MicroRNA-155 Implication in M1 Polarization and the Impact in Inflammatory Diseases.
Macrophages are known to have an impact in cytokine signaling in the myriad of organs in which they reside and are classically known to be either pro-inflammatory (M1), anti-inflammatory (M2). Different classes of signaling molecules influence these states, of which, microRNAs represent key modulators. These are short RNA species approximately 21 to 23 nucleotides long that generally act by binding to the 3' untranslated region of mRNAs, regulating their translation, and, thus, the quantity of protein they encode. From these species, microRNA-155 was observed to be of great importance for M1 polarization. Because of it's major implication in M1 polarization microRNA-155 was shown to be implicated in different inflammatory diseases. To name a few, microRNA-155 was shown to be modified in patients with asthma and to correlate with asthma symptoms in mouse model; it has been shown to modulate the activity of foam cells and influence the dimensions of the atherosclerotic plaque and it has also been shown to be of crucial influence in transducing the signal of LPS in septic shock. Because of this, the current review aims to offer an overview of the role of microRNA-155 in M1 polarization, the implication that this poses for the pathophysiology of inflammatory diseases and the potential therapeutic possibilities that this knowledge might bring. Currently, microRNA-155 has been used in clinical trials as a marker of inflammation, but the question remains if it's inhibition will be useful in inflammatory diseases, as other products might have a better cost/benefit ratio.


NREM sleep EEG slow waves in autistic and typically developing children: Morphological characteristics and scalp distribution.
Autism is a developmental disorder with a neurobiological aetiology. Studies of the autistic brain identified atypical developmental trajectories that may lead to an impaired capacity to modulate electroencephalogram activity during sleep. We assessed the topography and characteristics of non-rapid eye movement sleep electroencephalogram slow waves in 26 boys aged between 6 and 13 years old: 13 with an autism spectrum disorder and 13 typically developing. None of the participants was medicated, intellectually disabled, reported poor sleep, or suffered from medical co-morbidities. Results are derived from a second consecutive night of polysomnography in a sleep laboratory. Slow waves (0.3-4.0 Hz; >75 µV) were automatically detected on artefact-free sections of non-rapid eye movement sleep along the anteroposterior axis in frontal, central, parietal and occipital derivations. Slow wave density (number per minute), amplitude (µV), slope (µV s-1 ) and duration (s) were computed for the first four non-rapid eye movement periods. Slow wave characteristics comparisons between groups, derivations and non-rapid eye movement periods were assessed with three-way mixed ANOVAs. Slow wave density, amplitude, slope and duration were higher in anterior compared with most posterior derivations in both groups. Children with autism spectrum disorder showed lower differences in slow waves between recording sites along the anteroposterior axis than typically developing children. These group differences in the topography of slow wave characteristics were stable across the night. We propose that slow waves during non-rapid eye movement sleep could be an electrophysiological marker of the deviant cortical maturation in autism linked to an atypical functioning of thalamo-cortical networks.


A Longitudinal Assessment of the Home Literacy Environment and Early Language.
This longitudinal assessment concentrated on the relation between the Home Literacy Environment (HLE) and early language acquisition during infancy and toddlerhood. In Study 1, after controlling for SES, a broadly-defined HLE predicted language comprehension in 50 infants. In Study 2, 27 children and their primary caregivers returned for further analyses. Findings revealed that the HLE measured in infancy predicted language production in toddlerhood, and maternal redirecting behaviors measured in toddlerhood were negatively associated with expressive language. Results across both studies indicate the importance of a broadly-defined HLE (including joint attention and parent-child conversation) for language development. Taken together, these findings highlight the importance of the HLE in supporting both receptive and expressive vocabulary growth in the second and third years of life.


Tumor-induced disorder of iron metabolism in major organs: a new insight from chemical speciation of iron.
Objective To investigate the evolution of iron speciation in major organs of tumor-bearing mice and its role in cancer formation and cancer-associated complications. Methods The concentration and chemical speciation of iron in the spleen, liver, lung, kidney, heart, blood, muscle, and tumor tissue of healthy mice and tumor-bearing mice were studied by synchrotron radiation-based total reflection X-ray fluorescence spectrometry (SR-TXRF) coupled with X-ray absorption spectroscopy (XAS). Results The TXRF and XAS results showed that the iron content, especially the ferritin content, significantly decreased in the blood and spleen but significantly increased in the liver, lung, and muscle of mice after tumor implantation. The chemical speciation of iron in the tumor mainly comprised ferrous-sulfide-like iron and ferritin. Conclusion The tumors disturbed the iron metabolism in major organs, and the evolution of iron may be involved in iron deficiency anemia, cancer growth, and immunity. Additionally, iron speciation-based markers may be further developed as clinical indicators for cancer and cancer-associated complications.


Improving half-projected spin-contaminated wave functions by multi-configuration perturbation theory.
Allowing triplet components of individual geminals, spin-contaminated strongly orthogonal geminal wave functions may emerge, which can be ameliorated by spin-projection techniques. Of the latter, half-projection was previously shown to be useful, offering a compromise between the amount of remaining spin-contamination and the violation of size consistency generated by projection. This paper investigates how a half-projected spin-contaminated geminal wave function can be improved by multi-configuration perturbation theory to incorporate dynamical correlation effects.


Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review.
Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, and also detected in many plant species such as Abelmoschus manihot, Ribes nigrum, Rosa rugosa, Agrostis stolonifera, Apocynum venetum and Nelumbo nucifera. This compound exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects, etc. This review summarizes the quantification, original plant, chemical structure and property, structure-activity relationship, pharmacologic effect, pharmacokinetics, toxicity and clinical application of hyperoside, which will be significant for the exploitation for new drug and full utilization of this compound.


Growth and bacteriolytic activity of a soil amoeba, Hartmannella glebae.
A soil amoeba, Hartmannella glebae, could grow on a variety of gram-positive and gram-negative bacteria, although the rate of growth was faster in the presence of gram-negative bacteria. The amoeba, however, could not use yeasts, molds, or a green alga as a nutritional source. The extract prepared from amoebae grown in the presence of Aerobacter aerogenes and Alcaligenes faecalis could lyse intact cells and cell walls of many gram-positive bacteria at different rates. The spectrum of lytic activity was similar to that of egg-white lysozyme, with the exception that several species and strains of Bacillus, Micrococcus, and Staphylococcus were resistant to lysozyme and susceptible to the extract. The gram-negative bacteria tested were resistant.


Microbial invasion of the amniotic cavity in midtrimester pregnancies using molecular microbiology.
The objective of the study was to determine the frequency of microbial invasion of the amniotic cavity in the midtrimester of pregnancy in patients undergoing amniocentesis for clinical indications. This was a prospective investigation of the amniotic fluid of 344 asymptomatic women recruited in midpregnancy for the presence of microbial DNA. Amniotic samples obtained at the time of amniocentesis for genetic testing on women between 15 and 22 weeks of gestation were tested specifically for the presence of Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, and Mycoplasma genitalium as well as for other bacteria and fungi using broad-range polymerase chain reaction only. Pregnancy outcomes were reviewed independent of all molecular test results. Using broad-range polymerase chain reaction, the prevalence of microbial invasion of the amniotic cavity in women between 15 and 22 weeks of gestation was 0% (0 vs 344). Early preterm delivery occurred in only 4 women (1%); 1 delivered electively and 3 spontaneously. None were associated with Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, or Mycoplasma genitalium. In addition, broad range polymerase chain reaction did not reveal the presence of other bacterial or fungal microbes. Microbial invasion of the amniotic cavity in midtrimester gestations of low-risk pregnant women was not detected using molecular methods in 344 patients.


Phytofiltration of arsenic from drinking water using arsenic-hyperaccumulating ferns.
Arsenic contamination of drinking water poses serious health risks to millions of people worldwide. Current technologies used to clean arsenic-contaminated water have significant drawbacks, such as high cost and generation of large volumes of toxic waste. In this study, we investigated the potential of using recently identified arsenic-hyperaccumulating ferns to remove arsenic from drinking water. Hydroponically cultivated, two arsenic-hyperaccumulating fern species (Pteris vittata and Pteris cretica cv. Mayii) and a nonaccumulating fern species (Nephrolepis exaltata) were suspended in water containing 73As-labeled arsenic with initial arsenic concentrations ranging from 20 to 500 microg L(-1). The efficiency of arsenic phytofiltration by these fern species was determined by continuously monitoring the depletion of 73As-labeled arsenic concentration in the water. With an initial water arsenic concentration of 200 microg L(-1), P. vittata reduced the arsenic concentration by 98.6% to 2.8 microg L(-1) in 24 h. When the initial water arsenic was 20 microg L(-1), P. vittata reduced the arsenic concentration to 7.2 microg L(-1) in 6 h and to 0.4 microg L(-1) in 24 h. At similar plant ages, both P. vittata and P. cretica had similar arsenic phytofiltration efficiency and were able to rapidly remove arsenic from water to achieve arsenic levels below the new drinking water limit of 10 microg L(-1). However, N. exaltata failed to reduce water arsenic to achieve the limit under the same experimental conditions. The significantly higher efficiency of arsenic phytofiltration by arsenic-hyperaccumulating fern species is associated with their ability to rapidly translocate absorbed arsenic from roots to shoots. The nonaccumulating fern N. exaltata was unable to translocate the absorbed arsenic to the shoots. Our results demonstrate that the arsenic-phytofiltration technique may provide the basis for a solar-powered hydroponic technique that enables small-scale cleanup of arsenic-contaminated drinking water.


