Frequency-Unspecific Effects of θ-tACS Related to a Visuospatial Working Memory Task.
Working memory (WM) is crucial for intelligent cognitive functioning, and synchronization phenomena in the fronto-parietal network have been suggested as an underlying neural mechanism. In an attempt to provide causal evidence for this assumption, we applied transcranial alternating current stimulation (tACS) at theta frequency over fronto-parietal sites during a visuospatial match-to-sample (MtS) task. Depending on the stimulation protocol, i.e., in-phase, anti-phase or sham, we anticipated a differential impact of tACS on behavioral WM performance as well as on the EEG (electroencephalography) during resting state before and after stimulation. We hypothesized that in-phase tACS of the fronto-parietal theta network (stimulation frequency: 5 Hz; intensity: 1 mA peak-to-peak) would result in performance enhancement, whereas anti-phase tACS would cause performance impairment. Eighteen participants (nine female) received in-phase, anti-phase, and sham stimulation in balanced order. While being stimulated, subjects performed the MtS task, which varied in executive demand (two levels: low and high). EEG analysis of power peaks within the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) frequency bands was carried out. No significant differences were observed between in-phase and anti-phase stimulation regarding both behavioral and EEG measurements. Yet, with regard to the alpha frequency band, we observed a statistically significant drop of peak power from pre to post in the sham condition, whereas alpha power remained on a similar level in the actively stimulated conditions. Our results indicate a frequency-unspecific modulation of neuronal oscillations by tACS. However, the closer participants' individual theta peak frequencies were to the stimulation frequency of 5 Hz after anti-phase tACS, the faster they responded in the MtS task. This effect did not reach statistical significance during in-phase tACS and was not present during sham. A lack of statistically significant behavioral results in the MtS task and frequency-unspecific effects on the electrophysiological level question the effectiveness of tACS in modulating cortical oscillations in a frequency-specific manner.


Angiotensin II receptor blocker losartan exacerbates muscle damage and exhibits weak blood pressure-lowering activity in a dysferlin-null model of Limb-Girdle muscular dystrophy type 2B.
There is no cure or beneficial management option for Limb-Girdle muscular dystrophy (MD) type 2B (LGMD2B). Losartan, a blood pressure (BP) lowering angiotensin II (AngII) receptor type 1 (ATR1) blocker (ARB) with unique anti-transforming growth factor-β (TGF-β) properties, can protect muscles in various types of MD such as Duchenne MD, suggesting a potential benefit for LGMD2B patients. Herein, we show in a mild, dysferlin-null mouse model of LGMD2B that losartan increased quadriceps muscle fibrosis (142%; P<0.0001). In a severe, atherogenic diet-fed model of LGMD2B recently described by our group, losartan further exacerbated dysferlin-null mouse muscle wasting in quadriceps and triceps brachii, two muscles typically affected by LGMD2B, by 40% and 51%, respectively (P<0.05). Lower TGF-β signalling was not observed with losartan, therefore plasma levels of atherogenic lipids known to aggravate LGMD2B severity were investigated. We report that losartan increased both plasma triglycerides and cholesterol concentrations in dysferlin-null mice. Other protective properties of losartan, such as increased nitric oxide release and BP lowering, were also reduced in the absence of dysferlin expression. Our data suggest that LGMD2B patients may show some resistance to the primary BP-lowering effects of losartan along with accelerated muscle wasting and dyslipidemia. Hence, we urge caution on the use of ARBs in this population as their ATR1 pathway may be dysfunctional.


Masticatory performance and areas of occlusal contact and near contact in subjects with normal occlusion and malocclusion.
This preliminary study evaluated relationships between masticatory performance and areas of interocclusal distance contact (<50 microm) and near contact (50-350 microm) of the buccal segments during maximum intercuspation. The sample included subjects with normal occlusion (n = 18) and Class I (n = 14), Class II (n = 13), and Class III (n = 6) malocclusions. Chewing performance was evaluated on the basis of the breakdown of CutterSil (Heraeus Kulze, South Bend, Ind); chewing ability was assessed by the number of chews necessary to swallow jerky and almonds. Impressions of the buccal segments, taken with Blu Mousse (Parkell Bio-Materials, Farmingdale, NY) impression material, were scanned and enlarged, and each subject's first molars and premolars were manually traced bilaterally to estimate the platform area. The areas of contact and near contact (ACNC) that measured between 0 and 350 microm thick were estimated optically on the basis of the amount of light transmitted through the impression. The results showed no significant differences in platform area between the right and left sides or between the malocclusion groups. ACNC were negatively related to median particle size and broadness of particle distribution. There were no correlations between ACNC and the number of chews necessary to swallow jerky or almonds. Subjects with normal occlusion had significantly larger ACNC than those with Class I, Class II, and Class III malocclusions, in descending order. Subjects with Class III malocclusions had the smallest areas of near contact (<350 microm). We concluded that ACNC are similar on the right and left sides; that subjects with larger ACNC are better able to break down foods; and that subjects with malocclusions have smaller ACNC than those with normal occlusions.


A home balance exercise program improves walking in people with cerebellar ataxia.
Physical therapy intervention is the primary treatment for gait ataxia and imbalance in individuals with cerebellar damage. Our aim was to determine if a home balance exercise program is feasible for improving locomotor and balance abilities in these individuals. A total of 14 patients with cerebellar ataxia participated in a 6-week individualized home-based balance exercise program and attended 5 testing sessions (2 pretraining, 1 midtraining, 1 posttraining, and 1 one-month follow-up visit). Pretraining, posttraining, and follow-up testing included a neurological assessment, clinical gait and balance tests, and laboratory assessments of balance and walking. Participants kept logs of the frequency and level of balance challenge during their training. Walking speed improved across visits, as did stride length, percentage double-limb support time, Timed Up and Go (TUG), and Dynamic Gait Index. Post hoc comparisons in these measures revealed that significant rehabilitative improvements occurred over the 6-week training period, and all but TUG gains were retained 1 month later. There were no changes across the other measures for the group. Regression analysis indicated that improvements in walking speed were affected by the level of balance challenge but not by age, ataxia severity, proprioception, or duration of exercise. Improvement in locomotor performance in people with cerebellar ataxia was observable after a 6-week home balance exercise program. The exercise program must be designed to provide a significant challenge to the person's balance.


Comparative proteomics analysis of kidney in chicken infected by infectious bronchitis virus.
The gamma coronavirus infectious bronchitis virus (IBV) is known to cause an acute and highly contagious infectious disease in poultry. Here, this study aimed to investigate the impact of virulent or avirulent IBV infection on the avian host by conducting proteomics with data-independent acquisition mass spectrometry (DIA-MS) in the kidneys of IBV-infected chickens. The results revealed 267, 489, and 510 differentially expressed proteins (DEPs) in the chicken kidneys at 3, 5, and 7 days postinfection (dpi), respectively, when infected with the GD17/04 strain, which is a highly nephrogenic strain and belongs to the 4/91 genotype. In contrast, the attenuated 4/91 vaccine resulted in the identification of 144, 175, and 258 DEPs at 3, 5, and 7 dpi, respectively. Functional enrichment analyses indicated distinct expression profiles between the 2 IBV strains. Upon GD17/04 infection, metabolic pathways respond initially in the early stage (3 dpi) and immune-related signaling pathways respond in the middle and late stages (5 and 7 dpi). The 4/91 vaccine elicited a completely opposite response compared to the GD17/04 infection. Among all DEPs, 62 immune-related DEPs were focused on and found to be mainly enriched in the type I interferon (IFN-I) signaling pathway and involved in humoral and cellular immunity. Notably, key molecules in the IFN-I signaling pathway including MDA5, LGP2, and TBK1 may serve as regulatory targets of IBV. Overall, this study highlights similarities and discrepancies in the patterns of protein expression at different stages of infection with virulent and avirulent IBV strains, with the IFN-I signaling pathway emerging as a critical response to IBV infection.


A QTL for genotype by sex interaction for anthropometric measurements in Alaskan Eskimos (GOCADAN Study) on chromosome 19q12-13.
Variation in anthropometric measurements due to sexual dimorphism can be the result of genotype by sex interactions (G×S). The purpose of this study was to examine the sex-specific genetic architecture in anthropometric measurements in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Maximum likelihood-based variance components decomposition methods, implemented in SOLAR, were used for G×S analyses. Anthropometric measurements included BMI, waist circumference (WC), waist/height ratio, percent body fat (%BF), and subscapular and triceps skinfolds. Except for WC, mean values of all phenotypes were significantly different in men and women (P < 0.05). All anthropometric measures were significantly heritable (P < 0.001). In a preliminary analysis not allowing for G×S interaction, evidence of linkage was detected between markers D19S414 and D19S220 on chromosome 19 for WC (logarithm of odds (lod) = 3.5), %BF (lod = 1.7), BMI (lod = 2.4), waist/height ratio (lod = 2.5), subscapular (lod = 2.1), and triceps skinfolds (lod = 1.9). In subsequent analyses which allowed for G×S interaction, linkage was again found between these traits and the same two markers on chromosome 19 with significantly improved lod scores for: WC (lod = 4.5), %BF (lod = 3.8), BMI (lod = 3.5), waist/height ratio (lod = 3.2), subscapular (lod = 3.0), and triceps skinfolds (lod = 2.9). These results support the evidence of a G×S interaction in the expression of genetic effects resulting in sexual dimorphism in anthropometric phenotypes and identify the chromosome 19q12-13 region as important for adiposity-related traits in Alaskan Eskimos.


