Proteomics analysis reveals multiple regulatory mechanisms in response to selenium in rice.
Selenium (Se) shows both beneficial and toxic effects on plant growth. Rice (Oryza sativa L.) seedlings cultivated under lower concentrations of sodium selenite showed enhanced growth, whereas higher concentrations of sodium selenite repressed seedling growth. To acquire detailed regulatory mechanisms underlying these effects, a comparative proteomics study using 2-dimensional gel electrophoresis and MALDI-TOF/TOF MS was performed. By comparison of gel images between Se treatments and control, 66 and 97 differentially expressed proteins were identified in shoot and root, respectively under at least one of the Se treatment concentrations. Gene Ontology and Clustering analysis reveal primary metabolism, photosynthesis and redox homeostasis are the most highly affected biological processes by Se treatments. Lower Se treatments (2 and 6 mg/L sodium selenite) activated antioxidative system, enhanced photosynthesis and primary metabolism. However, higher Se treatment (10mg/L sodium selenite) damaged photosynthesis apparatus, inhibited photosynthesis and primary metabolism. Protein ubiquitination and phosphorylation may also play important roles in Se response in rice. In conclusion, our study provided novel insights into Se response in rice at the proteome level, which are expected to be highly useful for dissecting the Se response pathways in higher plants and for producing Se enriched rice cultivars in the future.


The phylogeny of SARS coronavirus.
Different tree-building methods consistently place the SARS corona-virus (SARS-CoV) as a basal Group 2 coronavirus rather than as an ungrouped species as concluded by others. Detailed comparisons of the SARS-CoV genomic sequence with those of six other coronaviruses failed to find evidence of recombination or genomic rearrangement using computational methods designed for that purpose.


Investigating the Main Causes of Conflicts and the Management Strategies That Are Used by Healthcare Professionals: The Case of General Hospital of Arta.
Employees in healthcare systems are often conflict in the workplace due to the high-pressure environment and the diversity between different departments. The aim of the study was not only to investigate the main causes of creation of conflicts but also investigate conflict management strategies health professionals use in a public hospital. This is a cross-sectional study. An anonymous questionnaire was used on a sample of 25 physicians and 95 nurses. Conflicts exist between colleagues and other professional groups. The most common management strategy is to avoid conflict, and second-place behavior such as compromise and negotiation for mutual benefit come along. The results of the organizational causes of conflicts have shown that important factors are the workload, the commands received by more than one supervisor, their reward, and the fact that their present work does not look like as what they had in mind about ideal work. Finally, the results on the causes related to employee expectations have shown that significant causes in this direction are the differences in the level of education, the unfair rewards among the various professional groups are that they do not have common professional expectations with other professional groups and that professional development is not related to their expectations. The most popular proposals for conflicts solutions are nondiscrimination between the healthcare professionals, a fair approach to reward and punishment, communication and cooperation in the organization/hospital, establish a clear division of responsibilities, and establish professional management and the departments have to be autonomous.


Clinical Characteristics and Treatment Response to Lisdexamfetamine Dimesylate Versus Placebo in Adults With Binge Eating Disorder: Analysis by Gender and Age.
To describe clinical characteristics and lisdexamfetamine dimesylate (LDX) treatment effects, based on gender and age, in adults diagnosed with moderate to severe binge eating disorder (BED). Adults diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined BED of moderate to severe severity were randomized to 12 weeks of dose-optimized LDX (50 or 70 mg) or placebo in 2 studies (conducted from November 26, 2012, to September 25, 2013 [study 1] and from November 26, 2012, to September 20, 2013 [study 2]). These post hoc analyses pooled data by gender (men vs women) and age (< 40 vs ≥ 40 years) across studies; reported P values are nominal (descriptive and unadjusted). The pooled safety analysis and full analysis sets included 745 and 724 participants, respectively (men, n = 105 and n = 97; women, n = 640 and n = 627; < 40 years, n = 398 and n = 386; ≥ 40 years, n = 347 and n = 338). Across subgroups, most participants had a body mass index ≥ 30 kg/m² (63.0%-75.5%). The mean baseline number of binge eating days/wk was comparable across gender (4.6-4.7) and age (4.6-4.9), as was Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) total score (gender, 20.42-21.70; age, 21.40-21.63). Least squares mean (95% CI) treatment differences nominally favored LDX in all subgroups (all P < .001) for changes from baseline in binge eating days/wk at weeks 11-12 and in Y-BOCS-BE total score at week 12; no interactions by gender or age were reported. Consistent with the overall profile of LDX, across all subgroups LDX was associated with higher frequencies of treatment-emergent adverse events than placebo and with increases in blood pressure and pulse. Across gender and age, participants exhibited comparable clinical characteristics and responses to dose-optimized LDX compared with placebo. ClinicalTrials.gov identifiers: NCT01718483 and NCT01718509.