The operative evaluation of patients with cervical carcinoma by an extraperitoneal approach.
Seventy patients with cervical cancer who were not candidates for primary operative treatment underwent operative evaluation prior to radiation therapy. Thirty-one were explored through a transperitoneal approach and 39 through an extraperitoneal approach. The operative procedure consisted of bilateral pelvic and periaortic lymphadenectomy and exploratory laparotomy, with additional intraperitoneal biopsies taken as indicated by operative findings. Poor correlation was seen between operative findings, lymphangiography, and clinical staging. Radiation therapy was extended to include sites of biopsy proven metastases. The group of patients operated on through a transperitoneal approach experienced a 30% complication rate secondary to small bowel damage following radiation therapy, and 2 patients died as a result of complications. All patients with small bowel complications explored in this manner required surgical correction. The group of patients operated on through an extraperitoneal approach had a 2.5% morbidity secondary to small bowel complications, and there were not deaths or serious complications in these patients. No patients explored in this manner required subsequent operation for complications following radiation therapy.


Synergism between metformin and statins in modifying the risk of biochemical recurrence following radical prostatectomy in men with diabetes.
To determine the effect of statins and metformin in combination on biochemical recurrence (BCR) among diabetic men undergoing radical prostatectomy (RP). Diabetic men undergoing RP at our institution from January 1995 to March 2012 were retrospectively reviewed. Recipients of adjuvant radiation or hormonal therapy were excluded. Statin and/or metformin use was determined through review of electronic records. BCR-free survival was plotted using Kaplan-Meier analysis, and the effect of statins and metformin on BCR was assessed via a multivariate Cox proportional hazards model. Seven hundred and sixty-seven men met the inclusion criteria. Seventy-six (9.9%) were users of statins only, 56 (7.3%) were users of metformin only and 42 (5.5%) were dual users. Median follow-up time was 27 months. Dual users were less likely than nonusers or users of either medication alone to have a biopsy Gleason sum of 8-10 (P=0.033), and tended towards a lower rate of pathological T stage of pT3 or higher (P=0.064). Dual users had the highest 2-year and 5-year BCR-free survival, although this was not statistically significant (P=0.205). On multivariate regression, neither statin nor metformin use alone was significantly associated with BCR-free survival. However, their interaction led to a significantly lower BCR risk than would be expected from each medication's independent effects (hazard ratio=0.2; P=0.037). The combination of statins and metformin in men undergoing RP for prostate cancer (PCa) may be associated with a lower BCR risk than would be predicted based on the independent effects of both medications. A synergism between these two agents is biologically plausible based on our current understanding of their diverse molecular pathways of action. The results of future clinical trials involving the use of either medication in men with PCa should be carefully assessed for confirmatory evidence of such a relationship.


COVID-19 Social Restrictions' Impact on the Health-Related Physical Fitness of the Police Cadets.
We aim to examine the changes in health-related physical fitness components, before and after COVID-19 social restrictions, in Police Academy cadets by age, sex, and physical activity (PA) level. A longitudinal analysis of 156 cadets (29.5% women) aged 25.4 ± 5.3 years old was conducted. All variables were collected before and after the lockdown period (13 weeks). PA levels were assessed with a self-reported questionnaire. Health-related physical fitness components were assessed based on the standardized protocols of morphological evaluation, speed, agility, strength, flexibility, and aerobic capacity tests. Despite the high correlations between pre- and post-pandemic social restrictions, we found significantly higher values for anthropometric indicators and lower physical fitness levels in post-pandemic restrictions, except for lower-body strength. When stratifying the sample by sex, age, and PA categories, the results indicate that the COVID-19 lockdown tends to differently impact anthropometric indicators and the physical fitness of the cadets, according to their sex, age, and PA categories. Our findings show that our sample reduces several health-related physical fitness components due to the social lockdown, with emphasis on cardiorespiratory fitness in men and upper-limb strength in women, highlighting the need to create effective strategies to keep police officers active during situations of less physical work.


Selected clinical aspects of acute intoxication with baclofen.
Baclofen is a lipophilic analogue of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system. The aim of the study was to evaluate some clinical aspects of acute intoxication with baclofen. Fifty two patients (37 females and 15 males) aged from 14 to 58 (mean 30.6 +/- 13.7) years were analyzed. Patients were admitted to the Clinic of Internal Diseases and Acute Poisonings Medical University of Gdańsk and the Centre of Acute Poisonings of Praski Hospital in Warszawa during the years 1996-2004 because of suicidal intoxication with baclofen. The doses of baclofen varied from 100 to 1500 (mean 444.8 +/- 317.8) mg. There were twenty eight patients (53.8%) in deep coma (III and IV grade of Matthew scale). Acute respiratory failure which required mechanical ventilation was observed in 18 cases (34.6%). Cardiac abnormalities included bradycardia (36.5%), hypertension (32.7%) and hypotension (3.8%). Toxic psychoses were observed in 6 cases (11.5%). The dosage of baclofen in patients with acute respiratory failure (ARF) was significantly higher than in patients without ARF. Treatment of patients with acute baclofen intoxication should take place in hospitals appropriately equipped which can provide artificial respiration.


The Peripheral NK Cell Repertoire after Kidney Transplantation is Modulated by Different Immunosuppressive Drugs.
In the context of kidney transplantation, little is known about the involvement of natural killer (NK) cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e., calcineurin-inhibitors like Cyclosporin A vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56(dim) NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56(dim) NK cells was observed with significant differences between Cyclosporin A- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR, and increased CD94/NKG2A expression in CD56(dim) NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with peripheral blood mononuclear cells of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and interferon-γ-production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus, NK cells can serve as sensors for immunosuppression and may be utilized for future strategies of an individualized adjustment of immunosuppression.


Practical approach to linear endoscopic ultrasound examination of the rectum and anal canal.
Standard endosonographic examination of the rectal area is usually performed with radial endoscopic ultrasound (EUS). However, in recent years, widespread availability of linear EUS for assessing various anatomical regions in the gastrointestinal tract has facilitated its use in the assessment of anorectal disorders. Currently, many rectal and anal diseases, including perianal abscesses, fistulae, polyps, and neoplastic lesions, can be well-visualized and evaluated with linear EUS. The aim of this review is to shed light on the anatomy and systematic examination of the anorectal region with linear EUS and clinical implications for different anorectal pathologies.


The Effectiveness of Intravenous Dexmedetomidine on Perioperative Hemodynamics, Analgesic Requirement, and Side Effects Profile in Patients Undergoing Laparoscopic Surgery Under General Anesthesia.
There is an upward surge in the use of laparoscopic surgeries due to various advantages when compared to open surgeries. Major advantages are, due to small incisions which are cosmetically acceptable and most of them are now daycare procedures. Problem of economic burden and hospital bed occupancy has been overcome with laparoscopic surgeries. All these advantages are not free from disadvantages, as hemodynamic changes such as hypertension; tachycardia and other surgical-related complications are commonly observed intraoperatively. Dexmedetomidine is one of the α2 agonist drugs which acts at both supraspinal and spinal level and modulate the transmission of nociceptive signals in the central nervous system. The basic effect of dexmedetomidine on the cardiovascular system is to decrease the heart rate and systemic vascular resistance with additional feature of opioid sparing effect. This drug has become an ideal adjuvant during general anesthesia, especially when stress is expected. Hence, the drug was studied in laparoscopic surgeries. (a) To study the effect of dexmedetomidine on hemodynamic parameters during perioperative period in patients undergoing laparoscopic surgery. (b) To study the postoperative sedation score and analgesic requirement. (c) To study the side effect profile of dexmedetomidine. Randomized double blind controlled trial. After obtaining the Institutional Ethical Clearance, the study was conducted. Forty patients of American Society of Anesthesiologists Class I and II were enrolled in this randomized study. The patients were randomly divided into two groups; group normal saline (NS) and group dexmedetomidine. Patient received either NS or dexmedetomidine in group NS and group dexmedetomidine, respectively, depending upon the allocation. The infusion rate was adjusted according to; loading dose (1 μg/kg) over 10 min and maintenance dose (0.5 μg/kg/h) and perioperative hemodynamics was recorded. Routine general anesthesia was administered in all the patients with conventional technique without deviating from institutional protocols. Postoperatively, Rasmsay sedation score, time taken for request of first analgesic dose, and side effects if any were recorded. The categorical factors are represented by the number and frequency (%) of cases. The continuous variables are represented by measures of central frequency and standard deviation. The statistical analysis was done by using unpaired t-test and Chi-square. P < 0.05 was considered statistically significant. Significant hemodynamic changes are observed in NS group during laryngoscopy, intubation, during pneumoperitoneum formation, and during extubation. Hemodynamic stress response in dexmedetomidine group was significantly attenuated. Analgesic requirement during postoperative 24 h were much less in dexmedetomidine group when compared to NS group. No significant side effects were noted except for bradycardia; which was observed in two cases of dexmedetomidine group. Dexmedetomidine infusion in the dose of 1 μg/kg body weight as bolus over 10 min and 0.5 μg/kg/h intraoperatively as maintenance dose controlled the hemodynamic stress response in patients undergoing laparoscopic surgery. Use of dexmedetomidine extends the pain free period postoperatively and thereby reducing total analgesic requirement. Thus, dexmedetomidine can be utilized as an ideal anesthetic adjuvant during laparoscopic surgeries.


Review of the genus Myrmozercon Berlese (Acari: Laelapidae), with description of two new species from Iran.
This paper reports on three species of mites of the genus Myrmozercon Berlese, 1902 associated with ants in Iran--Myrmozercon crinitus Joharchi sp. nov. from Pheidole pallidula (Nylander), Myrmozercon michaeli Joharchi sp. nov. from Messor sp. and Myrmozercon tauricus Trach & Khaustov from Crematogaster schmidti (Mayr) in the bark of grape vines. Myrmozercon is redefined, the distribution, and the host-specificity and host range of its constituent species are discussed. A key to species of Myrmozercon occurring in the Palaearctic Region is presented.


