Focal Endolymphatic Hydrops as Seen in the Pars Inferior of the Human Inner Ear.
Endolymphatic hydrops of the human inner ear may be localized focally in the pars inferior of the human inner ear. Endolymphatic hydrops may be found in the human inner ear in patients who in life had suffered from Ménière's syndrome or a variety of other disorders. The degree of endolymphatic hydrops may differ based on location in the inner ear. A computer-assisted search of all cases in the collection of the Massachusetts Eye and Ear Infirmary in which endolymphatic hydrops was found in the inner ear yielded 13 specimens in which there was good evidence for focal endolymphatic hydrops in the pars inferior. Temporal bones were prepared for light microscopy. Semi-serial sections were reviewed to generate localization data for endolymphatic hydrops and also to search for evidence of a previous inflammatory process, including fibrosis or new bone formation. Endolymphatic hydrops was present in the saccule in 10 of 13 specimens. In the cochlear duct, there were segments of the cochlea in which there was no cochlear hydrops juxtaposed to other regions in which there was severe endolymphatic hydrops. Transition between hydropic and non-hydropic status in the cochlear duct was often abrupt.Evidence for a previous inflammation process was found in 6 of 13 specimens including fibrosis because of temporal bone fracture, or traumatic stapedectomy and in those cases in which the cause of hearing loss was idiopathic, fibrosis, and osteoid between the labyrinthine surface of the footplate and the hydropic saccular wall, and/or osteoid in the scala vestibuli, or in the proximate Rosenthal's canal. Evidence of a previous inflammatory process was uniformly seen in the perilymphatic compartment. Endolymphatic hydrops of the pars inferior in the human may have a focal distribution. This study suggests that the pathogenesis of endolymphatic hydrops is unlikely to be because of distal obstruction of longitudinal flow and was more consistent with the hypothesis that homeostasis of the endolymphatic and perilymphatic volumes occurs all along the cochlear duct. Other factors including variable distensibility of Reissner's membrane or disturbance of local solute homeostatic mechanisms may be responsible for wide variations in the degree of hydrops. A focal inflammatory process during life may be one cause of focal endolymphatic hydrops as seen histopathologically.


Modulation of inflammatory paw oedema by cysteamine in the rat.
Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Given subcutaneously (s.c.) 1 h before carrageenan, cysteamine caused significant, dose-dependent and long-lasting inhibition of rat paw oedema induced by carrageenan. At doses of 12.5, 25, 50 or 100 mg kg (-1), cysteamine significantly inhibited the carrageenan-induced paw oedema at 4 h by 52.3, 40, 40.7 or 26.3%. Cysteamine given at 300 mg kg (-1), a dose well known to deplete tissue somatostatin, reduced oedema by only 16.2% vs control values. Significant inhibition of the carrageenan-induced rat paw oedema was still evident 24 h post-injection at cysteamine doses of 12.5, 25, 50 or 100 mg kg (-1). Given s.c. at 300 mg kg (-1), 4 h prior to carrageenan, cysteamine decreased rat paw oedema at 4 h by 14.9%. Cysteamine (300 mg kg (-1)), 4 h beforehand, had little modulatory effect on the oedema induced by formalin (2.5%) but reduced that caused by intraplantar histamine (5 micromol). The anti-oedematogenic effect of indomethacin, but not that of the selective COX-2 inhibitor celecoxib, was less marked in rats pre-treated with cysteamine at 300 mg kg (-1). Cysteamine (0.3 microg- 0.3 mg paw (-1)) co-administered with carrageenan was devoid of anti-inflammatory effect and even promoted inflammation at low concentrations. Cysteamine given locally alone induced slight paw oedema. These data indicate that systemic cysteamine possesses potent and long-lasting anti-inflammatory effects and modulates the anti-inflammatory effect of cyclooxygenase inhibitors in a model of peripheral inflammation in the rat. The effect of cysteamine is likely to be mediated via central action.


[Comparative evaluation of biological availability and anti-arrhythmia effectiveness of Mexicard (mexiletine Polfa)].
In 16 healthy males bioavailability of Mexicord (Polfa) was studied, in comparison with mexiletine of foreign made. Bioavailability extent (EBA) of Mexicord was over 99% in comparison with a standard drug. Comparative study of antiarrhythmic activity and side effects was performed in 32 patients with frequent ventricular premalure beats and nearly in a half of them resistant to antiarrhythmic agents. Mexicord was effective in 47% of treated patients, and side effects (most often nausea) were observed in 28% of patients, but only in 1 case therapy withdrawal was necessary. Statistical study proved a lack of significant differences in antiarrhythmic effectiveness and side effects between Mexicord (Polfa) and a drug of foreign made.


Dendritic cell-based immunoregulatory strategies.
Dendritic cells (DC) are special subsets of professional antigen-presenting cells that play a dual role in initiating and silencing acquired immune responses. Thus, it should be feasible to control the magnitude and direction of immune responses by experimental manipulation of DC function. We will provide an overview of the recent progress in the development of DC-based immunostimulatory and immunosuppressive strategies, which are potentially applicable to the treatment of cancer, allergy, autoimmune disease, allograft rejection and graft versus host disease.


Limited macular translocation for atrophic maculopathy.
To report visual improvement following bilateral limited macular translocation for a patient with atrophic macular disease, and to discuss issues related to the selection of potential candidates for this technique. Case report. A 78-year-old woman with bilateral atrophic maculopathy and no choroidal neovascularization had slowly progressive loss of visual acuity for at least 17 months in the right eye and 25 months in the left eye. She underwent bilateral limited macular translocation, using scleral infolding in the right eye and scleral outpouching in the left eye. Following translocation of her maculae, her best-corrected visual acuity improved from 20/200 to 20/30 OD and from 20/180 to 20/100 OS. She remained stable during 30 months of follow-up for the right eye and 22 months of follow-up for the left eye. Macular translocation may allow visual recovery in selected patients with atrophic maculopathy, even after a prolonged period of poor vision.


How important is heart rate?
Mortality rises as resting heart rate increases. Patients who are less able to increase their heart rate while exercising are more likely to die than those whose heart rate does rise. The occurrence of silent ischaemic events shows a circadian distribution, with increased mortality, heart rate and systolic blood pressure early in the morning. Treatment with beta-blockers reduces the number of asymptomatic ischaemic episodes, and lowers heart rate during exercise and at rest. The ischaemic myocardium of the dog loses the ability to undergo wall thickening during exercise. Moreover, blood flow in the ischaemic subendocardium is reduced during exercise. These effects can be overcome using beta-blockers. The effects of beta-blockers in reducing heart rate are less pronounced during mental stress. Furthermore, changes in wall motion abnormalities during mental stress are not improved by beta-blockers. Treatment of patients with beta-blockers after a myocardial infarction reduces the mortality rate. The greater the reduction in heart rate, the greater the reduction in mortality.


Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl.
The mechanism of profound generalized iduronate sulfatase (IDS) deficiency in a developmentally delayed female with clinical Hunter syndrome was studied. Methylation-sensitive RFLP analysis of DNA from peripheral blood lymphocytes from the patient, using MspI/HpaII digestion and probing with M27 beta, showed that the paternal allele was resistant to HpaII digestion (i.e., was methylated) while the maternal allele was digested (i.e., was hypomethylated), indicating marked imbalance of X-chromosome inactivation in peripheral blood lymphocytes of the patient. Similar studies on DNA from maternal lymphocytes showed random X-chromosome inactivation. Among a total of 40 independent maternal fibroblast clones isolated by dilution plating and analyzed for IDS activity, no IDS- clone was found. Somatic cell hybrid clones containing at least one active human X chromosome were produced by fusion of patient fibroblasts with Hprt- hamster fibroblasts (RJK88) and grown in HAT-ouabain medium. Methylation-sensitive RFLP analysis of DNA from the hybrids showed that of the 22 clones that retained the DXS255 locus (M27 beta), all contained the paternal allele in the methylated (active) form. No clone was isolated containing only the maternal X chromosome, and in no case was the maternal allele hypermethylated. We postulate from these studies that the patient has MPS II as a result of a mutation resulting in both the disruption of the IDS locus on her paternal X chromosome and unbalanced inactivation of the nonmutant maternal X chromosome.


Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions.
Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.


Efficient solubilization of single-walled carbon nanotubes using tea solutions.
Here we describe the finding that oolong tea and black tea act as excellent carbon nanotube solubilizers to produce individually dissolved single-walled carbon nanotubes (SWNTs), which have been revealed using visible-near IR absorption, photoluminescence and Raman spectroscopy as well as AFM study. The oolong tea solution has a tendency to individually dissolve metallic SWNTs that can be detected by 514 nm-excition, and in solution, the (11,3)SWNTs enriched and (11,0)SWNTs that are contained in as-produced SWNTs were very few. Black tea solution shows similar tendency, while the separation performance was weaker compared to that of the oolong tea. We also used epigallocatechin gallate to solubilize the SWNTs and shed light on the mechanism of the SWNT dissolution. Tea contains numerous components with antioxidant activities; therefore biological and biomedical applications using the present soluble nanotubes might be of interest.


Myelin basic protein, oligoclonal bands, and IgG in cerebrospinal fluid as indicators of multiple sclerosis.
There currently are three clinical laboratory procedures for use with cerebrospinal fluid that assist in the diagnosis of multiple sclerosis: measurement of myelin basic protein and IgG, and demonstration of an oligoclonal band. We compared characteristics of these procedures, using CSF samples from 166 patients identified as having (54 patients) or not having (112 patients) multiple sclerosis. We find that oligoclonal band demonstration is the most useful single test in helping to establish the presence of multiple sclerosis; IgG quantitation is the least helpful. Myelin basic protein should be quantitated for following the activity of multiple sclerosis; it may be applied only selectively in the context of screening. The incidence of false-positive results reinforces the view that the diagnosis of multiple sclerosis must be made in clinical context. These laboratory procedures are not suitable for use as screening tests.


