Mupirocin resistance is not an inevitable consequence of mupirocin use.
The rate of mupirocin resistance in meticillin-resistant Staphylococcus aureus (MRSA) in Besançon University Hospital is low with a decreasing trend, from 10% in 2004 to 3% in 2009. This trend in resistance paralleled mupirocin consumption. Genotyping results showed that this decrease was not linked to a change in MRSA clones. It appears that the way in which the mupirocin is used, rather than the volume, plays a role in the emergence of resistance and that its cautious use is likely to maintain the mupirocin resistance at a low level, thus preserving its efficacy.


De novo variant in SCN4A causes neonatal sodium channel myotonia with general muscle stiffness and respiratory failure.
Variants of the skeletal muscle sodium channel gene SCN4A are associated with different neuromuscular disorders including sodium channel myotonia. Here, we report an infant with a de novo variant in SCN4A presenting with neonatal onset of severe muscle stiffness with involvement of facial and eyelid muscles, and life-threatening events with respiratory failure due to severe apnoea and thorax rigidity. The boy dramatically improved in both respiratory and motor function under carbamazepine therapy.


Ultra-low-level laser therapy.
A growing number of laboratory and clinical studies over the past 10 years have shown that low-level laser stimulation (633 or 670 nm) at extremely low power densities (about 0.15 mW/cm(2)), when administered through a particular emission mode, is capable of eliciting significant biological effects. Studies on cell cultures and animal models as well as clinical trials give support to a novel therapeutic modality, which may be referred to as ultra low level laser therapy (ULLLT). In cultured neural cells, pulsed irradiation (670 nm, 0.45 mJ/cm(2)) has shown to stimulate NGF-induced neurite elongation and to protect cells against oxidative stress. In rats, anti-edema and anti-hyperalgesia effects following ULLL irradiation were found. Clinical studies have reported beneficial effects (also revealed through sonography) in the treatment of musculoskeletal disorders. The present paper reviews the existing experimental evidence available on ULLLT. Furthermore, the puzzling issue of the biophysical mechanisms that lie at the basis of the method is explored and some hypotheses are proposed. Besides presenting the state-of-the-art about this novel photobiostimulation therapy, the present paper aims to open up an interdisciplinary discussion and stimulate new research on this subject.


Studies of cultured human and simian fetal brain cells. II. Infections with human (BK) and simian (SV40) papovaviruses.
Both simian virus 40 (SV40) and BK viruses infected and lysed not only oligodendroblasts and astrocytes, but also neuroblasts and epithelioid or mesenchymal cells in cultures of fetal brain cells derived from human, rhesus, and cynomolgus hosts. Lytic infections of these four cell types differed ultrastructurally in the amount and arrangement of virions in the nucleus, the extent of nuclear membrane redundancy, the presence of nuclear virion arrays, and the amounts of virions in the cytoplasm. However, major differences were not noted between SV40 and BK viruses, nor between different species of origin or region of brain explanted. Modified astrocytic cells persisted in cultures from all three sources after infection by either virus. These cells stained for glial fibrillary acidic protein (GFAP) and polyomavirus tumour (T) antigen, but did not subculture indefinitely.


Fatty acid changes in the hepatic endoplasmic reticulum during pregnancy in the rat.
In the rat, pregnancy caused a significant reduction of total hepatic and microsomal phospholipid content mainly manifesting in phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine fractions. Fatty acid content of the liver and microsomes was also reduced. The major components involved in this change were palmitic, stearic, oleic, linoleic and arachidonic acids. The level of docosahexaenoic acid was raised; the other acyl components remained unaltered. All these chnages were reversible; both hepatic and microsomal phospholipids and fatty acids returned to the non-pregnany level 2--3 weeks after delivery.


Serum phenobarbital concentration predictions by a personal computer software system.
The ability of a personal computer software system to predict actual serum phenobarbital concentrations (SPC) in outpatients taking phenobarbital chronically was assessed by comparing actual with predicted SPC for accuracy, bias, and precision. Data for a four-year period were collected on patients at an outpatient clinic's pharmacokinetic consultation service. The study group included 50 adults and children with at least one SPC taken at a known time after dose administration. Input variables were weight, sex, height, age, concomitant drugs and diseases, phenobarbital dosage regimen, and the time and reported value of all SPC. Initially, SIMKIN (SIMulated KINetics) simulated dosing regimens on the basis of literature estimates of pharmacokinetic parameters; SPC were then estimated for these regimens and compared with actual values. One or two additional SPC were added to the input data and analyzed, and the predicted SPC compared with actual values. Although SIMKIN's accuracy and bias as measured by regression analysis and mean prediction error, respectively, were within clinically acceptable limits, the precision was not. However, these results are limited by the population studied. Patient compliance, concomitant phenytoin therapy, changes in phenobarbital pharmacokinetic parameters with chronic dosing, and disease interactions may significantly affect predictive ability. The clinical effects of these factors need to be evaluated to further improve predictions.


Urban-rural disparity in the relationship between ambient air pollution and preterm birth.
Some studies have reported that air pollution exposure can have adverse effects on pregnancy outcomes. However, the disparity between urban and rural areas in the risk of preterm birth (PTB) has yet to be elucidated. Considering geographic contexts as homogeneous or ignoring urban-rural differences cannot accurately reveal the disparities in the health effects of air pollution under different geographic contexts. The aims of this study were to examine the disparities in the risks of PTB in three different regions and five urban-rural types and to investigate the extent to which fine particulate matter (PM2.5) exposure during the entire pregnancy can explain the variations. We collected data on 429,865 singleton newborns born in 2014 in Hubei Province, China, and divided Hubei Province into three regions. Spatial correlation methods were employed to measure the associations between the rate of PTB and air pollution using average annual indexes for the entire province and regions. A series of multilevel logistic models were conducted to examine disparities in the risks of PTB with decreases in urbanity and the effects of air pollution exposure on the occurrence of preterm births. The PM2.5 concentration was significantly different across the regions. The eastern region had the most wide-ranged and serious level of pollution, whereas the levels in the middle and western regions weakened. The odds of PTB and air pollution exhibited a positive spatial correlation for the entire province and in the east (BiMoran's I = 0.106 and 0.697, respectively). Significant urban-rural disparities in the risks of PTB were noted in the east and middle regions, and the mean PM2.5 exposure during the entire pregnancy was positively associated with PTB risk. However, in the west, the results showed weak differences in the risks of PTB among the five urban-rural types and an insignificant effect of PM2.5 exposure. The direction of the effect of district/county-level income on PTB varied by region. This study finds that air pollution exposure and PTB have significant and positive spatial relationships in areas with a serious air pollution burden. The risks of PTB in three regions of Hubei Province follow the same W-shaped pattern as urbanity decreases and rurality increases. High levels of air pollution exposure may be an important disadvantage for urban pregnant women in this setting.


Effect of body surface decolonisation on bacteriuria and candiduria in intensive care units: an analysis of a cluster-randomised trial.
Urinary tract infections (UTIs) are common health-care-associated infections. Bacteriuria commonly precedes UTI and is often treated with antibiotics, particularly in hospital intensive care units (ICUs). In 2013, a cluster-randomised trial (REDUCE MRSA Trial [Randomized Evaluation of Decolonization vs Universal Clearance to Eradicate MRSA]) showed that body surface decolonisation reduced all-pathogen bloodstream infections. We aim to further assess the effect of decolonisation on bacteriuria and candiduria in patients admitted to ICUs. We did a secondary analysis of a three-group, cluster-randomised trial of 43 hospitals (clusters) with patients in 74 adult ICUs. The three groups included were either meticillin-resistant Staphylococcus aureus (MRSA) screening and isolation, targeted decolonisation (screening, isolation, and decolonisation of MRSA carriers) with chlorhexidine and mupirocin, and universal decolonisation (no screening, all patients decolonised) with chlorhexidine and mupirocin. Protocol included chlorhexidine cleansing of the perineum and proximal 6 inches (15·24 cm) of urinary catheters. ICUs within the same hospital were assigned the same strategy. Outcomes included high-level bacteriuria (≥50 000 colony forming units [CFU]/mL) with any uropathogen, high-level candiduria (≥50 000 CFU/mL), and any bacteriuria with uropathogens. Sex-specific analyses were specified a priori. Proportional hazards models assessed differences in outcome reductions across groups, comparing an 18-month intervention period to a 12-month baseline period. 122 646 patients (48 390 baseline, 74 256 intervention) were enrolled. Intervention versus baseline hazard ratios (HRs) for high-level bacteriuria were 1·02 (95% CI 0·88-1·18) for screening or isolation, 0·88 (0·76-1·02) for targeted decolonisation, and 0·87 (0·77-1·00) for universal decolonisation (no difference between groups, p=0·26), with no sex-specific reductions (HRs for men: 1·09 [95% CI 0·85-1·40] for screening or isolation, 1·01 [0·79-1·29] for targeted decolonisation, and 0·78 [0·63-0·98] for universal decolonisation, p=0·12; HRs for women: 0·97 [0·80-1·17] for screening and isolation, 0·83 [0·70-1·00] for targeted decolonisation, and 0·93 [0·79-1·09] for universal decolonisation, p=0·49). HRs for high-level candiduria were 1·14 (0·95-1·37) for screening and isolation, 0·99 (0·83-1·18) for targeted decolonisation, and 0·83 (0·70-0·99) for universal decolonisation (p=0·05). Differences between sexes were due to reductions in men in the universal decolonisation group (HRs: 1·21 [95% CI 0·88-1·68] for screening or isolation, 1·01 [0·73-1·39] for targeted decolonisation, and 0·63 [0·45-0·89] for universal decolonisation, p=0·02). Bacteriuria with any CFU/mL was also reduced in men in the universal decolonisation group (HRs 1·01 [0·81-1·25] for screening or isolation, 1·04 [0·83-1·30] for targeted decolonisation, and 0·74 [0·61-0·90] for universal decolonisation, p=0·04). Universal decolonisation of patients in the ICU with once a day chlorhexidine baths and short-course nasal mupirocin could be a potential preventive strategy in male patients because it significantly decreases candiduria and any bacteriuria, but not for women. HAI Program from AHRQ, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program, CDC Prevention Epicenters Program.