MEMD-enhanced multivariate fuzzy entropy for the evaluation of complexity in biomedical signals.
Multivariate multiscale entropy (mvMSE) has been proposed as a combination of the coarse-graining process and multivariate sample entropy (mvSE) to quantify the irregularity of multivariate signals. However, both the coarse-graining process and mvSE may not be reliable for short signals. Although the coarse-graining process can be replaced with multivariate empirical mode decomposition (MEMD), the relative instability of mvSE for short signals remains a problem. Here, we address this issue by proposing the multivariate fuzzy entropy (mvFE) with a new fuzzy membership function. The results using white Gaussian noise show that the mvFE leads to more reliable and stable results, especially for short signals, in comparison with mvSE. Accordingly, we propose MEMD-enhanced mvFE to quantify the complexity of signals. The characteristics of brain regions influenced by partial epilepsy are investigated by focal and non-focal electroencephalogram (EEG) time series. In this sense, the proposed MEMD-enhanced mvFE and mvSE are employed to discriminate focal EEG signals from non-focal ones. The results demonstrate the MEMD-enhanced mvFE values have a smaller coefficient of variation in comparison with those obtained by the MEMD-enhanced mvSE, even for long signals. The results also show that the MEMD-enhanced mvFE has better performance to quantify focal and non-focal signals compared with multivariate multiscale permutation entropy.


Impact of periodontal status on oral health-related quality of life among police personnel in Virajpet, India.
The aim of the present study was to determine the association between oral health-related quality of life (OHRQoL) and periodontal status among police personnel in Virajpet, India. Police personnel were randomly selected from the 296 police staff working in Virajpet, India. A self-administered questionnaire was used to collect information on their demographics and dental visit behavior, and to determine their OHRQoL. The community periodontal index (CPI) and loss of attachment were used to assess periodontal status. All 72 invited participants joined this study. The majority (n = 133) had good OHRQoL. For those with a good OHRQoL, 74 had CPI = 0, 25 had CPI = 1, 20 had CPI = 2, and 14 had CPI ≥ 3. For those who had an average or poor OHRQoL (n = 37), 19 had CPI = 0, one had CPI = 1, eight had CPI = 2, and nine had CPI ≥ 3. There was a statistically-significant association between OHRQoL and CPI (P < 0.003). Most participants with good OHRQoL (127/133), but only less than half with an average or poor OHRQoL (22/37), had no loss of periodontal attachment (P < 0.0001). In the present study, there was an association between OHRQoL and periodontal status among police personnel in Virajpet, Coorg.


Phenotypic and genotypic antimicrobial resistance in Escherichia coli strains isolated from household dogs in Chile.
Antimicrobial resistance (AMR) is a major threat to animal and public health worldwide; consequently, several AMR surveillances programs have been implemented internationally in both human and veterinary medicine, including indicator bacteria such as Escherichia coli. However, companion animals are not typically included in these surveillance programs. Nevertheless, there have been reports of increasing levels of antimicrobial resistance in E. coli strains isolated from dogs worldwide. In Chile, there is limited information available on AMR in E. coli isolated from companion animals, which prevents the establishment of objective prevention and control measures. For this reason, the aim of this study was to characterize the phenotypic and genotypic AMR of E. coli strains isolated from healthy household dogs in Chile. For this purpose, a multi-stage sampling was carried out in the Metropolitan Region of Chile, obtaining samples from 600 healthy dogs. These samples were processed using traditional bacteriology and molecular techniques to isolate E. coli strains. We assessed the minimal inhibitory concentration of 17 antimicrobials and conducted a search of six antimicrobial resistance genes, as well as class 1 and 2 integrons, in the isolated strains. Two-hundred and twenty-four strains of E. coli were recovered, and 96.9% (n = 217) showed resistance to at least one drug and only 3.1% (n = 7) were susceptible to all analyzed antimicrobials. Most strains were resistant to cefalexin (91.5%, n = 205, 1st-generation cephalosporin), followed by ampicillin (68.3%, n = 153) and cefpodoxime (31.3%, n = 70, 3rd-generation cephalosporin). Moreover, 24.1% (n = 54) tested positive for extended-spectrum-β-lactamases and 34.4% (n = 77) were multidrug resistant. As for the AMR genes, the most detected was qnrB (28.1%, n = 63), followed by blaCTX-M (22.3%, n = 50), and blaTEM-1 (19.6%, n = 44). Additionally, 16.1% (n = 36) harbored class 1 integrons. Our study shows that E. coli strains isolated from healthy household dogs exhibit resistance to several relevant drugs and also antimicrobial resistance genes considered critical for human health. These results can be used as a starting point for the prevention and control of antimicrobial resistance from companion animals. This background should be considered when formulating future resistance surveillance programs or control plans in which companion animals must be included.


Demographic and clinical characteristics as predictors of length of hospitalization and readmission.
The present study investigated demographic and clinical characteristics of psychiatric patients in relation to the two criterion variables of length of hospitalization and readmission within 3 months of discharge. Stepwise multiple regression analysis identified five variables as the optimal set of predictors for length of hospitalization: age, history of commitment, number of prior psychiatric hospitalizations, recent employment history, and past history of suicidal behavior (R = .451). Regression analysis also identified six variables as the optimal set of predictors for readmission within 3 months of discharge: type of discharge, number of prior psychiatric hospitalizations, race, suicide attempt within 1 month prior to admission, subjective report of depression upon admission, and occupational level (R = .452). Implications of the findings for identifying short-term treatment candidates and factors related to readmission are discussed.


An algorithm to increase speech intelligibility for hearing-impaired listeners in novel segments of the same noise type.
Machine learning algorithms to segregate speech from background noise hold considerable promise for alleviating limitations associated with hearing impairment. One of the most important considerations for implementing these algorithms into devices such as hearing aids and cochlear implants involves their ability to generalize to conditions not employed during the training stage. A major challenge involves the generalization to novel noise segments. In the current study, sentences were segregated from multi-talker babble and from cafeteria noise using an algorithm that employs deep neural networks to estimate the ideal ratio mask. Importantly, the algorithm was trained on segments of noise and tested using entirely novel segments of the same nonstationary noise type. Substantial sentence-intelligibility benefit was observed for hearing-impaired listeners in both noise types, despite the use of unseen noise segments during the test stage. Interestingly, normal-hearing listeners displayed benefit in babble but not in cafeteria noise. This result highlights the importance of evaluating these algorithms not only in human subjects, but in members of the actual target population.


Competition between linker histones and HMG1 for binding to four-way junction DNA: implications for transcription.
Both lysine-rich histones and high mobility group proteins 1 and 2 bind to linker DNA in chromatin. While the members of the histone H1 class are considered general repressors of transcription, HMG1/2 are viewed as activators. Using stable four-way junction DNA as a model for cross-overs of linker DNA at the entry and exit to nucleosomes, we show that HMG1 can compete efficiently with H1 for binding to four-way junctions. In contrast, the erythrocyte-specific histone H5 seems to be refractory to displacement by HMG1. The results suggest that replacement of histone H1 by HMG1 may be part of the transcriptional activation by HMG1.


Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.
Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naïve macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 - 4Hz); theta: [4 - 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.


Morphological and allozymic variation in Hynobius boulengeri and H. stejnegeri (Amphibia: Urodela: Hynobiidae).
We studied morphological and allozymic variation in populations of Japanese salamanders, Hynobius boulengeri and H. stejnegeri. Adult H. boulengeri showed sexual dimorphism, and juveniles differed greatly from adults in many morphological characters. From the results of multivariate analyses of morphological characters, the populations were divided into four groups: (I) H. boulengeri from Honshu, (II) H. boulengeri from Shikoku, (III) H. boulengeri from the Sobo-Katamuki Mountains of Kyushu and H. stejnegeri, and (IV) H. boulengeri from the Amakusa Islands and the Osumi Peninsula. Phenotypic relationships among the four groups were identical to relationships clarified by allozymic analyses, except for group IV, which was included in group III in the allozyme tree. Some morphometric characters were significantly correlated with environmental variables. We consider H. stejnegeri to be a valid species based on its unique color pattern, morphometric characters, and allelic composition, even though it was nested within group III of H. boulengeri by both morphological and allozymic analyses. We propose that group I from Honshu and group II from Shikoku should be treated as H. boulengeri sensu stricto and H. hirosei, respectively. Resolving the taxonomic status of the remaining populations of groups III and IV from Kyushu requires further study.


von Kármán-Howarth relationship for helical magnetohydrodynamic flows.
We derive an exact equation for homogeneous isotropic magnetohydrodynamic (MHD) turbulent flows with nonzero helicity; this result is of the same nature as the classical von Kármán-Howarth (VKH-HM) formulation for the kinetic energy of turbulent fluids. Helical MHD is relevant to the astrophysical flows such as in the solar corona, or the interstellar medium, and in the dynamo problem. The derivation involves the new writing of the general form of tensors for that case, for either vectors or (pseudo)axial vectors. It is shown that, for general third-order tensors, four generating functions are needed when taking into account the nonmirror invariance of helical fluids, instead of two as in the fully isotropic case. The new equation obtained, denoted by VKH-HM, links the dissipation of magnetic helicity to the third-order correlations involving combinations of the components of the velocity, the magnetic field, and the magnetic potential. Finally, in the long-time and nonresistive limit, this relationship leads to a linear scaling with separation of the third-order tensor, correlating the two normal components of the electromotive force and of the magnetic potential.


