Regional deposition of inhaled Evans blue dye in mechanically ventilated rabbits with air or helium oxygen mixture.
An animal model has been used and further developed to examine and evaluate differences in regional deposition patterns of an Evans Blue dye (EB) tracer aerosol. This was done by using different carrier gas composition of either He-O2 (80% helium, 20% oxygen) or air (79% nitrogen, 21% oxygen) in histamine-provoked and nonprovoked rabbits. The ratio of peripheral deposition to total deposition (central + peripheral), in relation to percentage increase in intratracheal pressure (ITP delta %), was used as an evaluation tool. The animals were tracheostomized, cannulated, and ventilated in a volume-controlled mode until they were stable. Saline or histamine was then administrated for 2 min before the tracer aerosol EB was given. The percentage increase in intratracheal pressure before and after provocation was calculated (ITP delta %) and was, on average, 51 +/- 20% for air and 51 +/- 20% for He-O2. EB was extracted from lung tissues and measured with a spectrophotometer. The absorbance in different lung regions was used as a measure of the distribution of aerosol. Bronchial provocation gave a central deposition 0.55 +/- 0.11 (mean +/- SD, ratio = peripheral deposition/central + peripheral deposition) compared to 0.80 +/- 0.09 in the control group. He-O2-ventilated rabbits showed significantly higher peripheral deposition ratio (0.67 +/- 0.12) compared with air-ventilated rabbits (0.55 +/- 0.11). The latter finding may be due to the difference in the degree of turbulent flow. There were significant correlations between intratracheal peak pressure and peripheral deposition, r = -.60 and r = -.71 for air and He-O2, respectively. This study demonstrates the possibility of using a rabbit model and different carrier gases for evaluation of effects of bronchial provocation.


Resistance of Vibrio cholerae 01 to nalidixic acid.
Until 1987 all isolates of V. cholerae 01 at a tertiary care hospital in south India were susceptible to drugs commonly used to treat gastroenteritis including cholera. Since July 1987 strains resistant to co-trimoxazole have been encountered and since October 1995 strains resistant to nalidixic acid are being isolated. In this study the latter strains were examined by determining minimum inhibitory concentration levels of nalidixic acid as well as norfloxacin, the fluoroquinolone extensively used to treat diarrhoea. No cross resistance to norfloxacin was found in any of the nalidixic acid resistant V. cholerae 01 strains.


HIV-reverse transcriptase and human DNA polymerase alpha share amino acid sequence homologies to bacterial penicillin-binding proteins.
Penicillin-binding proteins are the specific targets for the beta-lactam antibiotics. Recently it was observed that beta-lactam antibiotics also have targets in proliferating eukaryotic cells (1), one of which most likely is the replicative DNA polymerase alpha. Here we show that HIV-reverse transcriptase and human DNA polymerase alpha share amino acid sequence homologies to five bacterial penicillin-binding proteins.


Process to evaluate hematological parameters that reflex to manual differential cell counts in a pediatric institution.
Each institution sets specific parameters obtained by automated hematology analyzers to trigger manual counts. We designed a process to decrease the number of manual differential cell counts without impacting patient care. We selected new criteria that prompt manual counts and studied the impact these changes had in 2 days of work and in samples of patients with newly diagnosed leukemia, sickle cell disease, and presence of left shift. By using fewer parameters and expanding our ranges we decreased the number of manual counts by 20%. The parameters that prompted manual counts most frequently were the presence of blast flags and nucleated red blood cells, 2 parameters that were not changed. The parameters that accounted for a decrease in the number of manual counts were the white blood cell count and large unstained cells. Eight of 32 patients with newly diagnosed leukemia did not show blast flags; however, other parameters triggered manual counts. In 47 patients with sickle cell disease, nucleated red cells and red cell variability prompted manual review. Bands were observed in 18% of the specimens and 4% would not have been counted manually with the new criteria, for the latter the mean band count was 2.6%. The process we followed to evaluate hematological parameters that reflex to manual differential cell counts increased efficiency without compromising patient care in our hospital system.


Peroxisome proliferator-activated receptor gamma regulates bone remodeling after midpalatal suture expansion in mice.
The effectiveness of rapid maxillary expansion is adversely affected by failure and relapse. It is important to identify key factors that increase new bone formation and improve bone remodeling of midpalatal sutures to improve the stability and effectiveness of this commonly used orthodontic procedure. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in modulating osteogenesis and bone resorption in long bones. This study was designed to explore the function of PPARγ in bone remodeling and tissue engineering of midpalatal sutures. Pioglitazone, a PPARγ agonist, and osteoclast PPARγ knockout mice were used to explore the impact of PPARγ activation and inactivation, respectively, on bone remodeling in a mouse model of midpalatal suture expansion (MSE). Histologic analysis including staining with hematoxylin-eosin, tartrate-resistant acid phosphatase, and alkaline phosphatase was used to evaluate tissue remodeling. Reverse-transcriptase quantitative polymerase chain reaction was used to measure gene expression. Pioglitazone decreased new bone formation after MSE. This was accompanied by an increased amount of osteoclasts and expression of genes promoting osteoclastogenesis, as well as a decreased amount of osteoblasts and expression of genes promoting osteoblastogenesis in midpalatal sutures. Conversely, osteoclast PPARγ knockout mice increased new bone formation and decreased the amount of osteoclasts and expression of genes promoting osteoclastogenesis. In the process of bone remodeling after MSE, PPARγ, particularly in osteoclasts, is an important regulator of osteoblast and osteoclast homeostasis and bone remodeling in midpalatal sutures. Blockade of PPARγ might be an effective strategy to improve stability and decrease relapse in the practice of rapid maxillary expansion.


PHYLOGENETIC ANALYSIS OF THE EVOLUTION OF ALTERNATIVE SOCIAL BEHAVIOR IN THE MANAKINS (AVES: PIPRIDAE).
Phylogenetic analyses of lekking, lek spatial organization, and cooperative and coordinated lek display in the manakins (Aves: Pipridae) demonstrate that variation in social behavior in the group has a strong, phylogenetic component. Two of the three classes of social behavior examined also show significant phylogenetic constraints. Current adaptive plasticity models are insufficient to explain the phylogenetic variation in these behaviors in the manakins. These findings support the conclusion that vertebrate reproductive social behavior has an evolutionary history, and that it is not determined solely by adaptive individual plasticity to current conditions. The evolution of social behavior, particularly through sexual selection, can have historical consequences that can limit subsequent behavioral adaptation.


Flouride. Ten-year prospective study of deciduous and permanent dentition.
A ten-year longitudinal prospective study compared the effect of fluoride on dentition of 1,500 children from infancy through age 10 years. In Kalamazoo, Mich, and Oneida, NY, parallel groups were given a fluoride-vitamin supplement from infancy and from age 4 and compared with fluoridated water and control groups. Incidence of new caries activity in both deciduous and permanent teeth was measured by mean number of new decayed and filled teeth, as well as percentage of children with no caries throughout the periods studied. Prevalence of caries was also studied in six-year molars. The results indicate a consistent (and, for selected groups, a statistically significant) diminution in caries activity for both deciduous and permanent teeth for groups ranked from greatest retardation of caries to least: infant fluoride group, water fluoride group, age 4 fluoride group, and controls.


Searching for voids in liquids with optical Kerr effect spectroscopy.
It has recently been shown [J. Chem. Phys. 2005, 122, 134506; J. Am. Chem. Soc. 2006, 128, 5119] that liquid tetrahydrofuran has an unusual structure that features voids of significant dimension. Such voids should affect other observable properties of this liquid. Here we present temperature-dependent, optical Kerr effect data for tetrahydrofuran and a number of related liquids (furan, cyclopentane, tetrahydropyran, cyclohexane, diethyl ether, and n-pentane) as well as hexamethylphosphoramide to test whether this technique can be used to reveal the presence of sizable voids in liquids.


Co-infection with Schistosoma mansoni and Human Immunodeficiency Virus-1 (HIV-1) among residents of fishing villages of north-western Tanzania.
Co-infection with S. mansoni and Human Immunodeficiency Virus-1 (HIV-1) has been described in sub-Saharan Africa. However, few community-based studies have been conducted to assess the association between the two diseases. The present study examined whether the infection with HIV-1 is associated with an altered susceptibility to S. mansoni infection by comparing the prevalence and intensity of S. mansoni infection among those infected and not infected with HIV-1. Any influence of HIV-1 associated immunodeficiency on the intensity of S. mansoni infection was also investigated. A cross-sectional study was conducted among 1,785 randomly selected adults (aged 21-55 years) in fishing villages of north-western Tanzania. Single stool samples were obtained and examined for S. mansoni eggs using the Kato Katz technique. Finger prick and venous blood samples were collected for HIV-1 screening and CD4(+) cell quantification. Demographic information was collected by questionnaire. Of the 1,785 individuals from whom complete data were obtained, 854 (47.85%, 95% CI; 40.46 - 56.57) were infected with S. mansoni and had a mean intensity of 183.21(95% CI; 165.61-202.70) eggs per gram of faeces (epg). A total of 125 individuals (6.29%, 95% CI 3.59-11.04) were infected with HIV-1 and only 40% (n=50) of them were co-infected with S. mansoni. No differences in prevalence of S. mansoni infection or intensities of infection, as estimated by egg count (epg), were observed between HIV-1 sero-positive individuals and HIV-1 negative individuals. In generalized regression models (adjusted for sex, age, occupation, residence and level of education), being infected with HIV-1 did not increase the risk (APR=1.01, 95%; 0.83-1.21, P=0.93) or intensity (AOR = 0.84, 95% CI; 0.56-1.25, P = 0.33) of S. mansoni infection. Among individuals co-infected with HIV-1 and S. mansoni infection, the intensity of infection (epg) was not associated (P = 0.21) or correlated (P = 0.13) with CD4(+) cell counts. Our findings suggest that HIV-1 infection may not have a major effect on S. mansoni infection or on the excretion of eggs from the co-infected individuals. However, further studies are needed to understand the biological interaction between HIV-1 and S. mansoni in a large cohort of co-infected individuals.