Analysis of pre-mRNA and pre-rRNA processing factor Snu13p structure and mutants.
Snu13p is a Saccharomyces cerevisiae protein essential for pre-messenger RNA splicing and pre-ribosomal RNA processing. Snu13p binds U4 snRNA of the spliceosome and box C/D snoRNAs of the pre-ribosomal RNA processing machinery to induce assembly of each ribonucleoprotein complex. Here, we present structural and biochemical analysis of Snu13p. The crystal structure of Snu13p reveals a region of the protein which could be important for protein interaction during ribonucleoprotein assembly. Using the structure of Snu13p we have designed the first temperature-sensitive mutants in Snu13p, L67W and I102A. Wild-type and mutant Snu13p proteins were assayed for binding to U4 snRNA and U3 snoRNA. Both temperature-sensitive mutants displayed significantly reduced RNA binding compared to wild-type protein. As the temperature-sensitive mutations are not in the known RNA binding region of Snu13p this indicates that these mutants indirectly influence the RNA binding properties of Snu13p. This work provides insight into Snu13p function during ribonucleoprotein assembly.


Identification and Validation of Stromal Immunotype Predict Survival and Benefit from Adjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer.
Purpose: This study aims to construct the stromal immunotype, which could improve the prediction of postsurgical survival and adjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC).Experimental Design: A total of 118 patients with MIBC from Shanghai Cancer Center, 140 patients with MIBC from Zhongshan Hospital, and 287 patients with MIBC from TCGA cohort were included in the study. Immune cell infiltration was evaluated by IHC staining or CIBERSORT method. Five immune features were selected out of 22 immune features to construct immunotypes based on the LASSO Cox regression model.Results: Using the LASSO model, we classified patients with MIBC into stromal immunotype A subgroup (CTLhighNKhighTreglowMacrophagelowMClow) and stromal immunotype B subgroup (CTLlowNKlowTreghighMacrophagehighMChigh). Significant differences were found between immunotype A and immunotype B in the combined cohort with 5-year overall survival (OS, 76.0% vs. 44.0%; P < 0.001) and 5-year disease-free survival (DFS, 62.8% vs. 48.3%; P < 0.001). Stromal immunotype was revealed to be an independent prognostic indicator in multivariate analysis in all cohorts separately. Either OS or DFS was not improved by adjuvant chemotherapy (ACT) in pT2 stage patients or pT3+pT4 patients, but further analysis revealed that OS and disease-free was significantly improved by ACT in pT3+pT4 patients (P = 0.016 and P = 0.006, respectively). Finally, stromal immunotype A showed higher immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) expression.Conclusions: The stromal immunotypes could effectively predict survival and recurrence of MIBC. Furthermore, the immunotypes might be a practical predictive tool to identify pT3+pT4 patients who would benefit from ACT. Clin Cancer Res; 24(13); 3069-78. ©2018 AACR.


Transforming our relationship with the social determinants of health: a scoping review of social justice interventions in Canadian Medical Schools.
This article was migrated. The article was marked as recommended. Background/Purpose: Physicians are in a powerful position to improve the health status of communities through mitigating disparities rooted in social inequities. However, it is uncertain whether medical schools are preparing future physicians with the skills needed to care for diverse populations. The current scoping review aimed to describe how Canadian medical schools teach social justice, comparing pedagogical strategies. Methods: A search was performed using OVID to identify published studies of implemented and evaluated social justice-based interventions within Canadian medical school curricula. Results: Six studies were included. Common themes included increased content knowledge, greater understanding of SDoH, acknowledgement of power and privilege imbalances, identification of physicians' roles as advocates, emphasis on the importance of interdisciplinary care, and increased capacity for self-reflection and personal growth. Experiential interventions were associated with greater personal transformation, but had limited accessibility. Conclusion: Despite the widespread recognition of physicians' roles as health advocates, there is a lack of consensus about an effective strategy for teaching social justice in medical education in Canada. While additional research focusing on the relative merits of didactic versus experiential learning is needed, these preliminary results suggest that experiential learning emphasizing self-reflection and personal growth may be optimal when approaching transformative learning.


[Relationship between EB virus and nasopharyngeal carcinoma. I. Detection of EBV DNA-related sequences in biopsy specimens of nasopharyngeal carcinoma].
Assay of biopsy materials of nasopharyngeal carcinoma (NPC) by nucleic hybridization (dot blot) technique with 32P labelled EBVDNA BamHIW fragment probe (specific radioactivity: 1-3 x 10(7) cpm/micrograms DNA) are described. 57 biopsies of different pathologic types were taken from NPC patients from Beijing and Qing Dao, Shandong province, and 54 control biopsies were taken from patients with other tumors and inflammatory tissues from the nasopharynx and head-neck regions. It was shown that EBVDNA positive reaction was found in 52 out of 57 NPC biopsies (91%), while only 10 positive reaction were observed in 54 control samples (18.5%). There was a significant statistical difference therein (P less than 0.001), but no significant difference of EBV DNA positive rates was found among the different pathological types (P greater than 0.05). Also no significant difference was found in biopsies taken from various geographical regions in both groups.


The Mediating Role of Perceived Stress in Associations Between Self-Compassion and Anxiety and Depression: Further Evidence from Chinese Medical Workers.
Medical workers report high rates of stress, anxiety and depression, which need urgent attention. Providing evidence for intervention measures in the face of a mental health crisis, the present study validates the relation between self-compassion and anxiety and depression mediated by perceived stress amongst medical workers. The goal is also to replicate a similar mediation model though multigroup analysis. Medical workers were randomly selected to investigate by paper-and-pencil survey among 1,223 medical workers from three hospitals in Shiyan, China. The measures were comprised of four parts: the Chinese version of the Goldberg Anxiety and Depression Scale (GADS), the Self-Compassion Scale-Short Form (SCS-SF), the Perceived Stress Questionnaire (PSQ) and a socio-demographic questionnaire. Applying structural equation modeling (SEM, single-group analysis), we estimated the effects of self-compassion on anxiety/depression through perceived stress. Furthermore, based on multigroup analysis, we used two sets of internal samples (gender groups, medical groups) and an external sample (nursing students) for testing multigroup invariance. The average scores of anxiety, depression, self-compassion and perceived stress in medical workers were 5.93 ± 2.46, 4.91 ± 2.62, 38.87 ± 4.66 and 71.96 ± 15.14, respectively. In some departments engaged in the research, the medical workers showed higher levels of anxiety and depression. The SEM results indicated that the original relationship between self-compassion and anxiety and depression was beta = -0.42 (P < 0.001) and reduced to beta = -0.17 (P < 0.001) while introducing perceived stress as a mediating variable. Perceived stress was positively associated with anxiety and depression (beta = 0.60, P < 0.001), and self-compassion was negatively associated with perceived stress (beta = -0.56, P < 0.001). Multigroup analysis showed acceptable changes in fit indices across gender (male and female), medical (clinician and non-clinician), and population (medical workers and nursing students) groups. Medical workers were experiencing high levels of anxiety and depression and perceived stress. Perceived stress might have a partial mediating effect on self-compassion and anxiety and depression amongst medical workers, which was similar to a previous study in nursing students. The findings supported multigroup invariance across gender, medical and population groups. The study concluded that the mediation model may be generalized across these multiple samples. Psychological intervention could be used to improve levels of self-compassion of medical workers.


Rupture of multiple catch-slip bonds: Two-state two-pathway catch-slip bonds.
We performed Monte Carlo simulation of the detachment of a polymorphonuclear (PMN) leukocyte immersed in a Newtonian fluid and adhered to a substrate by multiple catch-slip bonds. We found that at certain loading rates the interplay of multiple catch-slip bonds leads to a bimodal distribution of the bond rupture force. We also found that the low force peak in these bond rupture force distributions switches to a high force peak with a gradual increase in the loading rate. These trends in the bond rupture force distributions are characteristics of two-state systems. Consequently, though individual catch-slip bonds follow one-state two-pathway energy landscape, their interplay mimics a two-state two-pathway energy landscape.


Workshop on pediatric trauma care: low-cost simulation.
to assess nursing students' and nurses' knowledge, satisfaction and self-confidence after a theoretical workshop on emergency care for traumatized children and clinical simulation. a quasi-experimental study, carried out with nursing students and nurses residing at a public university in southern Brazil. A workshop on pediatric trauma care was created and a mannequin was created for simulations. A knowledge pre-test and post-test and the Student Satisfaction and Self-Confidence in Learning instrument were applied to measure satisfaction and self-confidence in learning. For analysis, descriptive statistics and the Wilcoxon test were used to compare means before and after intervention. the difference between misses and hits was statistically significant (p<0.005), demonstrating an increase in participants' knowledge after the workshop. Satisfaction and self-confidence were demonstrated in the instrument's high scores. the effectiveness of the workshop in teaching-learning emergency care for pediatric trauma was demonstrated.


A case of Good's syndrome complicated by erythema multiforme.
Good's syndrome (GS) is a rare, adult-onset combined B cell and T cell immunodeficiency with an associated thymoma. These patients have an increased risk of bacterial, fungal, viral and opportunistic infections. This report describes a 75-year-old female patient who presented with a full body rash and an anterior mediastinal mass. She underwent a biopsy of her rash and mass, which revealed erythema multiforme and WHO Type A thymoma, respectively. During her hospitalisation, she was also found to have oropharyngeal candidiasis, methicillin-susceptible Staphylococcus aureus bacteraemia and herpes simplex virus type 2 (HSV-2) skin lesions. Based on the number of infections and severity of her rash, an immunocompromised state was suspected. Immunological testing revealed a B cell and T cell deficiency as well as low serum immunoglobulins. This combination of hypogammaglobulinaemia and thymoma led to a diagnosis of GS. While there have been many case reports of GS, this is the first report of the immunodeficiency presenting with erythema multiforme.


