Postural control in isometric ramp pushes: the role of Consecutive Postural Adjustments (CPAs).
Postural adjustments, which occur after the end of a voluntary movement (termed Consecutive Postural Adjustments: CPAs), were studied and compared to the corresponding Anticipatory Postural Adjustments (APAs). Seven right-handed male adults were asked to perform horizontal two-handed maximal ramp pushes as quickly as possible, while sitting. A dynamometric bar measured the reaction to push force (Fx) and a custom-designed device measured the resultant reaction forces along the antero-posterior axis (Rx). Two ischio-femoral contacts (100 BP: full ischio-femoral contact of the ischio-femoral length; and 30BP: one-third contact) were considered. Each session consisted of ten pushes. The reaction forces, as well as push force, increased continuously, displaying similar time course profiles. However, Rx continued to increase after the end of push rise, which ascertained CPAs. CPAs were showed to be consistent kinetic phenomena, using a biomechanical analysis, based on time courses of reaction forces and CoG kinematics. Their coherence was checked precisely, by comparing theoretical and experimental occurrences of remarkable points (extrema and zero crossings). CPA durations and peak amplitudes (dCPA and pCPA) were significantly greater than the corresponding APA values (dAPA and pAPA). Moreover, dAPAs and dCPAs increased (p < 0.001), as did pCPAs (p<0.001) and pAPAs (p < 0.05) when the peak push force was greater (30 BP), showing that the probability of finding a statistically significant difference is greater for APA duration than amplitude, unlike CPAs. Finally, the present results were discussed in relation to the hypothesis according to which the focal and the postural components are parts of the same motor program.


Classifying and standardizing panfacial trauma according to anatomic categories and Facial Injury Severity Scale: a 10-year retrospective study.
The purpose of this study was to identify the epidemiologic factors of panfacial fractures (PFs), and to evaluate the significance of anatomic PF categories and the Facial Injury Severity Scale (FISS) in classifying and standardizing panfacial injuries. A retrospective review of all patients treated with PFs at our institution between June 2010 and April 2021 was performed. PF was defined as a concurrent fracture in at least 3 of 4 facial subunits (frontal, upper midface, lower midface, and mandible). Data regarding patient demographics, causes of injury, location of fractures, major concomitant injuries, and postinjury complications were collected, and the FISS score was collected from each patient. Statistical analysis was performed using IBM SPSS Statistics version 22.0. A total of 227 patients were enrolled. The most commonly fractured bones were the maxillary sinus wall (92.1%), mandible (82.8%), and zygomatic arch (75.3%), and the most common fracture sites in PFs were graphically presented. Four PF patterns were defined: FULM (n = 60), FUL (n = 39), ULM (n = 127), and FUM (n = 1). There was a significant association between PF patterns and sex (p = 0.018), the number of concomitant injuries (p = 0.014), and early surgical airway management (p = 0.003). Different PF patterns were significantly correlated with different types of concomitant injuries and complications. The FISS score showed a significant difference with PF patterns (p = 0.000) and sex (p = 0.007), and a FISS value of 11 or more is the appropriate cutoff for the prediction of multiple concomitant injuries and complications. Both the anatomic PF categories and FISS were significantly correlated with various concomitant injuries and complications. The combination of PF categories and FISS provided a better positive and negative prediction of concomitant injuries and complications for PF patients. Patients with FULM and FISS > 11 had an obviously higher proportion of the need for multiprofessional treatment.


Effects of ischemia on myocardial function during rapid left ventricular pacing.
Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. Significant differences (p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1+/-1.6 vs. 10.8+/-1.6%), and QRS duration (77.3+/-4.1 vs. 85.7+/-3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences (p < 0.05) were seen for myocardial contractility dP/dt(max) (1277+/-197 vs. 1158+/-156 mm Hg/s), segmental shortening (10.3+/-1.9 vs. 8.1+/-1.7%), left ventricular end-systolic pressure (76.9+/-7.5 vs. 69.6+/-7.9 mm Hg), and QRS duration, and for myocardial contractility dP/dt(max) (1033+/-209 vs. 917+/-207 mm Hg/s) and left ventricular end-systolic pressure (69.2+/-13.5 vs. 62.2+/-15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.


Rapid HIV screening: missed opportunities for HIV diagnosis and prevention.
Although rapid HIV tests increase the number of persons who are aware of their HIV status, they may fail to detect early HIV infection. To evaluate the sensitivity for early HIV infection of several rapid tests and third- and fourth-generation assays compared with nucleic acid amplification testing (NAAT). Sensitivity for early HIV infection was evaluated using 62 NAAT-positive/WB-negative or indeterminate specimens from the CDC Acute HIV Infection study. Specimens underwent third-generation testing with Genetic Systems 1/2+O(®) and rapid testing with Multispot HIV-1/HIV-2. A subset was also tested with four FDA-approved rapid tests and Determine HIV-1 Antigen/Antibody Rapid Test(®) and Architect HIV Antigen/Antibody Combo(®), both fourth-generation tests. Of 99,111 specimens screened from April 2006 to March 2008, 62 met the definition for early HIV infection (60 NAAT-positive/seronegative and 2 NAAT-positive/Western blot indeterminate). Third-generation testing correctly detected antibody in 34 specimens (55%; 95% confidence interval (CI): 42-67); Multispot detected antibody in 16 (26%; 95% CI: 16-38). Of the 62 specimens, 33 (53%) had sufficient quantity for further testing. Rapid test sensitivities for early HIV infection ranged from 22-33% compared with 55-57% for the third-generation assay and 76-88% for the fourth-generation tests. Many rapid HIV tests failed to detect half of the early HIV infection cases in whom antibody was present. Programs that screen high-incidence populations with rapid tests should consider supplemental testing with NAAT or other antigen-based tests. These data support the need for more sensitive antigen-based point-of-care screening tests for early HIV infection.


Application of sub-critical water technology for recovery of heavy metal ions from the wastes of Japanese scallop Patinopecten yessoensis.
Sub-critical water (sub-CW) technology was used as a new technology with environmental and financial benefits for the recovery of harmful heavy metal ions Cd (II), Zn (II), Cu (II), Fe (II), Mn (II) and Ni (II) in the waste of Japanese scallop Patinopecten yessoensis. The metals are responsible for environmental problems owing to the large amount of the waste. This study proposes a new method using sub-CW treatment to recover the metal ions from scallop waste and simultaneously produce harmless and valuable materials. Reactions were conducted in a temperature range of 473-653 K and for reaction times of 1-60 min. After the sub-CW reaction, four phases existed: an oil phase, metal-soap phase, aqueous phase and solid residual. Some oil was hydrolyzed by the sub-CW reaction and converted to free fatty acids and glycerin. Free fatty acids reacted with metal ions and became metal-soap phase. Both the metal-soap phase and oil phase caught almost all metal ions at low and medium reaction temperatures (473-573 K) from original wastes, although the concentrations of the metal ions in the metal-soap phase were much higher than those in the oil phase. With increasing temperature, these two phases decomposed and the metal ions concentrated in solid residual (un-reacted waste). The binding mechanisms in the oil and metal-soap phases are discussed including the key functional groups involved. The maximum concentrations of metal ions in metal-soap phase were 7225 ppm (Fe), 862 ppm (Zn), and 800 ppm (Cd) at 573 K. The aqueous phase showed the lowest concentration of metal ions especially at temperatures above 550 K (~1.5 ppm).


Urinary Excretion of Ecdysterone and Its Metabolites Following Spinach Consumption.
The phytosteroid ecdysterone is present in spinach. In this study, the urinary elimination of ecdysterone and its metabolites in humans is investigated following spinach consumption of two different culinary preparations. Eight participants (four males, four females) ingested 950 (27.1) g sautéed spinach (average [±standard deviation (SD)]) and 912 (70.6) g spinach smoothie as second intervention after washout. Post-administration urines are analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). After intake of both preparations, ecdysterone and two metabolites, 14-deoxy-ecdysterone, and 14-deoxy-poststerone, are excreted in urine. The maximum concentration of ecdysterone is ranging from 0.09 to 0.41 µg mL-1 after sautéed spinach and 0.08-0.74 µg mL-1 after smoothie ingestion. The total excreted amount (mean% [±SD]) in the urine as a parent drug plus the metabolites is only 1.4 (1.0) for both sautéed spinach and smoothie. The apparent sex related differences in 14-deoxy-poststerone excretion will need further investigations. Only a small proportion of ecdysterone from spinach is excreted into urine. No significant differences are found in concentration and recovered amount (%) of ecdysterone, 14-deoxy-ecdysterone, and 14-deoxy-poststerone in urine between sautéed spinach and smoothie ingestion. A discrimination between ecdysterone from food or preparations will be challenging based on urinary concentrations only, at least for later post-administration samples.


Median nerve entrapment syndrome in the proximal forearm.
Median nerve compression in the proximal forearm is relatively uncommon. This study reviews 71 cases over a 20 year period. Of the 71 in this series, 51 were treated surgically. The time of onset to definitive treatment ranged from 6 months to 5 years, with an average of 9 months. The ages of patients varied from 15 to 56 years and there were 13 males and 58 females. Past criteria for making the diagnosis are reviewed and an added series of clinical observations is made, including three definitive stress tests. In all cases surgically treated compression of the median nerve has been found at one of three levels, in the following order of frequency: the pronator teres, the flexor superficialis arch, and the lacertus fibrosus. Follow-up has been from 6 months to 19 years and four cases in the series were considered to be failures.