Metabolic changes in acute cerebral infarction: Findings from proton magnetic resonance spectroscopic imaging.
The purpose of this study was to investigate the clinical role of proton magnetic resonance spectroscopy (1H-MRS) in the diagnosis of acute cerebral infarction. Using databases available at the Fifth Affiliated Hospital of Zhengzhou University (Zhengzhou, China), the medical records of 47 patients with acute cerebral infarction treated between April 2010 and March 2012 were retrospectively reviewed. The patients underwent routine magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and multiple-voxel 1H-MRS examination within 12 h after the onset of stroke. The patients then received normal medical treatment for 2 weeks and underwent follow-up 1H-MRS examination at 1-2 months after stroke. The concentrations of the main metabolites [N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho) and lactate (Lac)] in the infarct center, the infarction border region and the contralateral brain areas (control) were analyzed. The 47 patients experienced changes in NAA, Cho and Lac levels at different stages after stroke. In the infarction center, the NAA/Cr and NAA/Cho ratios decreased, while the Lac/Cr ratio increased within 12 h compared with those in the contralateral side. Within 6-12 h after stroke, the Lac/Cr ratio increased and the NAA/Cho ratio decreased compared with those <6 h after stroke. During the 1-2 months post-stroke, significant reductions in the NAA/Cr, NAA/Cho, Cho/Cr and Lac/Cr ratios were observed in the infarction center. In the infarction border region, the Lac/Cr ratio increased significantly at 12 h and decreased during the 1-2 months after stroke. The NAA/Cr, NAA/Cho and Cho/Cr ratios were significantly increased in the infarction border regions of patients who received thrombolytic therapy for 1-2 months compared with those in patients who did not undergo thrombolysis. Our results highlight the usefulness of 1H-MRS-based metabolomics as a feasible and efficient prognostic tool for assessing the treatment effect of acute cerebral infarction.


Actual implementation of the Thai Asthma Guideline.
To determine the clinical impact of Thai Asthma Guideline implementation. A nationwide written questionnaire survey was used for 365 Thai physicians who were involved in routine asthma practice. The questionnaire consisted of two questions; the first concerning the criteria to define steps of asthma severity (16 parameters) and the second concerning controller use in each step of asthma severity, focusing on the use of inhaled corticosteroids (ICS). Of 272 physicians (74.5%) who responded to the questionnaire; 21, 76 and 175 were chest physicians, general practitioners (internists), and general doctors, respectively. All the non-responders could not provide answers to the questionnaire because they were unable to remember them all. More than 12 out of 16 parameters in the first question were filled out correctly by only 14%, 4% and 5% of chest physicians, general practitioners and general doctors, respectively, whereas fewer than 5 out of 16 parameters were answered correctly by 33%, 66% and 71% of these physicians, respectively. The most common parameters answered incorrectly by general doctors were FEV1 and PEF variability. ICS was the most common controller used in controlling each step of persistent asthma. However, only 46.8% of general doctors prescribed it for the management of mild persistent asthma. The Thai Asthma Guideline is impractical for clinical practice implementation, due to complicated severity grading and a very low rate of lung function tests for grading asthma severity. Although ICS is the most common controller prescribed, its use is still far from optimal in Thailand. The authors suggest that the Thai asthma guideline should be simplified and aimed towards optimal ICS use among generalists.


The Changing Landscape of Pulmonary Arterial Hypertension in the Adult with Congenital Heart Disease.
Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH) and a frequent complication of congenital heart disease (CHD). PAH-CHD represents a heterogeneous patient population and it is important to distinguish between the underlying cardiac defects considering the prognostic and therapeutic implications. Improved interventional techniques have enabled repair or palliation of most cardiac defects, though a substantial number of patients remain at high risk for PAH after closure. Traditionally, the treatment and management of PAH-CHD patients has been limited to palliative and supportive care, and based on expert opinion rather than clinical trials. Recently, however, the availability of advanced PAH-specific treatment has opened up a new field for the clinical management of this condition. Nevertheless, there is limited evidence on the optimal therapeutic approach for PAH-CHD. Herein, we discuss the current and novel therapeutic options for PAH-CHD as well as highlight several challenges in the clinical management at present.


Ayşe Şadiye Güvendiren and Hatice Azra Demirelli: Turkey's first certified female dentists.
Ayşe Şadiye Güvendiren and Hatice Azra Demirelli were the first Turkish female dentists. In a country that came out of the First World War and fought for her independence, they laid the foundations of women's presence in the Turkish dental community and took their honorable place in history with their courage, devotion, and determination.


NMDA receptor antagonists change behavioral activity of rats treated with (S)-4CPG.
The effect of (S)-4CPG [(S)-4-carboxyphenylglycine] (25, 50, 100 nmol icv) and the effect of AP-7 (5 nmol icv) or MK-801 (5 nmol icv) on the processes of acquisition, consolidation of conditioned reflexes and locomotor activity were tested in rats. Neither AP-7, MK-801 nor (S)-4CPG given alone changed locomotor activity. MK-801 significantly increased the effects of (S)-4CPG: on crossings at all applied doses, on rearings at 100 nmol, and on bar approaches at 50 nmol of (S)-4CPG. AP-7 enhanced the effects of 50 and 100 nmols of (S)-4CPG on crossings, 100 nmol of (S)-4CPG on rearings in the open field test. Neither AP-7, MK-801 nor (S)-4CPG at doses of 50 and 100 nmols influenced acquisition, but (S)-4CPG given alone at a dose of 25 nmol impaired acquisition. MK-801 impaired the action of 50 and 100 nmols of (S)-4CPG on acquisition. AP-7 only at a dose of 100 nmol inhibited (S)-4CPG-induced acquisition. Neither AP-7, MK-801 nor (S)-4CPG given alone changed consolidation in passive avoidance situation while co-administration of AP-7 and (S)-4CPG at the doses of 50 and 100 nmols, affected this process. The obtained results support our hypothesis concerning the co-operation between group I mGluRs and NMDA receptors in some behavioral tests and the modulating effect of group I mGluRs antagonist on central action of NMDA receptor antagonists.


Immediate Effect of Therapeutic Massage on Pain Sensation and Unpleasantness: A Consecutive Case Series.
Musculoskeletal pain is a common condition that poses a significant burden to its sufferers and costs the US economy billions of dollars each year in lost productivity. Individuals complaining of musculoskeletal pain make up a large proportion of clients treated by massage therapists in community practices, yet few studies have examined the immediate effect of therapeutic massage on this type of pain in the practice setting. To assess the immediate effect of therapeutic massage on musculoskeletal pain sensation and unpleasantness in a community setting. Solo private practice in central Virginia, United States. One hundred sixteen first-time clients who complained of musculoskeletal pain as a presenting symptom. Prospective, consecutive practice-based case series. A single 60-minute session of individualized therapeutic massage; techniques used included Swedish massage employing effleurage, petrissage, and friction,;deep tissue; myofascial; positional release; passive and resisted joint mobilization; and biofield modalities. Visual Analog Scales for pain sensation and unpleasantness. Both pain sensation and unpleasantness were significantly reduced by a single session of therapeutic massage. Mean pain sensation decreased from 3.76 (SD=1.87) prior to massage to .89 (SD=1.35) following massage, with t=18.87, P<.001. Mean pain unpleasantness decreased from 5.21 (SD=2.48) prior to massage to .64 (SD=1.23) following massage, with t =20.45, P<.001. Effect sizes were 1.76 and 1.90, respectively. In this case series, therapeutic massage appeared to be an effective intervention for common musculoskeletal pain that influenced both the physical and affective dimension of the pain experience. Although care was taken to reduce potential bias through limiting eligibility to first time clients and use of a standardized script, practice-based case series have inherent limitations. Issues in conducting practice-based research by massage therapists and recommendations for future research are discussed.


Backpack palsy with Horner's syndrome.
Traumatic injuries to the brachial plexus are typically high impact and can be debilitating, life-changing injuries. Backpack palsy is a rare but well-established cause of brachial plexus injury, arising as a result of heavy backpack use. We present an unusual case of backpack palsy with Horner's syndrome.


Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients.
Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. Sleep, fatigue, and depression as assessed by subjective questionnaire. TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 μmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 μmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores (r2 = 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients. Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.


Inheritance of maternal immunoglobulin G1 concentration by the bovine neonate.
Serum samples were collected between 24 and 48 h of age from 408 Herefored calves of a Selection Experiment and from 200 Angus, Hereford and Red Poll calves of another experimental population (Germ Plasm Utilization Project). Concentrations of immunoglobulin G1 (IgG1) were determined by single radial immunodiffusion. Breed or selection line of calf and age of dam were the most important factors influencing IgG1 concentrations (P less than .01). In the Germ Plasm Utilization (GPU) herd, Angus calves were highest, Red Polls were intermediate and Herefords were lowest in serum concentrations. Calves from Hereford lines selected for weaning weight, yearling weight or an index based on yearling weight and muscling score were lower in IgG1 concentration than calves from the randomly selected control line. In both populations immunoglobulin levels in the calf increased as age of dam increased. In Selection Experiment Herefords, increased calving difficulty was associated with a decrease in calf IgG1 levels (P less than .05). Heritabilities of calf serum IgG1 concentration, estimated from paternal half-sib analysis on a within line or breed basis, were .03 +/- .09 and .13 +/- .19 in the two populations. In the Selection Experiment Herefords, when the component of variance for selection line was added both to the numerator and denominator of heritability, the revised estimate was .09 +/- .09. Heritabilities of maternal effects on IgG1 concentration were also estimated (by nesting calves within maternal grandsires) on a within line or breed basis. These heritabilities were .23 +/- .17 and -.07 +/- .27 for the Selection Experiment and GPU populations, respectively. In the Selection Experiment population, when the variance component for selection line was added to the numerator and denominator of maternal effects heritability, the estimate was .27 +/- . .17. Those calves that died had a lower mean IgG1 concentration than the population average (P less than .01).