1. Among the species of the Carabid genus Pterostichus different types of annual periodicity can be found. P. cupreus and P. coerulescens were investigated as representatives of spring breeders with summer larvae (hibernating as adults) and P. vulgaris as a representative of autumn breeders with winter larvae. 2. The female spring breeders enter dormancy, irrespective of the photoperiod. This can be overcome by successive treatment with short-day followed by longday in continuous warmth (photoperiodic parapause). In the field the increasing length of day in spring terminates the parapause. In both species the percentage of mature females depends on the duration of short-day treatment. After eight weeks of short-day the percentage of females with ripe eggs reaches maximal values of up to 100%. By a repeated treatment with first short-day and then long-day old females can be stimulated to a second development of ripe eggs. A temporary drastic lowering of temperature for four months terminates the parapause of the females even under constant photoperiods (continuous short-day or long-day), but under these conditions less than 40% of the females of P. coerulescens and less than 20% of those of P. cupreus mature. The parapause in females can also be terminated by raising the light intensity under constant short-day. In this case, however, only 33% of the females of P. coerulescens became ripe. 3. Not more than 25% of the males of both species of spring breeders mature under continuous warmth after a change from short-to long-day. They do mature, however, when short-day treatment is combined with cold. If the influence of cold and short-day is prolonged from 2 to 4 months and if the temperature is lowered from +5\2-7\dg to +2\2-3\dg the percentage of mature males rises steeply (up to more than 80%). Females from laboratory cultures paired with males treated with cold and short-day are much more prolific than those paired with males which have been treated with warmth and short-day. The dormancy of a high percentage of the males of P. cupreus in warmth can also be terminated in continuous long or continuous short-day by temporary lowering of temperature (thermic parapause). Males of P. coerulescens mature due to changing temperatures only in continuous short-day, but not in long-day. 4. In warmth, development and metamorphosis of both the spring breeders under investigation takes place under short-as well as under long-day. Mortality is equal in both cases. The duration of development is prolonged in both species under long-day. 5. The adults of both sexes of the autumn breeder P. vulgaris mature irrespective of the photoperiod. They show no dormancy. 6. The larval development ofP. vulgaris is indepent of the photoperiod. In warmth, the 2nd or 3rd instar falls into a form of dormancy which will be called a thermic parapause of the larvae, because it can be terminated by a temporary treatment of the 3rd instar with cold.


Methodology of motor skill and laterality: new test of hand preference in Macaca nemestrina.
Ten female pig-tailed macaques (Macaca nemestrina) were tested for hand preference and hand skill (i.e., speed of performance and error rate). The experimental task was naturalistic, calling for adaptive manual skills and fine manipulation: the monkeys had to remove small food rewards embedded in a vertical array, and precision opposition of thumb and forefinger was needed to extract each pellet. Each monkey was tested 10 times on 10 different days. The results indicated individual hand preference rather than population-level handedness; however, a tendency toward right predominance was found. The results on hand skill showed a relation between error rate and hand preference, as the preferred hand made fewer errors. A different and unexpected finding was obtained when skill was evaluated in terms of speed of performance: in adult subjects the left hand was quicker than the right. Therefore, different kinds of skill showed different patterns in relation to hand preference.


Energy Minimisers with Prescribed Jacobian.
We consider the class of planar maps with Jacobian prescribed to be a fixed radially symmetric function f and which, moreover, fixes the boundary of a ball; we then study maps which minimise the 2p-Dirichlet energy in this class. We find a quantity λ [ f ] which controls the symmetry, uniqueness and regularity of minimisers: if λ [ f ] ≤ 1 then minimisers are symmetric and unique; if λ [ f ] is large but finite then there may be uncountably many minimisers, none of which is symmetric, although all of them have optimal regularity; if λ [ f ] is infinite then generically minimisers have lower regularity. In particular, this result gives a negative answer to a question of Hélein (Ann. Inst. H. Poincaré Anal. Non Linéaire 11(3):275-296, 1994). Some of our results also extend to the setting where the ball is replaced by R 2 and boundary conditions are not prescribed.


Radio-guided video-assisted parathyroidectomy: a preliminary report.
The surgical management of primary hyperparathyroidism is changing both in terms of the extent of cervical exploration and in technique. There are many new mini-invasive procedures for neck surgery. We describe our preliminary experience with a technique that combines two mini-invasive procedures--radio-guided and video-assisted parathyroidectomy. Six consecutive patients with no recurrent or persistent primary hyperparathyroidism, no previous cervical operations, and no thyroid pathologies were selected to undergo radio-guided video-assisted parathyroidectomy. One case was converted. There was no morbidity or mortality in the postoperative period. Six parathyroids were removed; the histological diagnosis was adenoma in all cases. All patients were discharged on the 1st postoperative day. Calcium serum levels normalized in all cases, with only one case of transient postoperative hypocalcemia. All patients were normocalcemic after 6 months. Radio-guided video-assisted parathyroidectomy is feasible in selected patients. However, longer follow-up and more cases are necessary before this procedure can be applied routinely.


Morphological effects of estrogen on the female rat liver nucleolus.
Prolonged administration of nonphysiological amounts of estrogen induced markedly enlarged nucleoli volumes in rat hepatocytes, indicative of increased nucleolar RNA synthesis. Physiological amounts of drug had no apparent morphological effects on the hepatocytes.


Rice body synovitis in systemic lupus erythematosus.
Rice bodies (RBs) synovitis in the shoulder joints of systemic lupus erythematosus patients is a rare clinical condition that has not been previously reported. Despite the fact that the diagnosis of RBs synovitis has primarily relied on MRI imaging, ultrasound has been used less frequently. In this report, we discuss a 43-year-old female diagnosed with systemic lupus erythematosus who presented with pain and swelling in the right shoulder. The ultrasound findings were typical, and the patient was diagnosed with RBs synovitis, as she had no history of tuberculosis or rheumatoid arthritis. Subsequently, the patient underwent ultrasound-guided percutaneous biopsy and surgical excision, which led to a good postoperative outcome. Based on this case, a literature review of RBs synovitis over the past 2 decades indicates that rice bodies synovitis is rare in clinical presentation accompanied by SLE. Moreover, ultrasound has not been extensively employed for diagnosing this condition. It is important to note the pivotal role of ultrasound in detecting RBs synovitis, and it should be the preferred method for early detection. Therefore, ultrasound physicians should be well informed about this condition to enhance diagnostic precision.


Classification of chinese fragrant rapeseed oil based on sensory evaluation and gas chromatography-olfactometry.
Fragrant rapeseed oils and traditional pressed oils are increasingly popular in China owing to their sensory advantages. Many fragrant rapeseed oils are labeled by different fragrance types; however, the scientific basis for these differences is lacking. To identify the distinctive aroma and achieve fragrance classification, the sensory characteristics and aroma components of nine different fragrant rapeseed oils were analyzed via sensory evaluation and gas-chromatography-mass spectrometry-olfactometry. A total of 35 aroma compounds were found to contribute to the overall aroma. By using chemometrics methods, rapeseed oils were categorized into three fragrance styles: "strong fragrance," "umami fragrance," and "delicate fragrance." In total, 10 aroma compounds were predicted to be the most effective compounds for distinguishing sensory characteristics of fragrant rapeseed oil. According to our results, this approach has excellent potential for the fragrance classification and quality control of rapeseed oil.


Trial of labor after one cesarean: role of the order and number of prior vaginal births on the risk of emergency cesarean delivery and neonatal admission.
To evaluate the influences of mode of immediate preceding delivery and number of prior vaginal births on the risk of repeat cesarean and neonatal admission at attempted vaginal birth after cesarean. We performed a retrospective study of the risk factors for emergency repeat cesarean delivery and neonatal admission in a trial of labor after prior cesarean section. The study comprised 342 women at term with at least one prior vaginal delivery in addition to one previous lower transverse cesarean. Clinical variables with crude p < 0.2 on Fisher's exact test for the defined primary outcomes of repeat cesarean and neonatal admission were included in the model for multivariable logistic regression analysis. Cesarean as the immediate preceding mode of delivery (adjusted odds ratio, 5.3; 95% confidence interval, 2.5-10.8) was an independent predictor of emergency repeat cesarean delivery but not of neonatal admission. Higher parity of two or more previous vaginal deliveries compared with only one prior vaginal delivery was not associated with repeat cesarean or neonatal admission. In women who have had prior vaginal birth attempting a trial of labor after cesarean, a vaginal delivery before cesarean delivery is an independent risk factor for repeat cesarean. Women with two or more prior vaginal births have a similar risk for repeat cesarean and neonatal admission to women with only one prior vaginal birth.


Ill-conditioning associated with the "end-point" method for the determination of kinetic parameters describing irreversible enzyme inactivation by an unstable inhibitor.
Study of the complete time-course of irreversible enzyme inhibition by an unstable inhibitor yields more information than can be obtained by recording data only at the end point of reaction. Time-course analysis of co-operative irreversible enzyme inhibition by an unstable inhibitor has been shown to be considerably less susceptible to ill-conditioning than the "end-point" method for the determination of kinetic parameters describing inactivation. As a result, mechanisms that cannot be distinguished by the "end-point" method are readily differentiated by time-course analysis without the need to isolate intermediate species.


[Special considerations in the management of cytomegalovirus infection in pediatric solid organ transplant recipients].
In pediatric patients, the main risk factor for the development of post-transplantation cytomegalovirus (CMV) is the absence of specific immunity to the virus in the pretransplantation period. CMV infection has become less of a problem in pediatric solid organ transplant (SOT) recipients mainly due to the availability of sensitive diagnostic techniques, the development of prevention strategies, and the possibility of starting effective antiviral treatments. Both polymerase chain reaction (PCR) techniques and pp65 antigenemia have proved to be effective in the diagnosis and monitoring of children with CMV infection. However, in some types of transplantation, such as lung transplantation, CMV infection continues to be an important risk factor for mortality or retransplantation in D+/R(-1) patients. Prophylaxis with ganciclovir followed by valganciclovir for between 3 and 6 months is recommended over preemptive therapy. In the treatment of CMV disease, the use of ganciclovir is recommended until a negative weekly result of PCR or pp65 antigenemia is obtained. The total duration of treatment, both in viral syndrome and organ disease, is the same as in adults. Treatment can be completed by substituting intravenous ganciclovir for oral treatment in older children and adolescents.