Functional outcome of patients 12 and 48 weeks after acute traumatic tetraplegia and paraplegia: data analysis from 2004-2009.
During the first rehabilitation of patients with traumatic spinal cord injuries (SCIs), professional skills are learned, which can be objectified in an independent measurement score. The aims of this study were to record the skills of patients 12 and 48 weeks after acute trauma and perform an analysis of the data to identify provisions of importance. All patients from 2004 to 2009 who experienced traumatic SCI were included in this investigation. Data recording were accomplished by the European Multi-Centre Study about Spinal Cord Injury (EMSCI) databank. Patients were divided into tetraplegia and paraplegia groups. Parameters were age at injury, the American Spinal Injury Association-Score, level of lesion and spinal cord independence measure (SCIM-Score) 12 and 48 weeks after traumatic spinal cord lesion. A questionnaire was also added to help clarify where deficiencies were prevalent. Data analysis of 103 tetraplegic and 110 paraplegic patients showed no correlation between the ASIA score, level of lesion, age and SCIM score. On average, tetraplegic patients had a SCIM score of 43 points 12 weeks after treatment, with 81% showing an increase to 58 points after 48 weeks. Paraplegic patients showed an average SCIM score of 60 points after 12 weeks, with 71% experiencing an increase to 71 points after 48 weeks. In all, 9% of tetraplegic patients and 19% of paraplegic patients experienced a decrease of SCIM points after 48 weeks, which occurred mainly in the bladder and intestinal control subgroups. Results of the questionnaire were not helpful for clarifying the location of the deficiencies. Most of the patients experienced an increase of SCIM points 48 weeks after traumatic SCI. However, data also showed that, especially in paraplegic patients, special attention must be given to bladder and intestinal management to avoid negative late-term consequences.


Guideline Adherence and Hospital Costs in Pediatric Severe Traumatic Brain Injury.
Adherence to pediatric traumatic brain injury guidelines has been associated with improved survival and better functional outcome. However, the relationship between guideline adherence and hospitalization costs has not been examined. To evaluate the relationship between adherence to pediatric severe traumatic brain injury guidelines, measured by acute care clinical indicators, and the total costs of hospitalization associated with severe traumatic brain injury. Retrospective cohort study. Five regional pediatric trauma centers affiliated with academic medical centers. Demographic, injury, treatment, and charge data were included for pediatric patients (17 yr) with severe traumatic brain injury. Percent adherence to clinical indicators was determined for each patient. Cost-to-charge ratios were used to estimate ICU and total hospital costs for each patient. Generalized linear models evaluated the association between healthcare costs and adherence rate. Cost data for 235 patients were examined. Estimated mean adjusted hospital costs were $103,485 (95% CI, 98,553-108,416); adjusted ICU costs were $82,071 (95% CI, 78,559-85,582). No association was found between adherence to guidelines and total hospital or ICU costs, after adjusting for patient and injury characteristics. Adjusted regression model results provided cost ratio equal to 1.01 for hospital and ICU costs (95% CI, 0.99-1.03 and 0.99-1.02, respectively). Adherence to severe pediatric traumatic brain injury guidelines at these five leading pediatric trauma centers was not associated with increased hospitalization and ICU costs. Therefore, cost should not be a factor as institutions and providers strive to provide evidence-based guideline driven care of children with severe traumatic brain injury.


Fecal metabolomics reveals products of dysregulated proteolysis and altered microbial metabolism in obesity-related osteoarthritis.
The objective of this exploratory study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA). Fecal samples were collected from obese individuals diagnosed with radiographic hand plus knee OA (n = 59), defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2-4 (or total knee replacement) in at least one knee. Controls (n = 33) were without hand OA and with KL grade 0-1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16 S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA. Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tripeptides and significant perturbations in microbial metabolites including propionic acid, indoles, and other tryptophan metabolites. Pathway analysis revealed several significantly perturbed pathways associated with OA including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the gut microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the rRNA-seq data. Adults with obesity and knee plus hand OA have distinct fecal metabolomes characterized by increased products of proteolysis, perturbations in leukotriene metabolism, and changes in microbial metabolites compared with controls. These metabolic perturbations indicate a possible role of dysregulated proteolysis in OA.


Effect of the SafeCare© intervention on parenting outcomes among parents in child welfare systems: A cluster randomized trial.
Child maltreatment has long-lasting negative impacts, and interventions are needed to improve caregiver's parenting skills to prevent maltreatment. This paper reports on a randomized trial comparing the SafeCare© model to services as usual (SAU) for child-welfare referred caregivers. SafeCare is an 18-session behavioral parenting program that teaches skills in positive parent-child interactions, home safety, and child health. SAU is generally unstructured and includes support, crisis management, referrals for need, and parenting education. Teams of providers at nine sites were randomized to implement SafeCare (19 teams; 119 providers) or continue SAU (17 teams; 118 providers). Two-hundred eighty eight caregivers (193 SafeCare; 95 SAU) with children aged 0-5 who were receiving services agreed to complete a baseline and 6-month assessment. Assessments measured positive parenting behaviors, parenting stress, protective factors, and neglectful behaviors using validated scales. Participants were primarily white (74.6%), female (87.0%), and low-income (68.6%), and had a mean age of 29. Latent change score models (LCSM) using a sandwich estimator consistent with the trial design were used to examine changes in 13 outcomes. Results indicated that SafeCare had small to medium effects for improving several parenting outcomes including supporting positive child behaviors (d = 0.46), proactive parenting (d = 0.25), and two aspects of parenting stress (d = 0.28 and .30). No differential change between groups was found for other indicators, including all indicators of neglect. Parenting programs such as SafeCare offer a promising mode of intervention for child welfare systems. Scale-up of parenting programs can improve parenting, improve child outcomes, and potentially reduce maltreatment. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT02549287.


Assertiveness, locus of control and coping behaviors used to diminish tension.
To investigate how coping behaviors may be preconditioned by assertiveness and locus of control, a questionnaire was given to 133 undergraduates of whom 87% reported recent tension attributed mainly to academic pressures. From a list of 22 common coping reactions, the students were asked to check those they use to deal with their tensions. The coping responses were also correlated with scores on an assertiveness inventory (AES) and Rotter's Internal-External Locus of Control (I-E) Scale. Reliance on one's own initiatives and turning to significant others were the responses most frequently reported as reactions to tension while seeking professional help was ranked last. Male students more frequently reported using marijuana or seeking sexual comfort than females, while females more frequently reported dysfunctional reactions such as spending endless hours thinking about the problem. The AES correlated significantly with problem-solving approaches. The IE Scale showed internals more inclined to meditate; externals indicated a greater likelihood to seek professional help, fantasize, or drink alcohol.


Evaluation of a chromatometer: a new method for blue-yellow or green-red visual comparisons, and anomaly screening techniques.
Malbrel's chromatometer is a new apparatus which allows color vision to be monitored. The aim of this study was to assess the accuracy of this new examination method. The color vision of a patient was analyzed using a chromatometer for direct heterochromatic visual comparisons. The patient's task was to adjust, using one eye only, the brightness of a yellow (or red) window to the one of a fixed blue (or green) window. Overall, 158 patients, aged 20 to 28, took part in the experiment. First, parametric means were used to study the response distributions and the luminous effects on the responses. Second, using non-parametric means, we considered that a patient had an anomalous color vision according to the chromatometer if the response was higher than the 95th percentile or lower than 5th percentile. Third, anomalous responses were compared with the Ishihara plates and Farnsworth 28-hue responses. The effect of a luminous stimulus on the response was significant (adjusted to the patient effect). Thus, the chromatometer appears to be a good method to analyze color vision. This apparatus was easy to use and constituted a sensitive and specific test with high negative predictive value. The chromatometer can be used as a first-line screening test to detect color vision anomalies during ophthalmology consultations. The chromatometer can be useful in identifying early ocular disease, monitoring disease development, or checking possible iatrogenic effects of a specific treatment.


Laparoscopic Heller's myotomy for achalasia after gastric bypass: A case report.
Disorders of the oesophagus have been linked to surgical bariatric procedures and obesity. However the relationship between achalasia and gastric bypass is not clearly understood and has only recently been reported following gastric bypass. We present the case of a 53-year-old woman who re-presented following a gastric bypass with a new diagnosis of achalasia. This was treated successfully with laparoscopic Heller's Myotomy with discharge from hospital 10 days post operatively. It is not clear whether achalasia is a complication of gastric bypass procedures. This is only the second reported case of the condition developing after this operation. The mechanism by which it may develop is yet to be clearly established. This case highlights the need to investigate further a possible link between achalasia and gastric bypass and to manage susceptible patients accordingly in the pre-operative stage.


Vitamin D Status in Israeli subjects before the initiation and after the cessation of vitamin D supplements.
Vitamin D supplements are often recommended to restore sufficiency, although the adherence to treatment is low. This study assessed vitamin D status at different time intervals following the cessation of treatment. The database of Clalit-Health-Services (CHS), a not-for-profit HMO covering more than half of the Israeli population, was retrospectively searched for all members with available serum 25OHD test results in 2009 (245,493). We then identified those who filled any cholecalciferol prescription in 2008-2009 (121,817). Subjects were included in the final analysis only if they started treatment in 2009, had serum 25OHD < 50 nmol/l before the first prescription in 2009, and had at least one additional test result after the last dated prescription in 2009 (5,461). Serum 25OHD increased from 32 ± 11 nmol/l at baseline to 58.6 ± 22.3 nmol/l after treatment (P < 0.001). The proportion of subjects with sufficient vitamin D after treatment increased with increasing cholecalciferol daily dose and treatment duration (P < 0.001) and decreased with increasing time from cessation of treatment (P < 0.001). The effect of time from treatment cessation persisted after controlling for baseline serum 25OHD, daily cholecalciferol dose, treatment duration, seasonality, gender, age, ethnicity, and BMI; the ORs for sufficient vitamin D were 2.02 (95% CI 1.66-2.45), 1.67 (1.39-2.01), and 1.23 (1.04-1.47) for >30-60, 61-99, and 100-155 days compared to >155 days, respectively. Long-term vitamin D treatment is needed to maintain sufficient levels in those with baseline serum 25OHD below 50 nmol/l.