A cytotoxic monoclonal antibody to colon adenocarcinoma.
We have produced a monoclonal antibody CCOL1 that is cytotoxic at a titer of 1:20,000 using human sera as a complement source. CCOL1 reacts to the immunizing colon carcinoma line as well as to one other colon carcinoma line. However, it does not react with another colon adenocarcinoma line or with 28 other cultured tumor cells. It is noncytotoxic to lymphocytes, monocytes, granulocytes, RBC, and platelets. When tested by enzyme-linked immunosorbent assay against the normal cell membranes, it did not react to colon, lung, kidney cortex, heart, pancreas, liver, stomach, intestine, or kidney medulla but was strongly positive to the cell membrane of the colon adenocarcinoma line. The antibody reacted with 4 colon cancer tissue sections by immunoperoxidase. Control tissue sections of skin, spleen, kidney, brain, and uterus were negative. CCOL1 showed slight staining of epithelial cells in the tissue sections of normal lung, esophagus, colon, pancreas, and stomach. From preliminary studies, the antigen appears to be a glycoprotein, since it was highly sensitive to Pronase and sodium periodate.


Management of Non-Reconstructable Critical Limb Ischemia.
At least 15% of patients with critical limb ischemia are not candidates for standard revascularization. In this day and age, with new techniques-including retrograde access to the foot-and numerous angioplasty and atherectomy techniques available, the critical limb ischemia patient can still be faced without options. Distal bypass surgery may still remain the gold standard, and likely permits the patient to have the best options for healing, but carries significant comorbidities after undergoing the procedure. There are patients who do not have targets of interest in their foot for arterial revascularization and there are patients who have very poor conduit or are very poor candidates due to their medical comorbidities. Guidelines as to who should and should not undergo surgery-or even percutaneous revascularization-are starting to become more widely accepted. We are starting to see the tide change and there is interest in this cohort of patients. There are patients with no distal target that may benefit from an arteriovenous bypass, which is regaining popularity and can be done completely endovascularly. The patient that may be a very poor candidate for intervention may benefit from arterial counterpulsation therapy and/or topical oxygen therapy (which are commercially available). They may also benefit from placental stem cell injection, which is undergoing Phase II trial assessment. We will review the current literature as it surrounds these potential therapeutic interventions for patients with significant lower extremity ischemia who do not have standard revascularization options.


Changes in lectin-binding pattern in the digestive tract of Xenopus laevis during metamorphosis. I. Gastric region.
The distribution of structural and secretory glycoconjugates in the gastric region of metamorphosing Xenopus laevis was studied by the avidin-biotin-peroxidase (ABC) histochemical staining method using seven lectins (concanavalin A, Con A; Dolichos biflorus agglutinin, DBA; peanut agglutinin, PNA; Ricinus communis agglutinin I, RCA-I; soybean agglutinin, SBA; Ulex europeus agglutinin I, UEA-I; and wheat germ agglutinin, WGA). Throughout the larval period to stage 60, the epithelium consisting of surface cells and gland cells was stained in various patterns with all lectins examined, whereas the thin layer of connective tissue was positive only for RCA-I. At the beginning of metamorphic climax, the connective tissue became stained with Con A, SBA, and WGA, and its staining pattern varied with different lectins. The region just beneath the surface cells was strongly stained only with RCA-I. With the progression of development, both the epithelium and the connective tissue gradually changed their staining patterns. The surface cells, the gland cells, and the connective tissue conspicuously changed their staining patterns, respectively, for Con A and WGA; for Con A, PNA, RCA-I, SBA, and WGA; and for Con A, RCA-I, and WGA. At the completion of metamorphosis (stage 66), mucous neck cells became clearly identifiable in the epithelium, and their cytoplasm was strongly stained with DBA, PNA, RCA-I, and SBA. These results indicate that lectin histochemistry can provide good criteria for distinguishing among three epithelial cell types, namely, surface cells, gland cells, and mucous neck cells, and between adult and larval cells of each type.


Iatrogenic superior mesenteric arteriovenous fistula. Report of a case and review of the literature.
Bowel resection can result in the formation of an arteriovenous fistula at the point of intersection of the feeding vessels. Iatrogenic arteriovenous fistula of the superior mesenteric vessels is rare, with only 11 cases reported in the English language literature. We report a case after small bowel resection, which was done because of adhesions from a laparoscopic sterilization. An anatomic classification of the fistulas into H and U types is suggested, with its significance for management. A review of the literature is included.


Unbuckling the Bible Belt: A State-Level Analysis of Religious Factors and Google Searches for Porn.
While the link between individual religious characteristics and pornography consumption is well established, relatively little research has considered how the wider religious context may influence pornography use. Exceptions in the literature to date have relied on relatively broad, subjective measures of religious commitment, largely ignoring issues of religious belonging, belief, or practice. This study moves the conversation forward by examining how a variety of state-level religious factors predict Google searches for the term porn, net of relevant sociodemog raphic and ideological controls. Our multivariate findings indicate that higher percentages of Evangelical Protestants, theists, and biblical literalists in a state predict higher frequencies of searching for porn, as do higher church attendance rates. Conversely, higher percentages of religiously unaffiliated persons in a state predict lower frequencies of searching for porn. Higher percentages of total religious adherents, Catholics, or mainline Protestants in a state are unrelated to searching for porn with controls in place. Contrary to recent research, our analyses also show that higher percentages of political conservatives in a state predicted lower frequencies of porn searches. Our findings support theories that more salient, traditional religious influences in a state may influence residents-whether religious or not-toward more covert sexual experiences.


Kaliuretic response to potassium loading in amiloride-treated dogs.
To assess whether an intact mechanism of sodium transport in the distal nephron is a prerequisite for the development of a kaliuresis in response to an acute potassium load (0.4 M KCl, 1 ml/min), the effects of a simultaneous infusion of KCl and amiloride (1 mg/kg/h) were evaluated in anesthetized dogs. A major reduction in potassium excretion mainly due to a sharp decrease in urine K+ concentration to one tenth of control levels was found after amiloride. The simultaneous infusion of KCl and amiloride resulted in a rapid and major increase in kaliuresis that was accounted for mostly by the rise in urine K+ concentration. The increased kaliuresis after the acute potassium infusion was of similar magnitude when expressed as percent value of control to that previously reported in dogs not receiving amiloride; the absolute rates of K+ excretion, however, were only 2.7 and 7.3% (before and after KCl infusion, respectively) of the values in dogs not receiving amiloride. Our observations suggest that potassium infusion in the intact dog increases kaliuresis primarily as a result of a more favorable chemical gradient of this cation between blood and/or distal tubular cells and urine. Yet, when a chemical gradient is the only driving force of potassium secretion, as was the case in our amiloride-treated dogs, the absolute rate of kaliuresis is very modest. The presence of an unimpaired electrical profile and sodium transport mechanisms in the distal nephron, although not critical for the development of kaliuresis in response to a K+ load, accounts for a severalfold rise in renal potassium excretion above basal levels.


[Effect of oral contraceptives on the proliferative activity of breast cancer].
In 471 breast cancer patients the possible influence of an antecedent oral contraceptive (OC) use on proliferative activity (PCNA-expression) of mammary carcinomas was investigated. PCNA-expression (Proliferating Cell Nuclear Antigen) was immunohistochemically assessed using formalin-fixed, paraffin-embedded tissue. PCNA-expression discriminated tumors of low (< 20%) and increased (> or = 20%) proliferative fractions. 297 (63%) patients had ever used OCs and 202 (43%) of them were long-term users (> or = 49 months). Age adjusted proliferative fractions showed no statistically significant differences dependent on duration of OC use (never, 1-48 months, > or = 49 months), despite a slightly higher frequency of tumors with an increased PCNA-expression in ever users of OCs (p = 0.125).


Sonographic analysis of gallbladder findings in Salmonella enteric fever.
The purpose of this study was to analyze gallbladder sonographic findings associated with Salmonella typhi enteric fever. Sixty-two patients with culture positive Salmonella enteric fever were analyzed with serial sonography. The following gallbladder sonographic findings were noted: globular gallbladder distention (33 of 62 patients, 530%), positive sonographic Murphy sign (25 patients, 40%), pericholecystic edema or fluid (25 patients, 40%), gallbladder wall thickening > 4 mm (21 patients, 34%), low-level nonshadowing intraluminal echoes or sludge (nine patients, 15%), intramural linear sonolucency or striation (eight patients, 13%), and mucosal irregularity or sloughed membrane (four patients, 6%). Using the sonographic findings a gallbladder score was devised to assess the severity of gallbladder changes, and the score was correlated with the following clinical parameters--duration of fever, multidrug resistance, and clinical outcome. An abnormal gallbladder score was noted in 37 patients (60%), and multidrug resistance was noted in 35 of these patients (95%). The gallbladder scores showed a strong positive correlation with the duration of fever and the frequency of multidrug resistance. All 62 patients were treated with intensive antibiotic therapy without any deaths.