The Use of Phononic Crystals to Design Piezoelectric Power Transducers.
It was recently proposed that the lateral resonances around the working resonance band of ultrasonic piezoelectric sandwich transducers can be stopped by a periodic array of circular holes drilled along the main propagation direction (a phononic crystal). In this work, the performance of different transducer designs made with this procedure is tested using laser vibrometry, electric impedance tests and finite element models (FEM). It is shown that in terms of mechanical vibration amplitude and acoustic efficiency, the best design for physiotherapy applications is when both, the piezoceramic and an aluminum capsule are phononic structures. The procedure described here can be applied to the design of power ultrasonic devices, physiotherapy transducers and other external medical power ultrasound applications where piston-like vibration in a narrow band is required.


A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen.
To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT. An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control. The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported. Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control.


[Ethology of panic disorders].
Animal's world is perfectly coded. According to genetical equipment, there are in natural sphere, signals whose bio-physical structure releases panics behaviours. But the mere fact that an organism is developing from birth to death makes it sensitive to different informations. Imprinting allows to young to incorporate another live-being or a sphere, category it. From now, if we change this sphere, it's a trouble of relation of world which panics the young. Surpopulation regarded in an animal world as an impossibility to classify its world, impairs animal's behaviours and released accidental panics. Overgenerational appears soon in animals, a long time before words. But when human language appears, it modifies memory's nature and allows therefore troubles released by a representation. The tranquilizing mechanism often consists of changing fear in anxiety, easier to manage.


Evaluation of pefloxacin activity against recent clinical isolates.
The in-vitro antibacterial activity of pefloxacin, a new quinolone carboxylic acid, was tested against 1140 bacterial strains, recently clinically isolated, by measuring the minimum inhibitory concentrations. Comparisons were made with other quinolones (enoxacin, norfloxacin, flumekin, oxolinic acid, pipemidic acid) and other drugs (piperacillin, cefotaxime, ceftazidime, gentamicin, tobramycin, amikacin) widely used for the treatment of bacterial infections. Pefloxacin was very active against the tested species and was the most active drug against all the bacterial strains, with a geometric mean of MICs, a MIC 50 and MIC 90 of 0.27, 0.12 and 4 microg/ml respectively.


Challenges in measuring individual differences in functional connectivity using fMRI: The case of healthy aging.
Many studies report individual differences in functional connectivity, such as those related to age. However, estimates of connectivity from fMRI are confounded by other factors, such as vascular health, head motion and changes in the location of functional regions. Here, we investigate the impact of these confounds, and pre-processing strategies that can mitigate them, using data from the Cambridge Centre for Ageing & Neuroscience (www.cam-can.com). This dataset contained two sessions of resting-state fMRI from 214 adults aged 18-88. Functional connectivity between all regions was strongly related to vascular health, most likely reflecting respiratory and cardiac signals. These variations in mean connectivity limit the validity of between-participant comparisons of connectivity estimates, and were best mitigated by regression of mean connectivity over participants. We also showed that high-pass filtering, instead of band-pass filtering, produced stronger and more reliable age-effects. Head motion was correlated with gray-matter volume in selected brain regions, and with various cognitive measures, suggesting that it has a biological (trait) component, and warning against regressing out motion over participants. Finally, we showed that the location of functional regions was more variable in older adults, which was alleviated by smoothing the data, or using a multivariate measure of connectivity. These results demonstrate that analysis choices have a dramatic impact on connectivity differences between individuals, ultimately affecting the associations found between connectivity and cognition. It is important that fMRI connectivity studies address these issues, and we suggest a number of ways to optimize analysis choices. Hum Brain Mapp 38:4125-4156, 2017. © 2017 Wiley Periodicals, Inc.


[Prophylactic use of ampicillin and sulbactam in colonic surgery].
The purpose of the work was an evaluation of the effectiveness of ampicillin and sulbactam administered parenterally in the prophylaxis of infections in patients after colonic surgery. The group of patients treated with ampicillin and sulbactam was compared with the control group in which penicillin, gentamicin and metronidazole were given prophylactically. Surgical wound infections were found in the group receiving ampicillin and sulbactam in 20% of cases, and in the control group in 13.3% of patients. This difference was not statistically significant (p > 0.05). In both groups infections of all perineal wounds were observed after abdominoperineal operations. No allergic reactions nor side effects were found in the group treated with ampicillin and sulbactam. Prophylactic administration of ampicillin and sulbactam in colonic surgery is similar in its effectiveness to prophylactic administration of penicillin, gentamicin and metronidazole.


An overview of medical malpractice litigation and the perceived crisis.
In this overview of medical malpractice litigation in the United States, practical and philosophic aspects of the so-called malpractice litigation crisis are addressed. After reviewing the historical, legal rationale for compensating victims of negligent conduct by others, attention is focused on the plight of physicians who are charged with medical negligence and the oppressive insurance premiums that impose a heavy burden on all health care providers, particularly those in the surgical fields. A variety of political solutions advanced to "correct" the problem is reviewed. A historical prospective of malpractice litigation in the United States is presented together with an analysis of various legislative proposals--many of which have already been enacted in various states that will ostensibly "cure" the problems that concern clinicians. Consideration of the various legislative proposals includes: arbitrary limits on pain and suffering awards (caps); elimination of joint and several liability; regulation of attorneys fees; elimination of the collateral source rule; abrogation of punitive damages; proposals for periodic payments; and statutes of repose. Various procedural changes in the processing of malpractice claims are reviewed and analyzed from the perspective of both fairness and efficacy.


Epidemiology and effect of gastrointestinal nematodes on dairy goats in Argentina.
The aim of this work was to study the epidemiology and harmful effects of gastrointestinal nematodes (GINs) on dairy goats maintained in an intensive system. Two groups of goats were studied: untreated group (UG) (subdivided into UGjun goats that kidded in June, and UGjul goats that kidded in July) and treated group (TG) (with no subgroups, treated with monepantel: 3.75 mg/kg, orally, monthly). Eggs per gram (epg) in faeces were counted, faecal culture was performed to differentiate nematode genera and milk production was measured. Differences between groups were compared using least squares means analysis of variance (milk production and milking period length) and Kruskal-Wallis test (faecal egg counts). Nematode infection was moderate, with Haemonchus and Trichostrongylus being the dominant genera; the faecal egg counts reached the level of 2000 only once throughout the study. Goats that kidded in June had higher egg count after parturition (UGjun = 1564 epg), with significant differences (p < 0.04) from those that still had not kidded (UGjul = 962 epg). Over the entire trial period, the mean total milk production of TG (399.5 L ± 34.0 L) was significantly higher (p < 0.05) than that of UG (281.6 L ± 37.5 L), representing an increase of 41.8% in total milk yield. The results of this study show a post-partum peak in egg count and a negative effect of GINs on milk yield, even with moderate infections.


Rapid screening of a large insert BAC library for specific 16S rRNA genes using TRFLP.
It is widely believed that the vast majority of microbes in the environment have-yet-to-be cultured using standard techniques. Bulk DNA from microbial communities is therefore often cloned into large insert vectors (e.g. bacterial artificial chromosomes [BAC] or cosmids) in order to study the genetic properties of these as yet (un)-cultured bacteria. In a typical BAC experiment, tens of thousands of clones are generated with only a small fraction of colonies containing the target(s) of interest. Efficient screening methodologies are therefore needed to allow targeted clone isolation. In this paper, we describe a rapid, inexpensive protocol that allows for the identification of specific 16S ribosomal RNA genes in a metagenomic library arrayed into 384-well microtiter plates. The rapid screening protocol employs Terminal Restriction Fragment Length Polymorphism (TRFLP) analysis to identify wells containing specific T-RF peaks. A nested approach using multiplexed samples of 384, 48, 8, and single colony analysis is described and applied in order to survey a BAC library generated from a marine microbial community off the coast of New Jersey. Screening revealed a total of 50 different 16 rRNA genes within the BAC library. Overall, the multiplexing format provided a simple, cost effective methodology for detecting clones bearing a target gene of interest in a large clone library. However, the limitations of screening BAC libraries using PCR methodologies and recommendations for improved screening efficiency using this approach are also discussed.


A Novel Prognostic Scoring System Using Inflammatory Response Biomarkers for Esophageal Squamous Cell Carcinoma.
We describe a novel scoring system, namely the inflammatory response biomarker (IRB) score. The aim of this study is to evaluate the clinical value of IRB score in patients undergoing curative resection for esophageal squamous cell carcinoma (SCC). We retrospectively reviewed patients who underwent curative esophagectomy. We evaluated IRB score in both non-elderly (<70 years) and elderly (≥70 years) SCC patients. The IRB score was determined as follows: a high lymphocyte-to-monocyte ratio (LMR) (>4), a high neutrophil-to-lymphocyte ratio (NLR) (>1.6), and a low platelet-to-lymphocyte ratio (PLR) (<147) were each scored as 1, and the remaining values were scored as 0; the individual scores were then summed to produce the IRB score (range 0-3). Univariate analyses demonstrated that the TNM pStage (p < 0.0001), tumor size (p = 0.002), LMR (p = 0.0057), PLR (p = 0.0328) and IRB score (p = 0.0003) were significant risk factors for a worse prognosis. On multivariate analysis, the TNM pStage (p < 0.0001) and IRB score (p = 0.0227) were independently associated with worse prognosis in overall patients. Among non-elderly patients, multivariate analyses demonstrated that the pStage (p = 0.0015) and IRB score (p = 0.0356) were independent risk factors for a worse prognosis. Among elderly patients, multivariate analysis demonstrated that the pStage (p = 0.0016), and IRB score (p = 0.0102) were independent risk factors for a worse prognosis. The present study provides evidence that the preoperative IRB score can be considered a promising independent prognostic factor of cancer-specific survival in patients undergoing curative resection for SCC, and that its predictive ability is useful in both non-elderly and elderly patients.