Identification of key gene networks controlling vernalization development characteristics of Isatis indigotica by full-length transcriptomes and gene expression profiles.
Isatis indigotica Fort., as a common Chinese medicinal raw material, will lose its medicinal value if it blooms early, so it is highly valuable to clarify the induction mechanism of the vernalization of I. indigotica at low temperature. In this study, the concentrations of soluble sugar, proline, glutathione and zeatin in two germplasms of I. indigotica with different degrees of low temperature tolerance (Y1 and Y2) were determined at 10 days, 20 days and 30 days of low-temperature treatment, and the full-length transcriptome of 24 samples was sequenced by Nanopore sequencing with Oxford Nanopore Technologies (ONT). After that, the data of transcripts involved in the vernalization of I. indigotica at low temperature were obtained, and these transcripts were identified using weighted gene co-expression network analysis (WGCNA). The results revealed the massive accumulation of soluble sugar and proline in Y1 and Y2 after low temperature induction. A total of 18,385 new transcripts, 6168 transcription factors and 470 lncRNAs were obtained. Differential expression analysis showed that gibberellin, flavonoids, fatty acids and some processes related to low temperature response were significantly enriched. Eight key transcripts were identified by WGCNA, among which ONT.14640.1, ONT.9119.1, ONT.13080.2 and ONT.16007.1 encodes a flavonoid transporter, 9-cis-epoxycarotenoid dioxygenase 3 (NCED3), growth factor gene and L-aspartate oxidase in plants, respectively. It indicated that secondary metabolites such as hormones and flavonoids play an important role in the vernalization of I. indigotica. qRT-PCR proved the reliability of transcriptome results. These results provide important insights on the low-temperature vernalization of I. indigotica, and provide a research basis for analyzing the vernalization mechanism of I. indigotica. The online version contains supplementary material available at 10.1007/s12298-021-01110-2.


Sleep and Athletic Performance: Impacts on Physical Performance, Mental Performance, Injury Risk and Recovery, and Mental Health: An Update.
Sleep health is an important consideration for athletic performance. Athletes are at high risk of insufficient sleep duration, poor sleep quality, daytime sleepiness and fatigue, suboptimal sleep schedules, irregular sleep schedules, and sleep and circadian disorders. These issues likely have an impact on athletic performance via several domains. Sleep loss and/or poor sleep quality can impair muscular strength, speed, and other aspects of physical performance. Sleep issues can also increase risk of concussions and other injuries and impair recovery after injury. Cognitive performance is also impacted in several domains, including vigilance, learning and memory, decision making, and creativity.


Urethane functions can reduce metal salts under hydrothermal conditions: synthesis of noble metal nanoparticles on flexible sponges applied in semi-automated organic reduction.
We report an additive-free one-pot hydrothermal synthesis of Au, Ag, Pd, and alloy AuPd nanoparticles (NPs) anchored on commercial polyurethane (PU) foams. While unable to reduce the precursor metal salts at room temperature, PU is able to serve as a reducing agent under hydrothermal conditions. The resulting NP@PU sponge materials perform comparably to reported state-of-the-art reduction catalysts, and are additionally very well suited for use in semi-automated synthesis: the NP anchoring is strong enough and the support flexible enough to be used as a 'catalytic sponge' that can be manipulated with a robotic arm, i.e., be repeatedly dipped into and drawn out of solutions, wrung out, and re-soaked.


Understanding the Conceptual Importance of the Differences Among Health Literacy Definitions.
This chapter aims to provide an overview of health literacy definitions, how the definitional work on health literacy has developed, and why it is important to understand the conceptual differences among diverse definitions. Since the introduction of the term 'health literacy' in the 1970s, research interest has grown exponentially.


Low rates of cutaneous adverse reactions to alcohol-based hand hygiene solution during prolonged use in a large teaching hospital.
We assessed cutaneous adverse reactions (CARs) to alcohol-based hand rub (ABHR) after the introduction of a hand hygiene culture change program at our institution. CARs were infrequent among exposed health care workers (HCWs) (13/2,750; 0.47%; 1 CAR per 72 years of HCW exposure) and were not influenced by the duration or intensity of ABHR use but were associated with the presence of irritant contact dermatitis.


Differential regulation of GUV mechanics via actin network architectures.
Actin networks polymerize and depolymerize to construct highly organized structures, thereby endowing the mechanical phenotypes found in a cell. It is generally believed that the amount of filamentous actin and actin network architecture determine cytoplasmic viscoelasticity of the whole cell. However, the intrinsic complexity of a cell and the presence of endogenous cellular components make it difficult to study the differential roles of distinct actin networks in regulating cell mechanics. Here, we model a cell by using giant unilamellar vesicles (GUVs) encapsulating actin filaments and networks assembled by various actin cross-linker proteins. Perturbation of these cytoskeletal vesicles using alternating current electric fields revealed that deformability depends on actin network architecture. While actin-free vesicles exhibited large electromechanical deformations, deformations of GUVs encapsulating actin filaments were significantly dampened. The suppression of electrodeformation of actin-GUVs can be similarly recapitulated by using aqueous poly(ethylene glycol) 8000 solutions at different concentrations to modulate solution viscoelasticity. Furthermore, networks cross-linked by alpha actinin resulted in decreased GUV deformability compared with actin-filament-encapsulating GUVs, and membrane-associated actin networks, through the formation of the dendritic actin cortex, greatly dampened electrodeformation of GUVs. These results highlight that the organization of actin networks regulates the mechanics of GUVs and shed insights into the origin of differential deformability of cells.


Isolation and characterization of two different cDNAs of delta1-pyrroline-5-carboxylate synthase in alfalfa, transcriptionally induced upon salt stress.
Two different cDNA clones, MsP5CS-1 and MsP5CS-2, encoding delta1 -pyrroline-5-carboxylate synthase (P5CS). the first enzyme of the proline biosynthetic pathway, were isolated from a lambdaZap-cDNA library constructed from salt stressed Medicago sativa roots. MsP5CS-1 (2.6 kb) has an open reading frame of 717 amino acids, as well as a non-spliced intron at a position corresponding to the evolutionary fusion point of the bacterial proA and proB genes. MsP5CS-2 (1.25 kb) is a partial clone. The clones share 65% identity in nucleotide sequences, 74% homology in deduced amino acid sequences, and both show a high similarity to Vigna aconitifolia and Arabidopsis thaliana P5CS cDNA clones. Southern blot analysis confirmed the presence of two different P5CS genes. The effect of salinity on the transcription of MsP5CS-1 and MsP5CS-2 in roots was studied, using northern blot analysis and a RT-PCR approach. A rapid increase in the steady-state transcript level of both genes in roots was observed by RT-PCR upon exposure of hydroponically grown 6-day old seedlings to 90 mM NaCl, suggesting that both are salt-inducible genes, yet a higher response was observed for MsP5CS-2.


Blue Fluorescent Materials Composed of Anthracene-Aryl Amine-Anthracene Derivatives for Organic Light-Emitting Diodes.
Blue fluorescent emitters based on anthracene-aryl amine-anthracene derivatives were studied for efficient OLEDs. Compound 1 exhibited efficient EL propereties with luminous and power efficien- cies of 4.50 cd/A and 1.75 lm/W at 200 mA/cm2, respectively and CIE coordinates of (0.18, 0.26) at 7.0 V.


Association of tumor necrosis with pathological features and clinical outcome in 754 patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma: an international validation study.
Tumor necrosis is associated with a poor oncological outcome in patients with upper tract urothelial carcinoma and other malignancies. We validated the association of tumor necrosis with pathological features and clinical outcomes in a large international cohort of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. This retrospective study included 754 patients treated with radical nephroureterectomy at a total of 9 centers. Tumor necrosis was scored as greater than 10% of tumor area based on microscopic evaluation. Tumor necrosis was present in 165 specimens (21.9%). The prevalence of tumor necrosis increased with advancing pathological stage, including 7%, 10.6% and 50% for T1, T2 and T3-4, respectively (p <0.001). Tumor necrosis was associated with features of aggressive upper tract urothelial carcinoma, such as high grade, lymph node metastasis, lymphovascular invasion, sessile tumor architecture and concomitant carcinoma in situ (p <0.002). Median followup in censored patients was 40 months (IQR 18 to 75). On univariate Cox regression analysis tumor necrosis was significantly associated with disease recurrence and cancer specific mortality (HR 2.4 and 2.7, p <0.001). However, on multivariate Cox regression analysis including patient age, stage, grade, lymph node status, lymphovascular invasion and adjuvant chemotherapy tumor necrosis was not associated with disease recurrence (HR 1.1, p = 0.49) or cancer specific mortality (HR 1.1, p = 0.51). Excluding 63 patients who received adjuvant chemotherapy and/or 49 with positive lymph nodes did not substantially change these results. In this large, multicenter international study tumor necrosis was associated with pathological features of biologically aggressive upper tract urothelial carcinoma. However, tumor necrosis was not an independent predictor of clinical outcomes.


Protection by superoxide dismutase and catalase in the isolated rat heart reperfused after prolonged cardioplegia: a combined study of metabolic, functional, and morphometric ultrastructural variables.
To determine the protective effect during ischaemia and reperfusion of removing oxygen radicals two groups of isolated Langendorff perfused rat hearts were arrested with cardioplegic solution at 4 degrees C and kept ischaemic at 15 degrees C for 210 min before being reperfused for 60 min at 37 degrees C. To remove oxygen radicals superoxide dismutase and catalase were added to the cardioplegic solution and to the buffer during the first 30 min of reperfusion in one group, the other group serving as control. At the end of reperfusion the first derivative of left ventricular developed pressure (dP/dt), coronary flow, high energy phosphate concentrations, and ultrastructure were determined. The ultrastructure was examined using a stereological method based on point counting and the results presented as volume fractions (Vv). DP/dt after 60 min of reperfusion was 61.6(5.6)% (mean (SEM)) of the initial values in the control group and 77.6(3.4)% in the superoxide dismutase and catalase supplemented group (p less than 0.05). In the supplemented group coronary flow was significantly higher than in the control group but only in the first part of reperfusion. The concentrations of adenosine triphosphate and creatine phosphate in the control group were 9.9(1.0) and 19.6(1.8) mumol.g-1 dry weight respectively; corresponding values in the supplemented group were 14.4(2.1) and 29.4(3.6) mumol.g-1 dry weight. The morphometric examination of the ultrastructure showed no significant difference in interstitial fluid accumulation evaluated by Vv(myocyte/myocardium) measurements and there was no difference in mitochondrial alteration between the two groups. There was, however, a significant reduction in the volume of cellular oedema (Vv(cell oedema/myocyte)) in the supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)


Enhanced T-cell responses to glioma cells coated with the anti-EGF receptor antibody and targeted to activating FcgammaRs on human dendritic cells.
The induction of effective immune responses to tumor vaccines requires the preferential activation of effector T cells relative to regulatory or suppressive T cells. Glial tumors commonly overexpress the epidermal growth factor receptor (EGFR), which can be targeted by monoclonal antibodies. Here we show that the coating of glial tumor cells with a clinical grade anti-EGFR antibody, cetuximab, leads to enhanced tumor-specific, interferon-gamma producing CD8+ T cells by dendritic cells (DCs). The selective targeting of monoclonal antibody coated glioma cells to activating Fcgamma receptors (FcgammaRs) on DCs, which is achieved with a blocking antibody to the inhibitory form of FcgammaR, leads to the induction of antitumor immunity without the need for an exogenous maturation stimulus. Importantly, this approach reduces the concurrent induction of regulatory T cells, which can also be depleted to further enhance immunity. These data suggest that immunity to EGFR expressing tumors, including glioma, can be enhanced through the concerted function of antitumor monoclonal antibodies, activating FcgammaR, and DCs.


Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus.
Most cases of autosomal-dominant hereditary spastic paraplegia are linked to mutations in SPG4 encoding spastin, a protein involved in microtubule dynamics and membrane trafficking. In pyramidal neurons of the motor cortex and in immortalized motor neurons, spastin is localized to the synaptic terminals and growth cones. However, in other neurons and in proliferating cells spastin is prevalently nuclear. The mechanisms that determine targeting of spastin to the nucleus or the cytoplasm are unknown. We show here that the SPG4 mRNA is able to direct synthesis of two spastin isoforms, 68 and 60 kDa, respectively, through usage of two different translational start sites. Both isoforms are imported into the nucleus, but the 68-kDa isoform contains two nuclear export signals that efficiently drive export to the cytoplasm. Nuclear export is leptomycin-B sensitive. The cytoplasmic 68-kDa spastin isoform is more abundant in the brain and the spinal cord than in other tissues. Our data indicate that spastin function is modulated through usage of alternative translational start sites and active nuclear import and export, and open new perspectives for the pathogenesis of hereditary spastic paraplegia.


9 Mb deletion including chromosome band 3q24 associated with unsuspicious facial gestalt, persistent ductus omphaloentericus, mild mental retardation and tic.
9 Mb deletion including chromosome band 3q24 associated with unsuspicious facial gestalt, persistent ductus omphaloentericus, mild mental retardation and tic.


Maps of receptor binding parameters in the human brain--a kinetic analysis of PET measurements.
A kinetic method is described for the estimation of neuroreceptor density as well as the rate constants for association and dissociation of rapidly equilibrating radioligands. The method is exemplified by positron emission tomographic measurements of the human brain using 11C-raclopride, a D 2 dopamine receptor antagonist, and 11C-Ro 15-1788, a benzodiazepine receptor antagonist. Using a linear non iterative algorithm, regional binding characteristics were calculated and displayed pixel by pixel in brain maps. Data from repeated experiments on the same subject with different amounts of the unlabeled ligand were utilized. The binding characteristics were determined according to a two step procedure in which the time course of the free radioligand concentration was estimated from a reference region considered to be free of specific receptor binding sites. Alternative methods to determine the concentration of free radioligand are discussed.


Nitrification at full-scale municipal wastewater treatment plants: Evaluation of inhibition and bioaugmentation of nitrifiers.
Batch nitrification tests were conducted with sludge and wastewater streams obtained from field implementations to evaluate nitrification inhibition and efficiency of a nitrifiers bioaugmentation technology at full-scale municipal wastewater treatment plants (WWTPs). The results showed that the substrate organic carbon and pH of wastewater streams were inhibitory factors to nitrification and the low pH was the cause of the WWTP experiencing poor nitrification. An ammonia-nitrogen removal rate of 0.21mg-N/gMLVSS-h was observed at pH 6.5, while the rate increased to 0.54mg-N/gMLVSS-h with an introduction of 6% bioaugmented nitrifiers, indicating that the integrated side-stream nitrifiers bioaugmentation process was beneficial in improving nitrification efficiency, even under low pH conditions not conducive to nitrification. The study provides new insights into effective upgrading of municipal WWTPs exposed to poor nitrification.


Pitfalls in treatment of acute cervical spinal cord injury using high-dose methylprednisolone: a retrospect audit of 111 patients.
Earlier studies suggested that the use of high-dose IV MP was the gold standard of care for the treatment of ASCI, but this has been debated. This study aims to identify the effects of high-dose MP in treatment of cervical SCI and how the treatment might be improved. The medical records of 138 patients with cervical spinal injury secondary to blunt injuries were retrospectively reviewed to determine the steroid administration protocol, effects, and complications. The findings on admission were compared with those at discharge and at the most recent outpatient follow-up visit. Significant neurologic improvement was defined as increase in at least 1 clinical grade according to the Frankel classification system. Significantly more motor and sensory recovery was noted (complete ASCI, 69% vs 0; incomplete ASCI, 70% vs 50%) in patients treated with surgery and MP than in patients without such treatment. Moreover, 87% (14/16) of patients with complete ASCI (unlike patients with incomplete [8/28, 28.6%] and mild [2/14, 14.3%] ASCI) treated with MP had steroid-related complications, and 1 patient died from sepsis related to a perforated peptic ulcer. Mean hospitalization was significantly shorter for the patients who underwent tracheostomy (49 days, ranged from 22 to 110 days) vs nontracheostomy(94 days, ranged from 28-268 days). Early intervention with surgery and MP is critical. Although treatment with MP for 24 or 48 hours significantly improves motor and sensory function of patients with ASCI, harmful side effects limit its functional efficacy in patients with complete ASCI. Early tracheostomy can shorten hospital stay in patients with complete ASCI.


[Experience in preventing early treatment discontinuance in patients with tuberculosis in the Kemerovo Region].
By taking into account the revealed reasons for early chemotherapy discontinuance, a package of measures to prevent this phenomenon has been worked out. The package includes improvement of hospital conditions; meticulous monitoring of the consumption of antituberculous drugs; social support of the destitute; creation of motivation for rather prolonged, and continuous chemotherapy via preparation at a tuberculosis patient school; provision of continuity in the treatment between the in- and outpatient stages, a penitentiary medical and civil health care tuberculosis facilities; the use of hospital-replacement technologies, judicial practice of attraction of the bacteria-discharging persons who deliberately avoid treating; and interdepartmental interaction. Introduction of a package of measures to prevent early treatment discontinuance could reduce the proportion of such patients among the first detected ones from 30 to 7% and from 51.9 to 32.8% among the ineffectively treated patients.


Smart Gene™ as an effective non-invasive point-of-care test to detect Helicobacter pylori clarithromycin-resistant mutation.
Smart Gene™ was developed based on the concept of point-of-care genetic testing. We evaluated the detection performance of a reagent for Helicobacter pylori (H. pylori) clarithromycin (CAM)-resistant mutation assessment and determined the association between the results of Smart Gene™ and those of eradication therapy for H. pylori. In 2020, the present study was conducted on participants of the H. pylori test and treat project in Saga Prefecture. The submitted stool samples were measured for H. pylori gene and CAM-resistant mutation by Smart Gene™, and the results were compared with real-time polymerase chain reaction (PCR) and sequencing analysis. Finally, the results of the eradication therapy were examined for each result of Smart Gene™. Stool samples were obtained from 139 patients who were tested positive by stool antigen test and were analyzed. The H. pylori detection rate was 95.7% by Smart Gene™, 92.8% by real-time PCR (P < 0.01), and 89.2% by sequencing analysis (P = 0.06). The overall concordance rate for CAM-resistant mutation between Smart Gene™ and sequencing analysis was 96.7%. Moreover, 35 of 48 students with CAM-resistant mutation and 33 of the 35 students with a mutation without CAM resistance succeeded in CAM-containing triple therapy, and the success rate was significantly higher for the mutation without CAM resistance (P = 0.012). The detection performance of Smart Gene™ was comparable with that of real-time PCR and sequencing analysis. It is expected that the success rate of eradication would be further improved by using the reagent.


Hypothalamic astrocytic-BMAL1 regulates energy homeostasis in a sex-dependent manner.
Here, we demonstrate that hypothalamic astrocytic BMAL1 computes cyclic metabolic information to optimize energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Thus, astrocytic BMAL1 contributes to the control of energy balance through the modulation of the metabolic rate, hepatic and white adipose tissue lipogenesis, and the activity of brown adipose tissue. Importantly, most of these alterations are specific to hypothalamic astrocytic BMAL1. Moreover, female mice with BMAL1 knockdown in astrocytes exhibited a "male-like" metabolic obese phenotype when fed a high-fat diet. Overall, our results suggest a sexually dimorphic effect of astrocytic BMAL1 on the regulation of energy homeostasis, which may be of interest in the physiopathology of obesity and related comorbidities.


Sub-processes of working memory in the N-back task: an investigation using ERPs.
The N-back task is frequently used in working memory studies. N-parameters allow experimental psychologists to analyze the sub-processes of N-back tasks in addition to general processing. However, previous imaging studies have not closely scrutinized these sub-processes. In the current study, three sub-processes in the N-back task were proposed using a logical task analysis: matching, replacement and shift. Domain-specific lateralization in spatial and verbal working memory was investigated in terms of this model. This model was tested with two ERP experiments during N-back tasks, one conceptual (top-down) and one data-driven (bottom-up). Domain-specific lateralization was observed as predicted in the shift sub-process of the conceptual task and in the replacement sub-process of the data-driven task. Match-specific lateralization was also found. The results support our three-sub-process model of the N-back task and our hypothesis that replacement is a data-driven process with a posterior locus whereas shift is a more conceptual process with a more frontal locus. The proposed model correctly predicted ERP patterns in conceptual and data-driven N-back tasks and is potentially useful in understanding the neurophysiologic basis of N-back task performance. The similarity between match- and domain-specific lateralization in N-back tasks raised several issues for further investigation.