Dissolution of an emplaced source of DNAPL in a natural aquifer setting.
Field-scale dissolution of a multicomponent DNAPL (dense nonaqueous-phase liquid) source intentionally emplaced below the water table is evaluated in a well-characterized natural aquifer setting. The block-shaped source contained 23 kg of a trichloromethane, trichloroethene, and perchloroethene mixture homogeneously distributed at 5% saturation of pore space. Dissolution was monitored for 3 yr via down-gradient samplers (1-m fence) and occasional intra-source sampling. Although intra-source equilibrium dissolution was shown and endorsed by supporting modeling and literature lab data, less than equilibrium concentrations were predominantly monitored in the 1-m fence. This was ascribed to significant by-passing of the source by groundwater flow due to its low permeability relative to the aquifer and associated dilution of concentrations emitted from the source. Heterogeneous source dissolution occurred despite the relative homogeneity of the source and aquifer and was ascribed to dissolution fingering, which has not been previously field-demonstrated. Bulk bypass of groundwater flow around the source zone caused slow dissolution rates, with 77% of the source remaining after 3 yr and a projected longevity of approximately 25 yr. Observed dissolution fingering would have significantly increased longevity as it increasingly caused intra-source bypass of remaining DNAPL. Our dissolution interpretations were endorsed by additional data collected after 6 yr during source remediation via permanganate oxidation.


Risk of subsequent invasive breast cancer after a diagnosis of ductal carcinoma in situ (DCIS).
Despite surgical removal of ductal carcinoma in situ (DCIS), recurrences still occur. This retrospective cohort study evaluated the risk of invasive recurrence following surgery and investigated factors which may be predictive of recurrence. We specifically investigated invasive recurrence with respect to mode of detection of DCIS. Patients whose DCIS was detected outside of the NHS Breast Screening Programme have a higher risk of subsequent ipsilateral invasive breast cancer than those whose DCIS is detected through screening. There is no significant difference in risk of subsequent contralateral invasive recurrence according to mode of detection.


Psychosocial mediation of fruit and vegetable consumption in the body and soul effectiveness trial.
In this study the authors examined psychosocial variables as mediators for fruit and vegetable (FV) intake in a clustered, randomized effectiveness trial conducted in African American churches. The study sample included 14 churches (8 intervention and 6 control) with 470 participants from the intervention churches and 285 participants from the control churches. The outcome of FV intake and the proposed mediators were measured at baseline and at 6-month follow-up. Structural equation modeling indicated that the intervention had direct effects on social support, self-efficacy, and autonomous motivation; these variables also had direct effects on FV intake. Applying the M. E. Sobel (1982) formula to test significant mediated effects, the authors confirmed that social support and self-efficacy were significant mediators but that autonomous motivation was not. Social support and self-efficacy partially mediated 20.9% of the total effect of the intervention on changes in FV intake. The results support the use of strategies to increase social support and self-efficacy in dietary intervention programs.


Changes in urea nitrogen and creatinine concentrations in the vitreous humor of cattle after death.
The mean urea nitrogen concentration in vitreous humor (VUN) in 97 healthy steers after death was 15.7 mg/dl. The mean serum urea nitrogen concentration in the same cattle was 20.0 mg/dl. The mean vitreous creatinine (VC) concentration was 0.7 mg/dl, and the serum creatinine value was 1.5 mg/dl. The VUN and VC were both significantly lower than serum urea nitrogen and serum creatinine, respectively, but varied in a consistent, predictable manner. In tests with 10 cows, postmortem intervals as long as 36 hours and ambient temperatures up to 30 C had no significant effects on VUN and VC. Evaluation of 8 animals with uremia confirmed that the vitreous humor is a stable fluid compartment after death, usable as an indicator of serum urea nitrogen and creatinine.


Adduct formation in electrospray ionisation-mass spectrometry with hydrophilic interaction liquid chromatography is strongly affected by the inorganic ion concentration of the samples.
Hydrophilic interaction liquid chromatography (HILIC)/ electrospray ionisation-mass spectrometry (ESI-MS) has gained interest for the analysis of polar analytes in bioanalytical applications in recent years. However, ESI-MS is prone to adduct formation of analytes. In contrast to reversed phase chromatography, small inorganic ions have retention in HILIC, i.e. analytes and inorganic ions may co-elute, which could influence the adduct formation. In the present paper, it was demonstrated that the co-elution of sodium ions or potassium ions and analytes in HILIC/ESI-MS affect the adduct formation and that different concentrations of sodium ions and potassium ions in biological samples could have an impact on the quantitative response of the respective adducts as well as the quantitative response of the protonated adduct. The co-elution also lead to cluster formation of analytes and sodium formate or potassium formate, causing extremely complicated spectra. In analytical applications using HILIC/ESI-MS where internal standards are rarely used or not properly matched, great care needs to be taken to ensure minimal variation of inorganic ion concentration between samples. Moreover, the use of alkali metal ion adducts as quantitative target ions in relative quantitative applications should be made with caution if proper internal standards are not used.


Haemodynamic response to tracheal intubation via intubating laryngeal mask airway versus direct laryngoscopic tracheal intubation.
To compare the haemodynamic response to tracheal intubation using either direct larygoscopy or Intubating Laryngeal Mask Airway. This was a prospective randomized controlled trial. One hundred adult ASA-I and ASA-II patients coming to the Anaesthesia Department of Aga Khan University Hospital were randomly divided into two groups. In group-I endotracheal intubation was done with the help of Macintosh laryngoscope while in group-II patients were intubated with the help of the Intubating Laryngeal Mask Airway. Systolic, diastolic, mean arterial blood pressure and heart rate were recorded at baseline, at laryngoscopy and at 1 minute interval for 10 minutes following intubation. There was no statistically significant difference between the groups with respect to age, weight, height and gender. The rise in systolic blood pressure in group-I was 26 and 13% when compared with the baseline for first two minutes, while in group II the increase was 8-12%. When both groups were compared statistically significant difference (P < 0.05) was observed. The rise in diastolic blood pressure was 23% and 7% in group-I and II respectively when compared with the baseline. Statistically significant difference (P < 0.05) was observed at first two minutes following intubation between the two groups. The rise in mean arterial blood pressure after intubation was statistically significant. The increase in heart rate was observed after intubation in both the groups and when both the groups were compared the rise was not statistically significant. We concluded that intubation through intubating laryngeal mask airway is accompanied by minimal cardiovascular responses than those associated with direct laryngoscopic tracheal intubation, so it can be used for patients in whom a marked pressor response would be deleterious.


The effect of sampling rate and lowpass filters on saccades - A modeling approach.
The study of eye movements has become popular in many fields of science. However, using the preprocessed output of an eye tracker without scrutiny can lead to low-quality or even erroneous data. For example, the sampling rate of the eye tracker influences saccadic peak velocity, while inadequate filters fail to suppress noise or introduce artifacts. Despite previously published guiding values, most filter choices still seem motivated by a trial-and-error approach, and a thorough analysis of filter effects is missing. Therefore, we developed a simple and easy-to-use saccade model that incorporates measured amplitude-velocity main sequences and produces saccades with a similar frequency content to real saccades. We also derived a velocity divergence measure to rate deviations between velocity profiles. In total, we simulated 155 saccades ranging from 0.5° to 60° and subjected them to different sampling rates, noise compositions, and various filter settings. The final goal was to compile a list with the best filter settings for each of these conditions. Replicating previous findings, we observed reduced peak velocities at lower sampling rates. However, this effect was highly non-linear over amplitudes and increasingly stronger for smaller saccades. Interpolating the data to a higher sampling rate significantly reduced this effect. We hope that our model and the velocity divergence measure will be used to provide a quickly accessible ground truth without the need for recording and manually labeling saccades. The comprehensive list of filters allows one to choose the correct filter for analyzing saccade data without resorting to trial-and-error methods.


Inhibition of tissue factor pathway inhibitor increases the sensitivity of thrombin generation assay to procoagulant microvesicles.
Patients with cancer have a seven-fold to 10-fold increased risk of developing venous thromboembolism (VTE). Circulating microvesicles could be a predictive biomarker for VTE in cancer. Thrombin generation assay (TGA) is a useful technique to detect procoagulant activity of microvesicles. However, TGA suffers from a lack of sensitivity due to the presence of tissue factor pathway inhibitor (TFPI) in plasma. The aim of the study was to improve the sensitivity of TGA to tissue factor by limiting the interference of TFPI. Serial dilutions of MDA-MB231 cells were incubated for 45 min at 37°C to generate microvesicles. Samples were then centrifuged and supernatants that contain microvesicles were used for TGA. Normal pooled plasma was incubated with inhibitor of TFPI or was diluted twice to decrease plasma level of TFPI. Lagtime was used as a surrogate marker of TGA to detect procoagulant activity of microvesicles. Inhibition of TFPI decreased twice the cell concentration needed for a significant reduction of lagtime and decreased 2.4-fold the intraassay variability. Plasma dilution had no impact on the TGA sensitivity when TGA was triggered by microvesicles derived from MDA-MB-231. Thrombin generation is a very sensitive method to study the procoagulant activity of tissue factor bearing microvesicles. The sensitivity can be increased by inhibition of TFPI with specific monoclonal antibody against its Kunitz domain I. A two times plasma dilution is an interesting cheaper alternative to study the procoagulant activity of microvesicles by TGA with a good sensitivity, especially when low plasma quantities are available.