Anti-human immunoglobulin G activity of membrane-bound monoclonal immunoglobulin M in lymphoproliferative disorders.
Lymphocytes from a patient with Waldenström's macroglobulinemia and known anti-immunoglobulin IgG activity of serum monoclonal IgM and lymphocytes from selected patients with chronic lymphocytic leukemia were studied by the membrane immunofluorescence procedure. Freshly drawn lymphocytes were shown to bear simultaneously mu, gamma, [unk], and lambda chain determinants. Experiments combining redistribution induced by antibody and double labeling proved that IgG was bound to surface IgM. After removal of surface immunoglobulins by treatment with trypsin followed by incubation in culture medium, or after redistribution induced by antibody, the exclusive presence of a newly synthetized monoclonal IgM was demonstrated. Several experiments showed that this surface IgM does specifically bind normal human IgG molecules devoid of aggregated material. The IgG molecules could be removed from the cell surface by lowering the pH. In addition to its high incidence among serum monoclonal macroglobulins, anti-IgG activity of membrane-bound monoclonal IgM is not uncommon in patients with chronic lymphocytic leukemia, a disease that provides homogeneous populations of lymphocytes derived from bone marrow, with receptor sites of defined antibody activity.


Initial mothering patterns of low-income black primiparas.
Observations at three separate intervals of 24 black, low-income primiparas revealed that there is not necessarily a progressive use of the mother's fingers, hands, and arms during the attachment process. Although the mothers did use fingertips to explore their new infants at some time during the first contact, this was not their immediate behavioral responses as defined by Rubin as well as Klaus, et al. The orderly sequence from fingertip exploration to encompassing behavior has been noted by Rubin to occur over a period of time. Klaus reports the interval to be only days. The mothers in this study exhibited encompassing behavior immediately by reaching out for their infants using both hands and arms. The majority held and looked at their new babies throughout the contact time indicating the instinct for the en-face position which Klaus, et al. have described so clearly. The study data would also support Perry's statement that eye contact is an indicator of the intensity of the mother-infant interaction. Over one-half of the subjects, during the first contact, initiated verbal response to their infants. None, however greeted their infants by using given names. Clark, Affonso, and Harris do not refer to the significance of identification of baby by the mother, only to verbal interaction. All mothers in the study made positive statements regarding their infants's appearance and behavior which compares exactly with findings of Robson and Moss.


Renal cancer seeding metastases following retroperitoneoscopic-assisted cryoablation: A case report.
Nephron-sparing laparoscopy is the standard surgical treatment for clinical T1a renal tumours. However, the laparoscopic technique brings in its specific oncological safety concerns. Seeding metastases are reported: peritoneal metastases, port-tract metastases, and (sub-) cutaneous metastases. The method of laparoscopic assisted renal mass cryoablation is marked by the fact that traumatic tumour tissue handling is unavoidable. This case report reviews the rare occasion of seeding metastases in the retroperitoneal space following laparoscopic cryoablation of a small renal mass. The primary tumour showed no focal recurrence as reported by histological examination. The combination of two events as harming the integrity of cancer tissue and gas-circulation leading to the development of metastases in the retroperitoneal cavity is discussed. The combination of iatrogenic harming cancer tissue integrity and CO2-circulation leads to metastases in the retroperitoneal cavity. Therefore, we recommend performing image-guided renal mass biopsies before considering cryoablative surgery.


Immunofluorescence studies on civatte bodies and dyskeratotic cells with anti-keratin antibody.
So-called Civatte bodies and dyskeratotic cells were investigated in some skin disorders by using indirect immunofluorescence techniques with anti-human keratin antibody. In the disorders with lichenoid tissue reaction such as lichen planus and DLE, Civatte bodies were observed in the lower epidermis and upper dermis and they reacted distinctly to the anti-keratin antibody. In malignant skin tumors which show dyskeratotic cells in the epidermis, such as basal cell epithelioma and Bowen's disease, dyskeratotic cells were more clearly reacted to the antibody than other keratinocytes. These observations present additional new evidence for the hypothesis that Civatte bodies are derived from tonofilaments of keratinocytes.


Apoptosis-linked gene 2-deficient mice exhibit normal T-cell development and function.
The apoptosis-linked gene product, ALG-2, is a member of the family of intracellular Ca(2+)-binding proteins and a part of the apoptotic machinery controlled by T-cell receptor (TCR), Fas, and glucocorticoid signals. To explore the physiologic function of ALG-2 in T-cell development and function, we generated mice harboring a null mutation in the alg-2 gene. The alg-2 null mutant mice were viable and fertile and showed neither gross developmental abnormality nor immune dysfunction. Analyses of apoptotic responses of ALG-2-deficient T cells demonstrated that ALG-2 deficiency failed to block apoptosis induced by TCR, Fas, or dexamethasone signals. These findings indicate that ALG-2 is physiologically dispensable for apoptotic responses induced by the above signaling pathways and suggest that other functionally redundant proteins might exist in mammalian cells.


Histone deacetylase inhibitor suberoyl bis-hydroxamic acid suppresses cell proliferation and induces apoptosis in breast cancer cells.
Suberoyl bis‑hydroxamic acid (SBHA) is a histone deacetylase inhibitor that has shown anticancer activity against numerous types of human cancer. The aim of the current study was to explore the effects of SBHA on the proliferation and apoptosis of breast cancer cells. MCF‑7 breast cancer cells were treated with different concentrations of SBHA and tested for cell viability, apoptosis and gene expression changes. The results showed that SBHA significantly inhibited the proliferation of MCF‑7 cells in a concentration‑dependent manner, as determined using a Cell Counting kit‑8 assay. SBHA‑treated MCF‑7 cells showed G0/G1 cell‑cycle arrest, coupled with elevated expression levels of p21 and p27 proteins. Hoechst 33258 staining revealed cell shrinkage, chromosomal condensation and nuclear fragmentation in MCF‑7 cells treated with SBHA. Flow cytometric analysis of Annexin V‑stained cells showed that SBHA treatment induced apoptotic cell death in a concentration‑dependent manner. Western blot analysis confirmed the upregulation of Bax and the downregulation of Bcl‑2 by SBHA. In conclusion, these results indicate that SBHA exerts cytotoxic effects against human breast cancer cells, which involves the modulation of p21, p27 and Bcl‑2 family proteins, consequently leading to cell‑cycle arrest and apoptosis.


Testicular prostheses - impact on quality of life and sexual function.
Orchiectomy is the recommended treatment for many testicular conditions. However, testicular prosthesis placement is not always performed for different reasons. In this study, we aimed to evaluate patients' opinions and the impact on sexual function and quality of life. This retrospective observational single-center study included patients who underwent orchiectomy between January 2014 and December 2020 at the Department of Urology, Braga's Hospital (Braga, Portugal), where testicular implants were always available and the decision to undergo the procedure was made fully independent of cost. Patients completed four questionnaires that assessed demographic data, satisfaction, self-esteem, and sexual function. Of the 96 patients who underwent orchidectomy, 59 replied to the questionnaires, and of these patients, 86.4% decided to undergo silicone-based testicular prostheses implantation. The remaining 13.6% refused the implant based on concerns about complications (37.5%), because they felt that it was unnecessary (37.5%), or because it was not offered by the doctor (25.0%). Overall, 96.1% of these patients were satisfied with the implant; however, 25.5% classified it as "too firm". No statistically significant differences were found in sexual function (all P > 0.05). However, it can be observed that there are more patients with prostheses presenting normal sexual activity compared to patients without prostheses (74.0% vs 50.0%), and none of them reported severe erectile dysfunction (0 vs 16.7%). Regarding self-esteem, both patients with and without prostheses present very similar average scores with no statistically significant differences. The present study highlights the highest level of satisfaction among patients who received testicular prostheses. Testicular prostheses implantation is a safe procedure that does not hamper sexual function after orchiectomy.


Intragenic recombination has a critical role on the evolution of Legionella pneumophila virulence-related effector sidJ.
SidJ is a Dot/Icm effector involved in the trafficking or retention of ER-derived vesicles to Legionella pneumophila vacuoles whose mutation causes an observable growth defect, both in macrophage and amoeba hosts. Given the crucial role of this effector in L. pneumophila virulence we investigated the mechanisms shaping its molecular evolution. The alignment of SidJ sequences revealed several alleles with amino acid variations that may influence the protein properties. The identification of HGT events and the detection of balancing selection operating on sidJ evolution emerge as a clear result. Evidence suggests that intragenic recombination is an important strategy in the evolutionary adaptive process playing an active role on sidJ genetic plasticity. This pattern of evolution is in accordance with the life style of L. pneumophila as a broad host-range pathogen by preventing host-specialization and contributing to the resilience of the species.


Retinal Toxicity in Patients Treated With Hydroxychloroquine: A Cross-Sectional Study.
Hydroxychloroquine (HCQ) is an antimalarial medication that can also be used to treat autoimmune diseases. However, it can produce irreversible changes to the retina that lead to visual impairment. The aim of this study was to determine the proportion of patients treated with HCQ who develop retinal toxicity and the risk factors for the development of HCQ-induced retinal toxicity among Iranian patients. The is a cross-sectional clinical study of 59 patients who were treated with HCQ during 2014-2015. A questionnaire was used to collect data on the following demographic and clinical factors: age, gender, type of rheumatic disease, history of cataract surgery, daily and cumulative HCQ dose, and duration of HCQ use. Retinal toxicity was diagnosed on the basis of the automated perimetry results of the central 10° of vision and spectral domain optical coherence tomography. The associations between the demographic and clinical factors and retinal toxicity were assessed, and P < 0.05 was considered statistically significant. Retinal toxicity was detected in 18 (30.5%) of the patients, and 5 (8.5 %) developed color vision impairments. There was no association between retinal toxicity and sex (P = 0.514), history of cataract surgery (P = 0.479), type of rheumatic disease (P = 0.539), or daily HCQ dose (P = 0.062). However, there was a significant positive association between retinal toxicity and age (P = 0.006), cumulative HCQ dose (P = 0.002), and duration of HCQ use (P < 0.001). In conclusion, the risk factors for retinal toxicity after HCQ treatment were advanced age, use of a higher cumulative HCQ dose, and a longer duration of treatment.