Relationships among experience level and value orientation and the performance of paraprofessional telephone counselors.
The effectiveness of indigenous paraprofessional helpers is thought to be partially due to the similarity in style and values between then and their clients. However, there is a concern that as they gain experience in an agency, their identification may shift from the clients to the agency. Also, there is a question as to how effective paraprofessionals (selected due to their shared values with a target population) are with value-dissimilar clients. Truax and Carkhuff's scales of facilitative conditions as well as a technique functioning scale were used to assess the helping behavior of paraprofessional telephone counselors at three levels of experience in response to value-similar and value-dissimilar simulated calls. The results indicate that performance generally improved with training and experience and that instead of a uniform deterioration with dissimilar value calls, a complex relationship existed between performance, values, and experience level.


Fluoride regulates the expression of extracellular matrix HSPG and related signaling pathways FGFR3 and Ihh/PTHrP feedback loop during endochondral ossification.
Skeletal fluorosis causes growth plate impairment and growth retardation during bone development. Longitudinal bone development is accomplished by endochondral ossification in growth plate. However, the mechanism of fluoride impairs growth plate is unclear. To explore the effect of fluoride on various glycosaminoglycans (GAGs) and related signaling pathways in growth plate during endochondral ossification, SD rats and ATDC5 cells were treated with fluoride and carried out a series of experiments. We found that the expression of heparan sulfate (HS), a kind of GAGs in extracellular matrix, was significantly increased in the growth plate of fluoride-treated rats compared with control rats. Furthermore, the expression of HS synthetic enzyme exostosin 1 (EXT1) and glypican 6 (GPC6), a core protein of HS proteoglycan (HSPG), were significantly increased in fluoride-treated ATDC5 cells compared with control cells (P < 0.05). The expression of related molecules including fibroblast growth factor receptor-3 (FGFR3), signal transducer and activator of transcription 1 (STAT1) and parathyroid hormone-related protein (PTHrP) were significantly increased in the fluoride-treated groups compared with control groups (P < 0.05), and there was significantly decreased in the expression of Indian hedgehog (Ihh) in fluoride-treated groups compared with control groups (P < 0.05). Our data suggested that fluoride increased the content of HSPG in extracellular matrix by promoting the expression of EXT1 and GPC6. Fluoride also activated FGFR3 signaling pathway, inhibited Ihh/PTHrP feedback loop and inhibited endochondral ossification. Nevertheless, the regulation of fluoride on HSPG and related pathways FGFR3 and Ihh/PTHrP feedback loop during endochondral ossification needs to be further studied.


Complete genome sequence of a novel avastrovirus in goose.
We report the complete genome sequence of a new avastrovirus of goose-origin (FLX). The 7299-nt-long genome consisted of three overlapping open reading frames (ORFs) that were in different reading frames. Pairwise comparisons showed that the FLX genome was 59% identical to its closest relatives and that the levels of amino acid identity shared by FLX with other astroviruses did not exceed 54% in ORF1a, 66% in ORF1b, and 50% in ORF2, respectively. Phylogenetic analysis based on the amino acid sequence of the full-length ORF2 demonstrated that FLX was highly divergent from all other avastroviruses. At the amino acid level the complete capsid region of FLX shared genetic distances of 0.574-0.719 with three official avastrovirus species, suggesting that it can be classified as a member of a novel species in the genus Avastrovirus.


Toll-like receptor 2 of tongue sole Cynoglossus semilaevis: Signaling pathway and involvement in bacterial infection.
Toll-like receptor (TLR) 2 is a member of the TLR family that plays a pivotal role in innate immunity. In mammals, TLR2 is known to recognize specific microbial structures and trigger MyD88-dependent signaling to induce various cytokine responses. In this study, we examined the expression and function of the tongue sole Cynoglossus semilaevis TLR2, CsTLR2. CsTLR2 is composed of 898 amino acid residues and shares 25.6%-27.3% overall sequence identities with known teleost TLR2. CsTLR2 is a transmembrane protein with a toll/interleukin-1 receptor domain and eight leucine-rich repeats. Expression of CsTLR2 occurred in multiple tissues and was upregulated during bacterial infection. Stimulation of the CsTLR2 pathway led to enhanced expression of MyD88-dependent signaling molecules. Recombinant CsTLR2 (rCsTLR2) corresponding to the extracellular region was able to bind to a wide range of bacteria. Under both in vitro and in vivo conditions, rCsTLR2 significantly reduced bacterial infection. These observations add new insights into the signaling and function of teleost TLR2.


Ultrashort single-wall carbon nanotubes reveal field-emission coulomb blockade and highest electron-source brightness.
We present here well-defined Coulomb staircases using an original field-emission experiment on several individual in situ-grown single-wall carbon nanotubes. A unique in situ process was applied nine times to progressively shorten one single-wall carbon nanotube down to ≃10 nm, which increased the oscillations periods from 5.5 to 80 V, the temperature for observable Coulomb staircase to 1100 K and the currents to 1.8 μA. This process led to the brightest electron source ever reported [9×1011 A/(str m2 V)].


Directed coping: A key to coping effectively?
Directed coping, or the use of fewer coping strategies, represents attempts of the individual to effectively cope with stressors. As individuals engage in this process, health and wellness (e.g., physical and mental) generally improve, suggesting directed coping may be an effective technique. However, little specific information is known about the directed coping construct beyond the results of the single study by Wright et al. among nurses dealing with work stressors. Therefore, the current study seeks to examine the directed coping construct in more depth. Following a pre/post study design, 611 undergraduate students participated in a health behaviour change program, completing an online questionnaire regarding their health, wellness and general life stressors as well as an in-person physical health assessment before and after the 6-week program. Consistent with hypotheses, directed coping was associated with and predictive of improved health and wellness subjectively (e.g., affect and stress) and objectively (e.g., heart rate, blood pressure and grip strength) relative to coping with general life stressors. Moreover, directed coping demonstrated stability over time and was related to personality characteristics. Thus, the results suggest directed coping is an effective method of coping and may be stable across situations.


Diagnosis of dorsal and palmar rotation of the lunate on a frontal radiograph.
Anatomic variations in the contours of the palmar and dorsal horns of 100 dry lunates were classified by symmetry, curvature, and angularity. Frequencies of the major forms were determined. An algorithm was constructed for the identification of the dorsal and palmar horns of the lunate on a frontal radiograph. By this algorithm, it is possible to diagnose intercalated segment instabilities without the use of a lateral radiograph.


A dynamic spatial gradient of Hebbian learning in dendrites.
Backpropagating action potentials (bAPs) are an important signal for associative synaptic plasticity in many neurons, but they often fail to fully invade distal dendrites. In this issue of Neuron, Sjöström and Häusser show that distal propagation failure leads to a spatial gradient of Hebbian plasticity in neocortical pyramidal cells. This gradient can be overcome by cooperative distal synaptic input, leading to fundamentally distinct Hebbian learning rules for distal versus proximal synapses.


The influence of temperature and urea on intrinsic fluorescence of Streptomyces subtilisin inhibitor. A study by fluorescence polarization and quenching.
Intrinsic fluorescence of new microbial protease inhibitor, Streptomyces subtilisin inhibitor was studied by observing fluorescence polarization degree and lifetime in the temperature range 25-81 degrees C. Striking thermal changes in these fluorescence properties of tryptophan residues were observed. The apparent molecular volumes for tryptophan and tyrosine residues in the native form were determined to be 89 and 75 A3, respectively. The fluorescence quenching by Br- or Cs+ was investigated to obtain a microenvironmental information around tryptophan residues both in the native and denatured form. Cs+ quenches the fluorescence slightly stronger than Br-, implying that there is not any distinctive electrostatic interaction between tryptophan residues and their neighborhood.


Colonoscopy for screening and follow up of patients with a family history of colorectal cancer.
To determine the minimum family history of colorectal cancer (CRC), which justifies colonoscopy and to establish whether further colonic assessment is necessary after a negative screening colonoscopy. A retrospective review of every colonoscopy undertaken for family screening at the Royal Berkshire and Battle Hospitals, Reading between October 1996 and July 2004. Four hundred and thirty-two patients (261 women) with an average age of 48 years (range 14-84) were screened. Three cancers in patients over the age of 60 years and 49 adenomas were found in 37 patients. Twenty three of 281 (8%) patients with a 'low-risk' family history (one in 12 or less lifetime risk of developing CRC) had either a cancer or an adenoma. Eighteen of 151 (12%) patients with a 'high-risk' family history (one in 10 or greater) had a similar positive colonoscopy. Thirteen of 15 patients who had an adenoma aged under 45 years had a high-risk family history. Seventy-three patients subsequently underwent two or more follow-up colonoscopies. There were 22 adenomatous polyps found in 12 patients (16%) at the first screening, nine adenomas in seven patients in the second colonoscopy and four adenomas found in four patients in all subsequent colonoscopies. Patients with a low-risk family history have a similar adenoma pick-up to that of the general population. These patients need not be screened below the age of 50 unless symptomatic. Follow up of low-risk family history (FH) patients with a negative screening colonoscopy is unlikely to be beneficial.


Novel cyclodextrin nanosponges for delivery of calcium in hyperphosphatemia.
Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional structures, have been used as delivery system of different drugs. In this work, new cyclodextrin-based nanosponges of calcium carbonate were prepared by polymer condensation method to release the calcium in controlled manner in the treatment of hyperphosphatemia as novel carriers. SEM measurements revealed their roughly spherical shape, porous nature and mean particle size of about 400 nm. Zeta potentials of the nanosponges were sufficiently high to obtain stable formulations. The encapsulation efficiencies of calcium in nanosponge formulations were found to be 81-95%. The moisture contents of the nanosponges were in the range of 0.1-0.7%. The optimized formulation produces enteric and controlled release kinetics of calcium in the management and treatment of hyperphosphatemia. It was also observed that calcium ions bound efficiently to free phosphate in a pH-dependent fashion especially at pH 7. In accelerated stability study no significant changes occurred in physical appearance, size and nature of drug in formulation for 3 months. The results of FTIR and DSC confirmed that calcium carbonate was encapsulated in nanosponges structure.