KIT, PDGFRalpha and EGFR analysis in nephroblastoma.
Nephroblastoma prognosis has dramatically improved, but an unfavourable prognostic subgroup warrants development of novel therapeutic strategies. Selective KIT, PDGFRalpha and epidermal growth factor receptor (EGFR) tyrosine kinase inhibition evolved as powerful targeted therapy for gastrointestinal stromal tumours and non-small-cell lung cancer. To investigate a potential role for tyrosine kinase inhibition, we analyzed 209 nephroblastomas for immunohistochemical KIT and EGFR expression, 63 nephroblastomas for mutations in KIT exons 9, 11, 13, EGFR exons 18, 19, 20 and 21, and all 209 nephroblastomas for PDGFRalpha exons 12, 14 and 18. Twenty-two tumours (10.5%) expressed KIT, 31 (14.8%) EGFR, and 10 (4.8%) both KIT and EGFR, respectively. KIT expression was relatively more common among high-risk tumours (6/27; 22.3%) compared to low-/intermediate-risk tumours (26/181; 14.4%). Nine patients deceased, four of which had high-risk tumours with KIT expression in two of four and EGFR expression in one of four. There were no KIT, PDGFRalpha or EGFR mutations. Our results suggest no significant contribution of KIT, EGFR or PDGFRalpha mutations to nephroblastoma pathogenesis. Despite a trend towards association of immunohistochemical KIT and EGFR expression with poor outcome in high-risk nephroblastomas, statistical analysis did not yield significant correlations in this subgroup. Therefore, it remains open if KIT, PDGFRalpha or EGFR tyrosine kinase inhibition constitute a therapeutic target in nephroblastoma in the absence of KIT, PDGFRalpha or EGFR mutations.


Multiple roles for TGFβ receptor type II in regulating the pancreatic response in acute pancreatitis.
In their recent publication in Journal of Pathology, Grabliauskaite and Sapanora and their colleagues in Zurich use a conditional ablation of the TGFβ type II receptor (TBRII) to analyse its specific role in pancreatic epithelial cells in response to a caerulein-induced model of acute pancreatitis. These experiments help to clarify some confusion that has existed in the literature stemming from the use of a dominant-negative transgenic TBRII mouse. The results point to a central role for TBRII in acinar cells in mitigating the overall response of the pancreas to the damage and inflammation of acute pancreatitis.


[Frequency of microclimatic measurements in ecosystem analysis].
In ecosystem analysis evaluation of the parameters (average values, extremes, correlations) may show errors if the frequency of measurements is too small. Radiation should be measured every 7 minutes in the open, in the vegetation layer even every 2 minutes as computer analysis of characteristic courses of irradiation has shown. Further reduction of the frequency of measurements can be obtained using electrical integrators.


Projections from the medial septum and diagonal band of Broca to the dorsal and central superior raphe nuclei: a non-cholinergic pathway.
The anatomical organization of projections from the medial septal nucleus (MS), and the vertical (VDB) and horizontal limb (HDB) of the diagonal band of Broca to the dorsal raphe nucleus (NRD) and the central superior raphe nucleus (RCS) of the rat were studied by anterograde [3H]-leucine, and True Blue and Fluoro Gold fluorescent retrograde tracing. Projections from the MS were found to enter the basal mesencephalon at the rostro-medial aspect of the pontine nuclei, curve dorsally and terminate throughout the RCS and in the caudal portion of the NRD. Fibers from the VDB were found to enter these raphe nuclei by two separate routes; some fibers reached the basal mesencephalon, curved dorsally and terminated in the RCS and NRD. Other fibers entered the pedunculopontine nucleus, curved medially and reached the NRD. Presumed terminal labelling was found overlaying the RCS and NRD throughout their rostro-caudal extensions. The brain stem projections from HDB entered the mesencephalon by the same routes as those from VDB, but the labelling over RCS was sparse, and the NRD labelling was preferentially distributed to the rostral portion of the nucleus. The present data indicate a crude topographic organization of the projections from the septal region to the NRD and RCS. In general, the distribution of presumed terminal labelling appeared to be more closely associated with the distribution of NRD and RCS 5-HT immunoreactive cell bodies, than with the cytoarchitectonically defined extensions of these raphe nuclei. By sequential evaluation of the distribution of retrogradely labelled and acetylcholine esterase-stained cells on the same section, and by selective tracing with radiolabelled choline, it appears that the vast majority, if not all, of the neurons in MS and diagonal band which project to the rostral raphe are non-cholinergic.


Ergostane-type sterols and sesquiterpenes with anti-neuroinflammatory activity from a Nigrograna species associated with Clematis shensiensis.
Nigrograna sp. LY66, an endophytic fungus associated with the herbal medicinal plant Clematis shensiensis, produced four undescribed steroids, nigergostanes A-D (1-4), including an unusual ketal-containing nigergostane (1), and four undescribed sesquiterpenoids decorated with cyclohexanone motifs, nigbisabolanes A-D (7-10), along with three known compounds, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (5), ergosta-5,7,22-trien-3β-ol (6), and curculonone A (11). The structures and absolute configurations of these undescribed compounds were confirmed using spectroscopic data (NMR and HRESIMS), modified Mosher's method, and ECD experiments. Additionally, compounds 5 and 8 displayed significant inhibition of nitric oxide generation in lipopolysaccharide-induced BV-2 microglial cells with IC50 values of 2.8 and 2.7 μM, respectively, and is thus more potent than that of the positive control, quercetin (IC50 = 8.77 μM). A molecular docking study revealed that 23-OH of 5 binds to the Y347 residue of inducible nitric oxide synthase (iNOS), whereas the 2-OH and 9,10-diol moieties of 8 bind to R381 and W463 and haeme residues of iNOS, respectively, which has rarely been reported in previous studies. These findings provide a set of undescribed lead compounds that can be developed into anti-neuroinflammatory agents.


Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo.
1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility.


Quantifying Gene Expression Domains in Plant Shoot Apical Meristems.
The shoot apical meristem is the plant tissue that produces the plant aerial organs such as flowers and leaves. To better understand how the shoot apical meristem develops and adapts to the environment, imaging developing shoot meristems expressing fluorescence reporters through laser confocal microscopy is becoming increasingly important. Yet, there are not many computational pipelines enabling a systematic and high-throughput characterization of the produced microscopy images. This chapter provides a simple method to analyze 3D images obtained through laser scanning microscopy and quantitatively characterize radially or axially symmetric 3D fluorescence domains expressed in a tissue or organ by a reporter. Then, it presents different computational pipelines aiming at performing high-throughput quantitative image analysis of gene expression in plant inflorescence and floral meristems. This methodology has notably enabled the quantitative characterization of how stem cells respond to environmental perturbations in the Arabidopsis thaliana inflorescence meristem and will open new avenues in the use of quantitative analysis of gene expression in shoot apical meristems. Overall, the presented methodology provides a simple framework to analyze quantitatively gene expression domains from 3D confocal images at the tissue and organ level, which can be applied to shoot meristems and other organs and tissues.


Extracts of scabies mites (Sarcoptidae: Sarcoptes scabiei) modulate cytokine expression by human peripheral blood mononuclear cells and dendritic cells.
We performed a series of experiments to determine if human peripheral blood mononuclear cells (PBMCs) from a healthy donor and dendritic cells (NHDCs) derived from these PBMCs reacted to molecules in a scabies extract. PBMCs extravasate from the circulatory system and enter tissues such as scabietic lesions, where monocytes become macrophages. Cells were cultured in medium alone or medium containing 50 microg/ml of Sarcoptes scabiei (SS) extract, 50 ng/ml E. coli lipopolysaccharide (LPS), or SS + LPS together. Supernatants were collected and assayed by enzyme-linked immunosorbent assay (ELISA) for specific cytokines. PBMCs stimulated with SS or LPS exhibited moderately upregulated production of interleukin (IL)-1beta and huge increases in secretions of IL-6, IL-8 and TNF-alpha. Cells co-stimulated with both SS and LPS generally secreted more of these cytokines than cells stimulated with either SS or LPS alone. LPS induced a small amount of IL-1alpha secretion, whereas SS did not, and neither additive resulted in the production of IL-10. NHDCs did not produce IL-1alpha, IL-1beta, IL-6, IL-8, or IL-10 in response to stimulation with SS. These cells did produce IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in response to LPS. When cells were co-stimulated with both LPS and SS, the production of IL-6 and IL-8 was significantly reduced compared with the levels secreted after LPS stimulation alone. These studies show that molecules in a whole body extract of S. scabiei modulate the function of PBMCs (probably monocytes) and dendritic cells.


Controllable hybrid plasmonic integrated circuit.
In this paper, a controllable hybrid plasmonic integrated circuit (CHPIC) composed of hybrid plasmonic waveguide (HPW)-based rhombic nano-antenna, polarization beam splitter, coupler, filter, and sensor has been designed and investigated for the first time. In order to control the power into a corresponding input port, a graphene-based 1 × 3 power splitter with switchable output has been exploited. The functionality of each device has been studied comprehensively based on the finite element method and the advantages over state-of-the-art have been compared. Moreover, the effect of connection of CHPIC to the photonic and plasmonic waveguides has been studied to exhibit the capability of variety excitation methods of the CHPIC. Furthermore, the performance of the proposed CHPIC connected to inter/intra wireless transmission links has been investigated. The wireless transmission link consists of two HPW-based nano-antennas as transmitter and receiver with the maximum gain and directivity of 10 dB and 10.2 dBi, respectively, at 193.5 THz. The suggested CHPIC can be used for applications such as optical wireless communication and inter/intra-chip optical interconnects.