Radiation therapy in non-surgically-treated nonmetastatic prostate cancer: geographic and demographic variation.
To examine the geographic variation in the use of radiation to treat nonmetastatic prostate cancer and to identify factors that explain the variation in the United States. This study was based on data from the nine geographic regions of the Surveillance, Epidemiology, and End Results Program for 1983 through 1996. Patients with localized or regional prostate cancer who did not undergo surgical treatment were included in the analysis. Logistic regression analysis was used to investigate the influence of geographic and demographic factors on the use of radiation. The squared multiple correlation coefficient R(2) was used to measure the proportion of variation in the selection of radiation explained by each factor of interest. Compared with San Francisco, the adjusted odds ratios for 6 of the 8 geographic areas had highly significant P values, suggesting the use of radiation therapy varies from region to region. However, geographic location only explained less than 3% of the total variation in the use of radiation. The geographic location explained a much higher proportion of variation in the youngest (younger than 55 years) and the oldest (80 years old or older) groups. Overall, age was the most important factor that influenced the use of radiation. The finding that geographic location explains a significant proportion of the variation in the use of radiation in the youngest and oldest age groups demonstrates the outcome of longstanding controversies in the nonsurgical treatment of prostate cancer. Documenting the impact of the interaction of age and geographic location on the treatment approaches provides for better understanding of the impact of patients and physicians making clinical decisions in the management of nonmetastatic prostate cancer.


Modification of Blair Approach With a Modified Endaural Component to Access the Parotid Region.
The aim of this study is to present our experience with a modification of the Blair approach to the parotid area, by means of a modified endaural component, which provides both excellent exposure and optimal functional and esthetic results, mainly over the preauricular area. A retrospective case series study was performed. It included surgical cases of patients who were operated on the parotid region in which the mentioned approach was indicated. The information was collected from the database available at the Universidad El Bosque Oral and Maxillofacial Surgery Department in Bogota, Colombia from 2008 to 2013. The sample consisted of 12 patients, with ages ranging from 23 to 56 years and a mean age of 38 years. A total of 8 patients were women and 4 patients were men. Parotid pathologies included salivary gland tumor (10 patients) and cranial base tumor (2 patients). Procedures executed were: superficial lobe and total parotidectomy resection, pharynx extended and cranial base tumor resections. This investigation presents our experience with a modified approach to the parotid region. This approach gives an extended and safe exposure to the region with excellent cosmetic outcomes.


Fishing amplifies forage fish population collapses.
Forage fish support the largest fisheries in the world but also play key roles in marine food webs by transferring energy from plankton to upper trophic-level predators, such as large fish, seabirds, and marine mammals. Fishing can, thereby, have far reaching consequences on marine food webs unless safeguards are in place to avoid depleting forage fish to dangerously low levels, where dependent predators are most vulnerable. However, disentangling the contributions of fishing vs. natural processes on population dynamics has been difficult because of the sensitivity of these stocks to environmental conditions. Here, we overcome this difficulty by collating population time series for forage fish populations that account for nearly two-thirds of global catch of forage fish to identify the fingerprint of fisheries on their population dynamics. Forage fish population collapses shared a set of common and unique characteristics: high fishing pressure for several years before collapse, a sharp drop in natural population productivity, and a lagged response to reduce fishing pressure. Lagged response to natural productivity declines can sharply amplify the magnitude of naturally occurring population fluctuations. Finally, we show that the magnitude and frequency of collapses are greater than expected from natural productivity characteristics and therefore, likely attributed to fishing. The durations of collapses, however, were not different from those expected based on natural productivity shifts. A risk-based management scheme that reduces fishing when populations become scarce would protect forage fish and their predators from collapse with little effect on long-term average catches.


Neural compensation within the human triceps surae during prolonged walking.
During human walking, muscle activation strategies are approximately constant across consecutive steps over a short time, but it is unknown whether they are maintained over a longer duration. Prolonged walking may increase tendinous tissue (TT) compliance, which can influence neural activation, but the neural responses of individual muscles have not been investigated. This study investigated the hypothesis that muscle activity is up- or down-regulated in individual triceps surae muscles during prolonged walking. Thirteen healthy subjects walked on a treadmill for 60 min at 4.5 km/h, while triceps surae muscle activity, maximal muscle compound action potentials, and kinematics were recorded every 5 min, and fascicle lengths were estimated at the beginning and end of the protocol using ultrasound. After 1 h of walking, soleus activity increased by 9.3 ± 0.2% (P < 0.05) and medial gastrocnemius activity decreased by 9.3 ± 0.3% (P < 0.01). Gastrocnemius fascicle length at ground contact shortened by 4.45 ± 0.99% (P < 0.001), whereas soleus fascicle length was unchanged (P = 0.988). Throughout the stance phase, medial gastrocnemius fascicle lengthening decreased by 44 ± 13% (P < 0.001), whereas soleus fascicle lengthening amplitude was unchanged (P = 0.650). The data suggest that a compensatory neural strategy exists between triceps surae muscles and that changes in muscle activation are generally mirrored by changes in muscle fascicle length. These findings also support the notion of muscle-specific changes in TT compliance after prolonged walking and highlight the ability of the CNS to maintain relatively constant movement patterns in spite of neuromechanical changes in individual muscles.


Clinical predictors for diagnosing pandemic (H1N1) 2009 and seasonal influenza (H3N2) in fever clinics in Beijing, China.
Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic (H1N1) 2009 and seasonal influenza (H3N2) in patients attending fever clinics. From 1 May 2009 to 1 January 2010, all adult patients admitted to fever clinics for suspected influenza, confirmed by real time RT-PCR, were enrolled. Predictors of influenza virus infection were selected with logistic regression models. Measures of sensitivity, specificity, positive and negative likelihood ratios (LRs) were calculated to identify the best predictors. The clinical features and routine blood test results of influenza (H1N1) 2009 and seasonal influenza were similar. The positive and negative LRs of current US CDC influenza-like illness (ILI) criteria were modest in predicting influenza infection. Our modified clinic predictors improved the ability of the positive and negative LRs to recognize pandemic (H1N1) 2009 and seasonal influenza. The revised criteria are: fever >38 °C accompanied by at least one of the following-cough, arthralgia or relative lymphopenia. Patients with symptoms and signs that meet the new criteria are likely to have influenza and timely antiviral therapy may be appropriate. In addition, physicians should ascertain if influenza is circulating within the community or if there is a contact history of influenza and combine this information with the newly developed criteria to clinically diagnose influenza.


Pleats in crystals on curved surfaces.
Hexagons can easily tile a flat surface, but not a curved one. Introducing heptagons and pentagons (defects with topological charge) makes it easier to tile curved surfaces; for example, soccer balls based on the geodesic domes of Buckminster Fuller have exactly 12 pentagons (positive charges). Interacting particles that invariably form hexagonal crystals on a plane exhibit fascinating scarred defect patterns on a sphere. Here we show that, for more general curved surfaces, curvature may be relaxed by pleats: uncharged lines of dislocations (topological dipoles) that vanish on the surface and play the same role as fabric pleats. We experimentally investigate crystal order on surfaces with spatially varying positive and negative curvature. On cylindrical capillary bridges, stretched to produce negative curvature, we observe a sequence of transitions-consistent with our energetic calculations-from no defects to isolated dislocations, which subsequently proliferate and organize into pleats; finally, scars and isolated heptagons (previously unseen) appear. This fine control of crystal order with curvature will enable explorations of general theories of defects in curved spaces. From a practical viewpoint, it may be possible to engineer structures with curvature (such as waisted nanotubes and vaulted architecture) and to develop novel methods for soft lithography and directed self-assembly.


How effective is melatonin as a preventive treatment for hemicrania continua? A clinic-based study.
To assess the efficacy of melatonin as a preventive therapy for hemicrania continua in a larger population of patients than has previously been studied. Hemicrania continua is defined by its sensitivity to indomethacin. Rarely can patients be fully tapered off indomethacin without headache recurrence; thus, the risks associated with chronic indomethacin usage are substantial for these individuals. Melatonin, a pineal hormone with a similar chemical structure to indomethacin, has shown efficacy as a preventive agent for hemicrania continua in isolated case reports. Melatonin would be a preferential alternative prophylactic treatment to indomethacin because of its minimal side effect profile. How truly effective melatonin is as a preventive for hemicrania continua is unknown at present and needs further study. Retrospective analysis of all International Classification of Headache Disorders-3 beta diagnosed hemicrania continua patients treated with both indomethacin and melatonin at the Geisinger Headache Center from July 2011 to January 2014. Eleven patients were treated (9 women, 2 men). Two patients became pain free on melatonin, while partial relief was noted in 3 other patients; thus, they were able to lower their dose of indomethacin but could not achieve pain freedom with melatonin alone. Six patients had no response. Melatonin dosing needed for response ranged from 3 to 30 mg. In the partial relief responders, indomethacin dosing decreased by 50% to 75%. From this single clinic investigation, only a small percent of subjects with hemicrania continua (less than 20%) will achieve pain freedom on melatonin, thus clearly not matching the effectiveness of indomethacin. However, the addition of melatonin to indomethacin may allow around 45% of patients to have complete or partial relief of their headache with the subsequent ability to reduce or eliminate their indomethacin dosage, which may lead to a decrease in medical morbidity over time secondary to less exposure to indomethacin.


When is violence planned?
We examine what types of violent offenses tend to be planned using self-report data from a nationally representative sample of state and federal inmates. We find mixed support for the idea that predatory offenses are more likely to be planned than dispute-related offenses. As expected, robbery offenders are much more likely to report that they planned their crime ahead of time than homicide and physical assault offenders. However, sexual assault offenders are no more likely to report planning than homicide offenders. We also find mixed support for the idea that domestic violence-the supposed crime of passion-is less likely to be planned than violent offenses involving strangers. Finally, we find substantial demographic variation depending on type of crime. Robberies involving offenders of lower socioeconomic status and homicides and assaults involving African American offenders and victims are less likely to involve planning.