Response patterning during stimulus generalization in the rat.
Nine rats were trained to bar press in the presence of a clicking sound of 6.67 cps (S(D)) for 1-min variable-interval food reinforcement randomly alternated with a clicking sound of 20 cps (S(Delta)) signifying extinction. After a criterion of 90% of total responses in the presence of the S(D) was obtained, a generalization test was administered, including values of 6.67, 10.00, 13.33, and 20.00 cps, with responses in the presence of the S(D) continuing to be reinforced during testing. The test yielded a gradient of response strength with rate highest in the presence of the S(D) and decreasing with increasing distance from this value. An interresponse time (IRT) analysis of responding during generalization testing revealed no systematic differences in modal IRT category or in median IRT to the different test stimuli. Mean IRT was lowest in the presence of the S(D) and increased systematically with increasing distance from this value, supporting the hypothesis that the generalization gradient of response rate is primarily the result of an increasing proportion of "long" IRT responses to stimuli increasingly distant from the S(D).


The DEAD-box RNA helicase Dbp2 connects RNA quality control with repression of aberrant transcription.
DEAD-box proteins are a class of RNA-dependent ATP hydrolysis enzymes that rearrange RNA and RNA-protein (ribonucleoprotein) complexes. In an effort to characterize the cellular function of individual DEAD-box proteins, our laboratory has uncovered a previously unrecognized link between the DEAD-box protein Dbp2 and the regulation of transcription in Saccharomyces cerevisiae. Here, we report that Dbp2 is a double-stranded RNA-specific ATPase that associates directly with chromatin and is required for transcriptional fidelity. In fact, loss of DBP2 results in multiple gene expression defects, including accumulation of noncoding transcripts, inefficient 3' end formation, and appearance of aberrant transcriptional initiation products. We also show that loss of DBP2 is synthetic lethal with deletion of the nuclear RNA decay factor, RRP6, pointing to a global role for Dbp2 in prevention of aberrant transcriptional products. Taken together, we present a model whereby Dbp2 functions to cotranscriptionally modulate RNA structure, a process that facilitates ribonucleoprotein assembly and clearance of transcripts from genomic loci. These studies suggest that Dbp2 is a missing link in RNA quality control that functions to maintain the fidelity of transcriptional processes.


Seasonal dynamics of the tick Haemaphysalis tibetensis in the Tibetan Plateau, China.
The tick Haemaphysalis tibetensis (Acari: Ixodidae) Hoogstraal is an important arthropod vector widespread in the Qinghai-Tibet Plateau, and knowledge of its seasonal dynamics is still poor. The current study investigated the seasonal dynamics of the parasitic and non-parasitic H. tibetensis over a 2-year period from March 2014 to February 2016 in the Tibetan Plateau, China. During this timeframe, non-parasitic ticks were collected weekly by flag-dragging in grassland and shrubland areas, and parasitic ticks were removed weekly from selected sheep. Plateau pikas were captured using traps and examined for immature ticks between May to September 2014. Results suggest that non-parasitic H. tibetensis were mainly distributed in the grassland, and the parasitic adults and nymphs were found mostly on sheep. Larvae were usually found on Plateau pikas and the prevalence of infestation and mean parasitic intensity were 72.1 and 1.81%, respectively. Adults were observed from March to July with the major peak occurring in mid-April. Nymphs were found from March to August and reached a peak in late June. Larvae were collected from April to September, and their numbers peaked in late May. In the parasitic and non-parasitic period, the overall sex ratio of males to females was 1.62 and 1.30, respectively. Results show that H. tibetensis can complete one generation per year, with a population overlap between stages over the spring-summer months. These findings provide additional information on the biology and ecology of H. tibetensis as well as insights on its control in the environment and on sheep.


Development of a laser controlled device to modulate intraocular pressure.
The current standard of treatment for glaucoma is trabeculectomy. The use of glaucoma drainage devices has increased in recent years since its efficacy and safety was established as it provides an alternative surgical option. A downfall of these devices is the lack of proper flow rate control. Areas covered: In this paper we describe a glaucoma drainage device regulator that has already been protoyped and undergone initial testing. It consists of an implantable device with a semipermeable membrane that is used during glaucoma surgery and can be opened with either thermal or photodisruptive laser to adjust the amount of flow precisely and non-invasively, addressing the current difficulties of glaucoma surgeries. A literature search was conducted using MEDLINE and manuscript references for studies published in English between 2000 and 2015 using the terms glaucoma, trabeculectomy and glaucoma drainage devices. Expert commentary: The GDDR device can decrease surgical risk and allow surgeons to post-operatively adjust flow as clinically needed using a non-invasive method. Further testing is planned to substantiate these initial results and evaluate the device's biocompatibility, tunability and efficacy.


An Epidemic Zika Virus Isolate Drives Enhanced T Follicular Helper Cell and B Cell-Mediated Immunity.
Zika virus (ZIKV) is a mosquito-borne pathogen that recently caused a series of increasingly severe outbreaks. We previously demonstrated that, compared with a pre-epidemic isolate (ZIKVCDN), a Brazilian ZIKV isolate (ZIKVBR) possesses a novel capacity to suppress host immunity, resulting in delayed viral clearance. However, whether ZIKVBR modulates CD4 T cell responses remains unknown. In this study, we show that, in comparison with ZIKVCDN infection, CD4 T cells are less polarized to the Th1 subtype following ZIKVBR challenge in mice. In contrast, we observed an enhanced accumulation of T follicular helper cells 10, 14, and 21 d postinfection with ZIKVBR This response correlated with an enhanced germinal center B cell response and robust production of higher avidity-neutralizing Abs following ZIKVBR infection. Taken together, our data suggest that contemporary ZIKV strains have evolved to differentially induce CD4 T cell, B cell, and Ab responses and this could provide a model to further define the signals required for T follicular helper cell development.


Cochlear implantation in children under 12 months of age.
Children with congenital hearing loss are being identified earlier, leading to earlier intervention. Current US Food and Drug Administration (FDA) criteria states a child must be 12 months or older for cochlear implantation. The purpose of this article is to review recent publications regarding the benefits of implanting infants under 12 months of age. Topics include: safety and efficacy of surgery, speech and language acquisition outcomes, audiologic components, and limitations. Since the early 1990s, the candidacy criteria evolved drastically. However, the FDA criteria for cochlear implantation in children has remained at 12 months of age or older since 2000. Recent research indicates implanting below 12 months of age a safe and effective procedure. Speech and language outcomes showed better speech and language advantages. In addition, infants implanted earlier showed normal auditory skills as early as 3 months post cochlear implant activation. This article will also address recent findings on the limitations of earlier implantation. Recent research demonstrates positive outcomes in children implanted under 12 months of age. Developing research on earlier implantation could lead to a change in the current FDA criteria allowing infants to reach their speech and hearing potential faster.


Tactile stimulation with kinesiology tape alleviates muscle weakness attributable to attenuation of Ia afferents.
Prolonged vibration stimulation to normal individuals could lead to muscle weakness attributable to attenuation of afferent feedback. This weakness is neurophysiologically similar to that seen in patients with knee injury. Theoretically, increasing input to gamma motor neurons could reverse this weakness. Sensory input to these neurons from skin could indirectly increase Ia afferent feedback. The present study examined the effect of this tactile stimulation in the form of Kinesiology tape on muscle weakness attributable to attenuation of afferent feedback. Randomized, crossover design. All participants were measured their eccentric maximal voluntary contractions under the 2 conditions (taping and non-taping). First, maximal voluntary contraction during eccentric contraction was measured as baseline. For the taping condition, Kinesiology tape was applied around each subject's knee joint during maximal voluntary contraction measurement after vibration. For the non-taping condition, tape was not applied during maximal voluntary contraction measurement after vibration. Mean percentage changes between pre- and post-vibration stimulation were compared between two conditions. Maximal voluntary contraction and average electromyography of taping condition was significantly larger than that of non-taping condition. Our results suggest that tactile stimulation in the form of Kinesiology tape inhibits the decline of both strength and electromyography. Alpha motor neuron activity attenuated by prolonged vibration would thus be partially rescued by tactile stimulation. These results indirectly suggest that stimulation of skin around the knee could counter quadriceps femoris weakness due to attenuated Ia afferent activity.


Homeostasis and function of regulatory T cells in HIV/SIV infection.
Regulatory T cells (Tregs) play a pivotal role in the maintenance of tolerance as well as in the control of immune activation, particularly during chronic infections. In the setting of HIV infection, the majority of studies have reported an increase in Treg frequency but a decrease in absolute number in all immune compartments of HIV-infected individuals. Several nonexclusive mechanisms have been postulated to explain this preferential Treg accumulation, including peripheral survival, increased proliferation, increased peripheral conversion, and tissue redistribution. The role played by Tregs during HIV infection is still poorly understood, as two opposing hypotheses have been proposed. A detrimental role of Tregs during HIV infection was suggested based on the evidence that Tregs suppress virus-specific immune responses. Conversely, Tregs could be beneficial by limiting immune activation, thus controlling the availability of HIV targets as well as preventing immune-based pathologies. Despite the technical difficulties, getting a better understanding of the mechanisms regulating Treg dynamics remains important, as it will help determine whether we can successfully manipulate Treg function or number to the advantage of the infected host. The aim of this review is thus to discuss the recent findings on Treg homeostasis and function in the setting of HIV infection.


Columnar Liquid-Crystalline Macrocycles Synthesized via Metal Ion-Assisted Self-Assembly.
Columnar assemblies of liquid-crystalline (LC) macrocycles hold promise for the construction of nanochannels in fluid materials. Metal-assisted self-assembly is an efficient way to prepare LC macrocycles. A large π-conjugated ligand, 9,10-diphenylanthracene (DPA) bearing two β-diketones, was prepared as a building unit for the macrocycle, and a series of side chains were incorporated into the DPA to yield LC materials. The bis(β-diketone) ligands on DPA allow for the efficient formation of triangular 3:3 metallomacrocycles in the presence of square-planar Cu2+ ions. The copper-containing 3:3 metallomacrocycle with the appropriate side chains exhibited thermotropic columnar LC phases in which the columns were arranged in rectangular arrays over a wide temperature range, and well-ordered birefringent textures were observed under a polarized microscope.