Clinical outcomes of off-pump coronary artery bypass graft in patients with diabetes and non-diabetics: A systematic review and meta-analysis.
Diabetes mellitus is a prevalent risk factor for developing coronary artery disease which worsens the clinical outcomes of patients undergoing coronary artery bypass grafting (CABG). This study aimed to determine the clinical outcomes of patients with diabetes and non-diabetic patients who underwent off-pump CABG surgery. Medline, Scopus, Proquest, Embase, Web of Science, and Google scholar were searched until September 10, 2021. The effect sizes including unstandardized mean difference and odds ratio with 95% confidence interval were calculated using "Metan" package. The Cochran's Q-test and I2 statistic were used to assess heterogeneity, a random-effects model was applied to estimate the pooled effect sizes, and meta-regression was used to investigate the factors affecting heterogeneity between studies. 10 studies with 6200 sample sizes were included in the study. In groups with diabetes, Summary odds ratio (SOR) and 95% confidence interval of infection was 2.18 more than non-diabetic groups. Also, odds renal complication was 1.74 more than non-diabetic groups, and the odds cardiovascular complication in groups with diabetes was 1.30 more than non-diabetics. There were no differences in mortality, neurologic, respiratory and surgical complications between groups with diabetes and non-diabetics. Based on meta-regression results, age (Coefficient: 0.942; p = 0.009) had a significant direct relationship and sample size (Coefficient: 0.001; p = 0.009) had an indirect significant relationship with heterogeneity of neurologic outcomes. There was no significant publication bias in our results. Our study revealed that off-pump CABG led to some significant outcomes in patients with diabetes compared to non-diabetics. Renal and infection complications were higher in patients with diabetes but no significant differences were seen in most of other postoperative outcomes between the two groups.


Retention of primitive reflexes and delayed motor development in very low birth weight infants.
Primitive reflexes and motor development were evaluated in 127 very low birth weight (VLBW) infants (birth weight less than 1501 grams) at four months corrected age. The asymmetrical tonic neck reflex, tonic labyrinth reflex, and Moro reflex were assessed for each child. The ability of each child to reach (obtain a red ring) and roll were observed. The child's performance on the gross motor scale of the Denver Development Screening Test was recorded. Thirty-seven term infants were administered identical evaluations at four months of age. The VLBW infants retained stronger primitive reflexes and exhibited a significantly higher incidence of motor delays than term infants. Significant correlations existed between the strength of the primitive reflexes and early motor development for VLBW infants. This study confirms a high incidence of motor delays among VLBW infants and demonstrates a clear association between retained primitive reflexes and delayed motor development in VLBW infants.


A cross-sectional cohort study on the skin microbiota in patients with different acne durations.
Acne is a chronic disease that often persists for years. Skin microbial communities play an essential role in the development of acne. However, limited information is available about the dynamic patterns of skin microbiota in acne. This study aimed to characterize microbial community changes in skin pores and surfaces of acne patients with varying disease time. In this study, a total of 70 skin samples from 22 subjects were collected and sequenced using 16S rRNA amplicon sequencing. Although microbial compositions in skin pores were similar over time, significant differences in microbial structure were observed on the skin surface, with the dominance of Cutibacterium in the first 3 years and replacement by Staphylococcus in 4-6 years. Lactobacillus and Acinetobacter were more abundant in the normal group and continuingly decreased with disease time on the skin surface. Microbial networks further revealed substantial increases in microbial interactions in the 4-6 years group in both skin surfaces and pores. These results demonstrate that the skin microbiota alters with the disease duration and may provide a potential guide in redirecting skin microbiota towards healthy states.


Thyroid Uptake and Effective Half-Life of Radioiodine in Thyroid Cancer Patients at Radioiodine Therapy and Follow-Up Whole-Body Scintigraphy Either in Hypothyroidism or Under rhTSH.
Adjuvant radioiodine therapy (RITh) for differentiated thyroid carcinoma is performed either with thyroid hormone withdrawal or with administration of recombinant human thyroid-stimulating hormone (rhTSH). Heterogeneous results have been obtained on the impact of the method of patient preparation on thyroid uptake and whole-body effective half-life. A higher radiation exposure using thyroid hormone withdrawal for several weeks compared with rhTSH was reported in prior studies. It was the aim to examine whether these findings are reproducible in a modern protocol with a short interval between surgery and RITh. Methods: A retrospective study was performed on patients admitted for adjuvant RITh for differentiated thyroid carcinoma at the University Hospital of Cologne over a 5-y period from 2010. Dose rate measurements were analyzed for 366 patients, and subgroup analyses were performed for papillary thyroid cancer (n = 341) and follicular thyroid cancer (n = 25) patients, sex, length of hypothyroidism, and normal versus decreased glomerular filtration rate (GFR). Results: The median interval between surgery and RITh was 18 d for thyroid hormone withdrawal and 25 d for rhTSH (P < 0.01). The mean thyroid uptake was 4.2% ± 1.8% for the 300 hypothyroid patients versus 3.8% ± 1.6% (P = 0.12) for the 66 rhTSH patients. Whole-body half-life in the hypothyroid group was significantly longer at 19.3 ± 7.7 h versus 16.4 ± 4.6 h in the rhTSH group (P < 0.01). Results were predominantly influenced by data from the largest subgroup, that is, female papillary thyroid cancer patients. Within this group, whole-body half-life was significantly shorter in the rhTSH treatment arm. Duration of hypothyroidism and a decrease in GFR less than 60 mL/min/1.73 m2 significantly influenced results, with an increased whole-body half-life occurring in the hypothyroid group. When patients returned for whole-body scintigraphy, thyroid, half-life, and whole-body half-life were significantly shorter in the rhTSH groups, resulting in a low thyroid and remaining-body dose. Conclusion: With a shortening of the time between surgery and adjuvant RITh, thyroid uptake is not significantly changed but whole-body half-life becomes longer in the hypothyroid group. Radiation exposure for most patients is not significantly different. However, patients with a hypothyroid phase of more than 4 wk, and in particular those with a decreased GFR, experience higher radiation exposure.


Biomechanical responses to open experimental spinal cord injury.
This study evaluates the dynamic biomechanical responses of the cat spinal cord during experimental impact injury. Temporal deformations of the laminectomized spinal cord were recorded by a high speed camera (1500-3000 frames/sec). The cinematograph revealed large deformations, the cord being compressed to half its posterior-anterior diameter 7 msec after the onset of the impact. Peak impact force produced by a 20 gm mass falling from 15 cm height (300 GCF) averaged about 1.2 pounds, and the corresponding stress acting on the dural surface reached 42 pounds per square inch (or 2200 mm Hg). Both positive and negative pressure waves were found to be propagated in the cerebrospinal fluid.


Transfer of tetracycline or clindamycin resistance among strains of Bacteroides fragilis in experimental abscesses.
The ability of strains of Bacteroides fragilis resistant to clindamycin and/or tetracycline to transfer resistance to a susceptible recipient strain in experimental subcutaneous abscesses in mice was investigated. The results indicated that such transfer took place at a frequency similar to that observed in vitro. Transfer of resistance determinants at infected sites may play a role in the epidemiology of disseminated resistance to antimicrobial agents.


Neutralization of acidic residues in helix II stabilizes the folded conformation of acyl carrier protein and variably alters its function with different enzymes.
Acyl carrier protein (ACP), a small protein essential for bacterial growth and pathogenesis, interacts with diverse enzymes during the biosynthesis of fatty acids, phospholipids, and other specialized products such as lipid A. NMR and hydrodynamic studies have previously shown that divalent cations stabilize native helical ACP conformation by binding to conserved acidic residues at two sites (A and B) at either end of the "recognition" helix II. To examine the roles of these amino acids in ACP structure and function, site-directed mutagenesis was used to replace individual site A (Asp-30, Asp-35, Asp-38) and site B (Glu-47, Glu-53, Asp-56) residues in recombinant Vibrio harveyi ACP with the corresponding amides, along with combined mutations at each site (SA, SB) or both sites (SA/SB). Like native V. harveyi ACP, all individual mutants were unfolded at neutral pH but adopted a helical conformation in the presence of millimolar Mg(2+) or upon fatty acylation. Mg(2+) binding to sites A or B independently stabilized native ACP conformation, whereas mutant SA/SB was folded in the absence of Mg(2+), suggesting that charge neutralization is largely responsible for ACP stabilization by divalent cations. Asp-35 in site A was critical for holo-ACP synthase activity, while acyl-ACP synthetase and UDP-N-acetylglucosamine acyltransferase (LpxA) activities were more affected by mutations in site B. Both sites were required for fatty acid synthase activity. Overall, our results indicate that divalent cation binding site mutations have predicted effects on ACP conformation but unpredicted and variable consequences on ACP function with different enzymes.


Persistent food insecurity is associated with higher levels of cost-related medication nonadherence in low-income older adults.
The purpose of this study was to examine relationships between changes in food insecurity (FI) and cost-related medication nonadherence (CRN) among Older Americans Act Nutrition Program participants and wait-listed individuals in Georgia. This study used data collected from 3 waves of self-administered mail surveys conducted 4 months apart in 2008 and 2009 (n = 664, mean age 74.6 ± 8.9 years, 71.5% female, 31.0% African American). FI was assessed by using a validated 6-item U.S. Household Food Security Survey Module. Practice of 5 CRN behaviors was evaluated. Changes in FI and CRN were determined based on ≥ 2 repeated measures. Participants with persistent FI and CRN were more likely to be younger, low-income, and in poorer health. After controlling for potential confounders, persistently food insecure individuals and those who became food insecure showed 8.2 (95% CI: 5.4-12.5) times and 5.3 (95% CI: 3.2-8.8) times increased odds of reporting higher levels of CRN than persistently food secure individuals.