Purification and biochemical characterization of a newly produced yellow laccase from Lentinus squarrosulus MR13.
A novel yellow laccase was produced from Lentinus squarrosulus MR13 under solid state fermentation. The yellow laccase was purified by a factor of 12.67-fold by ammonium sulfate precipitation, anion exchange chromatography and gel filtration chromatography to a specific activity of 3,772.86 IU mg-1. Its molecular mass was determined by SDS-PAGE and found to be 66 kDa. The activity of the enzyme was measured with 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) as substrate and found to be stable in a broad range of pH (pH 4-9). The optimum temperature of the enzyme was 40 °C. The enzyme was stable at temperatures between 25 and 55 °C and decreased rapidly when the temperature was above 65 °C. Circular dichroism spectra also supported the temperature stability of the enzyme. The Km and Vmax values of the purified yellow laccase were 0.0714 mM and 0.0091 mM min-1, respectively.


New CD20 alternative splice variants: molecular identification and differential expression within hematological B cell malignancies.
CD20 is a B cell lineage-specific marker expressed by normal and leukemic B cells and targeted by several antibody immunotherapies. We have previously shown that the protein from a CD20 mRNA splice variant (D393-CD20) is expressed at various levels in leukemic B cells or lymphoma B cells but not in resting, sorted B cells from the peripheral blood of healthy donors. Western blot (WB) analysis of B malignancy primary samples showed additional CD20 signals. Deep molecular PCR analysis revealed four new sequences corresponding to in-frame CD20 splice variants (D657-CD20, D618-CD20, D480-CD20, and D177-CD20) matching the length of WB signals. We demonstrated that the cell spliceosome machinery can process ex vivo D480-, D657-, and D618-CD20 transcript variants by involving canonical sites associated with cryptic splice sites. Results of specific and quantitative RT-PCR assays showed that these CD20 splice variants are differentially expressed in B malignancies. Moreover, Epstein-Barr virus (EBV) transformation modified the CD20 splicing profile and mainly increased the D393-CD20 variant transcripts. Finally, investigation of three cohorts of chronic lymphocytic leukemia (CLL) patients showed that the total CD20 splice variant expression was higher in a stage B and C sample collection compared to routinely collected CLL samples or relapsed refractory stage A, B, or C CLL. The involvement of these newly discovered alternative CD20 transcript variants in EBV transformation makes them interesting molecular indicators, as does their association with oncogenesis rather than non-oncogenic B cell diseases, differential expression in B cell malignancies, and correlation with CLL stage and some predictive CLL markers. This potential should be investigated in further studies.


Vagal stimulation in heart failure.
Vagal nerve stimulation (VNS) has a strong pathophysiological rationale as a potentially beneficial treatment for heart failure with reduced ejection fraction. Despite several promising preclinical studies and pilot clinical studies, the two large, controlled trials-NECTAR-HF and INOVATE-HF-failed to demonstrate the expected benefit. It is likely that clinical application of VNS in phase III studies was performed before a sufficient degree of understanding of the complex pathophysiology of autonomic electrical modulation had been achieved, therefore leading to an underestimation of its potential benefit. More knowledge on the complex dose-response issue of VNS (i.e., pulse amplitude, frequency, duration and duty cycle) has been gathered since these trials and a new randomized study is currently underway with an adaptive design and a refined approach in an attempt to deliver the proper dose to a more selected group of patients.


Sequential expression of surface antigens and transcription factor NFkappaB by hippocampal cells in excitotoxicity and experimental epilepsy.
Neurodegeneration and gliosis have been extensively described after long-lasting seizures; evidence for cytokine involvement in neuron-glia interactions does exist. We have therefore studied the hippocampal expression of molecules responsible for immune and inflammatory reactions, at different time-points following either experimental status epilepticus (SE) or direct excitotoxic damage. Experiments consisting of immunohistochemical labeling of glial markers, major histocompatibility complex (MHC) and nuclear factor kappaB (NFkappaB), were performed. NFkappaB nuclear translocation was controlled and measured using the electrophoretic mobility shift assay. One day after SE, neurodegeneration was obvious in CA3 pyramidal layers; NFkappaB staining in neurons and its translocation to the nucleus enhanced. From day 4 to at least day 8 post-SE, MHC-positive microglia, NFkappaB over-expression in thickened astrocytes, and increased levels of its activated form could be observed. The excitotoxic model caused more severe lesions, but NFkappaB and MHC expression were similar in both models. These results suggest that during long-lasting seizures: (i) neuronal firing activates NFkappaB expression and translocation; (ii) microglia expresses MHC; (iii) astrocytes, probably stimulated by microglial cytokines, over-express NFkappaB, the activation of which induces a cascade of reactions, particularly the transcription of cytokines and or neuroprotective molecules. Further clarification of the toxic or protective consequences of delayed inflammatory responses may be interesting in therapy of epilepsy.


New perspectives in arsenic-induced cell signal transduction.
Although the carcinogenicity of arsenic has been well established, the underlying molecular mechanisms have not yet been fully identified. Accumulating evidence indicates that the alteration of cellular signal transduction is directly related to the carcinogenesis of arsenic. This review focuses on recent advances in arsenic-induced signal transduction, including reactive oxygen species (ROS) production, tyrosine phosphorylation, MAPK signaling, NF-kappaB activation, cell cycle arrest, and apoptosis.


T-cell acute lymphoblastic leukemia relapsing as acute myelogenous leukemia.
We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.


Cross-reactive antigens and immunity to diseases caused by encapsulated bacteria.
Antigenic structures may be shared among naturally occurring polymers, including proteins and polysaccharides. Proteins are polymers of amino acids. Cross-reactions between proteins are due to similarities in their overall shape rather than their individual amino acid components. Cross-reactions have been demonstrated among proteins with similar evolutionary development and structure, such as serum albumins or immunoglobulins. Polysaccharides are polymers of monosaccharides. In contrast to proteins, antigenic specificities may be conferred by mono-, di-, and trisaccharides. Since there are about 150 known naturally occurring monosaccharides, it is not unexpected that cross-reactions are demonstrable between polysaccharides from widely divergent sources.


Research into the correlation between positional skull deformation and motor performance of infants aged under 4 months.
To investigate the correlation between positional skull deformation (PD) and motor performance of infants under 4 months of age. Infants aged under 4 months were enrolled in the children's healthcare and the premature infants follow-up Clinic of the Second Affiliated Hospital of Army Military Medical University. The cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants, and the infant motor performance test (TIMP) was used to evaluate the infant motor performance. The motor performances of infants with different types and degrees of PD were compared, so were the incidences of PD in infants with different motor performance levels. Overall, 2118 infants were recruited and divided according to the types of PD and TIMP scores. The comparison of TIMP scores within different types of PD at different months of age showed that, regardless of the types of PD, TIMP scores of infants with PD were lower than those of normal infants. In particular, the difference in TIMP scores was statistically significant (P < 0.05) in infants with dolichocephaly, plagiocephaly,dolicho-plagiocephaly and brachy-plagiocephy. In addition, the comparison of CVA values of infants with different TIMP score levels at different months of age showed that the CVA values of the extremely low-level group were significantly higher than those of the medium-level and high-level group, especially in the 3-month-old and 4-month-old groups, which showed significant statistical differences (P < 0.05). PD and motor performance of infants aged under 4 months seem to interact and influenc each other. The more serious the severity of PD were,the worse the motor performance of infants. Conversely, the incidence of PD increased in infants with poor motor performance.


Identification of a bacterium that specifically catalyzes the reductive dechlorination of polychlorinated biphenyls with doubly flanked chlorines.
A microorganism whose growth is linked to the dechlorination of polychlorinated biphenyls (PCBs) with doubly flanked chlorines was identified. Identification was made by reductive analysis of community 16S ribosomal DNA (rDNA) sequences from a culture enriched in the presence of 2,3,4,5-tetrachlorobiphenyl (2,3,4,5-CB), which was dechlorinated at the para position. Denaturing gradient gel electrophoresis (DGGE) analysis of total 16S rDNA extracted from the culture led to identification of three operational taxonomic units (OTUs 1, 2, and 3). OTU 1 was always detected when 2,3,4,5-CB or other congeners with doubly flanked chlorines were present and dechlorinated. Only OTUs 2 and 3 were detected in the absence of PCBs and when other PCBs (i.e., PCBs lacking doubly flanked chlorines) were not dechlorinated. Partial sequences of OTUs 2 and 3 exhibited 98.2% similarity to the sequence of "Desulfovibrio caledoniensis" (accession no. DCU53465). A sulfate-reducing vibrio isolated from the culture generated OTUs 2 and 3. This organism could not dechlorinate 2,3,4,5-CB. From these results we concluded that OTU 1 represents the dechlorinating bacterium growing in a coculture with a Desulfovibrio sp. The 16S rDNA sequence of OTU 1 is most similar to the 16S rDNA sequence of bacterium o-17 (89% similarity), an ortho-PCB-dechlorinating bacterium. The PCB dechlorinator, designated bacterium DF-1, reductively dechlorinates congeners with doubly flanked chlorines when it is supplied with formate or H(2)-CO(2) (80:20).


Upper Limb Dimelia.
A patient with upper limb dimelia including a double scapula, humerus, radius, and ulna, 11 metacarpals and digits (5 on the superior side, 6 on the inferior side) was treated with a simple amputation of the inferior limb resulting in cosmetic improvement and maintenance of range of motion in the preserved limb. During the amputation, the 2 limbs were found to be anatomically separate except for the ulnar nerve, which, in the superior limb, bifurcated into the sensory branch of radial nerve in the inferior limb, and the brachial artery, which bifurcated into the radial artery. Each case of this rare anomaly requires its own individually carefully planned surgical procedure.


Roles of micro-aeration on enhancing volatile fatty acids and lactic acid production from agricultural wastes.
Micro-aeration was proven to be an environmentally friendly strategy for efficiently enhancing volatile fatty acids (VFAs) and lactic acid (LA) production. The roles of micro-aeration on mono-digestion of swine manure (SM) for VFAs production and co-digestion of SM with corn silage (CS) for LA production were investigated, respectively. In this study, micro-aeration increased the maximum VFAs concentration by 20.3% to 35.71 g COD/L, and shortened the time to reach the maximum from 18 days to 10 days. Micro-aeration limited the conversion of LA into VFAs, leading to LA accumulation effectively to be 26.08 g COD/L. Microbial community analysis suggested that Clostridium and Terrisporobacter were always the dominant bacteria with or without micro-aeration for VFAs production, but the relative abundance increased notably during the same period. However, Bifidobacterium, which could use the higher productivity metabolism pathway, i.e., Bifidum pathway to produce LA, increased from lower than 1% to 22.9% by micro-aeration.


