract infections in kidney transplant patients.
Recurrent urinary tract infections (UTI) are a common clinical problem in kidney transplant recipients. Due to the complex urological anatomy derived from the implantation of the kidney graft, the spectrum of the disease and the broad underlying pathophysiological mechanisms. Recurrent UTI worsen the quality of life, decrease the graft survival and increase the costs of kidney transplantation. Areas covered: In this review, we describe the definitions, clinical characteristics, pathophysiological mechanisms and microbiology of recurrent urinary tract infections in kidney transplantations. The actual published literature on the management of recurrent urinary tract infections is based on case series, observational cohorts and very few clinical trials. In this review, the available evidence is compiled to propose evidence-based strategies to manage these complex cases. Expert commentary: The management of recurrent urinary tract infections in kidney transplant patients requires a proper diagnosis of the underlying mechanism. Early identification of structural or functional urological abnormalities, potentially amenable for surgical correction, is crucial for a successful management. The use of antibiotics to prevent recurrent infections should be carefully evaluated to avoid side effects and emergence of antibiotic-resistant microorganisms.


Effect of task complexity on intelligence and neural efficiency in children: an event-related potential study.
The present study investigates the effects of task complexity, intelligence and neural efficiency on children's performance on an Elementary Cognitive Task. Twenty-three children were divided into two groups on the basis of their Raven Progressive Matrix scores and were then asked to complete a choice reaction task with two test conditions. We recorded the electroencephalogram and calculated the peak latencies and amplitudes for anteriorly distributed P225, N380 and late positive component. Our results suggested shorter late positive component latencies in brighter children, possibly reflecting a higher processing speed in these individuals. Increased P225 amplitude and increased N380 amplitudes for brighter children may indicate a more efficient allocation of attention for brighter children. No moderating effect of task complexity on brain-intelligence relationship was found.


A quasi-experimental study on the effects of instrument assisted soft tissue mobilization on mechanosensitive neurons.
[Purpose] Instrument Assisted Soft Tissue Mobilization (IASTM) is a form of manual therapy. Despite its growing popularity and an increasing number of patients receiving IASTM each year, there is a lack of high-level evidence to elucidate its therapeutic mechanisms and to support its clinical applications. The purpose of this research project was to determine the effects of IASTM on activities of mechanosensitive neurons in skin. [Subjects and Methods] Twenty-three subjects, 9 females and 14 males, mean age 25.7 (SD 6.4) years old were recruited through a convenience sampling on the university campus. The study design was a quasi-experimental study using single group pretest-posttest design. The activities of mechanosensitive neurons were measured before and after the application of IASTM. [Results] The mean 2-point discrimination was 40.2 (SD 9.4) mm before IASTM and increased to 44.9 (SD 12.0) mm after IASTM. The increase was statistically significant pre and post IASTM. The mean pain threshold was 18.2 (SD 6.6) lb and increased slightly to 18.7 (SD 6.8) lb after IASTM; however, no statistical significance was found pre and post IASTM. [Conclusion] The data indicates that IASTM changes the neural activities in 2-point discrimination but not in pain threshold.


Early-phase of learning enhances communication between brain hemispheres.
In the somatosensory system, inputs from one side of the body are only transmitted to the contralateral primary somatosensory cortex, but both sides of the body representation can interact via interhemispheric connections. These interactions depend on the behavioural requirements of the animal and its level of arousal. During the process of learning, alertness and attention may modify the responsiveness of neuronal pathways. We functionally mapped the brains of mice by using [14C]2-deoxyglucose (2DG) autoradiography during the first and the third session of a classical conditioning paradigm, involving whiskers stimulation on one side of the muzzle paired with an aversive or appetitive unconditioned stimulus. During the first pairing session, an increased 2DG uptake was seen in the barrel cortex of both hemispheres, independently of the type of applied unconditioned stimulus. In the third session of the sensory pairing, activation of the barrel cortex was solely contralateral, as expected after unilateral whisker stimulation. Thus, sensory stimulation directed to one cerebral hemisphere during the initial stages of Pavlovian conditioning activates the primary sensory area in both hemispheres. These results suggest that during the early phase of conditioning, when alertness is presumably strongest, the interhemispheric interactions are enhanced.


Determination of connectivity in porous materials.
A method of practical use was set up to determine the connectivity in a porous material, modelling the physical system as a lattice, whose coordination number is assumed to be an index of connectivity itself. This task was approached through the theory of percolation and input data were provided by two different experimental techniques, that is, adsorption/desorption of nitrogen and mercury porosimetry. The overall procedure is based on the calculation of probability f(P) of occupation of the porous channels and of probability F(P) of percolation. In the framework of the above--mentioned lattice model, the average coordination number Z is calculated through the best fitting of a universal curve to the values found for F(P) and f(P), adopting as fitting parameter the ratio L between the characteristic linear dimension of the whole lattice and the characteristic linear dimension of each of its cells. The procedure described was implemented through a numerical code and applied to three commercial alumina. A simple empirical relationship was found between Z and the percolation threshold, showing an excellent coefficient of statistical correlation. The three products proved different in connectivity, allowing subtle distinctions from each other, despite their hysteresis cycles in the adsorption/desorption process appeared quite similar from a qualitative standpoint.


[Autopsy room and the July 30th 2004 memorandum].
With the July 30th 2004 memorandum, for the first time a text is specifically dedicated to the architecture of the autopsy room. This memorandum reaffirms certain technical specifications stated in the May 7th 2001 decree applicable to hospital mortuaries. It supplements or modifies certain elements, particularly liquid waste processing, which will require new arrangements in death chambers and new expenditures for hospital administrations. It includes the principle of precaution and requires a new approach to handling human corpses in the autopsy room.


Reporting and notification of adverse events in orthopaedics.
Surgeons should know how to alert the US FDA when an adverse event occurs with a device that has been approved by the FDA. Documentation of such events is critically important to help identify trends concerning a particular device, thereby helping surgeons and other health care professionals avoid similar events. The FDA created the MedWatch program to aid health care professionals in reporting adverse events. Orthopaedic surgeons can use the program to get up-to-date alerts and help protect their patients.


Minimally invasive technique for transcrestal sinus floor elevation: a case report.
The present report describes a minimally invasive technique for transcrestal sinus floor elevation, namely the Smart Lift technique, which is based on the controlled use of drills and osteotomes. The rationale of this technique is to provide predictable vertical bone augmentation into the sinus cavity by (1) using the existing residual bone as a viable graft and (2) limiting the incidence of membrane perforation and postsurgery morbidity. Surgical steps of the procedure are thoroughly illustrated by means of a paradigmatic case. The Smart Lift procedure was compatible with sinus floor elevation and implant stability for up to 1 year following surgery. No complications occurred during or after surgery. On periapical radiographs, a radiopaque area corresponding to the augmented sinus floor was present above the apical portion of the implant.


Reaction of 111Cd7-metallothionein with EDTA. A reappraisal.
The ligand substitution reaction of EDTA with Cd7-metallothionein (Cd7-MT) has been reinvestigated. NMR titration of the 111Cd-protein with EDTA showed that the ligand interacts preferentially and cooperatively with Cd2+ ions in the beta-domain cluster. NMR and ultrafiltration kinetic analysis of this reaction using 5.6 mM Cd2+ as 111Cd7-MT and 56 mM EDTA indicated that cadmium-EDTA formed less rapidly than 111Cd peak intensity declined. Spectrophotometric and gel filtration studies of the reaction with 20 microM Cd2+ as Cd7-MT with various concentrations of EDTA revealed biphasic kinetics with much larger rate constants than observed in the NMR experiments. The fraction of total ligand substitution occurring in each kinetic step varied with EDTA concentration. The EDTA concentration dependence of both kinetic steps was consistent with the initial formation of protein.EDTA adducts, followed by their breakdown into products. Kinetic measurements were also made for the reactions of the isolated Cd4-alpha- and Cd3-beta-domains with EDTA. The Cd4 domain reacted with EDTA with biphasic kinetics, in which one Cd2+ was removed rapidly with first-order kinetics, which were zero-order in EDTA. The other three reacted with kinetics like those for the slower step of the holoprotein. Cd3-beta reacted with EDTA like the faster rate process associated with the Cd7-protein. The observed rate constants for the reaction of Cd7-metallothionein with EDTA and the fraction of reaction in the faster rate process were sensitive to protein concentration. These results are consistent with the hypothesis that the monomer-dimer equilibrium of the protein controls its kinetic reactivity with EDTA.


[Hemoptysis--targets in diagnostic and therapy].
Hemoptysis (coughing up blood) is an extremely alarming situation for the patient, caused by various different underlying diseases. First of all, a peripheral venous catheter should be placed and oxygen should be supplied as patients are threatened by impaired gas exchange caused by the bleeding. Bronchoscopy should be performed immediately, although computed tomography of the thorax may give valuable diagnostic information and should be performed if permitted by the clinical situation. Rigid bronchoscopy should be performed as it allows a broader spectrum of therapeutic options.


[Bacterial type II topoisomerases as targets for antibacterial drugs].
Bacterial type II DNA topoisomerases are essential enzymes for correct genome functioning and cell growth. Gyrase is responsible for maintaining negative supercoiling of bacterial chromosome, whereas topoisomerase IV acts in disentangling daughter chromosomes following replication. Type II DNA topoisomerases possess an ATP binding site, which can be treated as a target for antibacterial drugs. Resolving crystal structures of protein fragments consisting of an ATP binding site complexed with ADPNP/antibiotics have proven to be valuable for the understanding of the mode of action of existing antibacterial agents and presented new possibilities for novel drug design. Coumarins, quinolones and cyclothialidines are diverse group of antibiotics that interfere with type II DNA topoisomerases, however their mode of action is different. Recently a new class of antibiotics, simociclinones, was characterized. Their mechanism of action towards gyrase is entirely distinct from already known modes of action, therefore demonstrating the potential for development of novel anti-bacterial agents.