The relationship between sleep problems and cortisol in people with type 2 diabetes.
Sleep problems are linked with negative health outcomes, including coronary heart disease. Neuroendocrine dysfunction has been associated with sleep problems and may be a pathway linking sleep and ill health. Dysregulated cortisol output has observed in people with type 2 diabetes (T2D), though little is known about the links between sleep and cortisol in this population at high risk of coronary disease. This study investigated the association between sleep problems and cortisol over the course of an ordinary day and in response to acute laboratory stress in a sample of 129 individuals with T2D. Sleep problems were assessed using the Jenkins sleep problems questionnaire. Mental stress was induced using two five-minute laboratory stress tasks: a mirror-tracing task and the Stroop color-word interference task. Sleep problems were positively associated with daily cortisol area under the curve (B = 17.051, C.I. = 6.547 to 27.554, p = 0.002) adjusting for age, sex, marital status, education, household income, body mass index and smoking; suggesting that those with greater sleep problems had greater cortisol concentrations over the course of an ordinary day. Participants reporting greater sleep problems also had raised evening cortisol levels (B = 0.96, C.I. = 0.176 to 1.746, p = 0.017) in adjusted models. In the laboratory sleep problems were negatively associated with cortisol immediately post-task (B = -0.030, C.I. = -0.059 to 0.000, p = 0.048) and 45 minutes post-task (B = -0.037, C.I. = -0.072 to -0.002, p = 0.039) in fully adjusted models; indicating that those who experienced greater sleep problems had lower cortisol concentrations after stress. Sleep problems were associated with disturbances in cortisol responses to stress, as well as changes diurnal cortisol output in people with T2D. Further research is needed to assess if neuroendocrine disturbance increases the risk of cardiovascular disease in this population.


Methodology and clinical value of transcutaneous blood gas measurements in the fetus.
Aiming at an improvement of fetal surveillance in high risk cases, a clinical trial was performed to evaluate the potential of fetal tcPco2 monitoring. An electrochemical tcPco2 sensor heated at 44 degrees C was applied in 119 fetuses after abnormal heart rate patterns had occurred. The number of operative deliveries for fetal distress was reduced to 14 cases by means of the biochemical parameters (tcPco2) and fetal blood analysis (FBA). In the majority of cases with pathologic heart rate patterns the tcPco2 values were prepathologic or normal (60%), while in 68% of cases with prepathologic heart rate patterns the tcPco2 level was normal. At all instances an intrauterine complication was indicated by a marked rise of the tcPco2 level. The clinical benefit of using the tcPco2 measurement is the better specificity of detecting fetal distress when compared with the use of cardiotocography alone. Furthermore the tcPco2 technique has the advantage of providing continuous information about one biochemical parameter and of avoiding the necessity of repeated incisions of the scalp, as compared with the technique of fetal blood analysis. In conclusion the use of this non-traumatic technique lends itself to avoid unnecessary operative deliveries in high risk cases.


Acoustic resonance spectroscopy of soft solids.
An acoustic resonance apparatus for probing mechanical properties of materials with soft to moderate hardness (elastic modulus <5 GPa) is described. The technique employs stereo phono-needle transducers suitable for measurements in the range from 40 Hz to 40 kHz which are very weakly perturbing to the sample and have polarized excitation and detection. Identification of the normal modes is facilitated by the polarization information, and the technique is applicable to materials ranging from soft elastomers to hard plastics. The experimental setup is described in detail, and the utility of the technique is showcased in three example applications.


Long nanofibers arrays through surfactant self-assembly.
Self assembly of molecules can be a simple and versatile approach that may lead to nanostructures. Here we report the formation of arrangements of exceptionally long nanofibers of cationic surfactant hexadecyltrimethylammonium bromide molecules with highly defined spatial and parallel ordering. Arrangements of approximately 1 microm long nanofibers were observed by non-contact atomic force microscopy. The long nanofiber patterns form structures in approximately 5 x 5 microm2 regions and consist of approximately 6 nm wide lines. The formation mechanism of the fibers is shown to be the coalescence of isolated surfactant micelles (approximately 3.2 nm diameter in solution) in the convection stream of the surfactant solution drop close to the pinned contact-line region during drying. The size of micelles formed in solution determines the diameter of the deposited fibers. New deposition schemes of micelles forming nanorods on bare silicon previous to the formation of surfactant bilayers are now being investigated based on the data obtained in this work.


Comparative effectiveness clinical trials to advance treatment of myasthenia gravis.
Myasthenia gravis (MG) presents many challenges for establishing treatment efficacy through clinical trials. Among these are the rarity and heterogeneity of the disease, spontaneous fluctuations, prolonged latency to effect for many immunosuppressive drugs, and the uncertain generalizability of results from randomized controlled trials (RCTs). Prospective observational study designs may overcome some of these limitations, but attention is required to ensure that internal validity is not compromised. Observational comparative effectiveness research (CER) utilizes data obtained during routine clinical care to evaluate the effectiveness of interventions in real-life practice conditions, thereby improving generalizability to the clinic. Compared with RCTs, observational CER studies may be less resource intensive and costly. Recent advances that have improved the feasibility of CER studies for MG are (1) the development of MG common data elements, (2) the publication of international consensus guidance for MG treatment, and (3) the development of a web-based REDCap database that can be shared and adapted to standardize data collection. This infrastructure could be used for multisite comparisons of commonly used therapies and provides longitudinal information on patient- and clinician-centered MG outcome measures. A challenge is to design studies that address the potential limitations of observational trials, such as confounding and selection and information bias.


Creation and application of immortalized bait libraries for targeted enrichment and next-generation sequencing.
Since the introduction of next-generation sequencing, several techniques have been developed to selectively enrich and sequence specific parts of the genome at high coverage. These techniques include enzymatic methods employing molecular inversion probes, PCR based approaches, hybrid capture, and in-solution capture. In-solution capture employs RNA probes transcribed from a pool of DNA template oligos designed to match regions of interest to specifically bind and enrich genomic DNA fragments. This method is highly efficient, especially if genomic target regions are large in size or quantity. Diverse in-solution capture kits are available, but are costly when large sample numbers need to be analyzed. Here we present a cost-effective strategy for the design of custom DNA libraries, their transcription into RNA libraries, and application for in-solution capture. We show the efficacy by comparing the method to a commercial kit and further demonstrate that emulsion PCR can be used for bias free amplification and virtual immortalization of DNA template libraries.


Dual Color Space Guided Sketch Colorization.
Automatic sketch colorization is a challenging task in both computer graphics and computer vision since all the color, texture, shading generation have to be created based on the abstract sketch. Besides, it is a subjective task in painting process, which needs illustrators to comprehend drawing priori (DP), such as hue variation, saturation contrast and gray contrast and utilize them in the HSV color space which is closer to human visual cognition system. As such, incorporating supplementary supervision in the HSV color space may be beneficial to sketch colorization. However, previous methods improve the colorization quality only in the RGB color space without considering the HSV color space, often causing results with dull color, inappropriate saturation contrast, and artifacts. To address this issue, we propose a novel sketch colorization method, dual color space guided generative adversarial network (DCSGAN), that considers the complementary information contained in both the RGB and HSV color space. Specifically, we incorporate the HSV color space to construct dual color spaces for supervising our method with a color space transformation (CST) network that learns transformation from the RGB to HSV color space. Then, we propose a DP loss that enables the DCSGAN to generate vivid color images with pixel level supervision. Additionally, a novel dual color space adversarial (DCSA) loss is designed to guide the generator at global level to reduce the artifacts to meet audiences' aesthetic expectations. Extensive experiments and ablation studies demonstrate the superiority of the proposed method over previous state-of-the-art (SOTA) methods.


Technical note: Development of a feed matrix as inoculum in Salmonella infection studies in piglets.
Current methods used for oral administration of pathogens to piglets are stressful for the animals because of fixation and use of inoculation methods such as oral gavage. In the present study an alternative way to challenge piglets with Typhimurium (ST) is investigated. The strategy was to incorporate the in a feed matrix, which is fed to the piglets and eaten voluntary. Different types of feed matrices were tested for their absorption capacity, handling properties, and palatability to piglets. Furthermore, the viability of ST in feed matrices was studied. The ST could be incorporated in ladyfinger biscuits; a 2-cm piece absorbs 1 mL of culture media. The ladyfinger biscuits were very well accepted by the piglets. After a short training period, the piglets consumed the -incorporated biscuits out of the feeding trough. In this way the animals were infected in a more natural way and without stress. The safety of farm workers was also increased because the incorporated ST results in less spoilage and spreading of ST during the infections. Results indicated that the ST cell count was reduced by only 0.2 log unit to 8.7 log cfu per inoculum after 24 h at 4°C incorporation of ST into the biscuits, which is sufficient for an infection study and indicates excellent viability of the . The viability was also indicated by increased fecal shedding of ST. Thus, it is concluded that ladyfinger biscuits are a suitable matrix to challenge piglets with ST.