A survey of radiation dose and image quality in mammography: an ongoing program in Italy.
A program for mammography optimization in individual x-ray units, named Dose and Quality in Mammography (DQM), is now underway in Italy. The project has three stages: measurement of the parameters that affect dose and image quality by means of devices that are practical to use (specifically designed for the purpose), analysis of data to evaluate dose and image quality and suggestion of possible improvements to each unit operator. Instruments and methods employed in our survey are described. Our results, like those of the American survey (Je78) Breast Exposure: Nationwide Trends (BENT), show widespread variations of exposure, half value layer (HVL), optical density, dose and resolution. Facilities using the same type of x-ray apparatus (Mo target-Mo filter) and film-screen combinations present very different exposure values, ranging from 1.6 X 10(-4) to 27.6 X 10(-4) C kg-1. The causes of these variations--ascribable to the individual units, radiologist preferences, processing condition, kVp indicator and timer accuracy--are being explored.


Exploring the hygroscopicity and chemical composition evolution in organic-inorganic aerosols: A study on internally mixed malonic acid-metal (Na+, Ca2+, Mg2+) nitrates.
Chemical transformations in mixed aerosols alter the particulate physical properties. Nitrates and water soluble dicarboxylic acids, such as malonic acid (MA), are major components of ambient aerosol particles. Various metal ions such as, Na+, Ca2+, Mg2+ also become part of these complex aerosol systems during their atmospheric lifetime. Interactions among the co-existing ionic and molecular species govern the chemical changes in the aerosol particles. In this work, we provide a comparative account of the effect of metal ion identity (Na+, Ca2+, Mg2+) on such chemical changes arising from ion-molecular interactions in NaNO3-MA, Ca(NO3)2-MA and Mg(NO3)2-MA mixed inorganic-organic aerosols. In-situ micro-Raman spectroscopy has enabled us to gain molecular level insight on formation of organic salt and simultaneously estimate nitrate depletion in these mixed aerosols during different stages of their hygroscopic cycle. In addition to the nitrate depletion often reported during the drying phase, this study has brought to light an intriguing observation: depletion of nitrate in the humidification phase as well, a phenomenon that has hitherto remained undocumented. For the mixed systems studied here, the extent of nitrate depletion follows the order Mg-MA (58%) > Ca-MA (43%) > Na-MA (15%). The comparatively huge forward shift in the acid displacement reaction equilibrium for the systems, Ca-MA and Mg-MA is driven by complexation. Our results highlight the profound effect of ion-molecular interactions on the acid displacement reaction equilibria in aerosols.


Maxillofacial Trauma Patterns in Bare-Knuckle Fighting.
The purpose of this study is to analyze patterns and trends of maxillofacial injuries in bare-knuckle fighting. Results comparisons with other combat sports are provided in the Discussion section. The study design is a retrospective cohort study. Data were collected by a single ringside physician who participated in all bouts. Predictor variables were number of rounds and final fight result (ie, knockout, technical knockout, and decision). The primary outcome variable was the frequency of maxillofacial injury, and secondary outcome variables were type of injury (laceration/fracture) and traumatic brain injury. The chi-square test was used to determine if there was any statistical significance between the predictor variables. Study sample consisted in fighters who suffered maxillofacial injuries during the matches from June 2018 to March 2022 (n = 177). A total of 177 fighters sustained maxillofacial trauma in 301 matches, and a total of 211 maxillofacial injuries were identified. Of the 211 injuries, 184 were lacerations and 27 were fractures. Proportionally more injuries occurred in matches that lasted 5 rounds (33%), and a significant association was found between the number of rounds fought and the frequency of injury (P < .00001). From a total of 107 technical knockouts, 74% of them caused at least 1 injury; from 96 knockouts, 60% caused at least 1 injury; and from 89 fights that ended in decision, 83% of them caused at least 1 injury. A statistically significant association was found between final fight result and frequency of injury (P < .00001). P value less than 0.05 (95% confidence interval) was considered statistically significant. Maxillofacial injuries were predominantly associated with longer fights and fights which result were knockout/technical knockout. Traumatic brain injury was associated with knockout results, which mostly occurred in the first and second rounds.


Brain response to food odors is not associated with body mass index and obesity-related metabolic health measures.
Smell perception plays a role in eating behavior and might be involved in the development of obesity. In fact, olfactory function is impaired in obesity and might depend on metabolic health factors. To date, the underlying neural mechanisms remain unclear. Here, we investigate neural processing of food-related odors in normal-weight, overweight and obese individuals. Fifty-three young and healthy participants (28.8 ± 4.4 years, 27 female; 24 normal-weight, 10 overweight, and 19 obese) were presented with high- (chocolate, potato chips) and low-caloric (orange, cucumber) food odors during a functional magnetic resonance imaging (fMRI). We also assessed olfactory identification ability, body mass index (BMI), body fat percentage, insulin resistance, and leptin levels. In brief, olfactory perception of food odors was linked to brain activity in the entorhinal and piriform cortex, and the insula, hippocampus, and amygdala. Insulin resistance was negatively related to olfactory identification. Additionally, perception of sweet versus savory odors was related to a higher brain activity in the right middle/superior frontal gyrus. Finally, we found no effect of obesity status, BMI, metabolic factors, or body fat percentage on neural responses to food odors. Overall, this suggests that food odor processing might depend on factors other than body weight status or associated markers of metabolic health.


A three-dimensional image-superimposition CAD/CAM technique to record the position and angulation of the implant abutment screw access channel.
Cement-retained, implant-supported restorations have advantages over screw-retained restorations, but retrievability can be a problem. By using computer-aided design and computer-aided manufacturing (CAD/CAM) technology, a working cast or mouth can be scanned, and a definitive record of the screw hole can be made in 3 dimensions and saved as a file. This information includes not only the position of the opening of the screw hole but also its angulation and orientation, which can be retrieved if required.


Characterization and primary sequence of a human hepatic microsomal estriol UDPglucuronosyltransferase.
A human liver microsomal UDP glucuronosyltransferase (UDPGT) that demonstrates reactivity with estriol (pI 7.4 UDPGT) has been purified to homogeneity and characterized further. No activity toward morphine, 4-hydroxybiphenyl, bilirubin, or tripelennamine was observed. The estriol UDPGT shows immunoreactivity with antibodies raised against rat hepatic microsomal 3 alpha- and 17 beta-hydroxysteroid UDPGTs but not with antibodies raised against rat hepatic microsomal p-nitrophenol UDPGT. The NH2-terminal sequence of the purified protein was determined and found to correspond to an identical sequence in the deduced amino acid sequence of a cDNA obtained from a human liver library in lambda gt11 (HLUG4). Sequence analysis revealed that HLUG4 is 2094 bp in length and encodes a protein of 523 amino acids which has a 16 amino acid leader sequence, followed by an untranslated 3' region of 525 bp. Three potential N-glycosylation sites were identified in the predicted sequence. The deduced amino acid sequence of estriol UDPGT showed 82% identity with the deduced amino acid sequence of another human hepatic cDNA (HLUG25), which has been expressed as a UDPGT capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid, strongly suggesting that these proteins are members of the same gene subfamily.


Positive surgical margins are a risk factor for significant biochemical recurrence only in intermediate-risk disease.
What's known on the subject? and What does the study add? Positive surgical margins (PSMs) after radical prostatectomy are common, although their impact on the risk of disease recurrence is unknown. We examined the impact of PSMs on the risk of 'significant' biochemical recurrence stratified by their risk of occult metastatic disease. We find that only in intermediate-risk disease does the presence of a PSM have a significant impact on the risk of recurrence, and this represents a failure of technique. By contrast, for high- and low-risk disease, the risk of recurrence is driven by intrinsic tumour biology, and the presence of a PSM has little impact on outcome. To determine the impact of surgical margin status on the risk of significant biochemical recurrence (prostate-specific antigen [PSA] doubling time <3, <6 or <9 months) after prostatectomy. Patients undergoing radical prostatectomy with complete clinical and pathological data and detailed PSA follow-up were identified from two prospectively recorded databases. Patients were stratified according to their risk of occult systemic disease (low risk: PSA < 10 ng/dL, pT2 stage and Gleason score ≤6; intermediate risk: PSA 10-20 ng/dL, pT2 stage and/or Gleason score 7; high: PSA > 20 ng/dL or pT3-4 stage or Gleason score 8-10) and the impact of a positive surgical margin (PSM) within each stratum determined by univariable and multivariable analysis. Of 1514 patients identified, 276 (18.2%), 761 (50.3%) and 477 (31.5%) were classified as having low-, intermediate- and high-risk disease respectively. A total of 370 (24.4%) patients had a PSM and with a median follow-up of 22.2 months, and 165 (7%) patients had a biochemical recurrence. Sufficient PSA data was available to calculate PSA doubling times in 151/165 patients (91.5%). The PSM rate rose significantly, from 11% in low-risk to 43% in high-risk disease (P < 0.001), with similar positive associations noted with tumour grade, stage and serum PSA (P < 0.001). Patients with low-risk disease had essentially identical risks of significant biochemical recurrence over the study period, regardless of surgical margin status. By contrast, in patients with both intermediate- and high-risk disease, a PSM was a strong predictor of significant biochemical recurrence on univariable analysis. On multivariable analysis, howver, PSM predicted significant disease recurrence in intermediate-risk disease only. PSM is a risk factor for significant biochemical recurrence only in intermediate risk disease.