Role of chromosomal instability in cancer progression.
Cancer cells often display chromosomal instability (CIN), a defect that involves loss or rearrangement of the cell's genetic material - chromosomes - during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes in over 90% of solid tumours and many haematological cancers. This trait is unique to cancer cells as normal cells in the body generally strictly maintain the correct number and structure of chromosomes. This key difference between cancer and normal cells has led to two important hypotheses: (i) cancer cells have had to overcome inherent barriers to changes in chromosomes that are not tolerated in non-cancer cells and (ii) CIN represents a cancer-specific target to allow the specific elimination of cancer cells from the body. To exploit these hypotheses and design novel approaches to treat cancer, a full understanding of the mechanisms driving CIN and how CIN contributes to cancer progression is required. Here, we will discuss the possible mechanisms driving chromosomal instability, how CIN may contribute to the progression at multiple stages of tumour evolution and possible future therapeutic directions based on targeting cancer chromosomal instability.


[Predictive factors of failure of intravenous corticosteroid treatment in acute severe colitis of Crohn's disease and ulcerative colitis].
We conducted a retrospective study on 78 cases of acute severe colitis (Crohn's disease in 51 cases, ulcerative colitis in 27 cases). Diagnosis of acute severe colitis was based on presence of Truelove's criteria and/or endoscopical gravity lesions. Failure of corticoid treatment was observed in 35 patients (45%). In overall patients, predictive factors of failure of intravenous corticoid treatment in univariate analysis are diagnosis of ulcerative colitis, number of bloody stool higher than 6/day. level of C-reactive protein lower than 25 mg/l. visibility of muscular mucosa at colonoscopy, absence of decrease in erythrocyte-sedimentation rate for more than 50% of initial value at day 3 of treatment, absence of decrease in C-reactive protein for more than 50% of initial value at day 3 of treatment, and a lower duration of corticoid treatment. In multivariate analysis, independent predictive factors of failure of corticoid treatment are a number of bloody stool higher than 6/day (p=0.01 adjusted OR [CI95%]: 10.2 [1.15 - 72.06]) and a value of initial C-reactive protein lower than 25 mg/l (p < 0.0001 adjusted OR [CI95%] : 3.25 [2.95 - 4.31]). In Crohn's disease, the only independent predictive factor of failure of corticoid treatment is an absence of decrease of C-reactive protein level for more than 50% of initial value at day 3 of treatment (p = 0.001 adjusted OR [CI95%] : 0.79 [0.45-0.95]). Existence of these predictive factors allows the early identification of patients who would be suitable for second-line therapy.


Older Adults Exhibit Greater Visual Cortex Inhibition and Reduced Visual Cortex Plasticity Compared to Younger Adults.
Recent evidence indicates that inhibition within the visual cortex is greater in older than young adults. Increased inhibition has been associated with reduced visual cortex plasticity in animal models. We investigated whether age-related increases in human visual cortex inhibition occur in conjunction with reduced visual cortex plasticity. Visual cortex inhibition was measured psychophysically using binocular rivalry alternation rates (AR) for dichoptic gratings. Slower ARs are associated with a greater concentration of the inhibitory neurotransmitter GABA within the human visual cortex. Visual cortex plasticity was measured using an established paradigm for induction of long-term potentiation (LTP) -like increases in visually evoked potential (VEP) amplitude. Following rapid visual stimulation, greater increases in VEP amplitude indicate greater visual cortex plasticity. The study involved two groups; young (18-40 years, n = 29) and older adults (60-80 years, n = 18). VEPs were recorded for a 1 Hz onset/offset checkerboard stimulus before and after 9 Hz visual stimulation with the same stimulus. ARs were slower in older than young adults. In contrast to most previous studies, VEP amplitudes were significantly reduced following the rapid visual stimulation for young adults; older adult VEP amplitudes were unaffected. Our AR results replicate previous observations of increased visual cortex inhibition in the older adults. Rapid visual stimulation significantly altered VEP amplitude in young adults, albeit in the opposite direction than predicted. VEP amplitudes did not change in older adults suggesting an association between increased inhibition and reduced plasticity within the human visual cortex.


The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation.
The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known to have no significant effect on the growth of Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in acne comedones. Linoleic acid significantly suppressed ROS generated by neutrophils. The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation. These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.


Radiation quality of a tomotherapy photon fan beam.
Tomotherapy, a novel radiotherapy technique, uses narrow fan beams for cancer patient treatment. Photon energy spectra for a rectangular 10 x 1 cm2 photon beam were analyzed in central axis and penumbra regions at depths of 3 to 10 cm in a water phantom. A 6 MV beam of a Varian 2100C/D Linear Accelerator was modeled using BEAM99 Monte Carlo calculations to simulate energy transport in a water phantom. Arrays of 4 x 2 mm2 scoring regions were arranged to cover the central axis and penumbra areas. Radiation quality factors were calculated based on dose-mean linear energy transfer. Although there appears to be a trend towards higher quality factor values in the penumbra area, this change is fairly small, at most 3% in penumbra region. We conclude that change in radiation quality is not likely to be an issue in a tomotherapeutic approach when 6 MV x rays are used.


[Acute suppurative parotitis caused by Pseudomonas aeruginosa].
Acute suppurative parotitis is a rare infection which usually occurs in hospitalized patients. Risk factors are dehydration, old age, the postoperative state and immunocompromised states. We describe a 66-year-old woman with acute myeloid leukemia who developed this condition. Pseudomonas aeruginosa was cultured from the blood and the orifice of Stensen's duct. Recovery followed a combination of antistaphylococcal medication with clindamycin, ofloxacin and gentamicin. We stress the need to recognize Gram-negative bacteria as possible pathogens in this condition.


[Causes and components of the metabolic syndrome in renal transplant recipients from a gender perspective].
the appearance of metabolic syndrome (MS) among renal recipients is one of the greatest post-transplant complications and is associated with an increased risk of graft failure and high rates of obesity and new onset diabetes. the objective of this work is to identify the relationship between the glomerular filtration rate measured by two different methods and the components of the metabolic syndrome and their combinations in kidney transplant patients according to gender. the samples consisted of 500 kidney transplant recipients, of whom 190 had MS, 121 men and 69 women. All subjects underwent clinical evaluation and blood sampling for laboratory measurements. The MS was determined according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III). Renal function was estimated using AMDRD equations and CrS determinations. the average age was 55.5 years. The prevalence of MS was significantly higher in men (23.1% < vs 9.8%). High blood pressure (HBP) was the most observed component of MS. Significant correlations (Pearson, p < 0.05) between TFG-AMDRD and TFG CrS and metabolic markers were observed more in men than in women. The body mass index (BMI) was significantly higher in women than in men. CONCLUSIONES: the decrease in renal function associated with the components of MS, HBP and obesity represent a high risk of adverse cardiovascular events and graft rejections.


Immunosuppressive acidic protein in patients with gynecologic cancer.
Immunosuppressive acidic protein (IAP) was determined in sera of patients with gynecologic tumors using the single radial immunodiffusion method. The normal limit of IAP of 490 micrograms/ml was derived from the mean value + 2 SD of IAP in 150 healthy females. Among 141 patients with gynecologic cancers, serum IAP was elevated in 87 patients (62%). Among 190 patients with benign tumors (98 uterine myoma, 92 benign ovarian tumors) serum IAP was elevated in 14 patients (7%). Elevated levels of IAP were recognized in 43% of 77 patients with cervical cancer, in 55% of 11 endometrial cancer patients, and in 91% of 53 ovarian cancer patients. The frequency of elevated levels showed a tendency to increase with advancing stage of disease. In ovarian cancer elevation of IAP was observed even in early stages. All of 13 patients with recurrent cervical cancer had elevated IAP while only 6 of 35 (17%) previously treated patients without evidence of recurrence had elevated IAP. Immunosuppressive acidic protein determinations may be useful in monitoring the recurrence of cervical cancer. The measurement of serum IAP as a marker for gynecologic cancer is recommended as an addition to diagnostic procedures.


Design and Validation of a Low-Cost Telepathology System.
This work sought to evaluate the precision and repeatability of a telepathology prototype based on open software and hardware. A prototype was designed with application in telepathology and telemicroscopy. Accuracy and prototype precision were evaluated by calculating the mean absolute error and the intraclass and repeatability correlation coefficients for a series of 190 displacements at 10, 25, 50, 75, and 100 μm. This work developed a low-cost prototype that is accessible, easily reproducible, implementable, and scalable; based on the use of technology created under principles of open software and hardware. A pathologist reviewed the obtained images and found them to be of diagnostic quality. Its excellent repeatability, coupled with its good accuracy, allows for its application in telemicroscopy and static, dynamic, and whole-slide imaging pathology systems.