RETRA: evaluating the transfusion rate with darbepoetin alfa 500 µg every 3 weeks in anaemic cancer patients receiving chemotherapy.
Anaemia is a highly prevalent condition in cancer patients impacting on morbidity, mortality and quality of life. Darbepoetin alfa (DA) 500 µg administered once every 3 weeks (Q3W) has been shown to be effective in patients with chemotherapy-induced anaemia. This non-interventional study investigated the efficacy and usage patterns of DA 500 µg Q3W in routine clinical practice. Prospective data on adult anaemic cancer patients receiving DA 500 µg Q3W during chemotherapy was collected. Efficacy of DA treatment was measured as the red blood cell transfusion (RBCT) incidence, the change in Hb over time, hospitalisations for anaemia, and the change in Eastern Cooperative Oncology Group (ECOG) performance status between baseline and study end. Usage patterns were evaluated in Hb categories at baseline and week 16, DA dosage information, and adherence to the guidelines issued by the European Organisation for Research and Treatment of Cancer (EORTC). A total of 309 patients were included. The median study duration was 16 weeks and the overall transfusion rate was 19%. Significantly fewer patients required transfusions when DA was initiated at Hb 9.0-10.0 g/dL (19%), as compared to later at a Hb < 9.0 g/dL (50%, p = 0.0002). Transfusion-independent patients had fewer anaemia-related hospitalisations and better ECOG scores at the end of the study. A total of 83% of patients reached a Hb ≥ 11.0 g/dL during weeks 1-16. Physicians' adherence to Hb thresholds for DA initiation as recommended by the EORTC was observed in 83% of patients. In accordance with the recommended treatment objective for DA to minimise RBCTs, 81% of study patients remained free of RBCTs during DA 500 µg Q3W treatment and at an even higher rate if DA treatment was initiated before Hb fell below 9.0 g/dL.


A participatory approach to evaluating a national training and institutional change initiative: the BUILD longitudinal evaluation.
The National Institutes of Health (NIH) funds training programs to increase the numbers and skills of scientists who obtain NIH research grants, but few programs have been rigorously evaluated. The sizeable recent NIH investment in developing programs to increase the diversity of the NIH-funded workforce, implemented through the Diversity Program Consortium (DPC), is unusual in that it also funds a Consortium-wide evaluation plan, which spans the activities of the 10 BUilding Infrastructure Leading to Diversity (BUILD) awardees and the National Research Mentoring Network (NRMN). The purpose of this article is to describe the evaluation design and innovations of the BUILD Program on students, faculty, and institutions of the 10 primarily undergraduate BUILD sites. Our approach to this multi-methods quasi-experimental longitudinal evaluation emphasizes stakeholder participation and collaboration. The evaluation plan specifies the major evaluation questions and key short- to long-term outcome measures (or Hallmarks of Success). The Coordination and Evaluation Center (CEC) embarked on a comprehensive evaluation strategy by developing a set of logic models that incorporate the Hallmarks of Success and other outcomes that were collaboratively identified by the DPC. Data were collected from each BUILD site through national surveys from the Higher Education Research Institute at UCLA (HERI), annual followup surveys that align with the HERI instruments, site visits and case studies, program encounter data ("tracker" data), and institutional data. The analytic approach involves comparing changes in Hallmarks (key outcomes) within institutions for biomedical students who participated versus those who did not participate in the BUILD program at each institution, as well as between institution patterns of biomedical students at the BUILD sites, and matched institutions that were not BUILD grantees. Case studies provide insights into the institutionalization of these new programs and help to explain the processes that lead to the observed outcomes. Ultimately, the results of the consortium-wide evaluation will be used to inform national policy in higher education and will provide relevant examples of institutional and educational programmatic changes required to diversify the biomedical workforce in the USA.


Bioelectronic detector with monoamine oxidase for halitosis monitoring.
Methyl mercaptan (MM) is known as one of the major chemicals of halitosis (bad breath). In this study, a bioelectronic gas sensor (bio-detector) for gaseous MM was developed and was applied to measure halitosis in breath. The bio-detector consisted of a Clark-type dissolved oxygen electrode, a monoamine oxidase type-A (MAO-A) immobilized membrane and a reaction unit that had liquid and gaseous compartments separated by a hydrophobic porous polytetrafluoroethylene (PTFE) diaphragm membrane. The tip of the electrode covered with MAO-A membrane was placed into the liquid compartment as touching to the PTFE diaphragm membrane. In order to amplify the bio-detector output, a substrate regeneration cycle caused by coupling the monooxygenase with l-ascorbic acid as reducing reaction with reagent system, was applied. The results of MM vapor measurements showed the calibration range of the bio-detector for MM vapor was from 0.087 to 11.5 ppm (correlation coefficient: 0.993) and included the human sense of smell level 5 (0.2 ppm). The bio-detector had good selectivity being attributed to enzyme specificity was obtained for several substances (trimethyl amine, ammonia, dimethyl sulfide, etc.). The bio-detector was applied for halitosis measurement. Expired gases in five subjects were sampled every hour and the concentrations of MM in the expired gases were monitored. The output of bio-detector showed behaviour of halitosis level changes in a day such as increasing with passage of time and decreasing after eating.


Screening and characterizing of xylanolytic and xylose-fermenting yeasts isolated from the wood-feeding termite, Reticulitermes chinensis.
The effective fermentation of xylose remains an intractable challenge in bioethanol industry. The relevant xylanase enzyme is also in a high demand from industry for several biotechnological applications that inevitably in recent times led to many efforts for screening some novel microorganisms for better xylanase production and fermentation performance. Recently, it seems that wood-feeding termites can truly be considered as highly efficient natural bioreactors. The highly specialized gut systems of such insects are not yet fully realized, particularly, in xylose fermentation and xylanase production to advance industrial bioethanol technology as well as industrial applications of xylanases. A total of 92 strains from 18 yeast species were successfully isolated and identified from the gut of wood-feeding termite, Reticulitermes chinensis. Of these yeasts and strains, seven were identified for new species: Candida gotoi, Candida pseudorhagii, Hamamotoa lignophila, Meyerozyma guilliermondii, Sugiyamaella sp.1, Sugiyamaella sp. 2, and Sugiyamaella sp.3. Based on the phylogenetic and phenotypic characterization, the type strain of C. pseudorhagii sp. nov., which was originally designated strain SSA-1542T, was the most frequently occurred yeast from termite gut samples, showed the highly xylanolytic activity as well as D-xylose fermentation. The highest xylanase activity was recorded as 1.73 and 0.98 U/mL with xylan or D-xylose substrate, respectively, from SSA-1542T. Among xylanase-producing yeasts, four novel species were identified as D-xylose-fermenting yeasts, where the yeast, C. pseudorhagii SSA-1542T, showed the highest ethanol yield (0.31 g/g), ethanol productivity (0.31 g/L·h), and its fermentation efficiency (60.7%) in 48 h. Clearly, the symbiotic yeasts isolated from termite guts have demonstrated a competitive capability to produce xylanase and ferment xylose, suggesting that the wood-feeding termite gut is a promising reservoir for novel xylanases-producing and xylose-fermenting yeasts that are potentially valued for biorefinery industry.


Venturi-based rapid expansion of supercritical solution (Vent-RESS): synthesis of liposomes for pH-triggered delivery of hydrophilic and lipophilic bioactives.
Multivitamin-loaded and surface-modified liposomes tailored for simultaneous intestinal delivery of both lipophilic and hydrophilic bioactives were synthesized from sunflower phosphatidylcholine (SFPC). Liposomes (SL) were generated with the aid of a novel, organic solvent free, and environmentally benign process which utilizes venturi-based rapid expansion of supercritical solution (Vent-RESS). Vitamins E and C were used as model lipophilic and hydrophilic bioactives and demonstrated an average encapsulation efficiency of 92 and 70 %, respectively. Synthesized liposomes were coated with a pH-responsive double-wall of chitosan and β-lactoglobulin (βlg-Cs-SL) to develop a biocompatible vehicle for pH-triggered delivery of bioactive cargo(s). To compare the efficacy of this newly developed dual-coating, SL was also coated with a commercially available pH responsive polymer, Eudragit® S100 (Eu-SL). No organic solvent was used during the surface coating of SLs with these two different types of enteric coatings. The performance of these two coatings was studied by conducting morphological characterization through diameter and ζ-potential measurements along with confocal laser scanning and freeze-fracture cryogenic scanning electron microscopies. The stability of coated and uncoated SFPC liposomes was determined in simulated gastrointestinal fluids. For βlg-Cs-SL and Eu-SL, after 2 h of incubation in simulated gastric condition, less than 5 % of the encapsulated vitamins C and E were released, whereas for SL, 41 and 28 % of vitamins C and E were released within 2 h of incubation period. In simulated intestinal fluid, coated liposomes released most of their remaining payload when incubated for 4 h. The newly developed dual coating was found to be as effective as its commercially available counterpart, Eudragit® S100 coating; nevertheless, the biocompatible, non-toxic, and non-synthetic nature of this coating makes it an attractive alternative. Modeling the release kinetics of vitamins from coated liposome showed that the release of payload from surface coated liposomes proceeded through a multistep structural disintegration involving both Fickian and non-Fickian types of diffusion. The ability of these surface-coated liposomes to maintain structural integrity under the gastric condition followed by site-specific, pH-triggered release of encapsulated cargo in the intestine will make them highly suitable for oral administration of bioactive compounds in pharmaceutical and food applications.


Experimental and clinical study of fast absorption cutaneous suture material.
Fast Absorption Vicryl was irradiated with gamma rays. The experimental study on 14 mice grafted with human skin showed a constant rupture of the sutures on the 12th day, with the development of a moderate macrophage reaction. Injection of isotonic saline around the suture material did not accelerate the process of resorption. The clinical study with 27 children operated on the limbs showed rupture of the sutures between the 12th and 16th days, without inflammatory reaction, infection or wound dehiscence. Simply wiping the wound with a compress removes the stitches painlessly. This is appreciated by the young subject and his or her family. Since we began to use FAV systematically we have not needed to conduct dressing under anesthesia. The long term results of healing (follow-up: 11.3 months) are similar to those obtained with conventional non-absorbable suture material. The tolerance, the rapid resorption, the comfort of the patient and the cost advantage make FAV the suture material of choice.