Correlation between release of reactive oxygen intermediates and inhibition of Toxoplasma multiplication in mouse peritoneal and alveolar macrophages and kidney cells after in vitro incubation with Obioactin, lonomycin A, muramyl dipeptide, lipopolysaccharide or Toxoplasma lysate antigen.
The inhibition of Toxoplasma multiplication inside cells does not correlate with an enhanced release of oxygen intermediates except in the case of peritoneal macrophages treated with Obioactin. The inhibition observed in alveolar macrophages treated with Obioactin, in kidney cells treated with Obioactin or lonomycin A and in peritoneal macrophages treated with lonomycin A was not accompanied by an increment of release of oxygen intermediates. Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) enhanced the release of toxic oxygen intermediates in peritoneal macrophages, but did not have any toxoplasmacidal effect. Adenosine triphosphate (ATP) content increased during Obioactin, MDP or Toxoplasma lysate antigen (TLA) treatment. The actual oxygen consumption of the peritoneal macrophages treated with Obioactin increased dose dependently, but that of TLA-, lonomycin A- or MDP-treated cells did not change. These results suggest that the relationship between the intracellular killing of Toxoplasma protozoa and the release of oxygen intermediates differs according to the cells and/or the stimuli, and that the cellular mechanism of Toxoplasma killing in the peritoneal macrophages treated with Obioactin involves an energy-dependent mechanism.


Genetic toxoids of Shiga toxin types 1 and 2 protect mice against homologous but not heterologous toxin challenge.
Shiga toxin type 1 (Stx1) and type 2 (Stx2) are produced by Escherichia coli O157:H7 and are responsible for the life-threatening sequela, the hemolytic uremic syndrome. Whether antisera to Stx1 or Stx2 are cross-neutralizing remains controversial, so we constructed genetic toxoids of Stx1 and Stx2 and evaluated them as vaccines. Antisera from mice immunized with a single toxoid type recognized and neutralized the homologous toxin but not the heterologous toxin. Furthermore, only mice immunized with Stx1 and Stx2 toxoids were protected against a lethal challenge of both toxins. We conclude that Stx1 and Stx2 are distinct antigens for mice.


Sub-lethal effects induced in Mytilus galloprovincialis after short-term exposure to sodium lauryl sulfate: Comparison of the biological responses given by mussels under two temperature scenarios.
Surfactants are among the most common PPCPs that reach coastal systems, being often used in large quantities in cleaning products such as detergents and soap powders. Sodium lauryl sulfate (SLS) is listed in this group of emerging contaminants. Previous studies have already demonstrated the presence of SLS in aquatic environments and the negative effects on organisms living there. However, with ocean acidification and warming predictions, SLS-induced impacts may differ from those currently known. In this context, the present study aimed to reproduce environmental conditions by assessing the release of substances over a short period and to understand the influence of a rapid increase in temperature on the impacts caused. The marine bivalve Mytilus galloprovincialis was exposed to 2.0 mg/L SLS at 17 °C and 21 °C for 7 days. To assess the possible biochemical changes resulting from the exposure of mussels to SLS, a series of biomarkers related to oxidative stress/damage, detoxification, and metabolic capacity were measured. The SLS accumulation in soft tissues was low (about 0.7 ng/g) at both temperatures. The results evidenced increased metabolic activity, especially in mussels exposed to SLS at 17 °C. An increase in protein content was also observed upon exposure to SLS and increased temperature compared to controls at 17 °C. Although no effects on antioxidant enzymes were observed, protein damage was recorded, especially at 21 °C. These findings confirmed that SLS induces toxic effects and predicted climate change factors may increase the impact on M. galloprovincialis.


Understanding Zika virus pathogenesis: an interview with Catherine Spong.
A recent outbreak of Zika virus has been linked to fetal abnormalities in pregnant women who have been infected. The scientific community is working toward understanding Zika virus pathogenesis to better manage affected women and children. In an interview with Dr. Catherine Spong, we discuss the aims and challenges of a forthcoming longitudinal study of a cohort of pregnant women in areas of current active Zika virus transmission.


Conservative management for adherent placenta after live birth in angular or interstitial pregnancies: A new entity "angular placenta attachment".
Angular and interstitial pregnancies have been reported with live births and are often complicated by adherent placentas. Most cases had been treated with hysterectomy or corneal resection. We successfully treated four patients with conservative management (including one reported previously). Case 1 had a vaginal delivery, but the placenta remained attached. We maintained the patient under observation and delivered the placenta on postpartum day 9. Case 2 underwent a C-section. Uterine artery embolization controlled the hemorrhage without placenta removal. The placenta had disappeared by postpartum day 136. Case 3 underwent a C-section. The right uterine angle, where the placenta was attached, was bulging. We manually removed the placenta. We propose a new entity in angular or interstitial pregnancies called "angular placenta attachment" that could be diagnosed during C-sections or after vaginal delivery without placental separation. Expectant management may be considered for adherent placentas in these cases.


Development of a two-step injector for GC-MS with on-column derivatization, and its application to the determination of amphetamine-type stimulants (ATS) in biological specimens.
A two-step auto-injector has been developed for the automated on-column derivatization and subsequent GC-MS of amine-type drugs and metabolites. To effectively derivatize such analytes, this injector has been designed to inject the derivatization reagent several seconds after the sample has been injected. Eleven kinds of amphetamine-type stimulants (ATS) and their typical metabolites were examined, using the trifluoroacetylation reagent N-methyl bis(trifluoroacetamide) (MBTFA). Although the quantitative derivatization of the hydroxyl groups was difficult, this technique was successfully applied to the determination of ATS in urine, blood, and hair specimens. The detection limits of methamphetamine and amphetamine in hair were 0.2 and 0.1 ng/mg hair, respectively, in the full-scan mode, when a 10 mg hair sample is analyzed.


Multihormonal responses to clonidine in patients with affective and psychotic symptoms.
The neuroendocrine responses to the alpha(2)-adrenoreceptor agonist clonidine (CLO) (0.35 mg if body weight <65 kg or 0.375 mg if body weight> or =65 kg, PO) were studied in a large group of subjects: 134 drug-free inpatients--with either DSM-IV schizophrenia (SCZ, n=31), schizoaffective disorder (SAD, n=16), or major depressive episode (MDE, n=87) - and 22 hospitalized controls (HCs). Comparison with a previous placebo test performed in a subgroup of 92 subjects (46 MDEs, 20 SCZs, 8 SADs, and 18 HCs) showed that CLO induced a significant increase of growth hormone, prolactin (PRL) and thyrotropin (TSH) levels but no significant change in adrenocorticotropin and cortisol release. According to diagnostic categories, we found significantly lower GH stimulation in MDEs and in SADs compared to HCs or to SCZs. In addition, we found significantly lower CLO induced PRL and TSH stimulations in paranoid SCZ patients compared to controls and disorganized SCZ patients. Taken together, these results suggest a hyposensitivity of noradrenergic alpha(2)-receptors in patients with affective symptoms.


Expressions of Angiopoietin-1, Angiopoietin-2, and Tie2 and their roles in rat renal allografts with chronic allograft nephropathy.
Angiopoietin-1 (Ang1) and -2(Ang2) are 2 ligands for the endothelium-specific tyrosine kinase Tie2. Previous studies have shown that reciprocal regulation of Ang1, Ang2, and Tie2 plays an important role in chronic cardiac allograft vasculopathy. This study investigated the expressions of Ang1, Ang2, and Tie2 in rat renal allografts undergoing chronic allograft nephropathy (CAN). Renal transplantations following the procedure of Kamada with our modification were orthotopically performed using Fisher (F344, RT1(1v1)) rats as both donors and recipients in the autograft group. Fisher and Lewis (LEW, RT1(1)) rats were used as donors and recipients in the allograft group, respectively, which was treated with cyclosporine (CsA; 10 mg/kg/d x 10 d). At 4w, 8w, and 12 weeks posttransplantation, serum creatinine (SCr) was measured and pathologic changes assessed according to the Banff 97 criteria. The mRNA (Deltact) and protein expressions of Ang1, Ang2, and Tie2 were localized by real-time fluorescence quantitative polymerase chain reaction (PCR) and by immunohistochemistry. The elevation in SCr and the pathologic changes in CAN were observed in all allografts at 8 and 12 weeks. The expressions of Ang1 and Ang2 were localized to epithelial cells and endothelium of the vascular bundles of the glomeruli; Tie2 was specifically expressed in endothelium of vessels both in auto- and allografts at all time points posttransplantation. At 4 weeks, the differences in mRNA expression of Ang1, Ang2, and Tie2 between the 2 groups were not significant (P > .05). Compared with autografts, the mRNA expression of Ang1 decreased significantly (P = .008 and .003 for 8 and 12 weeks, respectively), and the mRNA expressions of Ang2 and Tie2 significantly increased (P = .001/.006 and .005/.001 for 8 and 12 weeks, respectively). The changes in expression of all 3 genes showed significant correlation with the Banff score in the allografts. This study suggested that the abnormal expression and reciprocal regulation of Ang1, Ang2, and Tie2 may play important roles in the development of CAN in rat renal allografts.


Vacancy-Modified Porous g-C3N4 Nanosheets Controlled by Physical Activation for Highly Efficient Visible-Light-Driven Hydrogen Evolution and Organics Degradation.
As a promising photocatalyst material, g-C3N4 has great application potential in energy production and environmental improvement. In this work, surface-modified g-C3N4 nanosheets with excellent stability and high photocatalytic activity were successfully synthesized by physical steam activation. The charge transfer rate of carbon nitride was improved due to the synergistic effect of nitrogen defect and oxygen doping caused by steam activation. Meanwhile, the specific surface area and pore volume of the optimized sample reached 124.3 m2 g-1 and 0.42 cm3 g-1, respectively, which increased the exposed reaction sites of reactants, enhancing the photocatalytic activity of g-C3N4. In addition, this novel g-C3N4 displayed a great H2 evolution rate of 5889.39 μmol h-1 g-1 with a methylene blue degradation rate up to 6.52 × 10-3 min-1, which was 3.7 and 2.1 times of original g-C3N4, respectively. This study provided a simple and economical method to develop a highly efficient g-C3N4 photocatalyst for solar energy conversion.