Dynamics of brain activation during picture naming.
The cerebral representation of language, deduced from observing patients with brain lesions and from stimulations and recordings performed during brain surgery, has been further clarified by recent positron emission tomography and functional magnetic resonance imaging measurements. We now expand this static view into the dynamics of cortical activation using the accurate spatiotemporal resolution of whole-head magnetoencephalography. During picture naming, the conversion from visual to symbolic representation progressed bilaterally from the occipital visual cortex towards temporal and frontal lobes. Overt naming elicited the most widespread cortical activation. Some language-related sites also reacted, though more weakly or after a longer delay, during covert naming and even passive viewing.


Neurotoxicity Assessment of 1-[(2,3-Dihydro-1-Benzofuran-2-yl)Methyl]Piperazine (LINS01 Series) Derivatives and their Protective Effect on Cocaine-Induced Neurotoxicity Model in SH-SY5Y Cell Culture.
Excessive levels of dopamine in the synaptic cleft, induced by cocaine for example, activates dopaminergic receptors, mainly D1R, D2R, and D3R subtypes, contributing to neurotoxic effects. New synthetic 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine derivatives (the LINS01 compounds), designed as histaminergic receptor (H3R) ligands, are also dopaminergic receptor ligands, mainly D2R and D3R. This study aims to evaluate the neurotoxicity of these new synthetic LINS01 compounds (LINS01003, LINS01004, LINS01011, and LINS01018), as well as to investigate their protective potential on a cocaine model of dopamine-induced neurotoxicity using SH-SY5Y cell line culture. Neurotoxicity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and automated cell counting with fluorescent dyes (acridyl orange and propidium iodide) assays. Concentration-response curves (CRCs) were performed for all LINS compounds and cocaine using MTT assay. The results show that LINS series did not decrease cell viability after 48h of exposure-except for 100 µM LINS01018, which was discontinued from the study. Likewise, MTT, LDH, and fluorescent dyes staining showed no difference is cell viability for LINS compounds at 10 µM. When incubated with 2.5 mM cocaine (lethal concentration 50) for 48h, 10 µM of each LINS compound, metoclopramide (D2R antagonist) and haloperidol (D2R/D3R antagonist), ameliorated cocaine-induced neurotoxicity. However, only metoclopramide, haloperidol, and LINS01011 compound significantly decreased LDH released in the culture medium, suggesting that this new synthetic compound presents a more robust effect. This preliminary in vitro neurotoxicity study suggests that LINS01 compounds are not neurotoxic, and that they play a promising role in preventing cocaine-induced neurotoxicity.


Factors Affecting Patients' Preferences for and Actual Discussions About End-of-Life Care.
Discussions about end-of-life care are often difficult for patients and clinicians, and inadequate communication poses a barrier to patients receiving the care they desire. To understand factors that facilitate end-of-life care discussions that guide interventions to improve care. We examined baseline data from an ongoing randomized trial to evaluate associations between patients' self-reported desire for, and occurrence of, discussions about end-of-life care and factors influencing these discussions. Factors included emotional symptoms and barriers and facilitators to discussions. The sample included patients with serious illness (n = 473) and their primary or specialty care clinicians (n = 128). Regression analyses were adjusted for confounders and clustered patients under clinicians. Patients who endorsed each of three barriers to discussions were less likely to have had a discussion with their clinician (P-values ranging from <0.001 to 0.046). One facilitator (having had family/friends who died) was associated with past discussions (P = 0.037), and two facilitators were associated with wanting future discussion (P < 0.001): 1) concerns about future quality of life, 2) worries about being a burden on friends/family. Depression and anxiety were not associated with past discussions. However, patients with more anxiety were more likely to want future discussions (P = 0.001), as were patients with more depressive symptoms who had had discussions in the past (P < 0.001). The occurrence of, and desire for, patient-clinician communication about end-of-life care is associated with patient factors including communication barriers and facilitators and symptoms of depression and anxiety. Understanding these factors may facilitate design of effective communication interventions.


"No matter how old I am, I don't like what my stomach looks like." Lifespan perspective on the changes in self-assessment of attractiveness and life satisfaction in women.
The study aimed to examine the association between self-assessment of attractiveness and life satisfaction in women, where age was a potential moderator of this relationship. A cross-sectional study of 360 women aged 18 to 89 was performed. Participants assessed their overall attractiveness, the attractiveness of their individual body parts, and their life satisfaction. The relationship between the assessment of attractiveness of particular body parts and life satisfaction depended on age. The results indicate that not only overall self-attractiveness, but also the perceived attractiveness of particular body parts (different in each distinguished age group: 18-25, 30-45 and 60+) can be considered predictors of life satisfaction in women.


Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo.
Osteoprotegerin ligand (OPGL) targets osteoclast precursors and osteoclasts to enhance differentiation and activation, however, little is known about OPGL effects on osteoclast survival. In vitro, the combination of OPGL + colony-stimulating factor-1 (CSF-1) is required for optimal osteoclast survival. Ultrastructurally, apoptotic changes were observed in detached cells and culture lysates exhibited elevated caspase 3 activity, particularly in cultures lacking CSF-1. DEVD-FMK (caspase 3 inhibitor) partially protected cells when combined with OPGL, but not when used alone or in combination with CSF-1. CSF-1 maintained NF-kappaB activation and increased the expression of bcl-2 and bcl-X(L) mRNA, but had no effect on JNK activation. In contrast, OPGL enhanced both NF-kappaB and JNK kinase activation and increased the expression of c-src, but not bcl-2 and bcl-X(L) mRNA. These data suggest that aspects of both OPGL's and CSF-1's signaling/survival pathways are required for optimal osteoclast survival. In mice, a single dose of OPG, the OPGL decoy receptor, led to a >90% loss of osteoclasts because of apoptosis within 48 hours of exposure without impacting osteoclast precursor cells. Therefore, OPGL is essential, but not sufficient, for osteoclast survival and endogenous CSF-1 levels are insufficient to maintain osteoclast viability in the absence of OPGL.


To make a run for IT - A feasibility study of ICBT combined with physical exercise for patients with panic disorder.
Guided Internet-based cognitive behavioural therapy (ICBT) is a recommended treatment for panic disorder promising to increase treatment availability, but there are some concerns regarding adherence, including adherence to the in vivo exposure given as home assignments. The aim of this study was to assess the feasibility of combining ICBT with physical exercise with the aim of improving adherence and treatment response to ICBT. 12 participants were included via routine clinical practice to an open pre- post trial of feasibility using ICBT and an aerobe exercise protocol. We used a mixed model design investigating multiple areas of adherence, participants' experience and clinical outcome. 90.9% of the participants was considered completers in the ICBT program and the average adherence to the physical exercise was 93.1%. The experience of participating was summarized as "Hard work but worth it". Clinical outcomes effect sizes (d) ranged from 2.79 (panic severity) to .64 (Beck's anxiety index). The sum results on adherence, qualitative and quantitative data all suggest that augmenting ICBT with an aerobic exercise protocol is feasible. We conclude that further research is warranted.


Overview of Thyroid and Parathyroid Disease-The Endocrinology Perspective.
Thyroid and parathyroid disorders are quite common in the population and range from benign to malignant conditions that may be hormonally active or inactive. Select disorders of the thyroid and parathyroid can be managed medically, although there are a variety of circumstances that may require definitive management with surgery. Surgical intervention may be required for hormonal control, compressive symptoms, or for the removal and/or control of malignancy. The endocrinologist's perspective of the preoperative and postoperative management regarding thyroid and parathyroid surgeries will be discussed.


Dendritic cells and monocytes as accessory cells in T-cell responses in man. II. Function as antigen-presenting cells.
The main antigen-presenting cells (APC) of human blood are reported to be the dendritic cells (DC), whereas monocytes (Mo) are only weakly or not at all capable of inducing T-cell immune responses to the soluble antigen purified protein derivative (PPD). In contrast, we found Mo to have a suppressive effect on the APC function of DC in vitro. Removal of Mo by adherence resulted in an increased APC activity, even though Mo produce more interleukin 1 (Il-1) than DC. Furthermore, addition of the prostaglandin synthesis inhibitor indomethacin gave rise to increased Il-1 production, HLA-class II expression, and a stronger antigen-specific T-cell response to PPD. Taken together, our studies indicate that the superior accessory cell function of DC compared with Mo in in vitro cultures may, at least partly, be attributed to the prostaglandin E2 production by Mo and more stable expression of HLA-class II molecules on DC.


Cerebral circulation and oxygen metabolism in moyamoya disease of ischemic type in children.
Cerebral rCBF, rOEF, rCMRO2, and rCBV in moyamoya disease were studied by means of positron emmission tomography (PET), using 15O as a tracer. Steady-state methods with C15O2 and 15O2 were used to obtain the functional images of rCBF, rCMRO2, and rOEF. The 15O single-inhalation method was used to obtain the rCBV image. Five children (two boys and three girls) with mean age of 11 years and eight normal volunteers with mean age of 31 years were included in the study. The symptoms of moyamoya disease were due to cerebral ischemia, such as transient ischemic attack (TIA), reversible ischemic neurological deficit (RIND), and minor stroke. The interval between the latest ictus and PET scan ranged from 3 days to 3 years 6 months. Physiological parameters (rCBF, rCMRO2 etc.) in cerebral gray matter, cerebral white matter and basal ganglia were calculated from the single functional images. Any, low density areas appearing in X-ray-CT performed just prior to the PET study were carefully excluded from the analysis. The parameters of moyamoya disease were statistically compared with normal control parameters. Though the value of rCBF was slightly higher in moyamoya disease, this difference was not statistically significant. On the other hand, in moyamoya disease rCBV increased significantly in gray matter, white matter, and basal ganglia. The ratio of CBF to CBV is considered to be the index of perfusion pressure and reciprocal of cerebral mean transit time under the normal autoregulation of CBF. This ratio was calculated and compared with the normal value for each tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Imatinib plasma monitoring-guided dose modification for managing imatinib-related toxicities in gastrointestinal stromal tumor patients.
Imatinib, the first-line treatment in patients with advanced gastrointestinal stromal tumors (GIST), is generally well tolerated, although some patients have difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage by plasma level monitoring may facilitate management of patients who experience intolerable toxicities due to overexposure to the drug. We present two cases of advanced GIST patients in whom we managed imatinib-related toxicities through dose modifications guided by imatinib plasma level monitoring. Imatinib blood level testing may be a promising approach for fine-tuning imatinib dosage for better tolerability and optimal clinical outcomes in patients with advanced GIST.