Seroprevalence of cytomegalovirus, Epstein Barr virus and varicella zoster virus among pregnant women in Bradford: a cohort study.
To estimate the seroprevalence of cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella zoster virus (VZV) among pregnant women in Bradford by ethnic group and country of birth. A stratified random sample of 949 pregnant women enrolled in the Born in Bradford birth cohort was selected to ensure sufficient numbers of White UK born women, Asian UK born women and Asian women born in Asia. Serum samples taken at 24-28 weeks' gestation were tested for CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included socio-demographic information. CMV seroprevalence was 49% among the White British women, 89% among South Asian UK born women and 98% among South Asian women born in South Asia. These differences remained after adjusting for socio-demographic factors. In contrast, VZV seroprevalence was 95% among women born in the UK but significantly lower at 90% among South Asian women born in Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country of birth. Although about half of White British women are at risk of primary CMV infection in pregnancy and the associated increased risk of congenital infection, most congenital CMV infections are likely to be in children born to South Asian women with non-primary infection during pregnancy. South Asian women born in South Asia are at risk of VZV infection during pregnancy which could produce congenital varicella syndrome or perinatal chickenpox. Differences in CMV and VZV seroprevalence by ethnic group and country of birth must be taken into account when universal immunisation against these viruses is contemplated.


Comparison of active versus passive audiovisual distraction tools on children's behaviour, anxiety and pain in paediatric dentistry: a randomised crossover clinical trial.
To determine the effect of active distraction when playing PlayStation® video games, compared to passive distraction when watching a cartoon with audiovisual eyeglasses, on parental perception of patients' anxiety, and children's anxiety, pain, behaviour and heart rate during restorative procedures in paediatric dentistry. Study design: Randomised crossover clinical trial. There were 34 patients in the cartoon film group (passive distraction) and 34 in the Playstation® video game group (active distraction), aged 6-8 years, who required a minimum of 2 visits for restorative treatment. Rimax® iVision 5.0 eyeglasses were used in both groups. Parental perception of patients' anxiety (Modified Corah Dental Anxiety Scale), and children's anxiety (Venham Picture Test), pain (Wong-Baker Faces Scale), behaviour (Frankl Scale) and heart rate were evaluated at each of the treatment visits. Preference for and satisfaction with the audiovisual product were also assessed. There were significant differences in self-reported pain between control (P=0.016) and experimental (P=0.013) visits in both groups, with lower values in the Playstation® video game group. No significant differences were found (P>0.05) in the other variables evaluated with the use of active distraction. A significant increase in heart rate was recorded at each treatment visit (P=0.0001) when the anaesthetic was injected. All the patients wanted to continue watching or playing their chosen cartoon or Playstation® video game during subsequent visits. The use of PlayStation® video games for active audiovisual distraction, compared with passive distraction with a cartoon, improved self-reported pain but did not reduce parents' perception of patients' anxiety, pain, global behaviour, or heart rate. Both distraction methods were accepted by paediatric patients.


Method for the isolation of highly purified Salmonella flagellins.
Ten different Salmonella serotypes were grown in a chemically defined medium supplemented with 0.01% yeast extract. After sedimentation of the cells by centrifugation, flagella were detached by exposure to pH 2 for 30 min at room temperature. The flagellaless cells were removed by centrifugation, and the flagellin in the supernatant was further purified by high-speed centrifugation, ammonium sulfate precipitation, and dialysis in 50,000-molecular-weight-cutoff tubing. The 10 flagellin preparations were of a high degree of purity, as demonstrated by electron microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and measurement of salmonella H and O agglutination titers of antisera raised in rabbits with the flagellin preparations as immunogens.


Reflective Practice: A Tool for Readmission Reduction.
Factors intrinsic to local practice, but not captured by the medical record, contribute to readmissions. Frontline providers familiar with their practice systems can identify these. The objective was to decrease 30-day hospital readmissions. The intervention involved retrospective review by hospitalists of their own patients' readmissions, using reflective practice guided by a chart review tool. Subjects were patients discharged by hospitalists and readmitted to a tertiary care academic medical center. Hospitalists reviewed 193 readmissions of 170 patients. Factors contributing to readmission were grouped under patient characteristics, operational factors, and care transition. After reflection, physicians scheduled earlier follow-up appointments while nurse practitioners and physician assistants improved discharge instructions. Readmissions decreased during the review period, and the decrease sustained for one year after the review period. Hospitalists reflected on and identified local practice factors that contributed to their own patients' 30-day readmissions. Reflective practice may be an effective strategy to decrease hospital readmissions.


Production and preliminary characterization of monoclonal antibodies directed at two surface proteins of rhesus rotavirus.
A series of monoclonal antibodies was isolated which reacted with one of two major surface proteins of rhesus rotavirus. Thirty-six monoclonal antibodies immunoprecipitated the 82-kilodalton outer capsid protein, the product of the fourth gene, the viral hemagglutinin. These monoclonal antibodies exhibited hemagglutination inhibition activity and neutralized rhesus rotavirus to moderate or high titer. Three monoclonal antibodies immunoprecipitated the 38-kilodalton outer capsid glycoprotein, the eighth or ninth gene product. These three monoclonal antibodies neutralized rhesus rotavirus to high titer and also inhibited viral hemagglutination.


Eradication of multi-drug resistant bacteria by a novel Zn-doped CuO nanocomposite.
Zinc-doped copper oxide nanoparticles are synthesized and simultaneously deposited on cotton fabric using ultrasound irradiation. The optimization of the processing conditions, the specific reagent ratio, and the precursor concentration results in the formation of uniform nanoparticles with an average size of ≈30 nm. The antibacterial activity of the Zn-doped CuO Cu₀.₈₈Zn₀.₁₂O in a colloidal suspension or deposited on the fabric is tested against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) bacteria. A substantial enhancement of 10,000 times in the antimicrobial activity of the Zn-CuO nanocomposite compared to the pure CuO and ZnO nanoparticles (NPs) is observed after 10 min exposure to the bacteria. Similar activities are observed against multidrug-resistant bacteria (MDR), (i.e., Methicillin-resistant S. aureus and MDR E. coli) further emphasizing the efficacy of this composite. Finally, the mechanism for this enhanced antibacterial activity is presented.


Emergency care of acute myocardial infarction and the great East Japan earthquake disaster.
Although emergency care of acute myocardial infarction (AMI) could theoretically be improved through improved patient delay, this notion remains to be confirmed. Additionally, the influence of large earthquakes on the emergency care of AMI cases remains to be elucidated. The Great East Japan Earthquake (March 11, 2011) has enabled us to address these issues. We analyzed the data from 2008 to 2011 (n=3,937) in the Miyagi AMI Registry Study. In-hospital mortality was significantly lower in 2011 as compared with the previous 3 years (7.3% vs. 10.5%, P<0.05). This improvement was noted especially during the first 2 months after the Earthquake, associated with shorter elapsing time from onset to admission (120 vs. 240min, P<0.001) and higher performance rate of primary percutaneous coronary intervention (PCI) (86.8% vs. 76.2%, P<0.01). Importantly, after the Earthquake, patients with early admission (≤3h from onset) was significantly increased (59.1% vs. 47.0%, P<0.05) and their prognosis became better (7.9% vs. 11.4%, P=0.02), associated with a lower prevalence of heart failure on admission (6.9% vs. 16.2%, P=0.02) and higher performance rate of primary PCI (89.1% vs. 76.4%, P<0.01). Emergency care of AMI improved soon after the Great East Japan Earthquake compared with ordinary times by the contribution of earlier admission from onset and higher performance rate of primary PCI. (Circ J 2014; 78: 634-643).


Experience, Development, and Resilience: The Legacy of Stuart Hauser's Explorations of the Transition from Adolescence into Early Adulthood.
The legacy of Stuart Hauser's research into the developmental transformation that takes place from the adolescent living within his or her family to the young adult functioning independently is assessed. Four major themes are identified in this work: the interplay between the intrapsychic and the interpersonal; the need to understand the family in developmental context; the links between development and psychopathology; and the role of resilience in human psychological functioning. Hauser's broad, integrative, and fundamentally optimistic perspective on human nature is discussed as providing a roadmap to guide future research in this area.


Effectiveness of health-related quality-of-life measurement in clinical practice: a prospective, randomized controlled trial in patients with chronic liver disease and their physicians.
This study assessed the effectiveness of computerized measurement and feedback of health-related quality of life (HRQoL) in daily clinical practice in patients with chronic liver disease. One hundred and sixty-two patients (61% men; mean age 47.5 years) regularly completed computerized HRQoL questionnaires before each consultation for the duration of 1 year. Six physicians were randomly assigned to the experimental group and received an instant online graphical output of data. Five other physicians were randomly assigned to the control group and conducted their consultations as usual. Differences between groups on generic- and disease-specific HRQoL, patient management, and patient satisfaction with the consultation were assessed, as were physicians' experiences with HRQoL data and effects on their consultations. No direct effect of the experimental condition on patients' HRQoL was found. However, an interaction effect of the experimental condition and age was found: older patients in the experimental group had significantly better disease-specific HRQoL (F = 4.16; P = 0.04) and generic mental HRQoL (F = 4.62; P = 0.03) than patients in the control group. Also, male patients in the experimental group had better generic mental HRQoL than patients in the control group (F = 6.10; P = 0.02). Physicians in the experimental group altered their treatment policy significantly more often than did physicians in the control group (z = -3.73, P = 0.00), and their experiences with the availability of HRQoL information were generally positive. The scores on patient satisfaction with the consultation did not differ significantly between the experimental and control groups (z = -1.20, P = 0.23). Computerized measurement and feedback of HRQoL in a daily clinical practice of an outpatient department of hepatology did not improve HRQoL for the entire group of chronic liver patients but, rather, improved disease-specific HRQoL of older patients with chronic liver disease and mental HRQoL of older patients and male patients with chronic liver disease. It also had an effect on patient management.