Differential scanning calorimetry study of reversible, partial unfolding transitions in dodecameric glutamine synthetase from Escherichia coli.
Partial unfolding of dodecameric glutamine synthetase (GS) from Escherichia coli has been studied by differential scanning calorimetry (DSC). A single endotherm (tm = 51.6 +/- 0.1 degrees C and delta Hcal = 211 +/- 4 kcal/mol of enzyme) was observed in DSC experiments with Mn.GS in the presence of 1.0 mM free Mn2+ and 100 mM KCl at pH 7. The dodecameric structure of Mn.GS was retained throughout heating cycles, and thermal transitions were reversible as shown by rescans [with 6-18 mg of GS (Mr 622,000) from 15 to 68 degrees C at 20-60 degrees C/h] and by greater than 93% recovery of activity. A cooperative ratio delta Hcal/delta HvH of 1.6 +/- 0.1 and deconvolution analysis show two cooperative units (two-state transitions): t1 = 50.4 and t2 = 51.7 degrees C; the ratio of the relative sizes of thermally labile domains is approximately 1:2 as judged by delta H2/delta H1 approximately equal to 2. However, the thermally induced overall enthalpy change (0.34 cal/g) for GS dodecamer is only 5-10% of that for thermal unfolding of small globular proteins at 50 degrees C. The t1 and t2 values from deconvolutions of DSC data agree with t0.5 values previously calculated from spectral measurements of temperature-induced exposures of approximately 0.7 of 2 Trp and approximately 2 of 17 Tyr per subunit, respectively [Shrake et al. (1989) Biochemistry 28, 6281-6294], over a 14 degrees C temperature range using both stabilizing and destabilizing conditions for Mn.GS.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of Serum Perampanel Concentration on Sporadic Amyotrophic Lateral Sclerosis Progression.
To clarify the effect of perampanel (PER) on sporadic amyotrophic lateral sclerosis (sALS) progression, the relationship between the changes in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores and serum PER concentrations was investigated. 12 patients with sALS from our hospital who agreed to participate and completed the PER for sALS randomized phase 2 study were included. After completing the study, we retrospectively obtained serum PER concentration data from the patients. Based on their mean PER concentrations, we divided the patients who had been taking PER into two groups: four patients with a mean PER concentration of ≥400 ng/mL were assigned to the H group, and three with a mean PER concentration of <400 ng/mL were assigned to the L group. The control group consisted of five patients who had been taking a placebo. We obtained the ALSFRS-R scores of each patient at 36 and 48 weeks after randomization. The differences in ALSFRS-R scores at baseline (0 weeks) and each subsequent week were used in the analysis. At 48 weeks, there were no differences in the degree of deterioration of the bulbar, upper and lower limb, and respiratory ALSFRS-R subscores and total ALSFRS-R score. However, at 36 weeks, the bulbar subscore was significantly lower in the H group than in the control group (p=0.032). Because high PER concentrations may exacerbate bulbar symptoms in patients with sALS, serum PER measurements may be beneficial when patients with sALS are taking PER.


OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer.
A Ser326Cys amino acid variant encoded by OGG1 that removes the highly mutagenic 8-oxo-7,8-dihydroguanine adducts resulting from the oxidative damage produced by reactive oxygen species, has been suggested to reduce activity of the enzyme and result in an increase in G:C --> T:A transversions. Carriers homozygous for the Cys326 variant have been associated with increased risk in some cancers. In this study, we tested the association of this polymorphism with epithelial ovarian cancer (EOC) (n=91 cases) in comparison with women unaffected by the disease (n=57). Although the genotype encoding the homozygous Cys326 variant was found more often in cases (11%) than controls (9%), this was not statistically significant (p=0.297). As OGG1 at chromosome band 3p25.3 overlaps a region exhibiting allelic imbalance (AI) in EOC, we also examined the frequency of AI of the OGG1 locus and its association with somatic mutations in the TP53 tumor suppressor gene, which is frequently mutated in EOC. The frequency of AI and TP53 mutations in EOC was 32 and 37%, respectively. Although the proportion of EOC cases harboring the genotype homozygous for Cys326 was greater in TP53 mutation-positive cases (5 of 34, 15%) than mutation-negative cases (5 of 57, 9%), the distribution of genotypes was not significantly different (p=0.289). Four of the six heterozygous Ser326/Cys326 samples exhibiting AI, displayed loss of the Ser326 variant. About 16% of samples exhibited both AI of the OGG1 locus and a TP53 mutation. Proportionately more EOC samples harbored a mutation in the group of samples exhibiting AI (15 of 29, 52%) in comparison to the group of samples with no AI (19 of 62, 31%) (p=0.036). Although the OGG1 Cys326 variant appears to play a minor role in conferring increased risk of ovarian cancer, the observed AI of the OGG1 locus in association with TP53 somatic mutations warrants further investigation in this disease.


Thymidine phosphorylase is regulated by tamoxifen in T47D breast cancer cell line.
Thymidine phosphorylase (TP) has diverse functions within cells, including increasing the sensitivity of cancer cells to cytotoxic drugs including 5-fluorouracil (5-FU) and methotrexate. However, the regulators of TP still remains largely unknown. In this study, we examined whether tamoxifen has specific effects on TP expression in the T47D breast cancer cell line. We studied the TP expression in the T47D cell line before and after tamoxifen treatment using Western blot analysis and ELISA. We found that TP expression is significantly up-regulated in tamoxifen-treated cells compared with control. Our findings suggest that tamoxifen may increase chemotherapy sensitivity through TP up-regulation for treatment regimens including doxifluridine, capecitabine, and/or methotrexate.


Sleep disturbance and neurocognitive function during the recovery from a sport-related concussion in adolescents.
Sleep disturbances are a hallmark sign after a sport-related concussion (SRC). Poor sleep has been shown to adversely affect baseline neurocognitive test scores, but it is not comprehensively understood how neurocognitive function is affected by disrupted sleep during recovery from a concussion. To identify the correlation between adolescent athletes' neurocognitive function and their self-reported sleep quantity and sleep disturbance symptoms during recovery from SRC. Cross-sectional study; Level of evidence, 3. Immediate Post-Concussion Assessment and Cognition Testing (ImPACT) data were retrospectively collected for 545 adolescent athletes treated for SRC at a sports medicine concussion clinic. Patients were stratified into groups based on 2 criteria: self-reported sleep duration and self-reported sleep disturbance symptoms during postinjury ImPACT testing. Sleep duration was classified as short (<7 hours), intermediate (7-9 hours), and long (>9 hours). Sleep disturbance symptoms were self-reported as part of the Post-Concussion Symptom Scale (PCSS) as either sleeping less than normal, sleeping more than normal, or having trouble falling asleep. One-way analyses of variance were conducted to examine the effects that sleep duration as well as self-reported sleep disturbance symptoms had on composite scores. A total of 1067 ImPACT tests were analyzed: test 1, 545; test 2, 380; and test 3, 142. Sleeping fewer than 7 hours the night before testing correlated with higher PCSS scores (P < .001), whereas sleeping longer than 9 hours correlated with worse visual memory (P = .01), visual motor speed (P <.001), and reaction time (P = .04) composite scores. With regard to self-reported sleep disturbance symptoms, patients demonstrated worse composite scores during ImPACT testing when they self-reported sleeping more than normal (ImPACT test 1: verbal memory, P < .001; visual motor speed, P = .05; reaction time, P = .01; ImPACT test 2: verbal memory, P < .001; visual memory, P < .001; visual motor speed, P < .001; reaction time, P = .01). Adolescent patients recovering from SRC demonstrated higher (worse) PCSS scores (P < .001) when they sensed that their sleep had been disrupted. Adolescent patients who perceive that their sleep is somehow disrupted after SRC may report a greater number of concussion symptoms during their recovery. In addition, the study results suggest that sleeping more than normal may identify an individual who continues to be actively recovering from concussion, given the correlation between lower neurocognitive function and this self-reported symptom.


A Fluorescent-Labeled Phosphono Bisbenzguanidine As an Activity-Based Probe for Matriptase.
Activity-based probes are compounds that exclusively form covalent bonds with active enzymes. They can be utilized to profile enzyme activities in vivo, to identify target enzymes and to characterize their function. The design of a new activity-based probe for matriptase, a member of the type II transmembrane serine proteases, is based on linker-connected bis-benzguanidines. An amino acid, introduced as linker, bears the coumarin fluorophore. Moreover, an incorporated phosphonate allows for a covalent interaction with the active-site serine. The resulting irreversible mode of action was demonstrated, leading to enzyme inactivation and, simultaneously, to a fluorescence labeling of matriptase. The ten-step synthetic approach to a coumarin-labeled bis-benzguanidine and its evaluation as activity-based probe for matriptase based on in-gel fluorescence and fluorescence HPLC is reported. HPLC fluorescence detection as a new application for activity-based probes for proteases is demonstrated herein for the first time.


Parotid Gland Venolymphatic Malformation Presentation As Macroglossia.
Venolymphatic malformations (VLM) are the rare congenital disorders but the parotid gland VLMs are the rarest. Most of the parotid lesions present with unilateral swellings. Aetiology is unknown. Interestingly, this case came in OPD with the macroglossia and only complaint was cosmetic problem. Diagnosis was confirmed on the basis of Magnetic resonance imaging which is gold standard. Doppler ultrasonography showed low flow. Intra lesion electro cautery was done. There is need to focus on malformations and work to find out the causes.


Comorbidities Might Condition the Recovery of Quality of Life in Survivors of Sepsis.
To assess how preexisting disabling comorbidities (DC) affect the recovery rate of quality of life (QOL) over time in sepsis survivors. A prospective study was conducted on sepsis survivors who answered the 36-Item Short Form Health Survey (SF-36) 7 days after discharge from the intensive care unit. Subsequent interviews were held at 3, 6, and 12 months. The results of the physical component score (PCS) and mental component score (MCS) of the SF-36 were evaluated. Patients were divided into 2 groups to compare patients with DC (DC group) and without DC (no-DC group). Quantile regression was used to model changes in PCS and MCS between different time points. Seventy-nine sepsis survivors were enrolled. After controlling for baseline age and QOL, the QOL scores were lower among patients with DC than in no-DC patients. The QOL of DC group got worse when compared to no-DC group. Recovery rate of PCS and MCS was higher in the DC group than in the no-DC group (PCS: 20.51 vs 16.96, P < .01; MCS: 19.24 vs 9.66, P < .01). Their baseline QOL was recovered only by 6 months after the sepsis episode. Quality-of-life impairment and its recovery rhythm in patients with sepsis appear to be conditioned by coexisting DC.