Modification of high-lignin kraft pulps with laccase. Part 2. Xylanase-enhanced strength benefits.
The effects of xylanase pretreatment of high lignin content softwood (SW) kraft pulp on subsequent pulp treatment with laccase in combination with gallic acid were investigated. Although xylanase pretreatment was ineffective in enhancing the laccase-facilitated biografting of gallic acid to kraft fibers, it was beneficial for subsequent treatment with laccase exclusively. Treating pulp fibers with xylanase followed by laccase provided a collective 25% and 46% increase in dry and wet tensile strength properties, respectively.


Insight into the Effective Aerobic Oxidative Cross-Esterification of Alcohols over Au/Porous Boron Nitride Catalyst.
Boron nitride (BN) has attracted great attention with an unexpected ability in aerobic catalysis. Still, its related probe reactions are relatively rare, and the effect of the BN-supported metal catalyst on O2 activation is still ambiguous, and opinions are varied. In this work, the porous BN (pBN)-supported Au catalyst with a porous structure and exposed edges exhibits high activity in the oxidative cross-esterification reactions between the aromatic and C1-C3 aliphatic alcohols at ambient temperature. The turnover frequency value for methyl benzoate is 118 h-1 at 30 °C, and the calculated apparent activation energy (Ea, 58 kJ/mol) is comparable to that of AuPd/TiO2, Ru/Al2O3, and PdBiTe catalysts. Combined with temperature-programmed desorption (TPD) results, the loading of Au enhances the desorption of O2 and the interaction with alcohols; thus, a synergistic effect between the O-rich pBN and Au is considered. The free-radical scavenger can dramatically suppress the conversion (∼6%), suggesting that the reaction proceeds via the O2* radicals. According to the vibration of νO-O, δOO-H, and νB-O-O-B detected by attenuated total reflectance-infrared spectroscopy (ATR-IR), we are prone to consider the oxygen activation route by the edge B atoms. Then, a possible L-H reaction mechanism was proposed: benzyl alcohol and O2 adsorb on the Au/pBN initially, then O2 is converted to O2*, and the α-H elimination proceeds; as the semi-acetal formed, another α-H elimination proceeds and methyl benzoate is finally formed.


Wnt signaling: An attractive target for periodontitis treatment.
Periodontitis is the most common chronic inflammatory disease, and a leading cause of tooth loss. Characterized by resorption of alveolar process and destruction of periodontal ligaments, periodontitis can impact not only periodontal tissues but also systemic diseases, such as diabetes, cardiovascular diseases, and respiratory infections. Currently, it is a hotspot to manage destruction and gain regeneration of periodontal tissues. Increasing evidence indicates that the Wnt signaling plays an important role in homeostasis of periodontal tissues, functions of periodontal derived cells, and progression of periodontitis. Its molecule expressions were abnormal in periodontitis. As such, modulators targeting the Wnt signaling may be an adjuvant therapy for periodontitis treatment. This review elucidates the role of Wnt signaling and its molecules, with a view to develop a potential application of drugs targeting the Wnt signaling for periodontitis treatment.


Desmin intermediate filaments and tubulin detyrosination stabilize growing microtubules in the cardiomyocyte.
In heart failure, an increased abundance of post-translationally detyrosinated microtubules stiffens the cardiomyocyte and impedes its contractile function. Detyrosination promotes interactions between microtubules, desmin intermediate filaments, and the sarcomere to increase cytoskeletal stiffness, yet the mechanism by which this occurs is unknown. We hypothesized that detyrosination may regulate the growth and shrinkage of dynamic microtubules to facilitate interactions with desmin and the sarcomere. Through a combination of biochemical assays and direct observation of growing microtubule plus-ends in adult cardiomyocytes, we find that desmin is required to stabilize growing microtubules at the level of the sarcomere Z-disk, where desmin also rescues shrinking microtubules from continued depolymerization. Further, reducing detyrosination (i.e. tyrosination) below basal levels promotes frequent depolymerization and less efficient growth of microtubules. This is concomitant with tyrosination promoting the interaction of microtubules with the depolymerizing protein complex of end-binding protein 1 (EB1) and CAP-Gly domain-containing linker protein 1 (CLIP1/CLIP170). The dynamic growth and shrinkage of tyrosinated microtubules reduce their opportunity for stabilizing interactions at the Z-disk region, coincident with tyrosination globally reducing microtubule stability. These data provide a model for how intermediate filaments and tubulin detyrosination establish long-lived and physically reinforced microtubules that stiffen the cardiomyocyte and inform both the mechanism of action and therapeutic index for strategies aimed at restoring tyrosination for the treatment of cardiac disease.


Partial purification and functional characterization of Ts19 Frag-I, a novel toxin from Tityus serrulatus scorpion venom.
The yellow scorpion Tityus serrulatus (Ts) is responsible for the highest number of accidents and the most severe scorpion envenoming in Brazil. Although its venom has been studied since the 1950s, it presents a number of orphan peptides that have not been studied so far. The objective of our research was to isolate and identify the components present in the fractions VIIIA and VIIIB of Ts venom, in order to search for a novel toxin. The major isolated toxins were further investigated for macrophage modulation. The fractions VIIIA and VIIIB, obtained from Ts venom cation exchange chromatography, were rechromatographed on a C18 column (4.6 × 250 mm) followed by a reversed-phase chromatography using another C18 column (2.1 × 250 mm). The main eluted peaks were analyzed by MALDI-TOF and Edman's degradation and tested on macrophages. The previously described toxins Ts2, Ts3-KS, Ts4, Ts8, Ts8 propeptide, Ts19 Frag-II and the novel peptide Ts19 Frag-I were isolated from the fractions VIIIA and VIIIB. Ts19 Frag-I, presenting 58 amino acid residues, a mass of 6,575 Da and a theoretical pI of 8.57, shares high sequence identity with potassium channel toxins (KTx). The toxins Ts4, Ts3-KS and the partially purified Ts19 Frag-I did not produce cytotoxic effects on macrophage murine cells line (J774.1). On the other hand, Ts19 Frag-I induced the release of nitric oxide (NO) by macrophages, while Ts4 and Ts3-KS did not affect the NO production at the tested concentration (50 μg/mL). At the same concentration, Ts19 Frag-I and Ts3-KS increased the production of interleukin-6 (IL-6). Ts19 Frag-I and Ts4 did not induce the release of IL-10, IL-1β or tumor necrosis factor-α by macrophage cells using the tested concentration (50 μg/mL). We partially purified and determined the complete sequence and chemical/physical parameters of a new β-KTx, denominated Ts19 Frag-I. The toxins Ts4, Ts3-KS and Ts19 Frag-I showed no cytotoxicity toward macrophages and induced IL-6 release. Ts19 Frag-I also induced the release of NO, suggesting a pro-inflammatory activity.


Receptor-mediated toxicity of pahutoxin, a marine trunkfish surfactant.
Pahutoxin (PHN, choline chloride ester of 3-acetoxypalmitic acid) is a natural fish-killing (ichthyotoxic) agent derived from the defensive secretions of trunkfish. In spite of its obvious structural resemblance to synthetic cationic long-chain quaternary ammonium detergents, we show that PHN's action does not rely on its surfactant properties and is in fact, receptor-mediated. The above conclusion is supported by the following data: 1. Ichthyotoxicity is not related to its detergency or surfactivity, as indicated by the fact that the lethal concentration is about 1.5 orders of magnitude below its critical micelle concentration value (69 microM) and its liposomal/seawater partition coefficient is low (62-85); 2. The trunkfish is tolerant to its own pahutoxin; 3. Ichthyotoxicity occurs only upon application to the surrounding water, suggesting the existence of externally located receptors; 4. The receptor hypothesis was supported by the aid of equilibrium saturation binding assays revealing the presence of specific binding sites to PHN on the fish gill membranes; 5. The PHN tolerant trunkfish was shown to be devoid of PHN-binding sites. Some chemo-ecological, and environmental implications are discussed.


Neonatal Persistent Exposure to 6-Propyl-2-thiouracil, a Thyroid-Disrupting Chemical, Differentially Modulates Expression of Hepatic Catalase and C/EBP-β in Adult Rats.
Persistent exposure of rats to 6-propyl-2-thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP-β). Catalase promoter region (-185 to +52) that contains binding sites for C/EBP-β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP-β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid-disrupting properties of PTU. It is possible that besides thyroid-disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter.


Latent profile analysis of self-perceptions of ageing among Chinese community-dwelling older adults.
Self-perceptions of ageing (SPA) is an important predictor for physical and mental health of older adults in successful ageing. SPA is mainly studied from negative or positive perspectives using variable-centred methodologies. The aim of the current study was to explore distinct profiles of SPA among Chinese community-dwelling older adults using a person-centred method and validate the SPA profiles by examining associations with psychological outcomes. Participants aged 65 and over were randomly divided into test and validation samples (n = 451, respectively). SPA was measured by the Brief Ageing Perceptions Questionnaire using latent profile analysis. Three SPA profiles were identified. One adaptive subgroup was designated as 'Low ageing awareness and high positive control' (LAPC, 84.7% and 75% in both samples, respectively). Two maladaptive SPA subgroups were designated as 'Low positive consequences and control' (LPCC, 3.9% and 8.2% in both samples, respectively), and 'High ageing awareness and negative control' (HANC, 11.4% and 16.8% in both samples, respectively). Similar to negative/positive SPA, the HANC and LAPC subgroups showed the highest and lowest levels of depressive symptoms and cognitive decline. Low cognitive function was found in the LPCC subgroup. These findings highlight the heterogeneity of older adults' SPA. SPA profiles may aid community healthcare providers in China to identify individuals with high risk of maladaptive SPA and to tailor targeted interventions for psychological health in later life. Distinct SPA profiles require different interventions targeting negative or positive control or both aspects. More positive control strategies might be beneficial for cognitive functioning in older adults from the LPCC subgroup.