Effect of antibody to neuraminidase on the maturation and hemagglutinating activity of an influenza A2 virus.
Antiserum to a recombinant between an A(o) and an A(2) influenza virus had no detectable antibody against an A(2) virus in standard hemagglutination-inhibition tests, and inhibited 95% of viral neuraminidase activity at a 1 to 400 dilution. However, on mixing virus with antiserum, a drop of up to 90% in hemagglutinin titer was observed. The effects of ultrasonication and direct electron microscopic examination indicated that the antiserum caused aggregation of virus particles. When antiserum was added to A(2) virus-infected chick embryo fibroblasts, release of virus appeared markedly inhibited. After ultrasonication to disrupt aggregates, an increase in released hemagglutinin was observed, but the resulting level was considerably lower than that in control cultures containing normal rabbit serum. In thin sections of infected cells, similar numbers of virus profiles were observed in control and antiserum-treated cultures. A marked increase in release of hemagglutinin was noted if receptor-destroying enzyme was added to antiserum-treated cultures. The results indicate that antibody to neuraminidase does not exert a direct effect on viral maturation, but inhibits the detachment of viral progeny from cell surface receptors.


Nelson's syndrome due to an intracavernous corticotropin-secreting adenoma.
To report the first case of Nelson's syndrome due to an ectopic intracranial corticotropin-secreting tumor arising entirely within the cavernous sinus. We present a case report of Nelson's syndrome with clinical, laboratory, and radiologic features throughout a 25-year period. A 54-year-old woman had been treated for Cushing's disease with bilateral adrenalectomy in 1971. Subsequently, Nelson's syndrome developed, and she had severe generalized hyperpigmentation and substantially increased plasma corticotropin levels. In 1976, she underwent a transsphenoidal hypophysectomy. Postoperatively, despite the development of panhypopituitarism and diabetes insipidus, she remained hyperpigmented and had persistently increased plasma corticotropin levels. Throughout the years, efforts to identify the site of the corticotropin-secreting tumor were unsuccessful until 1988, when magnetic resonance imaging revealed a mass in the right cavernous sinus; subsequently, petrosal sinus cannulation corroborated the intracavernous source of excess corticotropin. Cobalt-60 gamma knife radiotherapy in 1992 was followed by a clinical and hormonal response 4 1/2 years later. This report describes only the second reported case of an intracranial corticotropin-secreting tumor arising entirely within the cavernous sinus and the first such case associated with Nelson's syndrome. Although rare, the possibility of an ectopic intracranial or extracranial pituitary adenoma should be considered in patients with pituitary hypersecretion without clear-cut intrasellar abnormalities or those with no response to surgical resection of the pituitary gland.


HFACS with an additional layer of granularity: validity and utility in accident analysis.
This paper represents an attempt to evaluate the effectiveness of the Department of Defense's Human Factors Analysis and Classification (DOD-HFACS) system. DOD-HFACS delineates the human factors causes of aviation mishaps, and is based upon Wiegmann and Shappell's HFACS coding system. The main difference from HFACS is that DOD-HFACS includes an additional level of fine-grain classification. This layer consists of 147 detailed nanocodes that are to be used to identify the mishap causes. The internal validity, external validity, and utilitarian criteria of DOD-HFACS were evaluated. A total of 123 naval aviators used DOD-HFACS to identify the human factors causes of two aviation mishap scenarios. There were reasonable levels of inter-rater reliability in the majority of the nanocodes that were not considered to be causal to the mishaps. However, for those nanocodes of which at least half of the raters thought applied to the mishaps, acceptable levels of inter-rater reliability were not achieved. Similarly, when compared to 'expert' reference ratings, there were acceptable levels of agreement for those nanocodes that were discarded, but not for the majority of the nanocodes that were identified by the experts as being causal to the mishap. This study has identified that more parsimony, increased mutual exclusivity, and training are required to use DOD-HFACS effectively.


Porphyrias in Japan: compilation of all cases reported through 2002.
The first case of porphyria on record in Japan was a patient with congenital erythropoietic porphyria (CEP) reported by Sato and Takahashi in 1920. Since then until the end of December 2002, 827 cases of porphyrias have been diagnosed from characteristic clinical and/or laboratory findings (463 males, 358 females, and 6 of unknown sex). Essentially all inherited porphyrias have been found in Japan, with the incidences and clinical symptoms generally being similar to those reported for other countries. The male-female ratio was approximately 1:1 for CEP, whereas it was higher for erythropoietic protoporphyria. In contrast, preponderances of female patients exist with acute hepatic porphyrias, such as acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP), and with undefined acute porphyria. Although porphyria cutanea tarda (PCT) is believed to be increasing recently in women in other countries because of smoking and the use of contraceptives, it is still by far more prominent in males in Japan than in females. The recent increasing contribution of hepatitis C virus infection to PCT in Japan has also been recognized. but there have been no PCT cases in Japan with HFE gene mutations. Familial occurrence and consanguinity were high for CEP, as expected; however, significant consanguinity was also noted in families where CEP, AIP, HCP, VP, or PCT occurred as a single isolated case without a family history of disease. This survey also revealed that as many as 71% of acute hepatic porphyria cases were initially diagnosed as nonporphyria and later revised or corrected to porphyria, indicating the difficulty of diagnosing porphyria in the absence of specific laboratory testing for porphyrins and their precursors in urine, stool, plasma, and erythrocyte samples.


Effect of tryptophan and selected analogues on body temperatur of endotoxin-poisoned mice.
The effect of endotoxin on the body temperature of mice was studied in animals housed without bedding at an environmental temperature of 15 C. Rectal temperatures were measured during the initial 3 to 5 hr of exposure. Doses of endotoxin ranging from 0.01 to 1 ld(50), as determined for mice maintained at 25 C, produce a hypothermia in proportion to dose. Concurrent injection of tryptophan magnified this response in a dose-dependent manner. Cyproheptadine, an antiserotonin drug, antagonized both the hypothermia produced by serotonin alone, and the augmentation of hypothermia produced by tryptophan in endotoxin-poisoned mice. alpha-Methyltryptophan, an analogue of the amino acid that is known to induce tryptophan pyrrolase, also antagonized the increased hypothermia produced by tryptophan. These data support a previous suggestion that inhibition of tryptophan pyrrolase in endotoxin-poisoned mice has the effect of funneling injected tryptophan into the serotonin pathway.


What can patients see during glaucoma filtration surgery under peribulbar anesthesia?
To describe the visual sensations experienced by patients during glaucoma filtration surgery under peribulbar anesthesia and to determine possible risk factors that may affect the visual sensations experienced. King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. In this prospective questionnaire study, 75 consecutive adult patients listed for glaucoma filtration surgery (trabeculectomy or Ahmed tube implantation) under peribulbar anesthesia were interviewed postoperatively about the visual sensations experienced in their operated eye during the surgery. The mean age of the 75 patients was 59.7 years (range, 27 to 83, SD +/-12.1). Sixty-five patients (86.7%) perceived light perception during the surgery and the overall light intensity fluctuated in 45 patients (60.0%). The mean age of the patients who retained light perception intraoperatively was significantly lower compared with those who lost light perception (58.3 y vs. 68.8 y; P=0.009). Forty-six patients (61.3%) were able to perceive colors, 32 patients (42.7%) perceived movement, 31 patients (41.3%) saw surgical instruments, and 33 patients (44.0%) reported seeing the surgeon's hands or fingers. The severity of glaucoma did not affect the proportion of patients who perceived the various visual sensations. One patient (1.3%) was frightened by his intraoperative visual experience. Of the remaining patients, 53 (70.7%) said the visual sensations did not affect them, whereas 21 (28.0%) found them unpleasant. The majority of patients undergoing glaucoma filtration surgery retained light perception intraoperatively and many also experienced various visual sensations. Only 1.3% of patients were frightened by their visual experience.


Microbiota, Immune Subversion, and Chronic Inflammation.
Several host-adapted pathogens and commensals have evolved mechanisms to evade the host innate immune system inducing a state of low-grade inflammation. Epidemiological studies have also documented the association of a subset of these microorganisms with chronic inflammatory disorders. In this review, we summarize recent studies demonstrating the role of the microbiota in chronic inflammatory diseases and discuss how specific microorganisms subvert or inhibit protective signaling normally induced by toll-like receptors (TLRs). We highlight our work on the oral pathogen Porphyromonas gingivalis and discuss the role of microbial modulation of lipid A structures in evasion of TLR4 signaling and resulting systemic immunopathology associated with atherosclerosis. P. gingivalis intrinsically expresses underacylated lipid A moieties and can modify the phosphorylation of lipid A, leading to altered TLR4 signaling. Using P. gingivalis mutant strains expressing distinct lipid A moieties, we demonstrated that expression of antagonist lipid A was associated with P. gingivalis-mediated systemic inflammation and immunopathology, whereas strains expressing agonist lipid A exhibited modest systemic inflammation. Likewise, mice deficient in TLR4 were more susceptible to vascular inflammation after oral infection with P. gingivalis wild-type strain compared to mice possessing functional TLR4. Collectively, our studies support a role for P. gingivalis-mediated dysregulation of innate and adaptive responses resulting in immunopathology and systemic inflammation. We propose that anti-TLR4 interventions must be designed with caution, given the balance between the protective and destructive roles of TLR signaling in response to microbiota and associated immunopathologies.


mRNA expression of CK19, EGFR and LUNX in patients with lung cancer micrometastasis.
To evaluate the clinical significance of mRNA expression of cytokeratin 19 (CK19), epidermal growth factor receptor (EGFR) and lung-specific X protein (LUNX), a total of 42 patients who were diagnosed with non-small cell lung cancer (NSCLC) by pathology were studied retrospectively. The messenger RNA (mRNA) expression levels of CK19, EGFR and LUNX in the peripheral blood were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). The expression of CK19 mRNA did not differ significantly according to the location, size, clinical stage or differentiation of the primary tumor (all P>0.05). However, there was a significant difference in the level of CK19 mRNA expression between squamous carcinoma and adenocarcinoma. The positive rates of EGFR mRNA in the patient and the healthy control groups were 69.0 and 12.5%, respectively, and were significantly different (P<0.05). The positive rates of LUNX mRNA in the two groups were 40.5 and 0%, respectively, and were significantly different (P<0.05). The results indicate that the mRNA expression of CK19, EGFR and LUNX in the peripheral blood is of significant clinical value for the diagnosis of micrometastasis and the prognosis of lung cancer.