Social Determinants of Alcohol and Other Drug Misuse Among Women Living with HIV in Economically Underserved Communities in Cape Town, South Africa: A Cross-Sectional Study.
This study aimed to understand how social determinants-the economic and social factors that affect health and well-being-are associated with self-reported and biological alcohol and other drug misuse in South Africa among women living with HIV. Logistic regression analyses were performed using baseline data from an implementation science trial conducted from 2015 to 2018 with 480 Black and Coloured women who were living with HIV and reported recent alcohol or other drug misuse. Educational attainment, type of housing, access to running water, food insecurity, and housing instability were examined. Women with higher education had reduced odds of any drug misuse-both biological (aOR: 0.53; 95% CI: 0.33-0.84) and self-reported (aOR: 0.37; 95% CI: 0.22-0.64). Women living in formal housing had increased odds of a positive alcohol screening test (aOR: 1.92; 95% CI: 1.16-3.18) and women with housing instability had increased odds of self-reported alcohol misuse-daily (aOR: 1.99; 95% CI: 1.18-3.35) and weekly (aOR:1.91; 95% CI: 1.19-3.07). Food insecurity was associated with reduced odds of self-reported alcohol misuse (aOR: 0.40; 95% CI: 0.25-0.64) and increased odds of self-reported drug misuse (aOR: 2.05; 95% CI: 1.16-3.61). These findings indicate the complexity of the relationship between social determinants and alcohol and other drug misuse, and may have implications for addressing social and structural determinants as part of multilevel interventions focused on reducing alcohol and other drug misuse among key populations of women in South Africa.


[Levosimendan. Clinical indications of a new vasoactive substance].
Levosimendan is a recently developed drug which is not yet approved for clinical routine use in Germany. The clinical use is limited to a few selected cases and it has been used as a salvage therapy in patients with severe heart insufficiency. As a potent inodilator it has been given to patients with severe heart failure, when all other therapeutic options have failed. However, in some European countries levosimendan is used in clinical routine situations and the European Society of Cardiologists has included the drug in their guidelines for treatment of acute heart failure. The following article describes the main pharmacological characteristics of levosimendan and summarises the indications for this new drug for physicians working in the field of anaesthesia or intensive care.


Phenoxybenzamine in neurogenic bladder dysfunction after spinal cord injury. I. Voiding dysfunction.
Phenoxybenzamine is a welcomed adjunct in the pharmacologic management of patients with neurogenic bladder dysfunction resulting from spinal cord trauma. Side effects are infrequent. Bladder balance was predictably and effectively achieved and maintained in patients with 1) lower motor neuron lesions, 2) upper motor neuron lesions and coexisting autonomic dysreflexia and 3) intact sympathetic innervation and upper motor neuron bladders. The response was unpredictable in patients with upper motor neuron lesions without coexisting dysreflexia.


N-Terminal pyroglutamate formation of Aβ38 and Aβ40 enforces oligomer formation and potency to disrupt hippocampal long-term potentiation.
Pyroglutamate (pGlu)-modified amyloid peptides have been identified in sporadic and familial forms of Alzheimer's disease (AD) and the inherited disorders familial British and Danish Dementia (FBD and FDD). In this study, we characterized the aggregation of amyloid-β protein Aβ37, Aβ38, Aβ40, Aβ42 and ADan species in vitro, which were modified by N-terminal pGlu (pGlu-Aβ3-x, pGlu-ADan) or possess the intact N-terminus (Aβ1-x, ADan). The pGlu-modification confers rapid formation of oligomers and short fibrillar aggregates. In accordance with these observations, the pGlu-modified Aβ38, Αβ40 and Αβ42 species inhibit hippocampal long term potentiation of synaptic response, but pGlu-Aβ3-42 showing the highest effect. Among the unmodified Aβ peptides, only Aβ1-42 exhibites such propensity, which was similar to pGlu-Aβ3-38 and pGlu-Aβ3-40. Likewise, the amyloidogenic peptide pGlu-ADan impaired synaptic potentiation more pronounced than N-terminal unmodified ADan. The results were validated using conditioned media from cultivated HEK293 cells, which express APP variants favoring the formation of Aβ1-x, Aβ3-x or N-truncated pGlu-Aβ3-x species. Hence, we show that the ability of different amyloid peptides to impair synaptic function apparently correlates to their potential to form oligomers as a common mechanism. The pGlu-modification is apparently mediating a higher surface hydrophobicity, as shown by 1-anilinonaphtalene-8-sulfonate fluorescence, which enforces potential to interfere with neuronal physiology.