Experimental evidence of negative interference in Daphnia magna.
Individuals of Daphnia magna Straus living together in groups were found to influence each other in a density-dependent manner. The effect appeared as an inhibition in offspring production and was demonstrated to be induced in part or completely by metabolic products released by Daphnia itself (negative interference). Negative interference was measurable even when there were only two individuals in 50 ml medium (40 animals · 1-1) and increased up to a density of six animals per 50 ml (120 animals · 1-1). Also, animals living singly in Daphnia-conditioned water showed a decrease in reproduction. For the measurements a cascade of vessels was developed in which flow-through conditions ensured a constant concentration of algae throughout the system.


A Historical-Genetic Reconstruction of Human Extra-Pair Paternity.
Paternity testing using genetic markers has shown that extra-pair paternity (EPP) is common in many pair-bonded species [1, 2]. Evolutionary theory and empirical data show that extra-pair copulations can increase the fitness of males as well as females [3, 4]. This can carry a significant fitness cost for the social father, who then invests in rearing offspring that biologically are not his own [5]. In human populations, the incidence and correlates of extra-pair paternity remain highly contentious [2, 6, 7]. Here, we use a population-level genetic genealogy approach [6, 8] to reconstruct spatiotemporal patterns in human EPP rates. Using patrilineal genealogies from the Low Countries spanning a period of over 500 years and Y chromosome genotyping of living descendants, our analysis reveals that historical EPP rates, while low overall, were strongly impacted by socioeconomic and demographic factors. Specifically, we observe that estimated EPP rates among married couples varied by more than an order of magnitude, from 0.4% to 5.9%, and peaked among families with a low socioeconomic background living in densely populated cities of the late 19th century. Our results support theoretical predictions that social context can strongly affect the outcomes of sexual conflict in human populations by modulating the incentives and opportunities for engaging in extra-pair relationships [9-11]. These findings show how contemporary genetic data combined with in-depth genealogies open up a new window on the sexual behavior of our ancestors.


Association between gastric myoelectrical activity and intraluminal nitric oxide.
We have previously shown that the intraluminal concentration of NO in H. pylori-positive patients is significantly reduced compared to that in H. pylori-negative patients. The aim of this study was to evaluate the effect of H. pylori infection on gastric motor activity in relation to the level of NO and nitrite in the stomach in humans. Thirty-two H. pylori-negative and 32 H. pylori-positive patients with dyspepsia were studied. Gastric myoelectrical activity was recorded for 24 h using surface electrogastrography. Intraluminal gas and juice were endoscopically collected from the stomach to determine NO and nitrite and nitrate (NOx) levels using a chemiluminescence system. The percentage of tachygastria in the morning preprandial state was significantly higher (P = 0.005) in H. pylori-positive than -negative patients. In H. pylori-negative patients, there was a significant positive correlation between NO levels and the percentage of bradygastria (r = 0.56, P = 0.001) and a significant negative correlation between NOx levels and the percentage of normal electrical activity (r = - 0.57, P=0.001) in the preprandial state. Gastric motor activity is associated with NO and NOx levels in the gastric lumen. H. pylori infection may play a role in the pathogenesis of abnormal gastric myoelectrical activity.


Kinetic magnetic resonance imaging analysis of lumbar segmental motion at levels adjacent to disc herniation.
A retrospective radiographic study was carried out to analyze the effect of lumbar disc herniation on the kinetic motion of adjacent segments. A total of 162 patients with low back pain or radicular pain in the lower limbs without a prior history of surgery were evaluated using kinetic magnetic resonance imaging. Translational motion, angular variation, and disc height were measured at each segment from L1-L2 to L5-S1. Other factors including the degree of disc degeneration, age, gender, and vertebral segment location were analyzed to determine any predisposing risk factors for segmental instability adjacent to disc herniations. Spinal levels above the disc herniation exhibited, on average, a 6.4 % increase in translational motion per mm of disc herniation (P = 0.496) and a 21.4 % increase in angular motion per mm herniation (P = 0.447). Levels below the herniation demonstrated a 5.2 % increase in translational motion per mm of disc herniation (P = 0.428) and a decrease of 10.7 % in angular motion per mm (P = 0.726). The degree of disc degeneration had no significant correlation with adjacent level motion. Similarly, disc herniation was not significantly correlated with disc height at adjacent levels, although there was a significant relationship between gender and adjacent segment disc height. Although disc height, translational motion, and angular variation are significantly affected at the level of a disc herniation, no significant changes are apparent in adjacent segments. Our results indicate that herniated discs have no effect on range of motion at adjacent levels regardless of the degree of disc degeneration or the size of disc herniation, suggesting that the natural progression of disc degeneration and adjacent segment disease may be separate, unrelated processes within the lumbar spine.


Altered perception of apparent motion in schizophrenia spectrum disorder.
Apparent motion (AM), the Gestalt perception of motion in the absence of physical motion, was used to study perceptual organization and neurocognitive binding in schizophrenia. Associations between AM perception and psychopathology as well as meaningful subgroups were sought. Circular and stroboscopic AM stimuli were presented to 68 schizophrenia spectrum patients and healthy participants. Psychopathology was measured using the Positive and Negative Syndrome Scale (PANSS). Psychopathology was related to AM perception differentially: Positive and disorganization symptoms were linked to reduced gestalt stability; negative symptoms, excitement and depression had opposite regression weights. Dimensions of psychopathology thus have opposing effects on gestalt perception. It was generally found that AM perception was closely associated with psychopathology. No difference existed between patients and controls, but two latent classes were found. Class A members who had low levels of AM stability made up the majority of inpatients and control subjects; such participants were generally young and male, with short reaction times. Class B typically contained outpatients and some control subjects; participants in class B were older and showed longer reaction times. Hence AM perceptual dysfunctions are not specific for schizophrenia, yet AM may be a promising stage marker.


Prognostic significance of survivin and caspase-3 immunohistochemical expression in patients with diffuse large B-cell lymphoma treated with rituximab and CHOP.
Survivin is an inhibitor of apoptosis whose expression may be associated with inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated without rituximab. Caspase-3 is the final caspase of the apoptotic cascade and its pattern of expression may also be related to patients' outcome. In this study we investigated immunohistochemical expression of survivin and caspase-3 (CPP32) in 57 patients with DLBCL treated with rituximab and CHOP (R-CHOP). According to previously published criteria, we separately analyzed correlation of different types of survivin expression with patients' outcome. Nuclear survivin was expressed in only 26% of cases, cytoplasmic survivin was expressed in 81% of cases while application of immunoreactivity scoring system yielded 58% of survivin positive cases. Caspase-3 was expressed in 77% of cases. There were no significant correlations between any type of survivin expression and response to treatment or survival of the patients. The expression of caspase-3 was also not associated with patients' outcome. We conclude that survivin and caspase-3 have no significant prognostic significance in patients with DLBCL treated with R-CHOP.


Electrodiagnostic evaluation of ulnar neuropathy and other upper extremity mononeuropathies.
Upper extremity mononeuropathies are some of the common disorders seen in neurophysiology laboratories. Electrophysiologic studies rely on accurate localization based on knowledge of applicable anatomy and features of history and physical examination. Careful electrodiagnostic studies provide an accurate diagnosis, help localize the lesion site, exclude alternate diagnoses, reveal unsuspected diagnoses, determine pathophysiology of lesions, and assess severity, timeframe, and prognosis of lesions. This article discusses the electrodiagnostic approach to ulnar neuropathy, proximal median neuropathy, radial neuropathy, musculocutaneous neuropathy, axillary neuropathy, suprascapular neuropathy, and long thoracic neuropathy. Pertinent aspects of the history and physical examination, nerve conduction studies, and electromyography are presented.


Outcomes of short segment distal radius resections and wrist fusion with iliac crest bone grafting for giant cell tumor.
Distal radius is third most common site for occurrence of Giant cell tumor (GCT) of bone. Most of Campanacci grade II & III cases require resection. Reconstructions of these defect are challenging. Though fibular arthroplasty provides mobility at wrist but is fraught with complications of donor site morbidity and instability with wrist pain. Wrist arthrodesis with ulna translocation provides stable reconstruction but is cosmetically less appealing. We present a series of 12 cases of GCT of distal radius treated with short segment (6 cm or less) resections and wrist fusion with iliac crest grafting. We evaluated donor site morbidity, functional and oncological outcomes. To assess time to union, donor site morbidity, functional and oncological outcomes after wrist fusion with iliac crest bone grafting for distal radius resection (≤6 cm). Retrospective analysis was performed from a prospectively maintained database between January 2011 and December 2017, 12 patients (7 male and 5 female; 9 primary and 3 recurrent; all Campanacci grade III) were included. Mean age was 29 years (15-41 years) with mean resection length of 5.1 cm (4.5-6 cm). The dominant hand was involved in 6 patients. Time to union, donor site morbidity, functional and oncologiacal outcomes were evaluated. Functional outcomes were evaluated using Musculo-Skeletal Tumor Society (MSTS) score and Patient Rated Wrist Evaluation (PRWE) score. Grip strength and arc of forearm rotation were also evaluated. All patients were available for analysis. No symptomatic donor site morbidity was observed. One patient had prominent implant following a fall and delayed union. Mean time to union for 22 osteotomy sites in rest of 11 patients (both proximal and distal) was 6 months (4-11 months). At median follow up of 45 months (18-78 months) 2 patients had soft tissue recurrence, 1 had a stable pulmonary metastasis. Local Recurrence rate was 17%. All patients returned to their pre surgery activity. Mean MSTS score was 25 (19-29) and PRWE score was 12 (6-28). Grip strength and Prono - supination measurements were available in 10 patients. Grip strength was 69% of non operated limb. Mean supination was 53° (0° to 80°) and mean protonation was 73° (40° to 80°). Mean arc of rotation was 126° (80° to 160°). Reconstruction of distal radius bone defects with Iliac crest bone grafting and wrist arthrodesis retains prono-supination while maintaining wrist girth (cosmesis). The oncologic and functional outcomes make it an acceptable modality in selected cases of distal radius tumours with short resection length (≤6 cm).