Evaluation of alum-based adjuvant on the immunogenicity of salmonella enterica serovar typhi conjugates vaccines.
The function of adjuvant in maintaining the long-term immune response to Typhoid conjugate vaccine (TCV) was evaluated in. Two TCV products, Vi-DT and Vi-TT, were formulated in either aluminum phosphate (AlPO4) or aluminum hydroxide (AlOH) as adjuvants and TCV formulated in phosphate buffer saline were used as controls. In each case, a group of Balb/c mice was injected intramuscularly with two doses of the formulated vaccine at two-week intervals. The anti-Vi IgG responses were monitored by Enzyme-Linked Immunosorbent Assay and the levels of CD4+ T-cells expressing cytokine were characterized using intracellular cytokine staining. All mice immunized by TCV formulated in adjuvant elicited anti-Vi response to a higher level than the group receiving TCV formulated in PBS. The extent of adsorption of TCV in AlOH was greater than that in AlPO4, and this finding correlated well with the observation that the mice immunized with two doses of Vi-DT(AlOH) elicited anti-Vi IgG to a level higher than that seen with Vi-DT(AlPO4). The mice primed with Vi-TT(AlOH) produced lower anti-Vi IgG (25.901 GM) compared to those receiving Vi-TT(AlPO4) (49.219 GM). However, after the second injection, the former raised the antibody level significantly to 137.008 GM while the latter provided a value of only 104.966 GM. The groups of mice vaccinated by TCV formulated in AlOH expressed IL4 at higher levels than the other groups, which correlated positively with the high Anti-Vi IgG in these animals. In conclusion, AlOH could be recommended as an effective adjuvant for TCV to provide a long-term immune response.


Frequency of neuropathological abnormalities in very low birth weight infants.
The occurrences of histologic changes in the central nervous system of very low birth weight infants (500 to 1500 grams) according to gestational age and postnatal age are incompletely reported. In order to better understand the abnormalities present in this patient population, the brains of 67 very low birth weight infants who died after having had at least one cranial ultrasound scan were studied. More than half the infants were born at gestational ages of 24 to 26 weeks, and only 28% died within 24 hours (h) of birth. The slides of the brains of all 67 infants were reviewed simultaneously by 3 neuropathologists who had to agree on the presence and/or absence of each histologic characteristic. Among infants who died within 24 h of birth, fully one quarter had parenchymal hemorrhage, 42% had petechial hemorrhages in the white matter, and more than 20% had hypertrophic astrocytes. These data indicate that in utero, prepartum, injury to the nervous system was common. Compared with infants who died before the sixth day, those who survived at least 6 days were twice as likely to have moderate/severe ventriculomegaly, rarefaction, amphophilic globules, hypertrophic astrocytes, macrophage foci, coagulative necrosis, and hemorrhagic necrosis than those who died before the 7th postnatal day. Parenchymal hemorrhage and moderate/severe ventriculomegaly decreased in frequency with increasing gestational age. On the other hand, the older the gestational age, the higher the likelihood of finding amphophilic globules, hypertrophic astrocytes, macrophage foci, and zones of coagulative necrosis upon neuropathologic examination. Our data indicate that several central nervous system abnormalities appear to increase with both older gestational age and older postnatal age for infants born weighing less than 1500 grams. We were unable, however, to determine the relative contribution of gestational age and postnatal age to the specific neuropathologic findings in this study.


Effects of sedation with dexmedetomidine and buprenorphine on echocardiographic variables, blood pressure and heart rate in healthy cats.
Objectives Sedative agents are occasionally used to enable echocardiographic examination when screening cats for heart disease, such as hypertrophic cardiomyopathy (HCM). Owing to their haemodynamic effects, sedative agents may alter echocardiographic measurements. The aim of the study was to evaluate the effects of the sedative combination dexmedetomidine and buprenorphine on echocardiographic variables, blood pressure (BP) and heart rate (HR) in healthy cats. Methods Fifty healthy, client-owned cats were prospectively recruited and included after physical examination. Cats were sedated intramuscularly with dexmedetomidine and buprenorphine, according to body weight. Blood pressure and HR measurements, echocardiographic and Doppler examinations were performed prior to sedation and repeated once cats had achieved acceptable sedation. Results Left ventricular internal diameter at end-diastole and systole, right ventricular internal diameter at end-diastole, left atrium (LA), pulmonary artery (PA) deceleration time, and systolic, diastolic and mean arterial blood pressure increased after sedation ( P ⩽0.022). Aortic and PA maximum velocity, fractional shortening, PA acceleration/deceleration time and HR decreased after sedation ( P <0.0001). Interventricular septum at end-diastole and systole, left ventricular posterior wall at end-diastole and systole, aortic diameter (Ao), left atrial/aortic diameter (LA/Ao) and pulmonic acceleration time did not change. Conclusions and relevance Blood pressure increased and HR decreased post-sedation. While wall thickness and LA/Ao were not affected by sedation, indices of LA and left ventricular size increased. Further studies are needed using cats with HCM to assess the effect of this sedative combination on HCM screening results.


The role of primary surgical repair technique on late outcomes of Tetralogy of Fallot: a multicentre study.
Repair of Tetralogy of Fallot (TOF) has currently excellent results with either transventricular or transatrial approach. However, it is unclear as to which has better late outcomes and what role of residual pulmonary valve (PV) regurgitation in the long term is. We report on late clinical outcomes after repair in a large series of patients with TOF, focusing on the type of surgical technique. This analysis is a retrospective multicentre study on patients undergoing TOF repair in infancy. The exclusion criteria of the study were TOF with pulmonary atresia or absent PV. We selected 720 patients who had undergone TOF repair (median age 5.7 months, interquartile range 3.7-11.7). Preoperative cyanotic spells occurred in 18%. A transatrial repair was performed in 433 (60.1%) patients. The PV was preserved in 249 (35%) patients, while the right ventricular outflow tract was reconstructed with a transannular patch (60.4%) or a conduit (4.6%) in the rest of the patients. At a median follow-up of 4 years (range 1-21, 86% complete), 10 (1.6%) patients died, while 39 (6.3%) patients required surgical reoperation and 72 (11.7%) patients required an interventional procedure. The propensity match analysis showed that the incidence of postoperative complications and adverse events at follow-up were significantly increased in patients undergoing transventricular approach repair with transannular patch (P = 0.006) and PV preservation was a significant protective factor against postoperative complications (P = 0.009, odds ratio 0.5) and late adverse events (P = 0.022). Surgical repair of TOF in infancy is a safe procedure, with good late clinical outcomes. However, transatrial approach and PV preservation at repair are associated with lower early and late morbidity.


Ataxia-telangiectasia-mutated protein kinase levels stratify patients with pancreatic adenocarcinoma into prognostic subgroups with loss being a strong indicator of poor survival.
Recently, aberrations in the gene encoding for ataxia-telangiectasia-mutated (ATM) protein kinase have been reported for pancreatic ductal adenocarcinomas (PDAC). These findings argue that ATM deficiency may play a role during carcinogenesis. Therefore, in this study, we investigated the clinical relevance of ATM expression and ATM activation in PDAC. Both ATM expression and nuclear phosphoSer1981-ATM levels were assessed by immunohistochemistry in a cohort of 133 PDAC and correlated with clinicopathological parameters. We found stratification in prognostic subgroups. Complete loss of Ser1981-ATM was indicative of the worst prognosis (median survival, 10.8 vs 14.3 months [low expression] vs 31.1 months [high expression], P < 0.001). Similarly, analysis of ATM expression demonstrated absent expression levels of ATM to be associated with dismal prognosis (median survival, 9.6 months), whereas expression of ATM in general was associated with increased survival (17.7 months, P = 0.001). Our analysis shows that both ATM expression and activated ATM are prognostic markers in PDAC with respect to standard clinicopathological parameters. These results suggest that ATM should be further explored as prognostic as well as predictive factor with respect to conventional chemotherapies and for putative synthetic lethal approaches.


Morphology and histogenesis of anal region and clitoral gland tumors induced in mice by 1,2-dimethylhydrazine.
Ninety-seven tumors induced in the anal region in female CBA and BALB/c mice by 1,2-dimethylhydrazine were examined histologically. Tumors originated mainly from the following sources: epidermis (papillomas and basal cell neoplasms), pilosebaceous complexes of the anal region (keratoacanthomas, cystic squamous cell tumors, and adenomas of the perianal sebaceous glands), and clitoral (preputial) glands (adenomas and adenoacanthomas). A subcutaneous location and late ulceration were characteristics of many tumors originating from the pilosebaceous complexes and clitoral glads. From 31 to 43% of all anal tumors were of sebaceous gland (perianal or clitoral) origin. Cystic squamous cell tumors were morphologically similar to type II keratoacanthomas of rodents. Squamous cell tumors of any origin finally became squamous carcinomas.


Influence of physostigmine upon consolidation of memory in mice.
The influence of physostigmine upon the consolidation process was investigated in a series of four experiments. Male mice of a DBA/2J strain were trained to escape shock in a Y-maze. In Experiment 1, physostigmine (.4 mg/kg, ip) impaired a previously learned task 2 days after initial learning but improved performance 11 days after initial learning. In experiments 2 and 3, it was determined that the impairment of memory found on Day 3 was transitory and no longer evident once the drug was no longer active in an animal's system. The findings of Experiment 4, in which the Day 12 facilitory effect was examined, were essentially the same as those of Experiments 2 and 3. The results of the experimentation tend to support an inhibitory or motivational hypothesis rather than a consolidation hypothesis.