[Differential diagnosis of chronic peripancreatic pseudocysts on the computerized tomogram. Possibility of error and pitfalls].
Cystic masses within the pancreas and in its neighbourhood are often really pseudocysts. In most cases, centrally necrotic solid tumours or genuine cystic neoplasms are easy to differentiate from such pseudocysts. They are in fact rare pathologic conditions. The exclusion of a pseudocyst is sometimes more difficult, especially in peripancreatic cystic masses. Computed tomography has significantly improved the diagnostics of the upper abdomen. Nevertheless, it sometimes creates new problems. This study is a selection of cases pointing to differential diagnostic difficulties that may become pitfalls for the examiner. An image-imminent approximative diagnosis is attempted. The importance of the localisation of these lesions and of the topographical anatomy of the upper abdomen are pointed out.


Anti-herpes simplex virus (HSV) effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in rabbit cornea.
The anti-herpes simplex virus (HSV) effect and cytotoxicity of a new nucleoside analogue, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in rabbit cornea were studied. In tests of the anti-HSV effect of DHPG, even 0.03% ointment, given 5 times per day for 2 days, prevented lesion formation. The preventive effect of DHPG was much stronger than that of acyclovir (ACV) or 5-iodo-2'-deoxyuridine (IDU). In tests on the therapeutic effect of DHPG against dendritic ulcers, 0.3% ointment, given 5 times per day for 4 days, had a dramatic therapeutic effect. The effect was stronger than that of 3% ACV or 0.5% IDU ointment. Application of 0.3%, 1% or 3% DHPG ointment to normal rabbit corneas, 5 times per day for 2 weeks resulted in no histopathological abnormalities. The above results show that DHPG is superior to ACV or IDU for treatment of HSV infections.


Attentional and non-attentional systems in the maintenance of verbal information in working memory: the executive and phonological loops.
Working memory is the structure devoted to the maintenance of information at short term during concurrent processing activities. In this respect, the question regarding the nature of the mechanisms and systems fulfilling this maintenance function is of particular importance and has received various responses in the recent past. In the time-based resource-sharing (TBRS) model, we suggest that only two systems sustain the maintenance of information at the short term, counteracting the deleterious effect of temporal decay and interference. A non-attentional mechanism of verbal rehearsal, similar to the one described by Baddeley in the phonological loop model, uses language processes to reactivate phonological memory traces. Besides this domain-specific mechanism, an executive loop allows the reconstruction of memory traces through an attention-based mechanism of refreshing. The present paper reviews evidence of the involvement of these two independent systems in the maintenance of verbal memory items.


Clinical picture and problems of keratoplasty in Richner-Hanhart syndrome (tyrosinemia type II).
The Richner-Hanhart syndrome seen in a middle-aged woman is described. The patient had the typical clinical manifestations of tyrosinemia II with a bilateral keratopathy, palmar and plantar hyperkeratosis. The patient was subjected to a specific diet and to perforating keratoplasty. Postoperative systemic therapy with steroids had a negative influence on the clinical manifestations; dendritic lesions which developed on the corneal graft disappeared after interruption of the systemic steroid therapy. This suggests that cortisone treatment after keratoplasty should be avoided in this special metabolic disorder.


Hydrodynamic analysis of the human progesterone receptor A-isoform reveals that self-association occurs in the micromolar range.
Human progesterone receptors exist as two functionally distinct isoforms, an 83 kDa A-receptor (PR-A) and a 99 kDa B-receptor (PR-B). The isoforms are identical except that PR-B has an additional 164 amino acids at its N-terminus. We have previously characterized the hydrodynamics and solution assembly energetics of PR-B [Heneghan, A. F., et al. (2005) Biochemistry 44, 9528-9537], and here we present an analysis of PR-A. At micromolar concentrations of the receptor, sedimentation velocity studies demonstrate that PR-A undergoes a concentration-dependent change in its sedimentation coefficient distribution, indicative of a self-associating system. Global analysis of data sets collected at multiple PR-A concentrations supports the presence of a hydrodynamically homogeneous 3.50 S monomer species in equilibrium with a 7.15 S dimer species. Sedimentation equilibrium analysis demonstrates that self-association can be rigorously described by a monomer-dimer assembly reaction and a dimerization free energy of -7.6 +/- 0.6 kcal/mol. Both the PR-A monomer and dimer are structurally asymmetric, although the extent of asymmetry is significantly decreased for the dimer, indicative of quaternary-induced hydrodynamic compaction. Limited proteolysis studies suggest that PR-A asymmetry arises from an ensemble of partially folded conformations within the N-terminal half of the molecule. Finally, comparison to our previous work on PR-B self-association energetics demonstrates that it dimerizes, under identical solution conditions, with an affinity at least 8-fold weaker than that of PR-A. Thus, residues unique to the B-isoform destabilize receptor assembly energetics. Importantly, the physical and chemical driving forces underlying isoform-specific dimerization suggest that B-unique amino acids modulate the energetics through an allosteric mechanism.


Broadband terahertz absorber with tunable frequency and bandwidth by using Dirac semimetal and strontium titanate.
A bifunctional broadband absorber in the terahertz band based on patterned bulk Dirac semimetal (BDS) and strontium titanate (STO) is proposed. The properties of the absorber are investigated using the finite-difference time-domain (FDTD) method. The results show that the width of absorption can be modulated from 0.59 THz to 0.7 THz when the Fermi energy of the BDS is independently shifted from 40 meV to 50 meV. By tuning the temperature from 250 K to 400K, the center frequency of the broadband absorption spectrum can be changed from 1.311 THz to 1.505 THz, and the absorption bandwidth broadens from 0.66 THz to 0.81 THz. In addition, the simulation results show that the absorber is insensitive to electromagnetic wave polarization, and can still maintain a stable broadband absorption effect when the oblique incidence is within 40° for TE and TM modes. Based on the impedance matching theory, the physical mechanism of the broadband absorption is analyzed theoretically. This work can provide an alternative way to design high-performance multifunctional tunable terahertz devices.


Policy Iteration Algorithm for Optimal Control of Stochastic Logical Dynamical Systems.
This brief investigates the infinite horizon optimal control problem for stochastic multivalued logical dynamical systems with discounted cost. Applying the equivalent descriptions of stochastic logical dynamics in term of Markov decision process, the discounted infinite horizon optimal control problem is presented in an algebraic form. Then, employing the method of semitensor product of matrices and the increasing-dimension technique, a succinct algebraic form of the policy iteration algorithm is derived to solve the optimal control problem. To show the effectiveness of the proposed policy iteration algorithm, an optimization problem of p53-Mdm2 gene network is investigated.


Induction of insulin secretion by a component of Urtica dioica leave extract in perifused Islets of Langerhans and its in vivo effects in normal and streptozotocin diabetic rats.
The blood glucose lowering effect of Urtica dioica (Stinging Nettle) as a medicinal plant has been noted in old writings such as those of Avicenna. Recently, there has also been other investigators that indicated the hypoglycemic effect of Urtica dioica. But so far, the mechanism of this effect has not been deduced. In this report, a perifusion system is arranged in which an exact number of Langerhans Islets were exposed to several fractions of extracts of Urtica dioica by TLC. The active ingredient fraction named F(1), caused a marked increase in insulin secretion. A simultaneous assay of glucose showed that the increase in insulin level was associated with a decrease in glucose level. Furthermore, the active component of Urtica dioica was found to increase the insulin content of blood sera in normal and streptozotocin diabetic rats that were injected intraperitoneally (i.p.) with the active ingredient of the extract. The in vivo studies presented in this report show that not only an increase in insulin level of blood sera was observed in rats after 30 min from the initial point of injection but a simultaneous decrease of blood sugar was detected when similar sera was tested for glucose. The increase in insulin level was six times during the 120 min of our determination. The decrease in blood sugar was found to be similar both in the level and time of initiation. On the basis of our findings, we assume that F(1) is the active ingredient of plant leaves extract. The results show that the blood lowering effect of the extract was due to the enhancement of insulin secretion by Langerhance Isletes.


Urinary incontinence in the childbearing woman.
Urinary Incontinence (UI) is an often under-reported and untreated medical condition that affects the lives of women of all ages and backgrounds. Although there are six major types of UI, stress urinary incontinence (SUI) is the type most often associated with women of childbearing age. Development of SUI has also been linked to the childbirth process itself. This article will discuss the types, characteristics, and diagnosis of UI, with a focus on SUI. Precipitating factors for SUI, including the influence of pregnancy, childbirth, and aging on its development, will be reviewed.


[National cohort of patients with emphysema and alpha-1 antitrypsin deficiency].
The natural history and optimal therapeutic management of emphysema associated with alpha-1 antitrypsin deficiency are poorly understood. The purpose of this cohort of patients with emphysema associated with alpha-1 antitrypsin deficiency is to describe their characteristics and to study the factors associated with the evolution of their pathology. It is a multicentre, prospective, cohort study including all the patients in metropolitan France with alpha-1 antitrypsin deficiency associated with emphysema (diagnosed by CT scanning) and an obstructive ventilatory defect. All respiratory physicians will be approached. Patients meeting the inclusion criteria will be followed up every 6 months for 5 years. Clinical and spirometric data as well as those relating to quality of life will becollected. The principal criterion will be FEV1; the secondary criteria: quality of life, exacerbations requiring hospitalistion and mortality. 300-500 patients are expected to be included. At the conclusion incorporation of this cohort into AIR (Alpha-antitrypsin International Registry) will increase the statistical power. This study could also provide the base for prospective trials and research projects.