An extra-adrenal sodium-retaining factor in congestive heart failure.
The extra-adrenal sodium-retaining factor was first described in Circulation Research in 1964. This factor increases the responsiveness of the renal tubules to aldosterone in heart failure, and marked sodium retention occurs with resultant edema or ascites. Evidence for the extra-adrenal sodium-retaining factor is presented in two models of experimental heart failure in dogs and in dogs with thoracic caval constriction and a low cardiac output. Since the nature of this sodium-retaining factor remains unknown, several of the recently discovered factors that influence kidney function and that might alter the responsiveness of the renal tubules to a mineralocorticoid are described. These factors include atrial natriuretic peptide, nitric oxide, 11 beta-hydroxysteroid dehydrogenase activity, the endothelins, and the intrarenal tissue renin-angiotensin system. It is suggested that the nature and action of the sodium-retaining factor be reinvestigated in lieu of the new knowledge of kidney function. The applicability of newly developed experimental models of heart failure for study of the extra-adrenal factor is discussed; these include coronary artery ligation in rats, cardiac pacing in the dog, and application of transmyocardial direct current shock to local myocardial areas in dogs.


[Are There Segmental Differences of Lumbar Spondylodesis? - Comparison of the Segments L IV/V and L V/S I in Patients with Transforaminal Lumbar Intercorporal Fusion (TLIF)].
The aim of this study was to report surgical results with open TLIF (transforaminal lumbar intervertebral fusion) of segment L V/S I, in comparison with TLIF of segment L IV/V. 60 patients with degenerative spine disease were operated with TLIF spondylodesis and followed up in a clinical and radiological study. 30 patients were operated in segment L IV/V (group 1) and another 30 in segment L V/S I (group 2). These patients were followed up 2 weeks and 12 months after surgery, by means of a clinical examination and questionnaires on pain (visual analogue scale) and quality of life (Oswestry score). The rate of intra- and postoperative complications was 5 % in all 60 patients; the fusion rate was 100 %. In all patients, a 70 % improvement in back pain, leg pain and quality of life was achieved after 12 months. For leg pain and quality of life, a significantly better result was seen in group 1 than in group 2 two weeks after the operation. This may be explained by reversible dysaesthesias in 3 patients in group 2. In 2 patients in group 2, it was necessary to convert from TLIF to ALIF (anterior lumbar interbody fusion). Directly after the operation, the mean intervertebral height was 8.2 mm in group 1 and 7.3 mm in group 2, in comparison with 7.7 mm and 6.8 mm after one year, respectively. In patients with contraction osteochondrosis in segment L V/S I, spondylodesis in segment L V/S I is - for anatomical reasons - more likely to be linked to reversible nerve irritations than with segment L IV/V. In some cases, conversion from TLIF on ALIF is necessary. In patients with degenerative spine disease, TLIF in segments L IV/V and L V/S I is absolutely accepted as a safe and up-to-date procedure.


Dependence of fractal dimension of DLCA clusters on size of primary particles.
It is well known that clusters generated from colloidal aggregation driven by Brownian motion are typical fractal objects with the fractal dimension in the range of 1.75-1.85 under the diffusion-limited cluster aggregation (DLCA) conditions. In this work, we review and analyze the values of the fractal dimension for DLCA clusters experimentally determined in the literature. It is found that the value of the fractal dimension decreases significantly as the primary particle radius increases. Then, we have properly designed the DLCA experiments, using different radii of the primary particles, and determined the fractal dimensions of the generated clusters. Our results have well confirmed that the fractal dimension indeed decreases as the particle radius increases. To explore the mechanism leading to such dependence, we have performed intense computations through the full T-Matrix theory, and we conclude that this is not related to the effect of the intra-cluster multiple scattering on the slope of the scattering structure factor. The large fractal dimensions of the clusters generated by very small nanoparticles could be explained by thermal restructuring due to their low bonding energies, but no clear explanation can be given for the small fractal dimensions of the clusters made of large particles.