Regulation of insulin release by factors that also modify glutamate dehydrogenase.
Leucine and monomethyl succinate initiate insulin release, and glutamine potentiates leucine-induced insulin release. Alanine enhances and malate inhibits leucine plus glutamine-induced insulin release. The insulinotropic effect of leucine is at least in part secondary to its ability to activate glutamate oxidation by glutamate dehydrogenase (Sener, A., Malaisse-Lagae, F., and Malaisse, W. J. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 5460-5464). The effect of these other amino acids or Krebs cycle intermediates on insulin release also correlates with their effects on glutamate dehydrogenase and their ability to regulate inhibition of this enzyme by alpha-ketoglutarate. For example, glutamine enhances insulin release and islet glutamate dehydrogenase activity only in the presence of leucine. This could be because leucine, especially in the presence of alpha-ketoglutarate, increases the Km of glutamate and converts alpha-ketoglutarate from a noncompetitive to a competitive inhibitor of glutamate. Thus, in the presence of leucine, this enzyme is more responsive to high levels of glutamate and less responsive to inhibition by alpha-ketoglutarate. Malate could decrease and alanine could increase insulin release because malate increases the generation of alpha-ketoglutarate in islet mitochondria via the combined malate dehydrogenase-aspartate aminotransferase reaction, and alanine could decrease the level of alpha-ketoglutarate via the alanine transaminase reaction. Monomethyl succinate alone is as stimulatory of insulin release as leucine alone, and glutamine enhances the action of both. Succinyl coenzyme A, leucine, and GTP are all bound in the same region on glutamate dehydrogenase, where GTP is a potent inhibitor and succinyl coenzyme A and leucine are comparable activators. Thus, the insulinotropic properties of monomethyl succinate could result from it increasing the level of succinyl coenzyme A and decreasing the level of GTP via the succinate thiokinase reaction.


Long-Term Effects of Early Adolescent Marijuana Use on Attentional and Inhibitory Control.
This study sought to examine the prospective effects of early adolescent marijuana use on late adolescent attentional and inhibitory control. Alcohol use, antisocial problems, and gender were included as statistical control variables. The community sample of 387 adolescents and a caregiver was drawn from a longitudinal study of adolescent substance use that included nine annual assessments. Adolescents were eligible if they were between ages 11 and 12 at recruitment and did not have any disabilities that would preclude them from either understanding or completing the assessment. The sample was evenly split on gender (55% female) and was predominantly non-Hispanic White (83.16%) or African American (9.07%). Attentional and inhibitory control were assessed using parent and adolescent self-reports on the Early Adolescent Temperament Questionnaire-Revised and the Adult Temperament Questionnaire. Hypotheses were tested using structural equation modeling. High levels of early marijuana use at ages 12-14 significantly predicted low levels of adolescent attentional control at ages 18-21 (β = -.20, p < .05), above and beyond early attentional control, early alcohol use, and antisocial problems. Findings suggest that marijuana use may adversely affect cognitive development, especially during the sensitive period of early adolescence. Results emphasize the need for further prospective work to investigate relationships between early adolescent marijuana use and the development of executive functioning.


Epidemic Network Analysis for Mitigation of Invasive Pathogens in Seed Systems: Potato in Ecuador.
Seed systems have an important role in the distribution of high-quality seed and improved varieties. The structure of seed networks also helps to determine the epidemiological risk for seedborne disease. We present a new approach for evaluating the epidemiological role of nodes in seed networks, and apply it to a regional potato farmer consortium (Consorcio de Productores de Papa [CONPAPA]) in Ecuador. We surveyed farmers to estimate the structure of networks of farmer seed tuber and ware potato transactions, and farmer information sources about pest and disease management. Then, we simulated pathogen spread through seed transaction networks to identify priority nodes for disease detection. The likelihood of pathogen establishment was weighted based on the quality or quantity of information sources about disease management. CONPAPA staff and facilities, a market, and certain farms are priorities for disease management interventions such as training, monitoring, and variety dissemination. Advice from agrochemical store staff was common but assessed as significantly less reliable. Farmer access to information (reported number and quality of sources) was similar for both genders. However, women had a smaller amount of the market share for seed tubers and ware potato. Understanding seed system networks provides input for scenario analyses to evaluate potential system improvements. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .


Farnesyltransferase inhibitors in acute myeloid leukemia and myelodysplastic syndromes.
Farnesyltransferase inhibitors were initially developed as Ras inhibitors as they inhibit the prenylation necessary for Ras activation. It is clear now that their mechanism of action is more complex and probably involves other proteins unrelated to Ras. At least 3 drugs within this family have been investigated in acute myeloid leukemia, myelodysplastic syndromes, and other leukemias. These are tipifarnib (R115777, Zarnestra), lonafarnib (SCH66336, Sarasar), and BMS-214662. The first 2 are administered orally, whereas BMS-214662 is given intravenously. These drugs are at different stages of development, and design of treatment schedules and methodology of the available studies are very different. Although most of the information is still preliminary, these agents have demonstrated clear evidence of clinical activity in these diseases and very favorable toxicity profiles. Several studies are still ongoing to better define the efficacy of these agents in the treatment of leukemias, as well as to determine the best schedules, the role of combination with other agents, and the role of these agents in different settings, such as the management of minimal residual disease. It is very possible that these agents will soon find their way to the ranks of established agents for the management of myeloid malignancies


Time-Adaptive Unsupervised Auditory Attention Decoding Using EEG-Based Stimulus Reconstruction.
The goal of auditory attention decoding (AAD) is to determine to which speaker out of multiple competing speakers a listener is attending based on the brain signals recorded via, e.g., electroencephalography (EEG). AAD algorithms are a fundamental building block of so-called neuro-steered hearing devices that would allow identifying the speaker that should be amplified based on the brain activity. A common approach is to train a subject-specific stimulus decoder that reconstructs the amplitude envelope of the attended speech signal. However, training this decoder requires a dedicated 'ground-truth' EEG recording of the subject under test, during which the attended speaker is known. Furthermore, this decoder remains fixed during operation and can thus not adapt to changing conditions and situations. Therefore, we propose an online time-adaptive unsupervised stimulus reconstruction method that continuously and automatically adapts over time when new EEG and audio data are streaming in. The adaptive decoder does not require ground-truth attention labels obtained from a training session with the end-user and instead can be initialized with a generic subject-independent decoder or even completely random values. We propose two different implementations: a sliding window and recursive implementation, which we extensively validate on three independent datasets based on multiple performance metrics. We show that the proposed time-adaptive unsupervised decoder outperforms a time-invariant supervised decoder, representing an important step toward practically applicable AAD algorithms for neuro-steered hearing devices.


Pathological features and pyrimidine nucleotide synthesis in human gastric carcinomas.
5-Fluorouracil, a potent anticancer drug, is clinically known to be more effective on a poorly differentiated gastric carcinoma than on a well-differentiated type. We investigated activities of thymidylate synthetase (TS) and thymidine kinase (TK) involved in de novo and salvage pathways, respectively, for pyrimidine nucleotide synthesis and histological features in 57 human gastric carcinomas. The average activities of TS in 28 poorly differentiated carcinomas and TK in 29 well-differentiated type were significantly increased to 128 and 166%, respectively, of those in normal gastric mucosa. The TK/TS ratio in the well-differentiated type was 1.7-fold higher than that in the poorly-differentiated type. Therefore, the de novo pathway for pyrimidine nucleotide synthesis is so predominant in a poorly differentiated carcinoma, but not in a well-differentiated type, that the potent TS inhibitor 5-FU or its derivatives are suggested to suppress the growth of the poorly-differentiated gastric carcinoma.


Genetic diversity of influenza B virus in 2009-2010 and 2010-2011 in Tunisia.
The authors had for aim to characterize influenza B strains having circulated in Tunisia to identify new mutations and compare them with reference strains. The epidemiological surveillance of influenza allowed identifying 19 patients with symptoms related to respiratory infection, who had been infected by influenza B strains isolated in several regions of Tunisia in 2009-2010 and in 2010-2011. Laboratory identification and detection of mutations in the segment encoding hemagglutinin of influenza viruses was performed by real time PCR and sequencing. The two influenza B Tunisian strains of the 2009-2010 season belonged to the Victoria lineage, whereas 2010-2011 season strains belonged to B/Victoria/2/87 and B/Yamagata/16/88 lineages with a dominance of the Yamagata lineage (76%). This study allowed identifying amino acid substitutions: T121A, S150I, N165Y, T181A, G183R, D196N, S229D, M251V and K253R in the B/Yamagata lineage; L58P, N75K, K109N, N165K, S172P and K257R into the B/Victoria lineage. These mutations were specific of Tunisian groups of variants. Most influenza B-Yamagata lineage viruses (69%) were associated with severe cases. Molecular analysis of the various influenza B strains circulating in Tunisia is useful to detect new mutations that can modify the phenotype of influenza strains.


Chronic refractory idiopathic thrombocytopenic purpura (ITP) and anti-CD20 monoclonal antibody: a case report.
Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by accelerated and premature destruction of platelets by reticuloendothelial system. CD20, a trans-membrane B-cell-specific antigen, is a potential target for treatment of certain malignant and nonmalignant plasma cell disorders including refractory ITP. Rituximab is a genetically engineered human anti-CD20 monoclonal antibody, which is approved for the treatment of low-grade non-Hodgkin's lymphoma. Recent clinical reports suggest that rituximab may be useful in treating certain patients with chronic refractory ITP. A 59-year-old woman with refractory ITP was placed on rituximab (four weekly doses of 375 mg/m(2)) and her condition and platelet count were observed for 18 months. There was a gradual increase in platelet count and she was symptom free in this period and no side effects of the drug were reported. Anti-CD20 antibodies are likely to be used in the treatment of refractory ITP cases, but further studies about treatment schedule and criteria for patient selection should be done.