Examining the association between inflammation and motivational anhedonia in neuropsychiatric disorders: A systematic review.
Inflammation, motivational anhedonia, and neuropsychiatric disorders are associated with significant functional impairment and are a major public health concern. The objective of this systematic review is to examine the relationship between inflammatory activity and motivational anhedonia in neuropsychiatric disorders. Preclinical and clinical studies were qualitatively synthesized and summarized. We found an association between inflammation and neuropsychiatric disorders, and a transdiagnostic association between motivational anhedonia and neuropsychiatric disorders. This review also identified brain regions associated with motivational processes that might have a latent vulnerability to persistent inflammatory activity. Motivational processes might be impacted early in the development of neuropsychiatric disorders, and could lead to a precursory manifestation of motivational anhedonia before (eg, prodromal phase) or early in the clinical course of the disorder. Although inflammation, motivational anhedonia, and neuro psychiatric disorders are strongly associated, direct evidence of causal interactions are limited. Further research is required to understand the association and mechanical underpinnings, and improve assessment of this construct. The immune system could serve as a novel treatment target to improve symptoms of motivational anhedonia across diverse neuro psychiatric disorders; however, well-designed interventional studies are required to assess this hypothesis.


Effects of synthetic androgens on liver function using the rabbit as a model.
The objective of this study was to determine whether the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0-13 with 17α-methyltestosterone (MT) as a positive control and testosterone (T) as a negative control to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7, and 14, were determined. As expected, T (10 mg/kg/d) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/d) increased BSP retention, and AST, ALT, GGT, and SDH levels, indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/d) increased BSP retention and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/d did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/d. For the androgens that exhibited liver toxicity at 10 mg/kg/d (MT, DMAU, and MENT), a no-observed-effect level of 1 mg/kg/d was established. Overall ranking of the synthetic androgens from most to least hepatotoxic on the basis of percent BSP retention was: MT & DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury.


Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.
Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.


What is schizophrenic in acute and transient psychotic disorder?
Acute and transient psychotic disorder (ATPD) is supposed to differ from schizophrenia, but little research has been done on the subject. In a prospective longitudinal case control study we compared all inpatients with ATPD (ICD-10 F23) treated at Halle University Hospital during a 5-year period with matched controls with "positive" schizophrenia (PS) and with mentally healthy controls. Followup investigations were performed at a mean of 2.2 years after the index episode or 8.2 years after the first episode. Female preponderance in ATPD was marked (78.6%). ATPD and PS patients were similar to each other (but different from healthy controls) in the prevalence of a "broken home" situation and a family history for mental disorders. Compared with PS patients, ATPD patients showed better premorbid social adaptation, and they more often displayed rapidly changing symptoms in the index episode and a negative life event preceding the episode. Despite comparable relapse rates, at followup ATPD patients showed better social adaptation, less psychological impairment, and better global functioning than PS patients. These data support the delineation of ATPD from schizophrenia.


Effects of Cordyceps militaris spent mushroom substrate on mucosal and serum immune parameters, disease resistance and growth performance of Nile tilapia, (Oreochromis niloticus).
The aim of present study was determination effects of dietary administration of C. militaris spent mushroom substrate (SMS) on mucosal and serum immune parameters, disease resistance, and growth performance of Nile tilapia (Oreochromis niloticus). Two hundred twenty five fish of similar weight (37.28 ± 0.10 g) were assigned to the following diets [0 (T1- Control), 5 (T2), 10 (T3), 20 (T4) and 40 g kg-1 (T5) SMS]. After 60 days of feeding trial, growth performance, skin mucus lysozyme and peroxidase activities as well as serum innate immune were measured. In addition, survival rate and innate immune responses were calculated after challenge test (15 days) against Streptococcus agalactiae. The results revealed that regardless of inclusion levels, feeding Nile tilapia with SMS supplemented diets significantly increased skin mucus lysozyme and peroxidase activities as well as serum immune parameters (SL, ACH50, PI, RB, and RB) compared control group (P < 0.05). The highest increment of immune parameters was observed in fish fed 10 g kg-1 SMS which was significantly higher than other treatments (P < 0.05). Also, the relative percent survival (RSP) in T2, T3, T4, and T5 was 61.11%, 88.89%, 66.67, and 55.56%, respectively. Among the supplemented groups, fish fed 10 g kg-1 SMS showed significant higher RPS and resistance to S. agalactiae than other groups (P < 0.05). Regarding the growth performance, SGR, WG, FW, and FCR were remarkably improved (P < 0.05) in SMS groups; the highest improvement observed in 10 g kg-1 SMS treatment. According to these finding, administration of 10 g kg-1 SMS is suggested in tilapia to improve growth performance and health status.


Metabolic, inflammatory and oxidative stress markers in the nitric oxide variation of hemodialysis subjects.
Oxidative stress markers such as nitric oxide (NO) have been investigated in hemodialysis (HD). Evaluate the association of NO variation with adiposity indicators, metabolic, inflammatory and oxidative stress markers in individuals to HD. Cross-sectional study with 85 subjects on HD treatment (≥ 18 years). The clinical-nutritional status was evaluated through subjective global assessment modified (SGAm), anthropometric measurements and body composition. Dietary intake was evaluated using a food frequency questionnaire. Metabolic markers were obtained from medical records. Inflammatory markers (IL-6 and IL-10) and oxidative stress, (TACs), (SOD), (GST), (MDA) and NO were determined using standardized protocols. Those individuals with a high concentration of NO (> 4.32 μmol/L) had lower values for SGAm score (p = 0.012) and higher iron values (p = 0.050), Fe saturation (p = 0.037) and triacylglycerol (p = 0.003). The same subjects still had lower consumption of copper (p = 0.026), manganese (p = 0.035), vitamin E (p = 0.050), ω3 (p = 0.021) and ω6 (p = 0.020). In a multiple regression model, concentrations of ferritin, triacylglycerol, IL6 and SOD contributed to a 54.8% increase in NO concentrations, whereas triacylglycerol and SOD concentrations were independent factors for NO variation (p < 0.001). CONCLUSIONS: The clinical and nutritional status as well as intake of nutrients with antioxidant properties (Cu, Zn, Mn, vitamin C and ω3) appears to modulate the variation of NO in this population.


Visualization of Ca2+ entry through single stretch-activated cation channels.
Stretch-activated channels (SACs) have been found in smooth muscle and are thought to be involved in myogenic responses. Although SACs have been shown to be Ca(2+) permeable when Ca(2+) is the only charge carrier, it has not been clearly demonstrated that significant Ca(2+) passes through SACs in physiological solutions. By imaging at high temporal and spatial resolution the single-channel Ca(2+) fluorescence transient (SCCaFT) arising from Ca(2+) entry through a single SAC opening, we provide direct evidence that significant Ca(2+) can indeed pass through SACs and increase the local [Ca(2+)]. Results were obtained under conditions where the only source of Ca(2+) was the physiological salt solution in the patch pipette containing 2 mM Ca(2+). Single smooth muscle cells were loaded with fluo-3 acetoxymethyl ester, and the fluorescence was recorded by using a wide-field digital imaging microscope while SAC currents were simultaneously recorded from cell-attached patches. Fluorescence increases at the cell-attached patch were clearly visualized before the simultaneous global Ca(2+) increase that occurred because of Ca(2+) influx through voltage-gated Ca(2+) channels when the membrane was depolarized by inward SAC current. From measurements of total fluorescence ("signal mass") we determined that about 18% of the SAC current is carried by Ca(2+) at membrane potentials more negative than the resting level. This would translate into at least a 0.35-pA unitary Ca(2+) current at the resting potential. Such Ca(2+) currents passing through SACs are sufficient to activate large-conductance Ca(2+)-activated K(+) channels and, as shown previously, to trigger Ca(2+) release from intracellular stores.


The degree of bone mineralization in hyperthyroidism estimated from the phosphorus to hydroxyproline ratio in bone.
The proportion between mineral and collagen in bone tissue, "the degree of mineralization", can be evaluated from the phosphorus to hydroxyproline ratio (P/Hypro ratio), determined in bone biopsies. The ratio was measured in 27 unselected hyperthyroid patients. No significant correlation was found between the P/Hypro ratio and the age of the patient, the duration of the disease or the value of serum thyroxine. The mean value of the P/Hypro ratio for the group studied was not significantly different from the normal mean. The results of the study indicate a normal degree of mineralization in the bone of patients with hyperthyroidism.


Diabetes prevalence in NZO females depends on estrogen action on liver fat content.
In humans and rodents, risk of metabolic syndrome is sexually dimorphic, with an increased incidence in males. Additionally, the protective role of female gonadal hormones is ostensible, as prevalence of type 2 diabetes mellitus (T2DM) increases after menopause. Here, we investigated the influence of estrogen (E2) on the onset of T2DM in female New Zealand obese (NZO) mice. Diabetes prevalence (defined as blood glucose levels >16.6 mmol/l) of NZO females on high-fat diet (60 kcal% fat) in week 22 was 43%. This was markedly dependent on liver fat content in week 10, as detected by computed tomography. Only mice with a liver fat content >9% in week 10 plus glucose levels >10 mmol/l in week 9 developed hyperglycemia by week 22. In addition, at 11 wk, diacylglycerols were elevated in livers of diabetes-prone mice compared with controls. Hepatic expression profiles obtained from diabetes-prone and -resistant mice at 11 wk revealed increased abundance of two transcripts in diabetes-prone mice: Mogat1, which catalyzes the synthesis of diacylglycerols from monoacylglycerol and fatty acyl-CoA, and the fatty acid transporter Cd36. E2 treatment of diabetes-prone mice for 10 wk prevented any further increase in liver fat content and reduced diacylglycerols and the abundance of Mogat1 and Cd36, leading to a reduction of diabetes prevalence and an improved glucose tolerance compared with untreated mice. Our data indicate that early elevation of hepatic Cd36 and Mogat1 associates with increased production and accumulation of triglycerides and diacylglycerols, presumably resulting in reduced hepatic insulin sensitivity and leading to later onset of T2DM.