Atopic dermatitis in young children is associated with impaired interleukin-10 and interferon-gamma responses to allergens, vaccines and colonizing skin and gut bacteria.
A significant proportion of children with food allergy and more severe forms of atopic dermatis (AD) go on to develop persistent forms of allergic disease such asthma. Defining immune dysregulation in these children will be of great value in understanding disease pathogenesis. In this study we characterized the immune responses of young infants (6-18 months of age) with moderate-to-severe AD (a modified SCORAD>or=25) and compared these (n=53) with responses of non-allergic children with no history of dermatitis or sensitization of the same age (n=20). Mononuclear cell cytokine responses to allergens (egg ovalbumin (OVA), beta-lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus species (HKLB)), heat-killed Staphylococcus aureus (HKSA), S. aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared in children with AD with unaffected children. Children with AD had significantly lower spontaneous (unstimulated) production of regulatory cytokine IL-10 (P<0.001), as well as IFN-gamma (P<0.001) and TNF-alpha (P<0.001) compared with the unaffected children. After allowing for differences in baseline levels IL-10 responses to virtually all stimuli (food allergens (P=0.003), vaccines P=0.01, intestinal flora (heat-killed Lactobacillus species (HKLB), P=0.005) and skin flora (heat-killed Staphylococcus aureus (HKSA), P=0.003)) were also significantly attenuated in children with AD. The only exception was HDM, to which responses were stronger in children with AD [P=0.05]. Although there were no significant correlations between HDM IgE and HDM cytokine responses at this age, T-helper type 2 (Th2) IL-5 (P=0.014) and IL-13 (P=0.004) responses to HDM were significantly more frequent in the children with AD. However, while children with AD showed significantly attenuated Th1 IFN-gamma responses to food allergens (OVA, P=0.007 and BLG, P<0.001) and vaccines (DT, P=0.008 and TT, P<0.001), these children showed no difference in Th1 IFN-gamma responses to HDM or microbial agents (HKSA and HKLB). A increase in propensity for Th2 responses to aeroallergens in children with AD is associated with early impaired production of IL-10 regulatory cytokine to a broad range of environmental stimuli including foods, intestinal flora, S. aureus, and vaccines.


Jugular Foramen Syndrome Caused by Varicella Zoster Virus Infection.
Jugular foramen syndrome (JFS) is a lower cranial neuropathy syndrome characterized by dysphonia and dysphagia. The syndrome is caused by dysfunction of the glossopharyngeal, vagus, and spinal accessory nerves at the level of the pars nervosa and pars vascularis within the jugular foramen. There are numerous etiologies for JFS, including malignancy, trauma, vascular, and infection. Here, we present the case of a healthy adult man who developed JFS secondary to an atypical presentation of Varicella Zoster meningitis, and was promptly diagnosed and treated with rapid symptom resolution. We diagnosed the patient using specialized skull-based imaging which detailed the jugular foramen, as well as CSF analysis. This case highlights the clinical value of detailed structural evaluation, consideration for infection in the absence of systemic symptoms, and favorable outcomes following early identification and treatment.


Satisfaction of astigmatic patients with toric nesofilcon A contact lenses.
The purpose of this evaluation was to compare the experience of habitual contact lens wearers with that of nonwearers when fitted with a novel toric nesofilcon A contact lens (Biotrue ONEday for Astigmatism lens; Bausch & Lomb Incorporated, Rochester, NY, USA), for wearer comfort, vision, and satisfaction in a real-world setting. Participating eye care practitioners (ECPs) prescribed toric nesofilcon A lenses to their astigmatic patients as part of their routine clinical practices. Accordingly, 1,253 patients successfully completed the evaluation; of these, 51% wore contact lenses habitually, 41% wore eyeglasses, and 8% had no prior vision correction. All wore the lenses for at least 4 days, and 74% wore them for an average of 9 hours or more per day. After at least 4 days of wear, each patient completed an online survey to evaluate his or her level of satisfaction regarding comfort and vision. As this postmarket evaluation was observational, data were analyzed to determine whether more patients than not agreed with individual statements regarding lens performance, and whether there was any difference in response between habitual contact lens wearers and nonwearers. As a measure of general satisfaction, 96% of patients indicated that their overall opinion of the toric nesofilcon A lens was good to excellent. Further, more patients than not agreed that the lens performed well with regard to all aspects of vision and comfort queried (P<0.001). There was no difference in response between habitual contact lens wearers and nonwearers. All astigmatic patients with spherical contact lenses, other toric lenses, or eyeglasses, as well as those who had no prior correction, who had converted to the toric nesofilcon A lens expressed a high level of satisfaction with vision and comfort. ECPs should expect high success rates when converting astigmatic patients to the novel toric nesofilcon A lens.


Production of genetically identical sets of mammals: cloning?
In the past few years, there has been phenomenal progress in producing genetically identical mammalian multiplets by asexual means. The simplest method is to divide embryos into two, three, or four parts, and transfer the parts to surrogate mothers for gestation to term. Another approach is to inject nuclei from totipotent embryonic cells into fertilized one-cell embryos and to remove both male and female pronuclei. When these embryos reach the blastocyst stage, nuclei from their totipotent cells can be removed and injected into one-cell embryos, thus amplifying the process ad infinitum. Subsets of these embryos can be stored in liquid nitrogen to make genetic material for additional copies available indefinitely. Some of these techniques are fairly efficacious, others are not. No reliable techniques are available for making genetic copies of nonhomozygous adult mammals (or other vertebrates) unless samples of embryonic cells were cryopreserved when the individuals were embryos. However, injection of nuclei of spermatogonia into enucleated one-cell embryos is a promising strategy. The genetic totipotency of these nuclei is obvious since they become gamete nuclei. Moreover, the birth of mice from the diploidized genetic material of a single X-bearing spermatozoan after removal of the female pronucleus from a one-cell fertilized embryo suggests that we should eventually be able to make genetic copies of adult male mammals. This approach would not work for adult females because their oogonia have all become oocytes, and the DNA configuration in oocytes is not identical to somatic cells due to meiotic crossing over.


Untangling the fungal niche: the trait-based approach.
Fungi are prominent components of most terrestrial ecosystems, both in terms of biomass and ecosystem functioning, but the hyper-diverse nature of most communities has obscured the search for unifying principles governing community organization. In particular, unlike plants and animals, observational studies provide little evidence for the existence of niche processes in structuring fungal communities at broad spatial scales. This limits our capacity to predict how communities, and their functioning, vary across landscapes. We outline how a shift in focus, from taxonomy toward functional traits, might prove to be valuable in the search for general patterns in fungal ecology. We build on theoretical advances in plant and animal ecology to provide an empirical framework for a trait-based approach in fungal community ecology. Drawing upon specific characteristics of the fungal system, we highlight the significance of drought stress and combat in structuring free-living fungal communities. We propose a conceptual model to formalize how trade-offs between stress-tolerance and combative dominance are likely to organize communities across environmental gradients. Given that the survival of a fungus in a given environment is contingent on its ability to tolerate antagonistic competitors, measuring variation in combat trait expression along environmental gradients provides a means of elucidating realized, from fundamental niche spaces. We conclude that, using a trait-based understanding of how niche processes structure fungal communities across time and space, we can ultimately link communities with ecosystem functioning. Our trait-based framework highlights fundamental uncertainties that require testing in the fungal system, given their potential to uncover general mechanisms in fungal ecology.


Toll-like receptor interference in myeloid dendritic cells through head and neck cancer.
In head and neck squamous cell carcinoma (HNSCC) the secretion of various immunosuppressive mediators contributes to large-scale effects on the immune functions. The influence of HNSCC on the Toll-like receptor (TLR) expression profiles of human myeloid dendritic cells (MDCs), which have been identified in human solid tumor tissue of the head and neck, was analysed. MDCs were isolated from peripheral blood by 'magnetic bead separation' and subsequently incubated with supernatants of HNSCC permanent cell lines. TLR expression profiles were investigated using Af cytometry and SDS-PAGE. Human MDC from peripheral blood were found to express all human TLRs except TLR4 and TLR9. Incubation of MDC with supernatants of HNSCC resulted in an increased expression of TLR7. The data suggest an interference of TLR7 expression through HNSCC and provide novel evidence of TLR alterations as a potential tumor promoting event in head and neck cancer.


Design and evaluation of rufinamide nanocrystals loaded thermoresponsive nasal in situ gelling system for improved drug distribution to brain.
Rufinamide (Rufi) is an antiepileptic drug used to manage Lennox-Gastaut Syndrome and partial seizures. The oral bioavailability of Rufi is less due to its poor solubility and low dissolution rate in the gastrointestinal fluids. This results in less amount of drug reaching the brain following the oral administration of drug. Oral formulations of Rufi are prescribed at a high dose and dosing frequency to increase its distribution to the brain. A Rufi loaded thermoresponsive nasal in situ gel which showed significantly high brain concentrations compared to aqueous suspension of Rufi administered through nasal route was developed by our research group and published. In the current work, we have formulated nanocrystals of Rufi and suspended them in a xyloglucan based thermoresponsive gel to improve the nose-to-brain distribution. The particle size, polydispersity index, and yield (%) of the optimized Rufi nanocrystals were 261.2 ± 2.1 nm, 0.28 ± 0.08, and 89.6 ± 2.0 respectively. The narrow PDI indicates that the manufacturing process is reproducible and reliable. Higher % yield suggested that the method of preparation is efficient. The sol-to-gel transition of in situ gel loaded with Rufi nanocrystals was at 32°C which suggested that the formulation transforms into gel at nasal epithelial temperatures. The nasal pharmacokinetic studies showed that Rufi nanocrystals loaded in situ gel produced higher concentration of the drug in brain (higher brain Cmax) and maintained the drug concentrations for longer duration (higher mean residence time) compared to aqueous suspension of Rufi nanocrystals as well aqueous suspension of Rufi and Rufi loaded in situ gel, reported previously. Nanometric size of the Rufi nanocrystals combined with the in situ gelling properties helped the optimized formulation achieve higher brain distribution and also sustain the drug concentrations in brain for longer duration compared to any of the formulations studied by our research group.