RamA, a protein required for reductive activation of corrinoid-dependent methylamine methyltransferase reactions in methanogenic archaea.
Archaeal methane formation from methylamines is initiated by distinct methyltransferases with specificity for monomethylamine, dimethylamine, or trimethylamine. Each methylamine methyltransferase methylates a cognate corrinoid protein, which is subsequently demethylated by a second methyltransferase to form methyl-coenzyme M, the direct methane precursor. Methylation of the corrinoid protein requires reduction of the central cobalt to the highly reducing and nucleophilic Co(I) state. RamA, a 60-kDa monomeric iron-sulfur protein, was isolated from Methanosarcina barkeri and is required for in vitro ATP-dependent reductive activation of methylamine:CoM methyl transfer from all three methylamines. In the absence of the methyltransferases, highly purified RamA was shown to mediate the ATP-dependent reductive activation of Co(II) corrinoid to the Co(I) state for the monomethylamine corrinoid protein, MtmC. The ramA gene is located near a cluster of genes required for monomethylamine methyltransferase activity, including MtbA, the methylamine-specific CoM methylase and the pyl operon required for co-translational insertion of pyrrolysine into the active site of methylamine methyltransferases. RamA possesses a C-terminal ferredoxin-like domain capable of binding two tetranuclear iron-sulfur proteins. Mutliple ramA homologs were identified in genomes of methanogenic Archaea, often encoded near methyltrophic methyltransferase genes. RamA homologs are also encoded in a diverse selection of bacterial genomes, often located near genes for corrinoid-dependent methyltransferases. These results suggest that RamA mediates reductive activation of corrinoid proteins and that it is the first functional archetype of COG3894, a family of redox proteins of unknown function.


Globe penetration in a cat following maxillary nerve block for dental surgery.
Dental treatment was carried out in an 8.5-year-old castrated male domestic shorthair cat found to have tooth resorption. Right mandibular, and right and left maxillary nerve blocks were administered using a 1 ml syringe attached to a 25 G x 5/8 inch needle and an intraoral technique. The following day the cat displayed blepharospasm of the right eye. The ocular signs progressed and 5 days later an ophthalmologist confirmed a blind, glaucomatous right eye. It was suspected that the eye had suffered a penetrating injury during dental surgery. Enucleation of the right eye was performed and gross and histopathological examination revealed a penetrating wound consistent with a needle tract injury. Complications arising from veterinary dental regional anaesthesia appear to be rare; however, it may be that they are under-reported. This case report highlights the risks involved and reviews the safest and most efficacious regional anaesthesia technique for the feline maxilla.


Knockdown of cytochrome P450 2E1 inhibits oxidative stress and apoptosis in the cTnT(R141W) dilated cardiomyopathy transgenic mice.
Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme that catalyzes the metabolism of toxic substrates. CYP2E1 is upregulated in heart disease, including the dilated cardiomyopathy (DCM) mouse model. Here, knockdown of CYP2E1 significantly ameliorated the dilated left ventricle, thin wall, and dysfunctional contraction in the cTnT(R141W) and adriamycin-induced DCM mouse models. Interstitial fibrosis, poorly organized myofibrils, and swollen mitochondria with loss of cristae were improved in the myocardium of α-myosin heavy chain (MHC)-cTnT(R141W)×CYP2E1-silence double-transgenic mice when compared with the cTnT(R141W) transgenic mice. Oxidative stress, the activation of caspase 3 and caspase 9, the release of cytochrome c, and the apoptosis in the myocardium were significantly decreased in double-transgenic mice compared with the cTnT(R141W) transgenic mice. In summary, the expression of CYP2E1 is upregulated in heart disease and might be induced by hypoxemia in cardiomyopathy. The overexpression of CYP2E1 can enhance the metabolism of endogenous ketones to meet the energy demand of the heart in certain disease states, but the overexpression of CYP2E1 can also increase oxidative stress and apoptosis in the DCM heart. Knockdown or downregulation of CYP2E1 might be a therapeutic strategy to control the development of DCM after mutations of cTnT(R141W) or other factors, because DCM is the third most common cause of heart failure and the most frequent cause of heart transplantation.


High-dose oral medroxyprogesterone acetate or tamoxifen as adjuvant hormone therapy for node-negative early-stage breast cancer: randomized trial with 7-year update.
A randomized adjuvant trial compared tamoxifen 20 mg daily for 5 years with high-dose oral medroxyprogesterone acetate (MPA) 1 g orally for 9 months. One hundred ninety-four patients with histologically proven primary node-negative breast carcinoma were enrolled between December 1990 and October 1996, with 98 patients randomized into the tamoxifen arm and 96 into the MPA arm. At a median follow-up of 86 months, 25 relapses and 13 deaths were recorded. The relapse-free survival rate at 7 years in the tamoxifen arm was 93%, versus 81% in the MPA arm (P = 0.02). The difference was observed in patients with stage T2 disease (100% in the tamoxifen group vs. 64% in the MPA group; P = 0.01), in younger and/or premenopausal patients (in patients < 50 years of age, 100% in the tamoxifen arm vs. 81% in the MPA arm [P = 0.02], and in patients > or = 50 years of age, 90% in the tamoxifen arm vs. 82% in the MPA arm [P = 0.16]). Also, the overall survival rate at 7 years was lower in women < 50 years of age (P = 0.04).


Surface induced asymmetry of acceptor wave functions.
Measurements of the local density of states of individual acceptors in III-V semiconductors show that the symmetry of the acceptor states strongly depends on the depth of the atom below a (110) surface. Tight-binding calculations performed for a uniformly strained bulk material demonstrate that strain induced by the surface relaxation is responsible for the observed depth-dependent symmetry breaking of acceptor wave functions. As this effect is strongest for weakly bound acceptors, it explains within a unified approach the commonly observed triangular shapes of shallow acceptors and the crosslike shapes of deeply bound acceptor states in III-V materials.


Stage-specific expression of Smad2 and Smad3 during folliculogenesis.
Paracrine and autocrine growth factors can affect many different aspects of ovarian follicle development. Many members of the transforming growth factor beta (TGFbeta) family of growth factors and their receptors are expressed in developing follicles. However, the presence and function of the family of the TGFbeta signaling molecules known as Smads have not been evaluated during follicle development. We have demonstrated that two Smad family members that function as mediators for both activin and TGFbeta are expressed in granulosa cells of preantral follicles but not in large antral follicles. Smad2 expression, but not Smad3 expression, returns in luteal cells. Both Smad2 and Smad3 are translocated to the nucleus of granulosa cells in response to treatment with either TGFbeta or activin. However, Smad2 is more responsive to activin stimulation, and Smad3 is more responsive to TGFbeta stimulation. Stage-specific expression and differing ligand sensitivity of signaling molecules may work together to allow different effects of TGFbeta family ligands using the same signaling pathways over the course of follicular development.


Unusual case of necrotizing fasciitis caused by Vibrio cholerae O137.
We report a case of necrotizing fasciitis caused by Vibrio cholerae O137 in an immunocompromised 49-year-old man. The infection was acquired following a minor traumatic injury and exposure to seawater during the summer of 2009 in Italy. Although highly immunocompromised, the patient survived. The strain was cytotoxic, invasive, and adhesive and contained a fragment of the El Tor-like hemolysin (El Tor hlyA) gene.


Lived Experience and Risk Reduction Behaviors Among Sero-Negative Discordant Male Partners Living with HIV-Positive Women in Addis Ababa, Ethiopia, 2019: A Qualitative Phenomenological Study.
This study aimed to explore lived experience and risk reduction behaviors among sero-negative, discordant male partners living with HIV-positive women in Addis Ababa, Ethiopia, 2019. A phenomenological study was conducted to explore lived experience and risk reduction behaviors. The study participants were purposively selected 13 sero-negative male partners living with HIV-positive women. An in-depth interview was used to explore important information. A semi-structured interview guide was used to execute the in-depth interview. The in-depth interview was analyzed thematically through the support of ATLAS-ti 7 software. Scientific explanation of discordant result is not well understood rather, it is associated with religious, cultural, natural resistance, and passive carrier explanations. Sero-negative partners faced several challenges and lived dilemmatic life related to partner mood or behavioral change, maintaining the marital relationship, the desire of child, psychosocial, sexual life, and lack of support system. Risk reduction behaviors like condom use, safe sex practice, preventing sexually transmitted infection, avoiding substance use, continuous checkup and follow-up were not well reflected in their lived experience and were poorly understood. Personalized use of sharp materials to avoid blood contact and support of a partner in the proper use of ART drugs were positively reported risk reduction behaviors. Sero-negative partners need special attention just as HIV-positive partners in couples with the discordant result. Life suffering is not limited to HIV-positive partners, rather sero-negative partners also faced several challenges and dilemmatic life. HIV transmission risk reduction behavior is not well established and understood.


Status and Future Directions of Therapeutics and Prognosis of Cardiac Amyloidosis.
Accumulation of aberrant proteins in the heart causes cardiac amyloidosis, an uncommon and complicated illness. It can be classified into two main types: light chain (AL) and transthyretin (ATTR). The diagnosis of cardiac amyloidosis is challenging due to its non-specific clinical presentation and lack of definitive diagnostic tests. Diagnostic accuracy has increased with the advent of modern imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Depending on the severity of cardiac amyloidosis, a number of treatments may be attempted and specified according to the subtype of amyloidosis and the presence of complications. However, there are still significant challenges in treating this condition due to its complexity and lack of effective treatments. The prognosis for patients with cardiac amyloidosis is poor. Despite recent advances in diagnosis and treatment, there is still a need for more effective treatments to improve outcomes for patients with this condition. Therefore, we aim to review the current and future therapeutics reported in the literature and among ongoing clinical trials recruiting patients with CA.