Basal ganglia shape features differentiate schizoaffective disorder from schizophrenia.
There is growing evidence that schizophrenia and schizoaffective disorder represent closely related syndromes that vary in severity along a neurobiological continuum. In the present study, volume and shape of the basal ganglia was examined in people with schizophrenia and schizoaffective disorder relative to healthy controls and hypothesized that unique neuroanatomical differences would be observed in each patient group. Magnetic resonance 1.5T images were obtained from schizophrenia (n = 47), schizoaffective disorder (n = 15), and from healthy control (n = 42) participants, matched for age, gender, parental socioeconomic status, and race. The caudate, putamen, and globus pallidus were characterized using high-dimensional brain mapping procedures (Csernansky et al., 2004b). Results revealed significant shape deformations between schizophrenia and schizoaffective disorder that also differed from control subjects. Relative to schizophrenia, schizoaffective subjects showed exaggerated inward deformations indicative of localized volume loss in subregions of the caudate, putamen, and globus pallidus (all p < 0.001). These shape features correlated with mental flexibility and negative symptoms in schizophrenia (all p < 0.05), but not schizoaffective disorder. To the extent that differences in important basal ganglia substructures reflect biological heterogeneity among these two psychotic illnesses, this data could prove useful in improving diagnostic precision, as well as informing the affective component of mental illness.


Sestrin2 Suppresses Classically Activated Macrophages-Mediated Inflammatory Response in Myocardial Infarction through Inhibition of mTORC1 Signaling.
Myocardial infarction (MI) triggers an intense inflammatory response that is essential for dead tissue clearance but also detrimental to cardiac repair. Macrophages are active and critical players in the inflammatory response after MI. Understanding the molecular mechanisms by which macrophage-mediated inflammatory response is regulated is important for designing new therapeutic interventions for MI. In the current study, we examined the role of Sestrin2, which is a stress-inducible protein that regulate metabolic homeostasis, in the regulation of inflammatory response of cardiac macrophages after MI. We found that cardiac macrophages upregulated Sestrin2 expression in a mouse MI model. Using a lentiviral transduction system to overexpress Sestrin2 in polarized M1 and M2 macrophages, we revealed that Sestrin2 predominantly functioned on M1 rather than M2 macrophages. Sestrin2 overexpression suppressed inflammatory response of M1 macrophages both in vitro and in vivo. Furthermore, in the mouse MI model with selective depletion of endogenous macrophages and adoptive transfer of exogenous Sestrin2-overexpressing macrophages, the anti-inflammatory and repair-promoting effect of Sestrin2-overexpressing macrophages was demonstrated. Furthermore, Sestrin2 significantly inhibited mTORC1 signaling in M1 macrophages. Taken together, our study indicates the importance of Sestrin2 for suppression of M1 macrophage-mediated cardiac inflammation after MI.


Low-LET proton irradiation of A549 non-small cell lung adenocarcinoma cells: dose response and RBE determination.
Since 1957, broad proton beam radiotherapy with a spread out Bragg peak has been used for cancer treatment. More recently, studies on the use of proton therapy in the treatment of non-small cell lung cancer (NSCLC) were performed and although the benefit of using protons for the treatment of NSCLC is recognized, more work is needed to gather additional data for the understanding of cell response. Human A549 cell survival was evaluated by colony forming assay 11 days after 10 keV/μm proton beam irradiation at 0.1 and 1 Gy/min. The residual energy of the proton beam at the location of the irradiated cells was 3.9 MeV. In parallel, early effects on the cell viability and DNA damage were assessed and DNA synthesis was measured. The survival curve obtained was fitted with both the linear and the induced-repair models, as a hyper-radiosensitivity was evidenced at very low doses. Above 0.5 Gy, a linear shape was observed with the α parameter equal to 0.824 ± 0.029 Gy(-1). In addition, early cell death and cell proliferation arrest were enhanced. Moreover, a clear correlation between DNA damage and surviving fraction was observed. Finally, comparisons with X ray results indicate that proton irradiation at 10 keV/μm enhanced the tumor radiosensitivity with a significant dose-dependent decrease in the survival fraction. The RBE value of 1.9 ± 0.4 obtained for a 10% survival support this observation.


Measurement of Uranium Isotope Ratios in Keratinous Materials: A Noninvasive Bioassay for Special Nuclear Material.
Hair, toenail, and fingernail are noninvasive, integrative biological monitors routinely used to assess mineral intake.1-4 In this study, we demonstrate the feasibility of distinguishing between exposure to natural, depleted, and enriched U by measuring the (235)U/(238)U, (234)U/(238)U, and (236)U/(238)U ratios in the hair, fingernails, and toenails of occupationally exposed workers and control volunteers. The exposure history of cases and controls to non-natural U was assessed through voluntary self-reporting using a simple questionnaire. The measured U isotope ratios and U concentration in the hair, toenail, and fingernail of cases were compared to a nonexposed control group. No difference was observed in the uranium concentration between the two groups. Significant differences between the cases and the control group were observed in the (235)U/(238)U and (236)U/(238)U isotope ratios but not the (234)U/(238)U. This is the first time that hair, fingernail, and toenail have been demonstrated to be sensitive to occupational exposure to enriched and depleted U, a result with significant implications for proliferation compliance monitoring.


New Carcharhiniform Sharks (Chondrichthyes, Elasmobranchii) from the Early to Middle Eocene of Seymour Island, Antarctic Peninsula.
Seymour Island, Antarctic Peninsula, is known for its wealth of fossil remains. This island provides one of the richest fossiliferous Paleogene sequences in the world. Chondrichthyans seemingly dominate this Eocene marine fauna and offer a rare insight into high-latitude faunas during the Palaeogene. So far, only a few isolated teeth of carcharhinid sharks have been reported from Seymour Island. Bulk sampling in the well-exposed La Meseta and Submeseta formations yielded new and abundant chondrichthyan material, including numerous teeth of carcharhinid and triakid sharks. Here, we present a reevaluation of the previously described carcharhinid remains and a description of new taxa: Meridiogaleus cristatus, gen. et sp. nov., Kallodentis rythistemma, gen. et sp. nov., Abdounia richteri, sp. nov., and Abdounia mesetae, sp. nov. The carcharhiniforms Mustelus sp. and Galeorhinus sp. are reported based on rare material, whereas teeth previously assigned to Scoliodon represent a nomen dubium.


X-ray polarization spectroscopy to study anisotropic velocity distribution of hot electrons produced by an ultra-high-intensity laser.
The anisotropy of the hot-electron velocity distribution in ultra-high-intensity laser produced plasma was studied with x-ray polarization spectroscopy using multilayer planar targets including x-ray emission tracer in the middle layer. This measurement serves as a diagnostic for hot-electron transport from the laser-plasma interaction region to the overdense region where drastic changes in the isotropy of the electron velocity distribution are observed. These polarization degrees are consistent with analysis of a three-dimensional polarization spectroscopy model coupled with particle-in-cell simulations. Electron velocity distribution in the underdense region is affected by the electric field of the laser and that in the overdense region becomes wider with increase in the tracer depth. A full-angular spread in the overdense region of 22.4 degrees -2.4+5.4 was obtained from the measured polarization degree.


Endorsement of interpersonal strategies for dealing with hypothetical everyday arthritis problems as a function of marital status, gender, and problem severity.
We used hypothetical vignettes to examine whether older adults' endorsement of interpersonal strategies for dealing with health-related (arthritis) everyday problems varied as a function of marital status, gender, and the severity of the problem. Adults 60 years and older (N=127, M = 71.40 years, SD = 7.21) rated interpersonal (i.e., discuss with doctor, spouse, relative) and other strategies (e.g., deal with the problem alone, pray) for solving two hypothetical everyday problems (one mild and one severe arthritis problem). Women reported a greater likelihood of using interpersonal strategies. Married people rated interpersonal strategies that involved their spouse higher than other strategies. Greater severity of problems was associated with greater endorsement of interpersonal strategies. Implications of the results for understanding the conditions under which older adults endorse strategies that may initiate collaborative everyday problem solving are discussed.


Hemicrania continua: clinical review, diagnosis and management.
Hemicrania continua (HC) is an indomethacin-responsive primary headache disorder which is currently classified under the heading of trigeminal autonomic cephalalgias (TACs). It is a highly misdiagnosed and underreported primary headache. The pooled mean delay of diagnosis of HC is 8.0 ± 7.2 years. It is not rare. We noted more than 1000 cases in the literature. It represents 1.7% of total headache patients attending headache or neurology clinic. Just like other TACs, it is characterized by strictly unilateral pain in the trigeminal distribution, cranial autonomic features in the same area and agitation during exacerbations/attacks. It is different from other TACs in one aspect. While all other TACs are episodic, HC patients have continuous headaches with superimposed severe exacerbations. The central feature of HC is continuous background headache. However, the patients may be worried only for superimposed exacerbations. Focusing only on exacerbations and ignoring continuous background headache are the most important factors for the misdiagnosis of HC. A large number of patients may have migrainous features during exacerbation phase. Up to 70% patients may fulfill the diagnostic criteria for migraine during exacerbations. Besides migraine, its exacerbations can mimic a large number of other primary and secondary headaches. The other specific feature of HC is a remarkable response to indomethacin. However, a large number of patients develop side effects because of the long-term use of indomethacin. A few other medications may also be effective in a subset of patients with HC. Various surgical interventions have been suggested for patients who are intolerant to indomethacin. Several aspects of HC are still not defined. There is a great heterogeneity in types of patients or articles on the HC in the literature. Diagnostic criteria have been modified several times over the years. The current diagnostic criteria are too restrictive in some aspects. We suggest a more accommodating type of criteria for the appendix of International Classification of Headache Disorder (ICHD).