Structural and binding characteristics of the carboxyl terminal fragment of apolipophorin III from Manduca sexta.
The molecular basis of the interaction of apolipophorin III (apoLp-III), an exchangeable apolipoprotein from hemolymph of the sphinx moth. Manduca sexta, with lipoprotein surfaces and phospholipids was studied by investigating the structural and binding properties of the C-terminal fragment of the native protein. A 4K peptide, corresponding to the terminal helical segment of the native protein, was generated by cyanogen bromide treatment, purified by gel filtration and reverse-phase HPLC, and characterized by N-terminal sequencing and amino acid and mass spectrometric analysis. Circular dichroism (CD) spectroscopy of the peptide in buffer indicated a predominantly unstructured state while addition of trifluoroethanol (TFE), a helix-inducing agent, resulted in an alpha-helical structure. Sedimentation equilibrium studies revealed that the 4K peptide was monomeric in buffer. The 4K peptide assumed an alpha-helical conformation in the presence of sodium dodecyl sulfate (SDS) and lysolecithin, but was unstructured in the presence of dimyristoylphosphatidylcholine, either when added to preformed vesicles or upon cosonication, indicating an ability to bind to detergent micelles but not to phospholipid bilayers. Unlike native apoLp-III, the 4K peptide did not confer protection against turbidity development to human low density lipoprotein upon incubation with phospholipase C, indicating an inability to interact with the surface of lipoproteins. Upon interaction with SDS micelles, both the 4K peptide and apoLp-III were resistant to urea-induced denaturation when compared to free apoLp-III, as evaluated by CD spectroscopy. The structural stability conferred upon interaction with detergents was similar for both the peptide and the native protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Giant magnetoconductance oscillations in hybrid superconductor-semiconductor core/shell nanowire devices.
The magnetotransport of GaAs/InAs core/shell nanowires contacted by two superconducting Nb electrodes is investigated, where the InAs shell forms a tube-like conductive channel around the highly resistive GaAs core. By applying a magnetic field along the nanowire axis, regular magnetoconductance oscillations with an amplitude in the order of e(2)/h are observed. The oscillation amplitude is found to be larger by 2 orders of magnitude compared to the measurements of a reference sample with normal metal contacts. For the Nb-contacted core/shell nanowire the oscillation period corresponds to half a flux quantum Φ0/2 = h/2e in contrast to the period of Φ0 of the reference sample. The strongly enhanced magnetoconductance oscillations are explained by phase-coherent resonant Andreev reflections at the Nb-core/shell nanowire interface.


A cell line (LIM 2463) derived from a tubulovillous adenoma of the rectum.
We describe a new epithelial cell line (LIM 2463) derived from tubulovillous adenoma of the rectum. The cells grow as organoids and secrete large amounts of mucus. The cells are polarized, with a microvillar brush border, and express dipeptidyl peptidase IV in a polarized manner. No staining was seen with 3 other antibodies directed against other brush-border hydrolases or disaccharidases. Focal polarized staining was obtained with 2 antibodies directed against other brush-border-associated peptides. The cells are aneuploid with a distinctive karyotype (48, XX, +9, +13). All attempts to clone the cells in semi-solid agar or to grow them as xenografts in nude athymic mice have failed.


N-Heterocyclic carbene and cyclic (alkyl)(amino)carbene ligated half-sandwich complexes of chromium(II) and chromium(I).
The synthesis and characterization of a series of Cr(II) N-Heterocyclic Carbene (NHC) complexes of the type [{Cr(NHC)Cl(μ-Cl)}2] and [(Cyp)Cr(NHC)X] (Cyp = η5-C5H5, cyclopentadienyl; η5-C5Me5, pentamethylcyclopentadienyl; X = Cl, η3-C3H5; NHC = IMeMe, IiPrMe, IMes, IDipp) as well as the cyclic (alkyl)(amino)carbene cAACMe ligated complexes [(η5-C5H5)Cr(cAACMe)X] (X = Cl, NPh2), [(η5-C9H7)Cr(cAACMe)Cl] (C9H7 = Ind, indenyl) and [(η5-C13H9)Cr(cAACMe)Cl] (C13H9 = Fl, fluorenyl) are reported. The reduction of [(η5-C5Me5)Cr(IMeMe)Cl] with KC8 in the presence of CO afforded the NHC ligated Cr(I) metallo-radical [(η5-C5Me5)Cr(IMeMe)(CO)2]. Quantum chemical calculations performed on [(η5-C5Me5)Cr(IMeMe)(CO)2] confirm for this complex a predominantly chromium centered radical.


Toxicity and effects of the neonicotinoid thiamethoxam on Scaptotrigona bipunctata lepeletier, 1836 (Hymenoptera: Apidae).
The neonicotinoid thiamethoxam is widely used in different agricultural crops, and it has a spectrum of action against insects, affecting both pests and pollinators, such as bees. In this study, the effects of exposure to sublethal concentrations of thiamethoxam on stingless bees Scaptotrigona bipunctata were evaluated. Foragers bees were exposed to the insecticide and subjected to genetic biochemical, histochemical, and morphological analyses after 24, 48, and 72 h of ingestion. Analysis of isoenzyme esterases revealed significant alterations in the relative activity of EST-4, a type II cholinesterase. Evaluation of the S. bipunctata brain revealed changes in the state of chromatin condensation according to the exposure time and concentration of neonicotinoid compared with the control. Morphological changes were observed in the midgut of this species at all concentrations and exposure times, which may interfere with various physiological processes of these insects. We can conclude that, although thiamethoxam at the concentrations evaluated did not cause high mortality, it induced concentration-dependent changes in bees by activating enzymes related with the protection for xenobiotic, internal morphology and probably these changes may lead to alterations in the activity of bees.


Effects of Macroautophagy and Mitophagy on the Pathogenicity of Fusarium graminearum.
Fusarium graminearum is the main pathogen of Fusarium head blight (FHB), which causes huge economic losses every year. In this study, an attempt was made to control FHB from the point of view of the physiological behavior of the pathogen itself. Autophagic inhibitors and activators were used, and the pathogenicity-related indices of F. graminearum were measured. The results showed that under nitrogen-rich conditions, macroautophagy inhibition and activation greatly reduced the mycelium weight to 0.28 and 0.25 g/ml at 24 h, which were 17.82 and 24.77% lower than that of the control treatment, respectively. Mitophagy inhibition also significantly decreased the mycelium weight (P < 0.05). Conidial yield was found to be affected by factors related to autophagy occurrence. It was found that both autophagy inhibition and activation could reduce the conidiation of F. graminearum. The toxin contents in wheat medium of macroautophagy activation treatments were 0.678, 0.190, 0.402, and 0.195 μg/g when cultured for 8 and 24 h under 0% N and 100% N conditions, respectively, which were significantly higher than those of the control treatments (P < 0.05). The infection length was measured to characterize the infectivity of F. graminearum, and we found that the length was short under macroautophagy activation conditions. However, mitophagy did not seem to affect the infectivity of F. graminearum. In summary, the above results indicate that macroautophagy and mitophagy inhibition could reduce the pathogenicity of F. graminearum, which may provide a new perspective for management of plant fungal diseases.


Effect of a deproteinized blood extract on the recovery of blood circulation in an ischaemic skin lesion.
An experimental model was used to study the revascularization of an ischaemic skin lesion and the effect on this process of the blood extract Solcoseryl. Under the conditions given in the experiment, restoration of the circulation was by 2 modes--re-flow in the original vessels, and neovascularization. Solcoseryl given daily i.p. encouraged the re-flow phenomenon and therefore, by improving the microcirculation and nutrition, the healing of the ischaemic lesions.


Prevalence of Anaplasma phagocytophilum in small rodents in France.
Anaplasma phagocytophilum is an emerging zoonotic tick-borne pathogen affecting a wide range of mammals. Rodents are suspected to be natural reservoirs for this bacterium, but their role in the epidemiologic cycles affecting domestic animals and wild ungulates has not been demonstrated. This study aimed to improve our knowledge on A. phagocytophilum prevalence in Apodemus sylvaticus, A. flavicollis and Myodes glareolus using data collected in 2010 in one area in eastern France and in 2012-2013 in two others areas in western France. Rodents were captured in each site and infection was tested using qualitative real-time PCR assays on either blood or spleen samples. Prevalence showed high variability among sites. The highest prevalence was observed in the most eastern site (with an average infection rate of 22.8% across all species), whereas no rodent was found to be PCR positive in the south-west site and only 6.6% were positive in the north-west of France. Finally, a significant increase in prevalence was observed in autumn samples compared to spring samples in the north-west, but no change was found in the other two sites.


The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration.
Following an initial impact after spinal cord injury (SCI), there is a cascade of downstream events termed 'secondary injury', which culminate in progressive degenerative events in the spinal cord. These secondary injury mechanisms include, but are not limited to, ischemia, inflammation, free radical-induced cell death, glutamate excitotoxicity, cytoskeletal degradation and induction of extrinsic and intrinsic apoptotic pathways. There is emerging evidence that glutamate excitotoxicity plays a key role not only in neuronal cell death but also in delayed posttraumatic spinal cord white matter degeneration. Importantly however, the differences in cellular composition and expression of specific types of glutamate receptors in grey versus white matter require a compartmentalized approach to understand the mechanisms of secondary injury after SCI. This review examines mechanisms of secondary white matter injury with particular emphasis on glutamate excitotoxicity and the potential link of this mechanism to apoptosis. Recent studies have provided new insights into the mechanisms of glutamate release and its potential targets, as well as the downstream pathways associated with glutamate receptor activation in specific types of cells. Evidence from molecular and functional expression of glutamatergic AMPA receptors in white matter glia (and possibly axons), the protective effects of AMPA/kainate antagonists in posttraumatic white matter axonal function, and the vulnerability of oligodendrocytes to excitotoxic cell death suggest that glutamate excitotoxicity is associated with oligodendrocyte apoptosis. The latter mechanism appears key to glutamatergic white matter degeneration after SCI and may represent an attractive therapeutic target.