Guideline for the Treatment of Condylar Osteochondroma Combined With Secondary Dentofacial Deformities.
Surgical treatment of condylar osteochondroma combined with secondary dentofacial deformities is a significant clinical challenge. The authors present this review article to provide some guidelines for the surgical treatment for this severely complex condition. Diagnosis and treatment protocol of condylar osteochondroma patients combined with secondary dentofacial deformities are discussed at the basis of published literatures and the authors' own clinical experiences. Proper treatment protocol was designed according to features of tumor and dentofacial deformities. Follow-up and radiographic examination was performed to evaluate recurrence of tumor, occlusion, joint function, and facial appearance after surgery. The patients received 1 or several methods of resection of tumor, condylar reconstruction, correction of skeletal deformities, and treatment of malocclusion. The condylar ostechondroma and secondary dentofacial deformities were treated satisfactorily. Temporomandibular joint function, occlusion, and facial appearance were improved obviously after operation evidenced by radiographic examination and follow-up. Surgical management of condylar osteochondroma with secondary dentofacial deformities requires careful patient selection, treatment planning, and precise execution. This article has reviewed the current status of surgical treatment options and provided practical guidelines for oral and maxillofacial surgeons to consider their clinical practice.


Chlorhexidine varnish for preventing dental caries in children, adolescents and young adults: a systematic review.
This systematic review aimed to determine the caries-inhibiting effect of chlorhexidine (CHX) varnishes on the permanent dentition of children, adolescents and young adults, and to explore two possibly related factors, namely application frequency and the time between evaluation and the last application. The literature search identified 14 publications of randomized controlled trials or controlled clinical trials where the effect of CHX varnish was compared with placebo controls or controls that received no preventive treatment. To obtain uniform outcome effects, the prevented fraction and 95% confidence intervals of caries increment were calculated. Owing to insufficient data presentation, only eight publications were included. Another two publications were included after receiving additional data from the authors. This systematic review did not result in a meta-analysis as an overall prevented fraction could not be computed because of the large variation of outcome results. The variation could not be explained by the time between evaluation and last application but might be explained by application frequency. It is tentatively concluded that CHX varnish has a moderate caries-inhibiting effect when applied every 3-4 months. However, this effect seems to have diminished by around 2 yr after the last application. There is no evidence for a caries-inhibiting effect of CHX varnish with longer intervals between applications.


Application of new technology in clinical hyperthermia.
Two areas of technical progress related to hyperthermic oncology are presented: (1) numerical modelling of absorbed power and temperature distributions; and (2) non-invasive thermometry using magnetic resonance imaging. The results represent achievements made during the past 5 years at Duke University Medical Center's Departments of Radiation Oncology and Radiology. They represent examples of progress in the technology of hyperthermia that have potential for greatly improving the delivery, monitoring and assessment of clinical hyperthermia.


Obturator pyomyositis and labium majus cellulitis: A case report and literature review.
Pyomyositis is a rare, subacute, deep bacterial infection of the skeletal muscle. When treatment is delayed, pyomyositis causes abscess formation and progresses to sepsis; therefore, its early diagnosis is important. However, the clinical presentation and laboratory findings of pyomyositis are not specific; hence, diagnosis often takes time. We encountered the case of a girl with obturator pyomyositis and redness and swelling of the labium majus, which we considered as potentially important symptoms for distinguishing obturator pyomyositis from septic hip arthritis. An 8-year-old Japanese girl presented to our hospital with fever and right hip pain. On physical examination, she had redness and swelling of the right labium majus and a right limp. She was diagnosed with obturator pyomyositis and labium majus cellulitis with magnetic resonance imaging. Her clinical presentation markedly improved after starting antibiotic therapy with intravenous cefazolin for 2 weeks and oral cefaclor for 1 week. Improvement in the inflammation of the obturator muscle and labium majus was confirmed with follow-up magnetic resonance imaging. She recovered fully with no long-term sequelae. In conclusion, obturator pyomyositis rather than septic hip arthritis should be considered in children with a limp and hip and perineal pain, particularly girls with redness and swelling of the labium majus. In addition, imaging studies, including magnetic resonance imaging, should be performed for early diagnosis.


Effectiveness of a hydrophilic primer when different antimicrobial agents are mixed.
The purpose of this study was to determine whether different types of antimicrobial agents with hydrophilic primer applied to etched enamel surfaces will affect the shear bond strength (SBS) and the bracket/adhesive failure modes of metallic orthodontic brackets. Eighty noncarious human premolars were divided into four groups of 20 each. A composite resin (Transbond XT) was used to bond stainless steel brackets. Teeth in the first group were used as a control and bonded with standard procedures. For the other three groups, mixtures containing a hydrophilic primer (Transbond MIP) and one of three anti-microbial agents were prepared (Cervitec: in 1:2 ratio; chlorhexidine mouthwash and EC40 varnish in 1:1 ratio). These mixtures were applied to the etched enamel surfaces and thoroughly light cured for 20 seconds, and the brackets were bonded and light cured for 40 seconds. The SBS values of these brackets (Mpa) were recorded using a universal testing machine. Adhesive Remnant Index scores were determined after failure of the brackets. Data were analyzed using analysis of variance (ANOVA), Tukey honestly significant difference, and chi-square tests. Results of ANOVA revealed statistically significant differences in bond strengths among the various groups tested (P < .05). The bond strength values in these four groups compared favorably with those from other studies and the minimal bond strength values that are clinically acceptable. However, results of this study demonstrated that groups 1 (control) and 2 (Cervitec varnish) had higher SBS values than the other applications. Application of different antimicrobial agents may result in differences in the site of failure.


Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR) in Mammalian Oocyte Maturation and Preimplantation Embryo Development.
Mammalian oocytes and early embryos derived from in vitro production are highly susceptible to a variety of cellular stresses. During oocyte maturation and preimplantation embryo development, functional proteins must be folded properly in the endoplasmic reticulum (ER) to maintain oocyte and embryo development. However, some adverse factors negatively impact ER functions and protein synthesis, resulting in the activation of ER stress and unfolded protein response (UPR) signaling pathways. ER stress and UPR signaling have been identified in mammalian oocytes and embryos produced in vitro, suggesting that modulation of ER stress and UPR signaling play very important roles in oocyte maturation and the development of preimplantation embryos. In this review, we briefly describe the current state of knowledge regarding ER stress, UPR signaling pathways, and their roles and mechanisms in mammalian (excluding human) oocyte maturation and preimplantation embryo development.


Cardiac explant-derived cells are regulated by Notch-modulated mesenchymal transition.
Progenitor cell therapy is emerging as a novel treatment for heart failure. However the molecular mechanisms regulating the generation of cardiac progenitor cells is not fully understood. We hypothesized that cardiac progenitor cells are generated from cardiac explant via a process similar to epithelial to mesenchymal transition (EMT). Explant-derived cells were generated from partially digested atrial tissue. After 21 days in culture, c-Kit+ cells were isolated from cell outgrowth. The majority of explant-originated c-Kit+ cells expressed the epicardial marker Wt1. Cardiac cell outgrowth exhibits a temporal up-regulation of EMT-markers. Notch stimulation augmented, while Notch inhibition suppressed, mesenchymal transition in both c-Kit+ and c-Kit- cells. In c-Kit+ cells, Notch stimulation reduced, while Notch inhibition up-regulated pluripotency marker expressions such as Nanog and Sox2. Notch induction was associated with degradation of β-catenin in c-Kit- cells. In contrast, Notch inhibition resulted in β-catenin accumulation, acquisition of epitheloid morphology, and up-regulation of Wnt target genes in c-Kit- cells. Our study suggests that Notch-mediated reversible EMT process is a mechanism that regulates explant-derived c-Kit+ and c-Kit- cells.


Induction of 2',5'-oligoadenylate synthetase and interferon in mouse trigeminal ganglia infected with herpes simplex virus.
The activity of 2',5'-oligoadenylate synthetase, which is induced by interferon action, was detected in mouse trigeminal ganglia infected with herpes simplex virus (HSV) type 1. When HSV was inoculated on the left cheek of mice, the virus began to appear in the ipsilateral trigeminal ganglia on day 2, reached its maximum accumulation on day 4, declined thereafter, and was no longer detected in the tissue homogenate after 11 days. After this short acute productive phase, the virus entered into the latent phase of infection. 2',5'-Oligoadenylate synthetase appeard in the trigeminal ganglia shortly after the beginning of virus multiplication; the synthetase activity began to rise on day 3, reached a maxium level on day 4, and then declined. Interferon activity (type I) also appeared in the infected ganglia, but diminished more rapidly than the synthetase. The antibody against HSV in the sera began to appear at the time when the virus and synthetase were declining. From these results it may be hypothesized, although not concluded, that in the acute productive phase of HSV infection in mouse trigeminal ganglia, virus multiplication is suppressed by interferon action, including 2',5'-oligoadenylate synthetase induction.


Lipid peroxidation in the erythrocytes under condition of their increased aggregation.
The aim of the present study was investigation of the lipid peroxidation changes within the erythrocytes under conditions of increased RBC aggregation. This latter was produced both in the in vitro and in vivo conditions by the addition of Dextran T-500. For the in vitro studies blood samples were taken from the cubital veins of 15 healthy subjects. During the in vivo studies 10 ml of the 10 percent Dextran T-500 solution was administered intravenously in six chinchilla rabbits. Another six animals were treated with rheopolyglucyne. The RBC aggregation in blood was investigated with the "Georgian technique". The malondialdehyde (the end product of lipid peroxidation) was determined in all cases by its reaction with thiobarbituric acid. We found that in the in vitro conditions, as well as in the in vivo studies, the lipid peroxidation was significantly increased in the erythrocytes during the enhanced RBC aggregation induced by addition of Dextran T-500. Therefore we suppose that the elevated RBC aggregation cause an increase of cell's lipid peroxidation and it is possible to think that appropriate prooxidant: antioxidant balance is shifted toward the pro-oxidants in the erythrocytes.


Eculizumab for atypical hemolytic uremic syndrome in pregnancy.
Atypical hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy often caused by mutations in complement genes. During pregnancy, disease outcome is poor both for mother and fetus. Since 2009, the humanized monoclonal antibody eculizumab has been successfully used in the treatment of atypical HUS in nonpregnant patients. A 26-year-old woman with a homozygous mutation in complement factor H developed a relapse of atypical HUS at 17 weeks of gestation in her first pregnancy. Because the disease remained active despite multiple plasma exchanges, eculizumab was started at 26 weeks of gestation. It was well tolerated and has led to remission and to the delivery of a healthy neonate. Eculizumab may be useful for the treatment of atypical HUS during pregnancy.