Graph neural networks for the identification of novel inhibitors of a small RNA.
MicroRNAs (miRNAs) play a crucial role in post-transcriptional gene regulation and have been implicated in various diseases, including cancers and lung disease. In recent years, Graph Neural Networks (GNNs) have emerged as powerful tools for analyzing graph-structured data, making them well-suited for the analysis of molecular structures. In this work, we explore the application of GNNs in ligand-based drug screening for small molecules targeting miR-21. By representing a known dataset of small molecules targeting miR-21 as graphs, GNNs can learn complex relationships between their structures and activities, enabling the prediction of potential miRNA-targeting small molecules by capturing the structural features and similarity between known miRNA-targeting compounds. The use of GNNs in miRNA-targeting drug screening holds promise for the discovery of novel therapeutic agents and provides a computational framework for efficient screening of large chemical libraries.


Expanding and reprogramming the genetic code.
Nature uses a limited, conservative set of amino acids to synthesize proteins. The ability to genetically encode an expanded set of building blocks with new chemical and physical properties is transforming the study, manipulation and evolution of proteins, and is enabling diverse applications, including approaches to probe, image and control protein function, and to precisely engineer therapeutics. Underpinning this transformation are strategies to engineer and rewire translation. Emerging strategies aim to reprogram the genetic code so that noncanonical biopolymers can be synthesized and evolved, and to test the limits of our ability to engineer the translational machinery and systematically recode genomes.


Differentiating reconstructive techniques in partial nephrectomy: a propensity score analysis.
To assess whether volumetric measurements can differentiate functional changes between reconstructive techniques after partial nephrectomy. One hundred and fifty-six patients undergoing partial nephrectomy for a single renal mass were retrospectively studied between 2008 and 2012. Computed tomography scans were available for volume calculations on 56 (18 non-renorrhaphy and 38 renorrhaphy). Institutional review board approval was obtained. The primary outcome was %volume loss in the operated kidney, which was calculated from three-dimensional reconstructions using a semiautomatic segmentation algorithm. Multivariable regression and propensity score analysis was performed. Volumetric analysis detected a difference in mean %volume loss between two-layer reconstruction (cortical renorrhaphy and base-layer) and base-layer only (15.6% versus 3.8%, p < 0.001). The mean %glomerular filtration rate (GFR) loss was also greater in the two-layer group (8.9% versus 2.4%, p = 0.03). Demographics were similar between groups except the two-layer group was older, had more males, and increased ischemia time. On multivariable regression the presence of two-layer closure (β = -15.2%, p < 0.001) and tumor diameter (β = -7.4, p = 0.004) were significant predictors of %volume loss while ischemia time (p = 0.88) was not. Two-layer closure remained a predictor on propensity-adjusted analysis (β = -14.3, p = 0.004). The base-layer only group had two (5.3%) urine leaks and two (5.3%) bleeding complications. The two-layer group had two (1.7%) urine leaks and three (2.5%) bleeding complications (p = 0.23, 0.41). Volume loss calculated from CT scans can be used to monitor postoperative renal function. Techniques for renal reconstruction and tumor diameter are associated with volume and functional loss after partial nephrectomy and should be controlled for in future studies.


Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets.
There is now abundant evidence to substantiate an important role of hepatitis C virus (HCV) core protein in cellular gene expression as well as in the viral cycle. Thus the subcellular localization of this protein has important implications. However, several studies have shown controversial results: the HCV core has been, indeed, described as cytoplasmic or nuclear depending on the size of the protein or on the genotype analyzed. We have studied the localization of the HCV core protein in two different cell lines, one nonhepatic (CHO) and the other hepatic (HepG2). Double immunofluorescence staining using a nuclear membrane marker and confocal analysis showed the core protein pattern to be cytoplasmic and globular. This pattern is not cell cycle-regulated. Electron microscopy analysis revealed the nature of the globular staining observed in immunofluorescence. The HCV core protein accumulated at the surface of lipid droplets that were also the unique morphological feature of nonhepatic core transfected cells. The lipid droplets were isolated by sequential ultracentrifugation on the basis of their density; biochemical analysis revealed a prevalence of triglycerides. In addition the core protein colocalized with apolipoprotein AII at the surface of the lipid droplets as revealed by confocal microscopy. Moreover analysis of liver biopsies from chronically HCV-infected chimpanzees revealed that HCV core is cytoplasmic and localized on the endoplasmic reticulum and on lipid droplets. These results clearly define the subcellular localization of the HCV core protein and suggest a relationship between the expression of the HCV core protein and cellular lipid metabolism.


Phytoremediation as a management option for contaminated sediments in tidal marshes, flood control areas and dredged sediment landfill sites.
Polluted sediments in rivers may be transported by the river to the sea, spread over river banks and tidal marshes or managed, i.e. actively dredged and disposed of on land. Once sedimented on tidal marshes, alluvial areas or control flood areas, the polluted sediments enter semi-terrestrial ecosystems or agro-ecosystems and may pose a risk. Disposal of polluted dredged sediments on land may also lead to certain risks. Up to a few years ago, contaminated dredged sediments were placed in confined disposal facilities. The European policy encourages sediment valorisation and this will be a technological challenge for the near future. Currently, contaminated dredged sediments are often not valorisable due to their high content of contaminants and their consequent hazardous properties. In addition, it is generally admitted that treatment and re-use of heavily contaminated dredged sediments is not a cost-effective alternative to confined disposal. For contaminated sediments and associated disposal facilities used in the past, a realistic, low cost, safe, ecologically sound and sustainable management option is required. In this context, phytoremediation is proposed in the literature as a management option. The aim of this paper is to review the current knowledge on management, (phyto)remediation and associated risks in the particular case of sediments contaminated with organic and inorganic pollutants. This paper deals with the following features: (1) management and remediation of contaminated sediments and associated risk assessment; (2) management options for ecosystems on polluted sediments, based on phytoremediation of contaminated sediments with focus on phytoextraction, phytostabilisation and phytoremediation of organic pollutants and (3) microbial and mycorrhizal processes occurring in contaminated sediments during phytoremediation. In this review, an overview is given of phytoremediation as a management option for semi-terrestrial and terrestrial ecosystems affected by polluted sediments, and the processes affecting pollutant bioavailability in the sediments. Studies that combine contaminated sediment and phytoremediation are relatively recent and are increasing in number since few years. Several papers suggest including phytoremediation in a management scheme for contaminated dredged sediments and state that phytoremediation can contribute to the revaluation of land-disposed contaminated sediments. The status of sediments, i.e. reduced or oxidised, highly influences contaminant mobility, its (eco)toxicity and the success of phytoremediation. Studies are performed either on near-fresh sediment or on sediment-derived soil. Field studies show temporal negative effects on plant growth due to oxidation and subsequent ageing of contaminated sediments disposed on land. The review shows that a large variety of plants and trees are able to colonise or develop on contaminated dredged sediment in particular conditions or events (e.g. high level of organic matter, clay and moisture content, flooding, seasonal hydrological variations). Depending on the studies, trees, high-biomass crop species and graminaceous species could be used to degrade organic pollutants, to extract or to stabilise inorganic pollutants. Water content of sediment is a limiting factor for mycorrhizal development. In sediment, specific bacteria may enhance the mobilisation of inorganic contaminants whereas others may participate in their immobilisation. Bacteria are also able to degrade organic pollutants. Their actions may be increased in the presence of plants. Choice of plants is particularly crucial for phytoremediation success on contaminated sediments. Extremely few studies are long-term field-based studies. Short-term effects and resilience of ecosystems is observed in long-term studies, i.e. due to degradation and stabilisation of pollutants. Terrestrial ecosystems affected by polluted sediments range from riverine tidal marshes with several interacting processes and vegetation development mainly determined by hydrology, over alluvial soils affected by overbank sedimentation (including flood control areas), to dredged sediment disposal facilities where hydrology and vegetation might be affected or managed by human intervention. This gradient is also a gradient of systems with highly variable soil and hydrological conditions in a temporal scale (tidal marshes) versus systems with a distinct soil development over time (dredged sediment landfill sites). In some circumstances (e.g. to avoid flooding or to ensure navigation) dredging operations are necessary. Management and remediation of contaminated sediments are necessary to reduce the ecological risks and risks associated with food chain contamination and leaching. Besides disposal, classical remediation technologies for contaminated sediment also extract or destroy contaminants. These techniques imply the sediment structure deterioration and prohibitive costs. On the contrary, phytoremediation could be a low-cost option, particularly suited to in situ remediation of large sites and environmentally friendly. However, phytoremediation is rarely included in the management scheme of contaminated sediment and accepted as a viable option. Phytoremediation is still an emerging technology that has to prove its sustainability at field scale. Research needs to focus on optimisations to enhance applicability and to address the economic feasibility of phytoremediation.


Cao-sensing receptor (CaR)-mediated activation of K+ channels is blunted in CaR gene-deficient mouse neurons.
The extracellular Ca2+ (Cao)-sensing receptor (CaR) is expressed in hippocampus and other brain regions, suggesting that it could mediate some of the well recognized but poorly understood direct actions of Cao on neuronal function. This study presents evidence that the CaR is functionally coupled to Ca(2+)-activated K+ channels. The effects of CaR agonists on these channels in neurons from wild type (WT) and CaR-deficient (CaR -/-) mice were compared. Neomycin (100 mM) and elevation of Cao from 0.5 to 3 mM significantly increased the probability of channel opening (Po) in neurons from WT but not in those from CaR -/- mice. Thus the CaR activates neuronal K+ channels and could potentially inhibit neuronal excitability and neurotransmission via membrane repolarization.