Evidence of specialized tissue in human interatrial septum: histological, immunohistochemical and ultrastructural findings.
There is a paucity of information on structural organization of muscular bundles in the interatrial septum (IAS). The aim was to investigate histologic and ultrastructural organization of muscular bundles in human IAS, including fossa ovalis (FO) and flap valve. Macroscopic and light microscopy evaluations of IAS were performed from postmortem studies of 40 patients. Twenty three IAS specimens underwent serial transverse sectioning, and 17--longitudinal sectioning. The transverse sections from 10 patients were immunolabeled for HCN4, Caveolin3 and Connexin43. IAS specimens from 6 other patients underwent electron microscopy. In all IAS specimens sections the FO, its rims and the flap valve had muscle fibers consisting of working cardiac myocytes. Besides the typical cardiomyocytes there were unusual cells: tortuous and horseshoe-shaped intertangled myocytes, small and large rounded myocytes with pale cytoplasm. The cells were aggregated in a definite structure in 38 (95%) cases, which was surrounded by fibro-fatty tissue. The height of the structure on transverse sections positively correlated with age (P = 0.03) and AF history (P = 0.045). Immunohistochemistry showed positive staining of the cells for HCN4 and Caveolin3. Electron microscopy identified cells with characteristics similar to electrical conduction cells. Specialized conduction cells in human IAS have been identified, specifically in the FO and its flap valve. The cells are aggregated in a structure, which is surrounded by fibrous and fatty tissue. Further investigations are warranted to explore electrophysiological characteristics of this structure.


Role of the lone star tick, Amblyomma americanum (L.), in human and animal diseases.
We reviewed scientific literature pertaining to known and putative disease agents associated with the lone star tick, Amblyomma americanum. Reports in the literature concerning the role of the lone star tick in the transmission of pathogens of human and animal diseases have sometimes been unclear and even contradictory. This overview has indicated that A. americanum is involved in the ecology of several disease agents of humans and other animals, and the role of this tick as a vector of these diseases ranges from incidental to significant. Probably the clearest relationship is that of Ehrlichia chaffeensis and A. americanum. Also, there is a definite association between A. americanum and tularemia, as well as between the lone star tick and Theileria cervi to white-tailed deer. Evidence of Babesia cervi (= odocoilei) being transmitted to deer by A. americanum is largely circumstantial at this time. The role of A. americanum in cases of southern tick-associated rash illness (STARI) is currently a subject of intensive investigations with important implications. The lone star tick has been historically reported to be a vector of Rocky Mountain spotted fever rickettsiae, but current opinions are to the contrary. Evidence incriminated A. americanum as the vector of Bullis fever in the 1940s, but the disease apparently has disappeared. Q fever virus has been found in unfed A. americanum, but the vector potential, if any, is poorly understood at this time. Typhus fever and toxoplasmosis have been studied in the lone star tick, and several non-pathogenic organisms have been recovered. Implications of these tick-disease relationships are discussed.


Papillary carcinoma thyroid with anastomosing channels: An unusual morphology.
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, accounting for 70%-80% of all thyroid malignancies. It is biologically indolent and has an excellent prognosis. Variations in histopathologic patterns are known to influence prognosis and often result in a diagnostic dilemma. We report an unusual case of a 35-year-old female with papillary carcinoma of a thyroid isthmus showing anastomosing channels on histopathology, a distinctive pattern that has not been described in PTC. Similar to tumor cells, the lining cells of these channels were also positive for thyroid transcription factor 1, thyroglobulin, and cytokeratin-19 and negative for CD34 and CD31. The diagnosis of PTC should rely on nuclear morphology rather than architecture. Pathologists should be aware of different variants because some of these variants show aggressive behavior and poor outcome. The present report highlights the distinctive pattern of PTC, recognition of which is important to avoid any diagnostic pitfall.


Detection of crestal radiolucencies around dental implants: an in vitro experimental study.
The aim of this study was to compare the diagnostic potentials and practical advantages of different imaging modalities in detecting bone defects around dental implants. Crestal bone defects with sequentially larger diameters were randomly prepared around 100 implants that were inserted in bovine bone blocks. Conventional periapical radiography (PR), direct digital radiography (DDR), panoramic radiography (PANO), cone-beam computed tomography (CBCT), and multislice computed tomography (MSCT) were performed for all specimens. The diagnostic accuracies of the devices, confidence of the answers, subjective image quality, defect visibility in planar orientations, and duration of diagnosis were analyzed based on the interpretations of 7 calibrated observers. The agreement levels of intra- and interobserver scores were rated good. PR, DDR, and CBCT were mostly more accurate than PANO and MSCT (P < .05). Confidence levels were positively correlated with the defect size (ρ = 0.20, P < .01), and that of DDR was the highest (P < .05). The subjective image quality of PR and DDR was higher than that of CBCT, PANO, and MSCT (P < .05 for all comparisons). Axial-coronal-sagittal visibilities of the defects were higher for CBCT compared with MSCT (P < .05). The diagnostic time was shorter for DDR (P < .05) and longer for the tomographic systems (P < .05) than for the other devices. DDR may provide a faster and more confident diagnostic option that is as accurate as PR in detecting peri-implant radiolucencies. CBCT has a comparable potential to these intraoral systems but with slower decision making and lower image quality, whereas PANO and MSCT become more reliable when bone defects have a diameter that is at least 1.5 mm larger than that of the implant.


Analysis of different vibration patterns to guide blind people.
The literature indicates the best vibration positions and frequencies on the human body where tactile information is transmitted. However, there is a lack of knowledge about how to combine tactile stimuli for navigation. The aim of this study is to compare different vibration patterns outputted to blind people and to determine the most intuitive vibration patterns to indicate direction for navigation purposes through a tactile belt. The vibration patterns that stimulate the front side of the waist are preferred for indicating direction. Vibration patterns applied on the back side of the waist could be suitable for sending messages such as stop.


Biochemically silent phaeochromocytoma presenting with non-specific loin pain.
A 55-year-old woman presented with a 4-month history of right-sided non-specific loin pain and 6 kg weight loss. A CT scan of the abdomen and pelvis showed an incidental 4.5 cm right-sided adrenal lesion which was not typical of an adrenal adenoma. This was further confirmed on MRI of the adrenals. Biochemical investigations to investigate for a functional adrenal lesion included serum catecholamines and metanephrines, an aldosterone to renin ratio and an overnight dexamethasone suppression test. These were all negative. A laparoscopic adrenalectomy was performed in view of the large size of the lesion. Histology was consistent with a phaeochromocytoma, which confirmed the diagnosis of a non-secreting phaeochromocytoma. Non-secreting phaeochromocytomas are rare and usually found in patients with known genetic mutations. Adrenal lesions not related to any mutations similar to our case are even rarer and reported even less in the literature.


Clinical and pathologic factors affecting lymph node yields in colorectal cancer.
Lymph node yield is recommended as a benchmark of quality care in colorectal cancer. The objective of this study was to evaluate the impact of various factors upon lymph node yield and to identify independent factors associated with lymph node harvest. The records of 162 patients with Stage I to Stage III colorectal cancers seen in one institution were reviewed. These patients underwent radical surgery as definitive therapy; high-risk patients then received adjuvant treatment. Pathologic and demographic data were recorded and analyzed. The subgroup analysis of lymph node yields was determined using a t-test and analysis of variants. Linear regression model and multivariable analysis were used to perform potential confounding and predicting variables. Five variables had significant association with lymph node yield after adjustment for other factors in a multiple linear regression model. These variables were: tumor size, surgical method, specimen length, and individual surgeon and pathologist. The model with these five significant variables interpreted 44.4% of the variation. Patients, tumor characteristics and surgical variables all influence the number of lymph nodes retrieved. Physicians are the main gatekeepers. Adequate training and optimized guidelines could greatly improve the quality of lymph node yields.


Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1.
Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in Neurofibromin 1 (NF1). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited. We describe a minipig model that exhibits clinical hallmarks of NF1, including café au lait macules, neurofibromas, and optic pathway glioma. Spontaneous loss of heterozygosity is observed in this model, a phenomenon also described in NF1 patients. Oral administration of a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor suppresses Ras signaling. To our knowledge, this model provides an unprecedented opportunity to study the complex biology and natural history of NF1 and could prove indispensable for development of imaging methods, biomarkers, and evaluation of safety and efficacy of NF1-targeted therapies.


Synergistic use of Plantago major and effective microorganisms, EM1 to clean up the soil polluted with imidacloprid under laboratory and field condition.
Imidacloprid is known to induce soil pollution. Herein, we improved phytoremediation of soil contaminated with imidacoprid using Plantago major plus effective microorganisms (EM1) and peat-moss under laboratory conditions for 14-days and using P. major inoculated with EM1 in tomato field for 10-days. Concentration of imidacloprid in soil, roots and leaves was determined. Concentrations of Chlorophyll in leaves were also determined. Our results showed that lower imidacloprid degradation rate was observed in amended soil with peat-moss, while higher imidacloprid degradation rate was observed in soils vegetated with P. major, P. major inoculated by EM1, and P. major amended with peat-moss, respectively. However, degradation rate was high in the case of interaction between soil planted with P. major plus both of EM1 and peat-moss. Concentration of imidacloprid in P. major roots amended with EM1, peat-moss and both was significantly lower than that of P. major roots alone within 1-14 days of treatment. EM1 plus P. major and peat- moss plus P. major had increase of Chlorophyl content in leaves. Cultivation of P. major next to tomatoes crop and inoculated with EM-1 was found to be the most effective process for removing imidacloprid from the soil.


Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway.
Our laboratory has previously reported that acetaminophen confers functional cardioprotection following cardiac insult, including ischemia/reperfusion, hypoxia/reoxygenation, and exogenous peroxynitrite administration. In the present study, we further examined the mechanism of acetaminophen-mediated cardioprotection following ischemia/reperfusion injury. Langendorff-perfused guinea pig hearts were exposed to acute treatment with acetaminophen (0.35 mM) or vehicle beginning at 15 min of a 30-min baseline stabilization period. Low-flow global myocardial ischemia was subsequently induced for 30 min followed by 60 min of reperfusion. At the completion of reperfusion, hearts were homogenized and separated into cytosolic and mitochondrial fractions. Mitochondrial swelling and mitochondrial cytochromec release were assessed and found to be significantly and completely reduced in acetaminophen- vs. vehicle-treated hearts following reperfusion. In a separate group of hearts, ventricular myocytes were isolated and subjected to fluorescence-activated cell sorting. Acetaminophen-treated hearts showed a significant decrease in late stage apoptotic myocytes compared with vehicle-treated hearts following injury (58 +/- 1 vs. 81 +/- 5%, respectively). These data, together with electron micrograph analysis, suggest that acetaminophen mediates cardioprotection, in part, via inhibition of the mitochondrial permeability transition pore and subsequent apoptotic pathway.


Sedation before ventilator withdrawal: medical and ethical considerations.
... While clinical practice is clearly moving toward more compassionate use of sedatives and analgesics in the care of the dying, the legal system has been lagging behind most ethical opinions in this area. The criminal investigation into the administration of morphine to a patient before ventilator withdrawal in Minnesota was a grim reminder of the hazards sometimes involved in the practice of good medicine. We know of several instances where a nurse was willing to administer sedatives and analgesics at the request of a physician, but without documentation in the medical record, for fear of possible legal repercussions. The fact that the caregivers involved are willing to risk the potentially disastrous consequences of falsifying a medical record can be taken as evidence of their commitment to doing what they perceive to be morally required. Nevertheless, this practice should clearly be condemned, since it gives the impression that caregivers are engaged in an unlawful or unethical practice. Only through continued forthright discussion in the medical literature can we arrive at ethically defensible approaches to administering sedation and analgesia that assure the most compassionate care of the dying patient.


Treatment of a mixed acinar-endocrine carcinoma with uptake on 68Gallium-DOTATOC positron emission tomography-computed tomography: A case report.
The case of a 35-year old female patient with a diagnosis of metastatic mixed acinar-endocrine carcinoma (MAEC) is investigated in the present study. The patient was believed to have a well-differentiated neuroendocrine tumor (NET) with a high Ki-67 index and uptake on 68Gallium-DOTATOC positron emission tomography-computed tomography for 9 years, and was treated accordingly. The patient had long lasting disease control by treatment with sunitinib, and a response was observed in numerous lesions with peptide receptor radionuclide therapy (PRRT). Following treatment for metastatic disease for >4 years, liver transplantation was performed, as an exception to normal recommendations, at the time of progression of a centrally located liver lesion inducing obstructive jaundice. Following transplantation, the diagnosis of a Grade 3 NET, as defined by the WHO 2010 classification, was challenged and changed to MAEC. MAEC is a rare type of tumor of the pancreas, exhibiting endocrine and acinar differentiation. It is difficult to diagnose, often being misidentified as acinar cell carcinoma or predominantly as neuroendocrine neoplasms. Immunohistochemical labelling provides the only evidence for the dual differentiation of neuroendocrine (synaptophysin and chromogranin) and acinar (lipase, trypsin and chymotrypsin) cell markers. Studies investigating MAECs with a clear histopathological diagnosis are scarce, in addition to evidence of disease behaviour and treatment options. It is generally agreed that surgery is the primary treatment in patients with resectable tumors. The responses to sunitinib and PRRT suggested that treatments considered or developed for NETs may be beneficial in MAEC cases.


Transitional care: a multidisciplinary case management-based unit.
A major challenge confronting health professionals today is the provision of safe, effective, and quality care for patients with the available reimbursement funds. Multidisciplinary case management meets this challenge by providing planned, coordinated care based on patient needs. Children dependent on technology are logical choices for case management since they often experience prolonged hospitalization and require intervention from numerous specialists. To meet this need, LeBonheur Children's Medical Center in Memphis, Tennessee opened the Transitional Care Unit (TCU), which provides the family with a conducive environment for developmental, social, and educational interaction. A retrospective chart review on 10 patients was conducted to assess the efficiency of the unit. Findings demonstrated a decrease in daily costs and hospital stay. A TCU uses scarce hospital resources while efficiently saving health care funds for the individual patient.


Intravenous thrombolysis in acute ischemic stroke patients with negative CT perfusion: a case series.
Computed tomography perfusion (CTP) is a commonly used modality of neurophysiologic imaging to aid the selection of acute ischemic stroke patients for neuroendovascular intervention by identifying the presence of penumbra versus infarcted brain tissue. However many patients present with evidence of cerebral ischemia with normal CTP, and in that case, should intravenous thrombolytics be given? To demonstrate if tissue-type plasminogen activator (tPA)-eligible stroke patients without perfusion defects demonstrated on CTP would benefit from administration of intravenous thrombolytics. We retrospectively identified patients presenting with acute ischemic symptoms who received intravenous tPA (IV-tPA) from January to June 2012 without a perfusion defect on CTP. Clinical and radiographic findings including the NIHSS at presentation, 24 h, and at discharge, symptomatic and asymptomatic hemorrhagic transformation, and the modified Rankin score at 30 days were collected. A reduction of NIHSS of greater than 4 points or resolution of symptoms was considered significant. Seventeen patients were identified with a mean NIHSS of 8.2 prior to administration of intravenous thrombolytics, 3.5 after 24 h, and 2.5 at discharge. Among them, 13 patients had significant improvement of NIHSS with a mean reduction of 6.15 points at 24 h. One patient initially improved but had delayed hemorrhagic transformation and died. Two patients had improvement in NIHSS but were not significant and two patients had increased in NIHSS at 24 h, although one eventually improved at discharge. There was no asymptomatic hemorrhagic transformation. Mean mRS at 3 months is 1.76. The failure to identify a perfusion deficit by CTP should not be used as a contraindication for intravenous thrombolytics. Criteria for administration of intravenous thrombolytics should still be based on time from symptom onset as previously published by NINDS.


Relationship of breastfeeding self-efficacy with quality of life in Iranian breastfeeding mothers.
Due to the importance of breastfeeding, we decided to conduct a study to examine the relationship between breastfeeding self-efficacy and quality of life. This study was a cross-sectional study, which was carried out on 547 breastfeeding mothers that had 2-6 months old infants. The participants were selected randomly, and the sociodemographic characteristics questionnaire, Dennis' breastfeeding self-efficacy scale, and WHO's Quality of Life (WHOQOL) questionnaire were completed through interview. The multivariate linear regression model was used for data analysis. The means (standard deviations) of breastfeeding self-efficacy score and quality of life score were 134.5 (13.3) and 67.7 (13.7), respectively. Quality of life and all of its dimensions were directly and significantly related to breastfeeding self-efficacy. According to the results of multivariate linear regression analysis, there was a relationship between breastfeeding self-efficacy and the following variables: environmental dimension of quality of life, education, spouse's age, spouse's job, average duration of previous breastfeeding period and receiving breastfeeding training. Findings showed that there is direct and significant relationship between breastfeeding self-efficacy and quality of life. Moreover, it seems that the development of appropriate training programs is necessary for improving the quality of life of pregnant women, as it consequently enhances breastfeeding self-efficacy.


Hypothalamic resistin immunoreactivity is reduced by obesity in the mouse: co-localization with alpha-melanostimulating hormone.
Resistin is a new adipokine expressed in mouse, rat and human adipose tissue. Resistin may be an important link between obesity and insulin resistance, though this controversial view is complicated by the discovery of multiple sites of resistin expression, including human macrophages, placenta and pancreas. In previous studies we demonstrated that the mouse hypothalamo-pituitary system was also a site of resistin production. Pituitary resistin is developmentally regulated, reduced in the ob/ob mouse and severely down-regulated by food deprivation (24 h). An unexpected finding was that hypothalamic resistin mRNA remained unaffected by fasting. The present experiments examined the localization and possible regulation of hypothalamic resistin protein. Using immunohistochemistry we observed a complex network of resistin+ fibres extending rostrally from the arcuate nucleus of the hypothalamus (ARC) to the preoptic area. Labelled cell bodies occurred only in the ARC and in a periventricular region of the dorsal hypothalamus. Hypothalamic resistin immunoreactivity (ir) was unaffected by fasting (48 h) or by a high fat diet, but the periventricular staining was greatly increased in the lactating mouse. Marked reductions in resistin+ fibres were seen in brain tissue from: (a) ob/ob mice, (b) young mice made underweight for their age by raising them in large litters (20 pups per litter) and (c) mice with hypothalamic lesions induced by monosodium glutamate (MSG) or gold thioglucose (GTG). We speculate that the resistin-ir deficit in genetically obese mice, and in severely underweight mice, could be due to low or absent leptin. In contrast, though MSG- and GTG-treated mice have high levels of circulating leptin, in the presence of excessive visceral fat deposits, we hypothesize that damage to the ARC destroys the resistin+ cell bodies. This latter supposition led us to an additional hypothesis, that resistin-ir would be contained in neurons expressing the proopiomelanocortin (POMC) gene. This proved to be correct. Double label immunofluorescence histochemistry revealed that alpha-MSH-ir, a marker for POMC neurons, was co-localized with resistin-ir. In conclusion, our data reveal a second example of an adipocytokine co-localized with a hypothalamic neuropeptide. We reported previously that leptin was co-localized with oxytocin and vasopressin. RT-PCR analysis confirmed that resistin mRNA is readily detectable in ARC, but further work is required to determine whether the resistin gene is expressed in POMC neurons or if resistin is specifically accumulated by these cells. Nonetheless, our data suggest that the hypothalamus is a target tissue for resistin.