Predator-prey interactions between native brine shrimp Artemia parthenogenetica and the alien boatman Trichocorixa verticalis: influence of salinity, predator sex, and size, abundance and parasitic status of prey.
Trichocorixa verticalis (T. verticalis), native to North America and the Caribbean islands, is an invasive waterboatman species (Corixidae) in the southwest of the Iberian Peninsula. Previous studies in the native range have suggested that predation by T. verticalis can regulate the abundance of Anostracan and Cladoceran zooplankton in saline ecosystems, causing increases in phytoplankton through a trophic cascade. In this experimental study, we tested the predator-prey relationship between the native brine shrimp Artemia parthenogenetica, and T. verticalis from the Odiel salt ponds in SW Spain. In three experiments, we investigated (1) the effects of Artemia life stage (metanauplii, juveniles, and adults), (2) abundance (three, six, and 12 adult Artemia) and (3) parasitic status (Artemia infected with avian cestodes or uninfected) on predation rates by T. verticalis. We also considered how predation rates in all three experiments were influenced by the sex of T. verticalis and by different salinities (25 and 55 g l-1). Experiment 1 showed that predation rates were highest for metanauplii, possibly because their photophilic behavior makes them more prone to predation. In Experiment 2, we found that predation rate was higher for female T. verticalis and the higher salinity, although the strength of the sex effect varied between treatments. Experiment 3 showed that T. verticalis selectively predated adult Artemia infected with cestodes (red in color), as previously reported for predation by avian final hosts. Collectively, these results indicate that T. verticalis are important predators in their introduced range, and are likely to reduce the abundance of Artemia in more salt ponds as they expand their range, thus increasing phytoplankton abundance through trophic cascades.


First-trimester medical abortion service in Hong Kong.
Research on medical abortion has been conducted in Hong Kong since the 1990s. It was not until 2011 that the first-trimester medical abortion service was launched. Mifepristone was registered in Hong Kong in April 2014 and all institutions that are listed in the Gazette as a provider for legal abortion can purchase mifepristone from the local provider. This article aimed to share our 3-year experience of this service with the local medical community. Our current protocol is safe and effective, and advocates 200-mg mifepristone and 400-µg sublingual misoprostol 24 to 48 hours later, followed by a second dose of 400-µg sublingual misoprostol 4 hours later if the patient does not respond. The complete abortion rate is 97.0% and ongoing pregnancy rate is 0.4%. Some minor side-effects have been reported and include diarrhoea, fever, abdominal pain, and allergy. There have been no serious adverse events such as heavy bleeding requiring transfusion, anaphylactic reaction, septicaemia, or death.


Real-time detection of kinetic germination and heterogeneity of single Bacillus spores by laser tweezers Raman spectroscopy.
Germination is the process by which a dormant spore returns to its vegetative state when exposed to suitable conditions. We report on the real-time detection of kinetic germination and heterogeneity of single Bacillus thuringiensis spores in an aqueous solution by monitoring the calcium dipicolinate (CaDPA) biomarker with laser tweezers Raman spectroscopy (LTRS). A single B. thuringiensis spore was optically trapped in a focused laser beam, and its Raman spectra were recorded sequentially in time after exposure to a nutrient-rich medium, so that the CaDPA amount inside the trapped spore was monitored during the dynamic germination process. The CaDPA content in an individual spore was observed to remain almost constant in the first period and then decrease very rapidly due to its release into the medium (within approximately 2 min). The time-to-germination (t(germ)), defined as the time required for the CaDPA band intensity to decrease to the midpoint from its initial value, was found to be stochastic for individual spores with a typical value of approximately 30 min under the experimental conditions. The distribution of the time-to-germination was measured from a time lapse measurement of a population of spores. The results demonstrated that LTRS can be used to noninvasively detect the kinetic germination process at the single-cell level and explore cellular heterogeneity.


Atheroprotective nasal immunization with a heat shock protein 60 peptide from Porphyromonas gingivalis.
Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice. Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19. Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4+CD25+forkhead box P3 (FoxP3)+ human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4+CD25+FoxP3+ Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25- IL-17+ T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice. Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity.


Controlled reproducible alignment of cone targets and mitigation of preplasma in high intensity laser interactions.
The use of cone targets in high intensity laser-plasma experiments has been of recent interest because of their potential use in integrated fast ignition experiments. Simpler experiments provide a good avenue for understanding the underlying physics, however precise control of the alignment along with good pointing accuracy is of crucial importance. While on big laser facilities target alignment is done precisely with several microscopes, it is not always the case on smaller facilities. This can have a detrimental effect on the quality of the results. We have developed and characterized a method for accurate alignment of intense laser pulses into a cone target. This, along with optimal positioning of the focus compared to the tip, efficiently uses the shape of the target to microfocus the laser light and concentrates the hot electrons in the tip, and can mitigate preplasma issues.


Verb aspect, event structure, and coreferential processing.
We used an off-line story continuation task and an online ERP reading task to investigate coreferential processing following sentences that portrayed transfer-of-possession events as either ongoing or completed, using imperfective and perfective verb aspect (e.g., Amanda was shifting/shifted some poker chips to Scott). The story continuation task demonstrated that people were more likely to begin continuations with references to the Goal than to the Source, but that perfective aspect strengthened this bias. In the ERP task we probed expectations for Source and Goal referents by employing pronouns that matched one of the referents in gender. The ERP results were consistent with the biases revealed in the story continuation task and demonstrate that the difference in Goal bias for the two forms of aspect was manifested differently in the brain. These results provide novel behavioral and neurocognitive evidence that verb aspect influences the construction of situation models during language comprehension.


Identification of Head and Neck Cancer Subtypes Based on Human Papillomavirus Presence and E2F-Regulated Gene Expression.
Human papillomavirus (HPV) is present in a subset of head and neck squamous cell carcinomas (HNSCCs). The cell cycle regulatory Rb-E2F pathway is a major target of HPV and is perturbed by these viruses in cell culture and animal models, as well as in human tumors. In this study, we examined differences in the Rb-E2F pathway displayed by HPV-positive (HPV+) and HPV-negative (HPV-) HNSCC tumors. We created a computational approach that effectively categorizes gene expression as unchanged, downregulated, or upregulated by comparing the gene's mRNA levels in the tumor to the corresponding mRNA levels across normal tissue samples. Our findings suggest that there are three major HNSCC subtypes, defined by differences in the presence of HPV and in E2F-regulated gene expression. Most HPV+ HNSCC tumors show upregulation of E2F-regulated genes, which is consistent with inactivation of Rb by the virus-encoded E7 protein. In contrast, many HPV- HNSCCs show little or no change in the Rb-E2F pathway. However, we also identified a set of tumors that show alterations in the Rb-E2F pathway in the absence of HPV. Thus, one class of HPV- HNSCCs arise without significant alterations of the Rb-E2F pathway, while a second class of tumors appear to deregulate this pathway independently of the presence of HPV. IMPORTANCE Cancer is a complex disease that can be caused by a multitude of factors. HNSCC is complicated because some of these cancers are clearly associated with HPV, while others have no viral involvement. Determining the pathways that are commonly altered in both types of HNSCC, as well as those that are unique to viral and nonviral tumors, is important for a basic understanding of how these cancers arise and progress and critical to the development of targeted therapies. In this work, we show that all HPV-associated tumors have increased expression of E2F target genes, indicating that the tumor suppressor function of Rb is blocked. Importantly, Rb is also inhibited in a subset of nonviral tumors, suggesting that mutations present in these cancers mimic the action of the HPV E6 and E7 oncogenes.


Anticancer Platelet-Mimicking Nanovehicles.
A core-shell nanovehicle coated with a platelet membrane (PM) is developed for targeted and site-specific delivery of an extracellularly active drug and an intracellular functional small-molecular drug, leading to enhanced antitumor efficacy. This PM-coated nanovehicle can also effectively eliminate the circulating tumor cells in vivo and inhibit development of tumor metastasis.


Respiratory syncytial virus matrix protein induces lung epithelial cell cycle arrest through a p53 dependent pathway.
Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication.


Three new species of Pseudorhabdosynochus (Monogenea, Diplectanidae) from several species of Cephalopholis and Epinephelus (Perciformes, Serranidae) from Thailand.
Pseudorhabdosynochus suratthaniensis n. sp. is described from the gills of Cephalopholis argus; P. cephalopholi n. sp., from the gills of C. sonnerati; and P. samaesarnensis n. sp., from the gills of Epinephelus lanceolatus. These fish were all caught in the Gulf of Thailand. Pseudorhabdosynochus suratthaniensis n. sp. is distinguished from congeneric species by the structure of its sclerotized vagina, which has a wide sclerotized trumpet and a single large primary chamber, and by the number of rows of rodlets in each of its squamodiscs. Pseudorhabdosynochus cephalopholi n. sp. is also distinguished by the structure of its sclerotized vagina that, like the P. suratthaniensis n. sp., has a sclerotized trumpet, but it also has a long coiled or curved primary canal near its midlength, and a distal part with a primary chamber and a secondary chamber communicating with the primary chamber through a short secondary canal. In addition, P. cephalopholi n. sp. is distinguished by some sclerotized organs (ventral and dorsal hamuli, ventral bar, and quadriloculate organ) with different lengths, and by the number of rows of rodlets in each of its squamodiscs. Pseudorhabdosynochus samaesarnensis n. sp. is distinguished by its sclerotized vagina that has an anterior cup-shaped trumpet and a short straight or curved primary canal. For Thailand, these are the first species of Pseudorhabdosynochus described from species of Cephalopholis and the second species of Pseudorhabdosynochus described from Epinephelus.