Interaction between dolutegravir and folate transporters and receptor in human and rodent placenta.
Due to the critical role of folates in neurodevelopment, it is important to understand potential interactions between anti-HIV drugs used during pregnancy, and folate delivery pathways in the placenta. This study investigates the effect of dolutegravir (DTG) exposure on the functional expression of the reduced folate carrier (RFC), proton-coupled folate transporter (PCFT), and folate receptor-α (FRα) in the placenta. Human placental cell lines, human placental explants, and a pregnant mouse model treated with clinically relevant concentrations of DTG were used. Gene and protein expression were assessed by qPCR, immunoblot and immunohistochemical assays. Folate transport function was measured by applying radioisotope-based transport assays. In placental cells, clinically relevant DTG exposure for 3h or 6h was associated with a modest but significant reduction in the expression of RFC and PCFT both at the mRNA and protein levels, as well as decreased uptake of RFC and PCFT substrates [3H]-methotrexate and [3H]-folic acid, respectively. In pregnant mice, DTG administration was associated with an increase in both placental RFC and PCFT mRNA expression, accompanied by a decrease in placental FRα mRNA under folate-deficient dietary conditions. These findings demonstrate a potential interaction between DTG and folate transport pathways in the placenta, particularly in vivo, under folate deficient conditions, potentially impacting folate delivery to the foetus in the context of DTG-based ART during pregnancy. Funded by Ontario HIV Treatment Network, grant #506657; and Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, award #R01HD104553.


Polarization vision: Drosophila enters the arena.
Two new studies introduce the power of Drosophila genetics to polarization vision, revealing distinct photoreceptor inputs to polarotactic behaviour mediated by dorsal and ventral eye regions.


Amphetamine and methamphetamine have a direct and differential effect on BV2 microglia cells.
A comparative analysis of the direct effects of amphetamine and methamphetamine exposure on BV2 microglia cells in the presence and absence of cellular debris was performed. A significant dose-dependent and treatment-dependent effect of amphetamine and methamphetamine on BV2 cells was demonstrated: methamphetamine, but not amphetamine, inhibited phagocytosis, and a differential regulation of cytokines was observed in response to amphetamine and methamphetamine.


Wound infection due to fresh water contamination by Aeromonas hydrophila.
We report the case of a 24-year-old man who sustained a scalp laceration in a diving accident. His wound became infected, and he was treated with an oral cephalosporin, with subsequent progression of the infection. Cultures subsequently grew Aeromonas hydrophila. Many strains of Aeromonas are not sensitive to the antibiotics commonly used for wound infections. Aeromonas must be suspected as a pathogen in all wounds occurring in fresh water if proper treatment is to be initiated.


[Technical problems in achieving continence after radical retropubic prostatectomy by the "digitoclasia" technique].
Radical prostatectomy today has become a frequent operation in all urology wards. An increasing attention is nowadays paid to the question of post-operation continence, which is considered a fundamental aspect for a good quality of life. The Authors propose two variations to the Walsh's technique: conservation of the distal sphincter obtained by "digitoclasic" isolation of the same and conservation of the proximal sphincter obtained by means of a personal preparation technique of the vesical neck and anastomosis of the same to the urethral stump. The record of cases, not large enough, and in particular some initial failures occurred during the finalization phase of the technique, do not yet allow to draw final conclusions.


Evaluation of protein intake by dietary diaries and urea-N excretion in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.
In 1988 a European multicentre, randomized trial was started in order to analyse the influence of protein intake on the progression of chronic renal failure in children. Compliance to the dietary prescriptions, i.e. protein intake, was checked by written dietary diaries and in addition by urinary urea-N excretion. This provided a unique chance to compare both methods in non-hospitalized children. Of a total of 200 patients 123 were selected, in whom at least 4 consecutive dietary diaries plus 4 completely collected 24-hour urine samples were available. Whereas urea-N excretion and simultaneously recorded protein intake did not correlate well, mean urinary urea-N excretion and mean protein intake of at least 4 observations in each patient correlated highly (r = 0.803, p = 0.0001). The difference between protein-N intake and urea-N excretion was not a constant amount of 0.031 g/kg/day as proposed by Maroni et al. [1985] but figured at 0.085 +/- 0.061 g/kg/day and was highly correlated to protein intake (r = 0.839, p = 0.0001). The correlation of protein intake and urea-N excretion was best described by the formula: protein-intake (g/kg/day) = (urea-N excretion [g/kg/day]x 15.39) -0.8 or protein intake (g/kg/day) = urea-N excretion (g/kg/day) x 9.5. Maroni's formula underestimated the high protein intake of young children. In only a few patients dietary diaries severely underestimated protein intake as compared to calculation by urea-N excretion.(ABSTRACT TRUNCATED AT 250 WORDS)


Metabolic reprogramming of the tumor.
Cancer is classically considered as a genetic and, more recently, epigenetic multistep disease. Despite seminal studies in the 1920s by Warburg showing a characteristic metabolic pattern for tumors, cancer bioenergetics has often been relegated to the backwaters of cancer biology. This review aims to provide a historical account on cancer metabolism research, and to try to integrate and systematize the metabolic strategies in which cancer cells engage to overcome selective pressures during their inception and evolution. Implications of this renovated view on some common concepts and in therapeutics are also discussed.


Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer.
This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.


Clinical evaluation of laparoscopic-assisted radical vaginal hysterectomy with pelvic and/or paraaortic lymphadenectomy.
To report our experience with radical laparoscopic-assisted vaginal hysterectomy (LAVH) with bilateral pelvic and/or paraaortic lymphadenectomy. Retrospective review (Canadian Task Force classification III). University-affiliated hospital. Fifty-two women with invasive carcinoma of the cervix, stage Ib1, smaller than 3 cm. Radical LAVH with pelvic and/or paraaortic lymphadenectomy. Total operating time ranged from 230 to 650 minutes (mean 380 min). Major surgical complications were two cases of ureter injury, two cases of ureteral stricture, and one case of hematoma at the cannula site. Two cases were converted to laparotomy due to incomplete hemostasis of the uterine artery and obturator vein. The mean hemoglobin decrement was 1.7 g/dl the day after operation. Thirty patients received blood transfusion (mean 1.8 pints). Average numbers of pelvic and paraaortic lymph nodes removed were 27.7 (range 9-63) and 22.1 (range 6-52), respectively. After surgery, patients passed gas in 2.2 days and self-voided in 18.4 days on average. One woman had pelvic recurrence at 26 months after surgery. One died from brain metastasis 10 months after surgery. This technique is feasible for treatment of early cervical carcinoma. An experienced surgeon could shorten operating time and reduce complications.


Effects of LTP-inducing tetanic stimulations of the perforant path on the commissural inhibition and facilitation of dentate granule cell discharge.
Effects of diazepam (1 mg/kg, i.p.) on the commissural influences on granule cells were first examined to further assess its GABAergic inhibitory mechanism. Whereas the commissural inhibition at an interval of 5-8 ms of the contralateral dentate-perforant path (CP) combined stimulus was not enhanced by diazepam, the commissural facilitation at a CP interval of 11-20 ms was reduced, suggesting that the GABAergic inhibition is involved in rather a part of the commissural facilitation at a CP interval of 11-20 msec than a part of the 'commissural' inhibition at a shorter CP interval. Based on the results of diazepam, effects of high-frequency stimulations of the perforant path on the commissural inhibition of dentate granule cells were then examined, in relation to their effects on the dentate paired-pulse depression. These stimulations produced the long-term potentiation of the perforant path-dentate excitatory synapse and significant reduction of the paired-pulse depression. The commissural inhibition at a CP interval of 5-8 ms remained unchanged following tetanization. The commissural facilitation at a CP interval of 11-20 ms was, however, slightly enhanced by tetanic stimulations and a statistical significance was obtained at a CP interval of 19 ms. These results imply that tetanic stimulations of the perforant path selectively reduce the GABAergic component of the commissural inhibition, as well as that of the paired-pulse depression.


Partial purification and characterisation of a 31 kDalton putative enkephalin precursor from guinea pig striatum.
The presence of several putative precursors for Met-enkephalin (ME) and Leu-enkephalin (LE) has been demonstrated in guinea pig striatal extracts. The major high molecular weight (Mr) species (31000) contained 9% of the total ME-immunoreactivity (IR) after digest. This species has been partially purified and characterized using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and nitrocellulose blotting techniques as well as highly specific radioimmunoassay (RIA) for ME, LE and ME-Arg6-Phe7.


Degenerative scoliosis. Options for surgical management.
Adult degenerative scoliosis patients present a challenge in trying to achieve the greatest benefit with the least amount of intervention. Tailoring the treatment to the severity of the symptoms and the deformity appears to be vital. Full understanding of the deformity in the coronal and sagittal planes as well as the neural impingement can guide one to the appropriate intervention. The first operation is critical in providing the best prognosis for the long term. Decompression alone is performed in patients with small magnitudes of scoliosis and minimal lateral listhesis. Decompression and posterior fusion with instrumentation is performed on patients with moderate deformity and lateral listhesis, but a balanced sagittal plane. The more technically challenging and larger operation, a combined anterior and posterior fusion with instrumentation, is reserved for those patients with not only moderate to severe curves, but also coronal and sagittal imbalance. Performing a smaller operation on these patients may not only be short-lived but may also start a series of higher-risk revisions. There is a distinct lack of studies identifying and documenting the risks, morbidity, and reoperation rates in this patient population as compared with other deformity groups. Treatment of degenerative scoliosis patients presents a challenge that is only growing larger in numbers with the aging population.