Physiological effects of modified hemoglobin as an oxygen-carrying macromolecule.
A stabilized hemoglobin as oxygen-carrying macromolecules was developed. It had approximately 90,000 dalton molecular weights and its intravascular half life was 36 hours. Its molecular size was less than 0.1 micron. Its hemoglobin concentration was 6% and P50 value was 24 mmHg. The oxygen carried inside the plasma performs differently than the oxygen carried inside the red cells. Only less than 0.3 ml of oxygen in 100 ml of blood is available inside the plasma while 14-19 ml of oxygen is carried inside the red cells. Thus, less than 5 ml of oxygen is available inside the plasma of the entire body. When a patient develops hypovolemic shock, the red cells are bypassed and are not perfused directly inside the tissues. However, the plasma should reach such hypoxic tissues. Thus, infusion of oxygen-carrying macromolecules in the plasma should be therapeutically effective even if less than 100 ml of stabilized hemoglobin solution were infused under shock conditions. The basic physiology of oxygen-carrying macromolecules is described in detail, which is different from the oxygen carried inside the red cells.


Role of percent positive biopsies and endorectal coil MRI in predicting prognosis in intermediate-risk prostate cancer patients.
This study was performed to determine the clinical factors that can optimize preoperative staging for clinically localized intermediate-risk prostate cancer patients. Logistic and Cox regression multivariable analyses were performed on 480 prostate cancer patients whose disease was confined to the prostate to evaluate the ability of clinical stage, prostate-specific antigen (PSA), biopsy Gleason sum, percent positive biopsies, and endorectal coil magnetic resonance imaging (MRI) results to predict pathologic established extracapsular extension, seminal vesicle invasion, and time to postoperative PSA failure in patients with clinically localized prostate cancer. Intermediate risk was defined as PSA 4-10 ng/mL and Gleason sum 5-7; PSA 10-20 ng/mL and Gleason sum < or = 7. Intermediate-risk patients with at least 50%, 67%, 83%, or 100% positive biopsies have disease pathologically confined to the prostate at least 45% of the time; however, if an endorectal coil MRI is positive for either capsular penetration or seminal vesicle invasion, no more than 29% of patients have pathologically determined organ-confined disease. No intermediate-risk patient with both a positive MRI and at least 50% positive biopsies had pathologically determined organ-confined disease. Intermediate-risk patients with less than 50% positive biopsies had pathologically determined organ-confined disease in at least 77% of the cases. Intermediate-risk patients with an endorectal coil MRI showing extracapsular extension or seminal vesticle invasion are at high risk for early postoperative PSA failure. The concomitant presence of at least 50% positive biopsies increases this risk to unity. Therefore, these patients are not good candidates for surgery alone because of their high risk of extraprostatic disease and should be considered for entry onto phase III trials examining the effect of adding androgen-deprivation therapy to definitive local therapy (external-beam radiation therapy or surgery) on overall survival. The subgroup of intermediate-risk patients likely to benefit from an endorectal coil MRI are those patients with PSA > 10-20 ng/mL; biopsy Gleason score < or = 7, and at least 50% positive biopsies representing approximately 7.5% of the total patient population.


Dose responsive effects of PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue in a guinea pig partial thickness skin excision model.
A guinea pig partial thickness skin excision model was used to evaluate the effects of recombinant human PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue (neodermis) formation. These growth factors tended to increase the thickness of the granulation tissue bed when assessed histologically at day 7. Using only four animals per group, PDGF-BB at 30 and 100 micrograms/ml consistently and significantly increased the thickness of the granulation bed 2-3 times that of control. Except for the increased thickness, the granulation tissue appeared normal. PDGF-AA and EGF also significantly increased the granulation tissue thickness, and bFGF gave indications of an effect. There was no evidence of synergistic effects between PDGF-BB, EGF, and/or bFGF.


Inhibition of coactivator-associated arginine methyltransferase 1 modulates dendritic arborization and spine maturation of cultured hippocampal neurons.
An improved understanding of the molecular mechanisms in synapse formation provides insight into both learning and memory and the etiology of neurodegenerative disorders. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein methyltransferase that negatively regulates synaptic gene expression and inhibits neuronal differentiation. Despite its regulatory function in neurons, little is known about the CARM1 cellular location and its role in dendritic maturation and synapse formation. Here, we examined the effects of CARM1 inhibition on dendritic spine and synapse morphology in the rat hippocampus. CARM1 was localized in hippocampal post-synapses, with immunocytochemistry and electron microscopy revealing co-localization of CARM1 with post-synaptic density (PSD)-95 protein, a post-synaptic marker. Specific siRNA-mediated suppression of CARM1 expression resulted in precocious dendritic maturation, with increased spine width and density at sites along dendrites and induction of mushroom-type spines. These changes were accompanied by a striking increase in the cluster size and number of key synaptic proteins, including N-methyl-d-aspartate receptor subunit 2B (NR2B) and PSD-95. Similarly, pharmacological inhibition of CARM1 activity with the CARM1-specific inhibitor AMI-1 significantly increased spine width and mushroom-type spines and also increased the cluster size and number of NR2B and cluster size of PSD-95. These results suggest that CARM1 is a post-synaptic protein that plays roles in dendritic maturation and synaptic formation and that spatiotemporal regulation of CARM1 activity modulates neuronal connectivity and improves synaptic dysfunction.


Spontaneous attachment of amines to carbon and metallic surfaces.
Primary alkylamines attach spontaneously from acetonitrile (ACN) solutions onto glassy carbon and metallic surfaces (Au, Pt, Cu, and Fe). The surface concentration of the organic layer measured from the integration of cyclic voltammograms appears close to or lower than that of a compact monolayer. The rate of the attachment depends on the concentration of the primary amino compound; it reaches a maximum after 3 h of immersion for the most concentrated solutions (20 mM). The modified surfaces have been characterized by cyclic voltammetry (CV), energy dispersive X-ray spectrometry (EDX), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (ATR). The possible reaction mechanisms are discussed.


Changes in cigarette prices, affordability, and brand-tier consumption after a tobacco tax increase in Thailand: Evidence from the Global Adult Tobacco Surveys, 2009 and 2011.
Despite the 2009 implementation of a tobacco tax increase in Thailand, smoking rates remained unchanged between 2009 and 2011. Prior evidence has linked cigarette tax increases to compensatory behaviours aimed at lowering the cost of smoking, such as switching to lower-priced cigarette brands. Using data from 2009 and 2011 Global Adult Tobacco Surveys in Thailand, we estimated unadjusted changes in cigarette prices paid, cigarette affordability, and consumption of cigarettes in three price categories classified as upper-, middle-, and lower-priced brand tiers (or price tertiles). We used ordered logit regression to analyse the correlates of price-tier choice and to estimate the change in price-tier consumption adjusted for demographic and region characteristics. Between 2009 and 2011, real cigarette prices increased, but the affordability of cigarettes remained unchanged overall. There was a significant reduction in the consumption of cigarette brands in the top price-tier overall, accompanied by increases in the consumption of brands in the bottom and middle price-tiers, depending on the region. Adjusted estimates from the logit models indicate that, on average, the proportion of smokers selecting brands from upper- and middle price-tiers decreased while consumption of lower price-tier brands increased during the study period. The estimated shifts in consumption from more expensive to less expensive cigarette brands and the overall lack of change in cigarette affordability in Thailand between 2009 and 2011 are both factors that may have contributed to the observed lack of change in smoking rates after the 2009 tax increase.


Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals.
Introduction: NLRP3 inflammasome plays a key role in dendritic cells (DC) activation in response to vaccine adjuvants, however we previously showed that it is not properly activated in DC from HIV-infected patients (HIV-DC), explaining, at least in part, the poor response to immunization of these patients. Taking in account that several cytoplasmic receptors are able to activate inflammasome, and that bacterial components are considered as a novel and efficient adjuvant, we postulated that bacterial flagellin (FLG), a natural ligand of NAIP/NLRC4 inflammasome, could rescue the activation of the complex in HIV-DC. Objective: Demonstrate that FLG is able to activate monocyte-derived dendritic cells from HIV-infected individuals better than LPS, and to what extent the entity of inflammasome activation differs between DC from HIV-infected patients and healthy donors. Methods: Monocyte-derived dendritic cells from HIV-infected patients (HIV-DC) and healthy donors (HD-DC) were stimulated with FLG, and inflammasome as well as DC activation (phenotypic profile, cytokine production, autologous lymphocytes activation) were compared. Chemical and genetic inhibitors were used to depict the relative contribution of NLRC4 and NLRP3 in HIV/HD-DC response to FLG. Results: FLG properly activates HD-DC and HIV-DC. FLG induces higher inflammasome activation than LPS in HIV-DC. FLG acts through NLRC4 and NLRP3 in HD-DC, but at a lesser extent in HIV-DC due to intrinsic NLRP3 defect. Conclusions: FLG by-passes NLRP3 defect in HIV-DC, through the activation of NAIP/NLRC4 inflammasome, indicating possible future use of the bacterial component as an efficient adjuvant in immunocompromised individuals.