Sero-prevalence and vaccination status of hepatitis A and hepatitis B among adults with cirrhosis in Sri Lanka: a hospital based cohort study.
As acute viral hepatitis can be fatal in patients with cirrhosis, vaccination against hepatitis A (HAV) and hepatitis B (HBV) is recommended for non-immune patients. With increasing affluence the incidence of hepatitis A in childhood has decreased leading to a significant proportion of non-immune adults. As part of their routine investigation, hepatitis A IgG antibodies (anti-HAV IgG), hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was checked and immunization status was assessed among consenting newly diagnosed cirrhotic patients presenting to a tertiary referral center. Out of 135 patients, 107 [79.3%; males 91; mean age (SD) at presentation: 55.5 (11.6) years] with complete data were included for analysis. Most patients had either cryptogenic cirrhosis (62.6%) or alcoholic cirrhosis (29.9%); 2 (1.9%) had HBV cirrhosis, none had hepatitis C (HCV) cirrhosis. None of the patients had received vaccination against hepatitis A, while 71 (67.6%) had been vaccinated against HBV. The majority [62 (58%)] were negative for anti-HAV IgG. Most cirrhotic patients in this cohort were not immune to hepatitis A. None had been vaccinated against HAV, while a third of patients had not been vaccinated against HBV. Cirrhotic patients should be routinely investigated for immunity against HAV and HBV, and vaccination offered to those found to be non-immune.


The dual protection of a micro land snail against a micro predatory snail.
Defense against a single predatory attack strategy may best be achieved not by a single trait but by a combination of different traits. We tested this hypothesis experimentally by examining the unique shell traits (the protruded aperture and the denticles within the aperture) of the micro land snail Bensonella plicidens. We artificially altered shell characteristics by removing the denticles and/or cutting the protruded aperture. These snails were offered to the carnivorous micro land snail Indoennea bicolor, which preys on the snails by gaining entry to their shell. B. plicidens exhibited the best defence when both of the traits studied were present; the defensive ability of B. plicidens decreased if either trait was removed and was further reduced if both traits were removed. These results suggest that a combination of different traits provides more effective defence against attack by the predator than either single trait by itself.


Haemodynamic changes in the rat femur and tibia following femoral vein ligation.
Interference with venous outflow from a limb to stimulate fracture repair and bone growth has a long history, and its beneficial effects have been confirmed by many experimental and clinical studies. With the development of fracture fixation systems, the therapeutic use of circulatory intervention became redundant. Recently, a venous tourniquet effect has been cited to explain the enhancement of bone healing observed after fracture fixation with the Aircast system. As bone appears to be altered by venous stasis, it is important to characterise the vascular perturbations leading to these changes. Previous studies have often given conflicting results. This study investigated the short and long term haemodynamic effects of femoral vein ligation. Changes in blood flow rate and blood volume in the distal femur and proximal tibia of the rat were examined at 6 h and 1, 3 and 7 d following unilateral femoral vein ligation, and at 8 and 16 wk. Blood flows and volumes were generally reduced in the ligated limb 6 h after femoral vein ligation. This initial depression was followed by a relative increase (comparing the ligated limb with the contralateral unoperated bone) in blood volume during the 1st week. A significant relative reduction in epiphyseal vascular space was observed after 16 wk. A sustained reduction of arterial input to whole femora and tibiae was present in the ligated limb throughout the investigation although, for the cancellous knee joint epiphysis of the tibia, a localised relative increase in flow was apparent during the 1st week, again comparing the ligated limb with the nonligated contralateral bone.(ABSTRACT TRUNCATED AT 250 WORDS)


Infectious Agents and Inflammation: The Role of Microbiota in Autoimmune Arthritis.
In higher vertebrates, mucosal sites at the border between the internal and external environments, directly interact with bacteria, viruses, and fungi. Through co-evolution, hosts developed mechanisms of tolerance or ignorance toward some infectious agents, because hosts established "gain of function" interactions with symbiotic bacteria. Indeed, some bacteria assist hosts in different functions, among which are digestion of complex carbohydrates, and absorption and supply of vitamins. There is no doubt that microbiota modulate innate and acquired immune responses starting at birth. However, variations in quality and quantity of bacterial species interfere with the equilibrium between inflammation and tolerance. In fact, correlations between gut bacteria composition and the severity of inflammation were first described for inflammatory bowel diseases and later extended to other pathologies. The genetic background, environmental factors (e.g., stress or smoking), and diet can induce strong changes in the resident bacteria which can expose the intestinal epithelium to a variety of different metabolites, many of which have unknown functions and consequences. In addition, alterations in gut permeability may allow pathogens entry, thereby triggering infection and/or chronic inflammation. In this context, a local event occurring at a mucosal site may be the triggering cause of an autoimmune reaction that eventually involves distant sites or organs. Recently, several studies attributed a pathogenic role to altered oral microbiota in rheumatoid arthritis (RA) and to gut dysbiosis in spondyloarthritis (SpA). There is also growing evidence that different drugs, such as antibiotics and immunosuppressants, can influence and be influenced by the diversity and composition of microbiota in RA and SpA patients. Hence, in complex disorders such RA and SpA, not only the genetic background, gender, and immunologic context of the individual are relevant, but also the history of infections and the structure of the microbial community at mucosal sites should be considered. Here the role of the microbiota and infections in the initiation and progression of chronic arthritis is discussed, as well as how these factors can influence a patient's response to synthetic and biologic immunosuppressive therapy.


Hormone replacement therapy and cognition in an Australian representative sample aged 60-64 years.
To investigate the relationship between hormone replacement therapy (HRT) and level of cognitive performance intra-individual variability, and interactions with statin use, progesterone therapy and type of menopause. A representative sample of 60-64 year olds was recruited from the Canberra and Queanbeyan regions in Australia. They were administered tests of verbal memory, working memory, speed of information processing, simple and complex reaction time, verbal intelligence and the Mini-Mental State Exam. Intra-individual variation (consistency) on performance on simple and complex reaction time tasks was calculated. Women provided information on HRT use and demographic, health and lifestyle variables. Four hundred and four (35.0%) current postmenopausal HRT users, 316 (27.4%) previous HRT users and 434 (37.6%) women who had never used HRT, were included in this study. There were significant overall differences between HRT current and previous users on age, prevalence of diabetes, alcohol use, body mass index, level of anxiety and lung function. After controlling for potentially confounding health and demographic variables, there were no significant main effects detected between HRT groups on any cognitive measure. Significant interactions were detected between HRT group and statin use on intra-individual variability on simple reaction time, and between HRT group and menopause type on intra-individual variability on choice reaction time. All other interactions were non-significant. HRT use had no effect on level of cognitive performance. Two interactions were detected between HRT use and statin use, and type of menopause on intra-individual variability. Given the large number of comparisons, little weight can be placed on these significant results.


Fourier transform infrared microspectroscopy monitoring of 5-fluorouracil-induced apoptosis in SW620 colon cancer cells.
Colon cancer is associated with a high incidence and a poor prognosis. The aim of the present study was to determine whether Fourier transform infrared (FTIR) microspectroscopy can be used to monitor the chemotherapy drug‑induced apoptosis of SW620 colon cancer cells. The 50% inhibitory concentration (IC50) of 5‑fluorouracil (5‑FU), the main chemotherapeutic agent used for the treatment of colorectal cancer, was determined as the inhibition of growth of the SW620 cells using an MTT assay. Cell starvation and 5‑FU treatment synergized to arrest the cells in the G1 and S phases of the cell cycle. FTIR combined with fluorescence activated cell sorting (FACS) analysis were used to analyze the SW620 cells following treatment with 5‑FU for 12, 24 and 48 h. The apoptotic cells had several spectral characteristics. The relative peak intensity ratio (I1740/I1460) was significantly increased (P<0.05), the I1740/I1460 ratio, associated with a band of amino acid residues at 1,410 cm‑1 was significantly increased at the early and late phases of cell death (P<0.05), the peaks at 1,240 cm‑1 increased in wave number, a band at 1,040 cm‑1, associated with polysaccharides, appeared at 24 and 48 h and then moved to a higher wave number and the I1040/I1460 ratio increased at the late stage of apoptosis. These results demonstrated that FTIR can be used as a label‑free technique to monitor cancer cell apoptosis and to understand the spectral fingerprints of apoptotic cells. This suggested that FTIR spectral features have potential as a powerful tool to monitor cancer cell apoptosis.


Differences of starch granule distribution in grains from different spikelet positions in winter wheat.
Wheat starch development is a complex process and is markedly difference by changes in spikelet spatial position. The present study deals with endosperm starch granule distribution and spatial position during filling development. The study was conducted with pure starch isolated from wheat (Triticum aestivum L.), Jimai20 and Shannong1391, at 7-35 days after anthesis (DAA). The results showed that grain number, spikelet weight and grain weight per spikelet in different spatial position showed parabolic changes. Upper spikelets had highest starch and amylose content followed by basal spikelets, then middle spikelets. The paper also suggested the volume percents of B-type and A-type granule in grain of middle spikelets were remarkably higher and lower than those of basal and upper spikelets, respectively. However, no significant difference occurred in the number percents of the two type granule. The ratio of amylase to amylopectin was positively correlated with the volume proportion of 22.8-42.8 µm, but was negatively related to the volume proportion of <9.9 µm. The results indicated that the formation and distribution of starch granules were affected significantly by spikelet position, and grains at upper and basal spikelet had the potential of increasing grain weight through increasing the volume of B-type granules.