The relationship between tree mortality from a pine beetle epidemic and increased dissolved copper levels in the upper Big Thompson River, Colorado.
Bark beetle outbreaks in the Rocky Mountains caused substantial tree mortality starting in the late 1990s, and continued into the 2000s, with the most severe mortality occurring from 2002 to 2012. Over the same time period, concentrations of dissolved copper in the Big Thompson River (BTR), Colorado, USA, increased significantly and are high enough to negatively affect aquatic life. We examined correlations between dissolved copper and tree mortality in the BTR. Two sites, one consisting of water from the western side of the continental divide and one consisting of water from the eastern side, demonstrated a positive relationship between percentage tree mortality and dissolved copper. The relationships were similar except that the best relationship occurred with a 3-year lag between tree mortality and subsequent dissolved copper levels at the eastern site and with a 5-year lag at the western site. The differential time lag is potentially the result of different levels of carbon in the soil in the watersheds associated with each site because carbon can affect copper mobility. Our results suggest that bark beetle-induced tree mortality may contribute significantly to dissolved copper levels in the BTR.


ABCB1 c.-6-180T>G polymorphism and clinical risk factors in a multi-breed cohort of dogs with refractory idiopathic epilepsy.
Epilepsy is the most common chronic neurological disorder in dogs. Approximately 20-30% of dogs do not achieve satisfactory seizure control with two or more anti-epileptic drugs at appropriate dosages. This condition, defined as refractory epilepsy, is a multifactorial condition involving both acquired and genetic factors. The P glycoprotein might play and important role in the pathophysiological mechanism and it is encoded by the ABCB1 gene. An association between a single nucleotide variation of the ABCB1 gene (c.-6-180T>G) and phenobarbital resistance has previously been reported in a Border collie population with idiopathic epilepsy. To date, the presence and relevance of this polymorphism has not been assessed in other breeds. A multicentre retrospective, case-control study was conducted to investigate associations between ABCB1 c.-6-180T>G, clinical variables, and refractoriness in a multi-breed population of dogs with refractory idiopathic epilepsy. A secondary aim was to evaluate the possible involvement of the ABCB1 c.-6-180T>G single nucleotide variation this population. Fifty-two refractory and 50 responsive dogs with idiopathic epilepsy were enrolled. Of these, 45 refractory and 50 responsive (control) dogs were genotyped. The G allele was found in several breeds, but there was no evidence of association with refractoriness (P=0.69). The uncertain role of the c.-6-180T>G variation was further suggested by an association between the T/T genotype with both refractoriness and responsiveness in different breeds. Furthermore, high seizure density (cluster seizure) was the main clinical risk factor for refractory idiopathic epilepsy (P=0.003).


Ictal infraslow activity in stereoelectroencephalography: Beyond the "DC shift".
The significance of infraslow activity (ISA) in focal epilepsies is largely unknown. Recent work has demonstrated ictal ISA to be more widespread in expression than originally understood. Analysis of ISA by stereoelectroencephalography (SEEG) may help to clarify its localizing value, namely the focal versus widespread expression of ISA. The ictal SEEG records for fifteen consecutive adult patients were retrospectively analyzed, using both conventional (1.6-70 Hz) and infraslow (0.01-0.1 Hz) bandpass filters. When justified, seizures were averaged in the infraslow band to clarify their stereotypy. Wavelets were used to quantify the time-frequency characteristics of ISA. All clinical seizures were found to possess ISA, and this was markedly invariant across seizures in a given patient. ISA showed biphasic peaks in power, both at ictal onset and offset, with this most prominent in the anatomical structures implicated by conventional analysis. In addition, ISA demonstrated an association with low voltage fast activity, and possessed a more restricted field than conventional activity. ISA is both widespread (anatomically distributed) and focal (closed electric field). Seizures possess an infraslow spatiotemporal signature. Beyond representing a "focus" of paroxysmal activity, ISA must arise from a network process as a component of wideband ictal dynamics. How this relates to clinical definition of the epileptogenic zone requires further study.


Family Communication in Inherited Cardiovascular Conditions in Ireland.
Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media.


Linker remodels human Galectin-8 structure and regulates its hemagglutination and pro-apoptotic activity.
Numerous articles have reported the involvement of linker in regulating bioactivity of tandem-repeat galectins. We hypothesize that linker interacts with N/C-CRDs to regulate the bioactivity of tandem-repeat galectins. To further investigate structural molecular mechanism of linker in regulating bioactivity of Gal-8, Gal-8LC was crystallized. Gal-8LC structure revealed formation of β-strand S1 by Asn174 to Pro176 from linker. S1-strand interacts with C-terminal of C-CRD via hydrogen bond interactions, mutually influencing their spatial structures. Our Gal-8 NL structure have demonstrated that linker region from Ser154 to Gln158 interacts with the N-terminal of Gal-8. Ser154 to Gln158 and Asn174 to Pro176 are likely involved in regulation of Gal-8's biological activity. Our preliminary experiment results revealed different hemagglutination and pro-apoptotic activities between full-length and truncated forms of Gal-8, indicating involvement of linker in regulating these activities. We generated several mutant and truncated forms of Gal-8 (Gal-8 M3, Gal-8 M5, Gal-8TL1, Gal-8TL2, Gal-8LC-M3 and Gal-8_177-317). Ser154 to Gln158 and Asn174 to Pro176 were found to be involved in regulating hemagglutination and pro-apoptotic activities of Gal-8. Ser154 to Gln158 and Asn174 to Pro176 are critical functional regulatory regions within linker. Our study holds significant importance in providing a profound understanding of how linker regulates biological activity of Gal-8.


The Correlation of Il28B Genotype With Sustained Virologic Response In Romanian patients With Chronic Hepatitis C.
Multiple variables influencing the sustained virologic response (SVR) in chronic hepatitis C have been evaluated. One of them is genetic polymorphism near the IL28B gene. The aim of this study was to evaluate the influence of IL28B genotypes on SVR rates in a group of patients with chronic hepatitis C from the western part of Romania. A retrospective study was performed in 107 consecutive patients, previously treated with standard-of-care medication for chronic hepatitis C, identified from the databases of 2 centers. Patient demographics, viral load before treatment and at 12, 24, and 72 weeks from the treatment start, and IL28B genotype were evaluated. Among the 107 patents in the study group, 54 patients had SVR (50.5%), and 62 (57.9%) showed a complete early virologic response (cEVR). The SVR rates according to IL28B genotype were as follows: 73.1% in patients with genotype C/C, 40.9% in those with genotype C/T, and 57.1% in those with genotype T/T (i.e., 73.1% among patients with the C/C genotype vs. 43.7% among those with non-C/C genotypes; P = 0.0126). The cEVR rates were 80.8% in patients with the C/C genotype vs. 51.2% in those with non-C/C genotypes (P = 0.011). In our cohort of 107 Caucasian HCV patients, the SVR rate was 50.5% with standard-of-care treatment. The SVR rate was directly related to the IL28B genotype: 73.1% in the C/C genotype vs. 43.7% in non-C/C genotypes (P = 0.0126).


A comparison of gambling by Minnesota public school students in 1992, 1995, and 1998.
The purpose of this study was to compare rates of gambling among Minnesota public school students between 1992, 1995, and 1998. The three samples included 75,806 students in the 9th and 12th grades in 1992; 73,897 9th and 12th grade students in 1995; and 78,564 9th and 12th grade students in 1998. Students were administered the Minnesota Student Survey, a 121-item, anonymous, self-administered, paper-and-pencil questionnaire that inquires about multiple behavioral domains, including gambling behaviors. The same questionnaire, with minor revisions to the gambling items, was administered in 1992, 1995, and 1998 to students in their classrooms by the Minnesota Department of Education. The results showed two opposite trends. On the one hand, fewer students gambled in 1998 than in 1995 and 1992. On the other hand, there was a small, but growing number of 12th grade students who gambled frequently. In terms of trends over time for specific games, the lottery showed a significant decline in the number of 9th grade students who played at all. There was also a significant increase in the number of 12th grade students who played the lottery weekly or more often. The findings that frequent lottery gambling has increased among 12th grade students and that underage gambling continues among these students, are both cause for concern. This is the first generation of youth to be exposed to widespread accessability to legalized gambling venues and gambling advertising. Legalized gambling may be a new "rite of passage" for some of today's youth. It will be important to continue to monitor youth gambling and to provide information and resources to assist youth in making healthy decisions about their gambling behavior.


Selfish DNA: new abode for homing endonucleases.
A 30-year old conundrum concerning the genetics of T-even bacteriophages has at last been solved, the answer turning out to involve free-standing homologs of intron-encoded homing endonucleases.


Preoperative imaging for hyperparathyroidism often takes upper parathyroid adenomas for lower adenomas.
We retrospectively evaluated how accurately preoperative imaging localizes parathyroid adenoma in superior versus inferior parathyroids. Over 6 years, 104 patients with primary hyperparathyroidism underwent parathyroid surgery in a single centre. Of these, 103 underwent ultrasound, 97 [99mTc]pertechnetate/MIBI SPECT/CT and 30 [18F]fluorocholine (FCH) PET/CT. One patient with a unilateral double adenoma was excluded from the analysis. Surgical findings with histopathologic confirmation of adenoma were used as the standard. Ultrasound misjudged 5 of 48 detected lower adenomas as upper, but 14 of 29 upper adenomas as lower (error rate 10 vs 48%, p = 0.0002). The corresponding error rates for [99mTc]pertechnetate/MIBI SPECT/CT were 3 versus 55% (p = 0.000014), and for [18F]FCH PET/CT 17 versus 36% (p = 0.26). Our results suggest that about half of the superior parathyroid adenomas which are detected, are erroneously assigned to the inferior position by both ultrasound and SPECT/CT imaging whereas the opposite mistake is significantly less frequent with ultrasound and SPECT/CT.


Image-Guided Percutaneous Treatment of Lumbar Stenosis and Disc Degeneration.
Low back pain, radicular leg pain, and lumbar spinal stenosis are the most common of all chronic pain disorders. Discogenic pain is related to distress of annular fibers and tears, whereas spinal stenosis is related to reduction of the spinal canal dimensions and compression of the neural elements; radicular pain is mainly related to disc herniation and is initially managed conservatively. The percutaneous minimally invasive approach in discogenic and radicular pain is designed to reduce the volume of the nucleus pulposus in patients with failure of medical and physical treatment prolonged for at least 6 weeks.