Kinetics of single and dual infection of pigs with swine influenza virus and Actinobacillus pleuropneumoniae.
Porcine respiratory disease complex (PRDC) is a common problem in modern pork production worldwide. Pathogens that are amongst other pathogens frequently involved in PRDC etiology are swine influenza virus (SIV) and A. pleuropneumoniae. The effect of dual infection with mentioned pathogens has not been investigated to date. The aim of the present study was to evaluate the kinetics of single and dual infection of pigs with SIV and A. pleuropneumoniae with regard to clinical course, pathogens shedding, lung lesions and early immune response. The most severe symptoms were observed in co-inoculated piglets. The AUC value for SIV shedding was lower in pigs single inoculated with SIV as compared to co-inoculated animals. In contrast, no significant differences were found between A. pleuropneumoniae shedding in single or dual inoculated pigs. Three out of 5 co-inoculated piglets euthanized at 10 dpi were positive against serotype 2 A. pleuropneumonie. All piglets inoculated with SIV developed specific HI antibodies at 10 dpi. In pigs dual inoculated the specific humoral response against SIV was observed earlier, at 7 dpi. The SIV-like lung lesions were more severe in co-inoculated pigs. In the groups inoculated with A. pleuropneumoniae (single or dual) the acute phase protein response was generally stronger than in SIV-single infected group. Co-infection with SIV and A. pleuropneumoniae potentiated the severity of lung lesions caused by SIV and enhanced virus replication in the lung and nasal SIV shedding. Enhanced SIV replication contributed to a more severe clinical course of the disease as well as earlier and higher magnitude immune response (acute phase proteins, HI antibodies) compared to single inoculated pigs.


Ultrasonography of the peripheral nervous system in the early stage of Guillain-Barré syndrome.
Ultrasonography can be used to visualize peripheral nerve abnormalities in immune-mediated neuropathies. The objective of this study was to prove the role of ultrasonography (US) in acute phase of Guillain-Barré syndrome (GBS). Systematic ultrasonic measurements of several peripheral nerves including the vagal nerve as well as the sixth cervical nerve root were performed in 18 patients with GBS at days 1-3 after symptom onset and compared to 21 healthy controls. Nerve conduction studies (NCS) of corresponding nerves were undertaken. Consequently, significant differences between the groups were found in compound muscle action potential amplitudes, F-wave latency, and persistency. Ultrasonic cross-sectional areas (CSAs) showed significant enlargement in all nerves except of the ulnar nerve (upper arm) and the sural nerve compared to healthy controls, most prominent in proximal and middle median nerve (p < 0.01). The vagal nerve also showed enlargement compared to controls (p < 0.05), which was most pronounced in patients with autonomic dysfunction compared to patients without (p < 0.05). C6 root diameter showed a significant correlation to the amount of cerebrospinal fluid (CSF)-protein (Pearson correlation, p < 0.05). US shows nerve enlargement in several peripheral nerves including vagal nerve and C6 root in acute phase of GBS and could be an additional diagnostic tool for example, in GBS of atypical onset and autonomic dysfunction.


Association between HIV status and psychological symptoms in perimenopausal women.
HIV-infected women are burdened by depression and anxiety, which may impact adherence to antiretroviral therapy and overall quality of life. Yet, little is known about the scope of psychological symptoms in the growing number of HIV-infected women reaching menopause, when affective symptoms are more prevalent in the general population. We conducted a longitudinal study to compare affective symptoms between perimenopausal HIV-infected and non-HIV-infected women. The Center for Epidemiologic Studies Depression Scale (CES-D), and the Generalized Anxiety Disorder scale (GAD-7) were completed at baseline and 12 months among 33 HIV-infected and 33 non-HIV-infected perimenopausal women matched by race, age, menstrual patterns, and BMI. Linear regression models estimated the relationship of baseline GAD-7 and CES-D scores with clinical factors. All women were perimenopausal at baseline, and the vast majority remained perimenopausal throughout follow-up. HIV status was associated with higher baseline CES-D scores (median [interquartile range] 21 [12, 29] vs 10 [5, 14]; P = 0.03) and GAD-7 scores (7 [5, 15] vs 2 [1, 7]; P = 0.01), controlling for smoking, substance use, and antidepressant use. Depressive symptoms and anxiety remained significantly higher in the HIV-infected women at 12 months (P ≤ 0.01). Significant relationships of depressive symptoms (P = 0.048) and anxiety (P = 0.02) with hot flash severity were also observed. Perimenopausal HIV-infected women experienced a disproportionately high level of affective symptom burden over a 12-month observation period. Given the potential for these factors to influence adherence to HIV clinical care and quality of life, careful assessment and referral for treatment of these symptoms is essential.


Intraocular dexamethasone penetration via subconjunctival or retrobulbar injections in rabbits.
Using high-performance liquid chromatography, we compared tissue levels of dexamethasone in the aqueous, vitreous, retina, and choroid of rabbits, 1 and 4 hours following subconjunctival or retrobulbar injection. One hour following injection, dexamethasone levels in all of these tissues were similar in both the subconjunctival and retrobulbar groups. Four hours following injection, the concentrations in the two groups also were similar, except in the choroid, in which the subconjunctival injection yielded significantly lower dexamethasone levels than the retrobulbar injection. Tissue steroid levels were comparable ipsilateral and contralateral to the injected eyes in both treatment groups after 4 hours, except in the retina, in which the levels were lower in the contralateral eye after subconjunctival injection. These data suggest that dexamethasone absorption and delivery is predominantly hematogenous following both subconjunctival and retrobulbar injection, especially in highly vascular tissues, such as the choroid. Hematogenous delivery of dexamethasone appears to peak earlier in the choroid and presumably in other intraocular tissues following subconjunctival injections, while retrobulbar injections provide more steady, long-term delivery.


Utilization of sequence variants as biomarkers to analyze population dynamics in cloned cell lines.
The inherent nature of cloned CHO cell lines includes the presence of genetic and phenotypic drift that leads to heterogeneous populations. The genetic heterogeneity exhibited by these cells can be exploited to understand the population dynamics of cloned cell lines. Understanding the interplay between heterogeneity, cell culture conditions, and population dynamics will allow for critical assessment of overarching cell line development methods and strategies in terms of population and monoclonality. Sequence variants (SVs) are protein isoforms of the gene-of-interest that contain unintended amino acid substitutions, extensions, or truncations that may contribute to heterogeneity. In this case, SVs are unique sequences in the genome of the integrated transgene that can be used as biomarkers to understand the heterogeneity of a monoclonal cell line and how production process conditions can impact population dynamics. In this study, orthogonal genetic and analytical methods were used to examine the variability of SV levels in four different SV-containing cell lines under varied culture conditions and generational ages. Culture conditions tested had little to no impact on SV levels. However, generational age studies showed two distinct trends: stability of SV levels out to approximately 100 generations in cell lines with higher level SVs (>10%) and a progressive decrease of SV levels as the cells age to approximately 100 generations in cell lines with lower level SVs (<10%). The results suggest that the four SV-containing cell lines fall into two distinct population models; SVs present in the whole population of cells and SVs present in only a sub-population of cells. The data presented here are one of the first studies to not only analyze and compare SV levels in both genetic and protein material but also to utilize SVs as biomarkers to probe distinct populations of cloned cell lines. Biotechnol. Bioeng. 2017;114: 1744-1752. © 2017 Wiley Periodicals, Inc.


Streptomyces monticola sp. nov., a novel actinomycete isolated from soil.
A novel actinobacterium, designated strain NEAU-GS4T, was isolated from soil collected from Mount Song and characterised using a polyphasic approach. 16S rRNA gene sequence similarity studies showed that strain NEAU-GS4T belongs to the genus Streptomyces, being closely related to Streptomyces spectabilis JCM 4308T (98.8%), Streptomyces sclerotialus DSM 43032T (98.3%) and Streptomyces lasiicapitis 3H-HV17(2)T (98.0%). A multilocus sequence analysis based on five house-keeping genes (atpD, gyrB, rpoB, recA and trpB) also indicated that strain NEAU-GS4T should be assigned to the genus Streptomyces. The major menaquinones were identified as MK-9(H6), MK-9(H8) and MK-9(H4). The polar lipid profile was found to contain diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositolmannosides and an unidentified phospholipid. The major fatty acids were identified as anteiso-C15:0, iso-C16:0 and anteiso-C17:0. Moreover, DNA-DNA hybridization results and some phenotypic characteristics indicated that strain NEAU-GS4T can be clearly differentiated from its closely related species of the genus Streptomyces. Therefore, it is concluded that strain NEAU-GS4T represents a novel species of the genus of Streptomyces, for which the name Streptomyces monticola sp. nov. is proposed. The type stain is NEAU-GS4T (=CGMCC 4.7467T = DSM 105116T).


Minimal Interspecies Interaction Adjustment (MIIA): Inference of Neighbor-Dependent Interactions in Microbial Communities.
An intriguing aspect in microbial communities is that pairwise interactions can be influenced by neighboring species. This creates context dependencies for microbial interactions that are based on the functional composition of the community. Context dependent interactions are ecologically important and clearly present in nature, yet firmly established theoretical methods are lacking from many modern computational investigations. Here, we propose a novel network inference method that enables predictions for interspecies interactions affected by shifts in community composition and species populations. Our approach first identifies interspecies interactions in binary communities, which is subsequently used as a basis to infer modulation in more complex multi-species communities based on the assumption that microbes minimize adjustments of pairwise interactions in response to neighbor species. We termed this rule-based inference minimal interspecies interaction adjustment (MIIA). Our critical assessment of MIIA has produced reliable predictions of shifting interspecies interactions that are dependent on the functional role of neighbor organisms. We also show how MIIA has been applied to a microbial community composed of competing soil bacteria to elucidate a new finding that - in many cases - adding fewer competitors could impose more significant impact on binary interactions. The ability to predict membership-dependent community behavior is expected to help deepen our understanding of how microbiomes are organized in nature and how they may be designed and/or controlled in the future.