[Our experiences with surgical treatment of iatrogenic colon perforation].
Coloscopy is a routine examination of high effectiveness. From the surgical point of view it has two main risks. The first one is the bleeding after endoluminal polypectomy. The other one is the perforation of the gut which is a severe and possibly lethal complication. We report on 6 iatrogenic colon perforations and its outcome.


The cost of screening for colorectal cancer.
The aim was to make projections of the likely costs and yield resulting from the implementation of a faecal occult blood screening programme for colorectal cancer. Cost and clinical data were derived from the MRC colorectal screening trial currently in progress in Nottingham, UK. The above data were used as the basis for modelling the likely implications were the trial to be reproduced as a screening programme within a "typical" family practitioner committee area. For an average family practitioner committee area with a target population of 75,000 subjects aged 50-74 years, the initial screening round might be expected to detect 85 cancers at a total cost of approximately 250,000 pounds. This represents a cost per cancer detected of 2700 pounds and a cost per person screened of approximately 5 pounds. For subsequent screening rounds, total costs might be expected to fall although average costs are likely to remain approximately constant. The model is successful in generating "order of magnitude" estimates for the costs of implementation of a screening programme for colorectal cancer. As benefit estimates are not yet available, however, no cost-effectiveness analysis can be undertaken at this stage. In general, sensitivity analyses reveal that programme costs are more sensitive to changes in clinical variables, especially detection and compliance rates, than they are to variations in the costs of resource inputs. A screening programme with a more elaborate protocol than that currently employed in the Nottingham trial will entail considerable cost increases.


Porfiromycin as a bioreductive alkylating agent with selective toxicity to hypoxic EMT6 tumor cells in vivo and in vitro.
Hypoxic cells may limit the curability of solid tumors by conventional chemotherapeutic agents and radiotherapy. Agents which are preferentially toxic to cells with low oxygen contents could therefore be useful as adjuncts to the regimens now used to treat these cancers. To date, the best agent of this type that we have tested is porfiromycin. Porfiromycin is similar to mitomycin C in its toxicity to hypoxic EMT6 cells in vitro but has much less toxicity than mitomycin C to well-oxygenated EMT6 cells. EMT6 cell sonicates reduce mitomycin C and porfiromycin to reactive electrophiles at similar rates under hypoxic conditions, a finding that correlates with cytotoxicity, whereas the rate of production of reactive species from both drugs is very slow under aerobic conditions. We also show that porfiromycin is capable of killing hypoxic radiation-resistant cells in solid EMT6 tumors. Appropriate regimens combining porfiromycin (which preferentially kills hypoxic cells) and radiation (which preferentially kills aerated cells) may therefore be especially efficacious for the treatment of solid tumors.


Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization.
Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional co-repressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing, and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This results in stabilization of SKI and consequently attenuation of TGF-β responses, both in knockin cells expressing an SGS mutation and in fibroblasts from SGS patients. Thus, we reveal that SGS is associated with an attenuation of TGF-β-induced transcriptional responses, and not enhancement, which has important implications for other Marfan-related syndromes.


Don't stop the champions of research now: a brief history of head and neck pathology developments.
The field of head and neck pathology was just developing 50 years ago but has certainly come a long way in a relatively short time. Thousands of developments in diagnostic criteria, tumor classification, malignancy staging, immunohistochemistry application, and molecular testing have been made during this time, with an exponential increase in literature on the topics over the past few decades: There were 3506 articles published on head and neck topics in the decade between 1969 and 1978 (PubMed source), with a staggering 89266 manuscripts published in the most recent decade. It is daunting and impossible to narrow the more than 162000 publications in this field and suggest only a few topics of significance. However, the breakthrough in this anatomic discipline has been achieved in 3 major sites: oropharyngeal carcinoma, salivary gland neoplasms, and sinonasal tract tumors. This review will highlight selected topics in these anatomic sites in which the most profound changes in diagnosis have occurred, focusing on the information that helps to guide daily routine practice of surgical pathology.


Sexual dimorphism for water balance mechanisms in montane populations of Drosophila kikkawai.
Conservation of water is critical to the ecological success of Drosophila species living in the drier montane localities of the Western Himalayas. We observed clinal variation in desiccation resistance for both sexes of Drosophila kikkawai from an altitudinal transect (512-2226 m above sea level). Since more than 90 per cent of body water is lost through cuticular transpiration, the target of selection may be cuticular lipids or cuticular melanization. We tested whether melanic females and non-melanic males of D. kikkawai have similar mechanisms of desiccation resistance. There is clinal variation in the amount of cuticular lipids per fly in males, but not in females. By contrast, for females, elevational increase in melanization is positively correlated with desiccation resistance and negatively with cuticular water loss, but there is no variation in the amount of cuticular lipids. Thus, sexual dimorphism for the mechanism of desiccation resistance in D. kikkawai matches the water proofing role of body melanization as well as cuticular lipids.


Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions.
After three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS), major depressive disorder (MDD) has proven to be the primary field of application. MDD poses a major challenge for health systems worldwide, emphasizing the need for improving clinical efficacy of existing rTMS applications and promoting the development of novel evidence-based rTMS treatment approaches. Several promising new avenues have been proposed: novel stimulation patterns, targets, and coils; combinatory treatments and maintenance; and personalization and stratification of rTMS parameters, and treatment of subpopulations. This opinion review summarizes current knowledge in the field and addresses the future direction of rTMS treatment in MDD, facilitating the establishment of this clinical intervention method as a standard treatment option and continuing to improve response and remission rates, and take the necessary steps to personalize rTMS-based treatment approaches.


Deformed whiskers in mice infected with certain exogenous murine leukemia viruses.
Mice infected at birth with replication competent Friend, Moloney, CasBr-M, C2S-M, and 1504-A murine leukemia viruses developed abnormalities of the vibrissae consisting of erratic curvature, shortening, and loss. A number of other virus strains, as well as endogenous AKR-type ecotropic virus and AKR-type, mink cell focus-inducing (MCF) viruses, did not produce these abnormalities. In mice with erythroid and myeloid leukemia, the perivibrissal sinus is the site of extramedullary hematopoiesis, but this did not appear to be the basis of the deformities. Genetic evidence indicated that newly arisen MCF-type recombinant viruses are involved in the pathogenesis of the abnormalities, at least with some of the virus systems studied.


Bacterial meningitis in HIV-1-infected patients in the era of highly active antiretroviral therapy.
The burden that spontaneous bacterial meningitis (SBM) currently represents among HIV-1-infected patients is poorly known. We prospectively evaluated 32 episodes of SBM in HIV-1-infected patients from the VACH (VIH-Aplicación de Control Hospitalario) Cohort and compared findings with those of 267 episodes in uninfected persons, matched by age and year of infection. A group of 13,187 HIV-1-infected patients from the VACH Cohort were used to identify predictors for acquiring SBM. Between 1997 and 2006, we found 32 episodes of SBM among HIV-1-infected patients for an annual incidence rate of 62.0 cases per 100,000 population compared with 3.2 (3.0 to 3.4) per 100,000 population for uninfected patients (P < 0.001). The last CD4 >or=200/mm count was the only predictor for developing SBM. Compared with uninfected, HIV-1-infected patients with SBM had a greater prevalence of primary extrameningeal infection, especially pneumonia (P = 0.02), bacteremia (P = 0.02), focal neurologic signs (P = 0.005), seizures (P = 0.06), a lower cerebrospinal fluid to blood glucose ratio (P = 0.02), and a lower prevalence of nuchal rigidity (P = 0.005). Streptococcus pneumoniae was the most frequent etiologic agent among HIV-1-infected patients. HIV-1-infected patients had neurologic complications more frequently (P = 0.02), a higher overall case fatality rate (P = 0.004), and greater incidence of neurologic sequelae (P = 0.001). Even in the highly active antiretroviral therapy era, the risk of developing SBM is 19 times higher among HIV-1-infected patients than among uninfected ones. It tends to present in severely immunosuppressed patients not previously vaccinated and off antiretroviral therapy, with a concomitant extrameningeal infection, bacteremia, and focal neurologic signs, and is caused by S. pneumoniae. SBM in HIV-1-infected patients carries a worse prognosis than in uninfected ones both in terms of lethality and sequelae.


What about the environment? Leveraging multi-omic datasets to characterize the environment's role in human health.
The environment plays an important role in mediating human health. In this session we consider research addressing ways to overcome the challenges associated with studying the multifaceted and ever-changing environment. Environmental health research has a need for technological and methodological advances which will further our knowledge of how exposures precipitate complex phenotypes and exacerbate disease.


Pseudoaneurysm of left ventricle.
Left ventricular free wall rupture is a dramatic but not always fatal complication from myocardial acute infarction. However, if proper diagnosis is delayed, surgical treatment may be compromised. The authors report a case of large pseudoaneurysm in left ventricular inferior wall diagnosed on angiography study.


Occurrence of polyoxouranium motifs in uranyl organic networks constructed by using silicon-centered carboxylate linkers: structures, spectroscopy and computation.
Four novel polyoxouranium-based uranyl carboxylates have been constructed by using a combination of three silicon-centered carboxylate ligands and polyoxouranium building blocks. Interesting oligomerization of the uranyl groups from three types of tetrameric units in 1 and 2 to octameric [(UO2)8(μ3-OH)6(μ2-OH)2(H2O)4]8+ in 3 and ultimately infinite polyoxouranium chains in 4 was observed. The 3D structure of 2 contains two different linear tetramers, whose structures are totally different from seven types of tetranuclear motifs previously observed in uranyl carboxylates. Compound 3 displays a rare octanuclear polyoxouranium brick; it is fabricated by the association of eight uranyl units in pentagonal-bipyramidal geometry that involves the edge-sharing polyhedral connection mode, which are further linked by four isolated UO7 pentagonal bipyramids to create a complicated 3D framework. These newly synthesized hybrid materials were extensively characterized by single crystal analysis, thermogravimetric analysis (TG) and different spectroscopic techniques (IR, UV-vis, and luminescence spectroscopy), which show well-resolved characteristic "five-finger" emission of the uranyl ions under excitation at 420 nm. Relativistic density functional theory (DFT) was used to explore five model compounds that theoretically simulate experimental real compounds. Experimental spectroscopy was rationalized by electronic-structure analysis.


CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.
To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.


Intraductal papillary mucinous neoplasms of the pancreas: performance of pancreatic fluid analysis for positive diagnosis and the prediction of malignancy.
The preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMN) of the pancreas must be as reliable as possible because large or even total pancreatectomy may be necessary. Early diagnosis of malignant forms is important to improve prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been confirmed in cystic lesions of the pancreas. It is not known if these results can be applied to IPMN. To determine the levels of biochemical and tumor markers in fluid from EUS-FNA in patients with IPMN and to assess the impact on the diagnosis of IPMN. In total, 41 patients (14 men, median age 64 yr) underwent EUS-FNA before surgical resection of IPMN in our center. Levels of amylase, lipase, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19.9, and CA 72.4 were measured in the cyst fluid. The performance of the markers was retrospectively evaluated for: (a) a positive diagnosis of IPMN, using cutoffs validated in the literature for mucinous pancreatic lesions and (b) an assessment of malignancy (i.e., high-grade dysplasia or invasive carcinoma) compared with the final pathological examination of the surgical specimen. EUS-FNA was performed in dilated branch ducts (BD) in 39 cases and in the main pancreatic duct in 2 cases. No serious complications occurred. The median fluid levels of amylase, lipase, CEA, CA 19.9, and CA 72.4 were 20,155 U/mL, 59,500 U/mL, 173 ng/mL, 6,400 U/mL, and 11.5 U/mL, respectively. A CEA level >200 ng/mL and a CA 72.4 >40 U/mL had a 44% and a 39% sensitivity, respectively, for the diagnosis of IPMN. The levels of CEA, CA 19.9, and CA 72.4 were significantly different between benign and malignant IPMN. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of a CEA level >200 ng/mL for the diagnosis of malignant IPMN were 90%, 71%, 50%, and 96%, respectively. The sensitivity, specificity, PPV, and NPV of a CA 72.4 level >40 U/mL for this purpose were 87.5%, 73%, 47%, and 96%, respectively. CEA and CA 72.4 in pancreatic cyst fluid have excellent NPVs in the preoperative differential diagnosis of benign versus malignant IPMN, and might reinforce the decision of not to operate on patients with BD-type without predictive factors of malignancy.


Pediatric Obesity Care via Telemedicine: Expanding the Path Forward-A Review.
Review latest data regarding the intersection of pediatric obesity epidemic with telemedicine expansion to meet the need of equitable obesity care in children. Prevalence of pediatric obesity in the USA continues to worsen particularly in rural, underserved areas. Although there is an increasing number of obesity medicine specialists over the last decade, availability varies by geographic location. Pre-pandemic centers were limited, rarely located in rural areas, and required in-person visits for reimbursement. Telemedicine changes, responding to pandemic needs, provided increase in telemedicine utilization and acceptance with similar or improved obesity care outcomes. Given pediatric obesity prevalence and need for chronic, effective obesity care, leveraging telemedicine to expand reach and decrease access barriers provides a critical and creative remedy. Data cites similar outcomes between telemedicine and in-person care. The time to reimagine a full spectrum of care delivery for pediatric obesity is now.


Epidemiological implications of environmental cadmium. I. The probable utility of human hair for occupational trace metal (cadmium) screening.
Some of the problems involved in the use of human hair sample as an indicator of trace metal exposure are discussed. The significant correlations of hair cadmium level with the respective kidney (r equals .52) and liver (r equals 0.36) levels in selected autopsies, and the fact that hair samples can distinguish between occupational and non-occupational exposure (t28 equals 4.88) in a New Jersey community are advanced as arguments in favor of hair sampling. The hair samples were washed with sodium lauryl sulphate, deionized water and acetone and then dried. All the samples were ashed at 450-500 degrees and analyzed by atomic absorption spectrophotometry.


Stimulation of CD5 enhances signal transduction by the T cell antigen receptor.
After the addition of a CD3 monoclonal antibody to peripheral T cells that have been previously stimulated with phytohemagglutinin, inositol phosphates are produced at a rapid rate for 2 min and at a much slower rate thereafter. Stimulation of CD5 allows CD3-mediated production of inositol phosphates to be sustained at a brisk rate for greater than 20 min and augments the initial CD3-mediated increase in inositol trisphosphate and release of intracellular Ca2+. Thus, perturbation of CD5 by monoclonal antibody enhances the ability of the CD3-antigen receptor complex to couple to the inositol phospholipid pathway. This effect of CD5 is independent of any direct effect of the CD5 monoclonal antibody on the levels of inositol phosphates.


[Intrarenal mechanisms of the regulation of homeostasis in children with nephrotic syndrome].
Overall 40 patients with associated glomerulonephritis and the nephrotic syndrome were examined for renal response to the induced shifts in water balance: tests with 18-hour water deprivation characterizing concentration function of the kidneys, followed by water loading (22 ml/kg bw) which allows estimation of water excretion function and osmotic dilution. Osmotic concentration defect was revealed. It manifested in a decrease of osmotic concentration of the urine, a reduction of the concentration index according to creatinine. It should be mentioned that the more preserved was the magnitude of the concentration index the more this was ensured by sodium reabsorption, decrease of its excretion. Meanwhile osmotic concentration of the urine was determined by urea excretion. Study of partial functions in water diuresis discovered a dramatic lowering of sodium-free water clearance characterizing participation of the kidney in the maintenance of effective osmotic pressure of the plasma and reflecting the intensity of distal sodium reabsorption.


Susceptibility of L-FABP-/- mice to oxidative stress in early-stage alcoholic liver.
Chronic ethanol consumption is a prominent cause of liver disease worldwide. Dysregulation of an important lipid uptake and trafficking gene, liver-fatty acid binding protein (L-FABP), may contribute to alterations in lipid homeostasis during early-stage alcoholic liver. We have reported the detrimental effects of ethanol on the expression of L-FABP and hypothesize this may deleteriously impact metabolic networks regulating fatty acids. Male wild-type (WT) and L-FABP(-/-) mice were fed a modified Lieber-DeCarli liquid diet for six weeks. To assess the response to chronic ethanol ingestion, standard biochemical indicators for alcoholic liver disease (ALD) and oxidative stress were measured. Ethanol ingestion resulted in attenuation of hepatic triglyceride accumulation and elevation of cholesterol in L-FABP(-/-) mice. Lipidomics analysis validated multiple alterations in hepatic lipids resulting from ethanol treatment. Increased immunohistochemical staining for the reactive aldehydes 4-hydroxynonenal and malondialdehyde were observed in WT mice ingesting ethanol; however, L-FABP(-/-) mice displayed prominent protein adducts in liver sections evaluated from pair-fed and ethanol-fed mice. Likewise, alterations in glutathione, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes, and protein carbonyl content all indicated L-FABP(-/-) mice exhibit high sustained oxidative stress in the liver. These data establish that L-FABP is an indirect antioxidant protein essential for sequestering FFA and that its impairment could contribute to in the pathogenesis of ALD.


Measurement of the healing of venous ulcers.
The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.


Some characteristics of acute poisoning with psychoactive substances in the period of socioeconomic transition 1990-2000.
Although scarce, the data about acute poisonings with psycho-active substances during the period of socioeconomic crisis in Bulgaria indicate the appearance and increase of the use of inhalants, prescribed and over-the-counter medications and the increase of acute poisoning rate with heroin. To ascertain some characteristics of acute poisonings with psycho-active substances in Plovdiv region from 01.01.1990 to 31.12.2000. The whole caseload of 571 acute poisonings with psycho-active substances in Plovdiv region (8.8% of the population of the country) between 1990 and 2000, treated in the only Clinic of Toxicology in the region is studied retrospectively. The variables gender, age, type of psycho-active substance (DSM-IV criteria), grade of severity, duration of use, times of poisoning and some differences between alcohol and opioid poisonings are investigated. Acute poisoning with psycho-active substances are 5.43% of all intoxications. The moderate grade of severity (48.5%), alcohol (62.8%) and opioid (15.3%) intoxications, debut poisoning (86.8%) and poisonings occurring in the initial period of use predominate. An increase of acute poisonings with psycho-active substances in the last third of the studied period (1990-2000) is established--severe forms (2.59 times) and recidivistic intoxication (4 times). Alcohol and opioid poisonings predominate among severe intoxications. The hospital stay is relatively short--1.75 +/- 0.67 and hospital lethality is 1.6%. 1. The moderate grade of severity, alcohol and opioid intoxications (especially in the severe grade cases), occurrence in the initial period of use and relatively short hospital stay predominate in acute poisonings with psycho-active substances in the period of socioeconomic crisis. Hospital lethality (1.6%) is ascertained only in severe alcohol intoxication. 2. An increase of acute poisonings with psycho-active substances--severe forms, mild forms and recidivistic intoxications is established in the last third (1998-2000) of the studied period. The most expressed increase is ascertained in 2000. 3. Urgent complex measures are necessary to contain the spread of psycho-active substances and acute poisonings with them.


[Disseminated pulmonary adiaspiromycosis. A case report].
A case of thoracoscopic lung biopsy proven diffuse human adiaspiromycosis is reported. The patient, a 26-year-old male farm worker presented with a three-week history of fever, sweating, dyspnea and unproductive cough. Radiographic findings were those of granulomatous pulmonary interstitial disease. Treated with ketoconazole he improved very well, resuming work normal activities a month later.