Role of c-Abl kinase in DNA mismatch repair-dependent G2 cell cycle checkpoint arrest responses.
Current published data suggest that DNA mismatch repair (MMR) triggers prolonged G(2) cell cycle checkpoint arrest after alkylation damage from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by activating ATR (ataxia telangiectasia-Rad3-related kinase). However, analyses of isogenic MMR-proficient and MMR-deficient human RKO colon cancer cells revealed that although ATR/Chk1 signaling controlled G(2) arrest in MMR-deficient cells, ATR/Chk1 activation was not involved in MMR-dependent G(2) arrest. Instead, we discovered that disrupting c-Abl activity using STI571 (Gleevec, a c-Abl inhibitor) or stable c-Abl knockdown abolished MMR-dependent p73alpha stabilization, induction of GADD45alpha protein expression, and G(2) arrest. In addition, inhibition of c-Abl also increased the survival of MNNG-exposed MMR-proficient cells to a level comparable with MMR-deficient cells. Furthermore, knocking down GADD45alpha (but not p73alpha) protein levels affected MMR-dependent G(2) arrest responses. Thus, MMR-dependent G(2) arrest responses triggered by MNNG are dependent on a human MLH1/c-Abl/GADD45alpha signaling pathway and activity. Furthermore, our data suggest that caution should be taken with therapies targeting c-Abl kinase because increased survival of mutator phenotypes may be an unwanted consequence.


Psychological and Situational Factors Affecting Dropout from Regular Visits in Diabetes Practice: The Japan Diabetes Outcome Intervention Trial-2 Large Scale Trial 004 (J-DOIT2-LT004).
This study explored the psychological and situational factors affecting dropout from regular visits to diabetes care using data obtained from the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) Large-scale Trial (LT). A total of 2,031 patients with type 2 diabetes who participated in the J-DOIT2-LT were included in the analysis. Responses to a baseline questionnaire with 17 items asking about the experience of dropout from regular visits in diabetes care and its reasons were analyzed using principal component analysis, and factors related to dropout were extracted. Using Cox regression analysis, the association of these factors with the incidence of dropout was investigated. The mean age of the 2,031 patients was 56.4 ± 5.9 years and 742 (36.5%) were women. They were followed for a median of 392 days, and 125 patients dropped out from regular visits during the follow-up period. In the principal component analysis of the questionnaire, there were four latent factors with eigenvalues of >1.0, which were labeled as "negative perceptions for regular visits," "social pressure," "lack of perceived necessity," and "environmental obstacles" based on the retained items. The Cox regression analysis demonstrated that patients with high scores of "lack of perceived necessity" and "environmental obstacles" had a significantly increased risk of dropout from regular visits. The present study revealed psychological and situational factors related to dropout, which may be useful for detecting patients at high risk of dropout. Effective measures focusing on such patients to prevent dropouts should be investigated in future studies (The trial registration number: UMIN000002186, registered at the University Hospital Medical Information Network-Clinical Trials Registry).


Structural changes in the thin filament during activation studied by X-ray diffraction of highly stretched skeletal muscle.
The actin layer-lines were recorded from a frog semitendinosus muscle stretched to a sarcomere length greater than 4.4 microM. On activation of the muscle, the equator, the second layer-line at 1/18 nm-1 and the 5.9 nm layer-line increased in integrated intensity. On the other hand, the integrated intensity of the first layer-line at 1/36 nm-1 decreased markedly on activation. This decrease was not fully attributable to shifts of tropomyosin strands and therefore suggested a structural change in the actin subunit. The decrease may account for the apparent lack of an intensity increase of this layer-line on activation at normal muscle lengths where attachment of myosin heads to actin increases the intensities of other layer-lines.


A short peptide encoded by long non-coding RNA small nucleolar RNA host gene 6 promotes cell migration and epithelial-mesenchymal transition by activating transforming growth factor-beta/SMAD signaling pathway in human endometrial cells.
Endometrial dysfunction is closely correlated with the development of multiple severe gynecological disorders including intrauterine adhesion. Accumulating evidence supports that some long non-coding RNAs (lncRNAs) have peptide-coding potential. In this text, the peptide-coding ability of lncRNA SNHG6 was examined. Also, the effects of an SNHG6-encoded peptide on the viability and migration of human endometrial stromal cells (hESCs) and human endometrial epithelial cells (hEECs) and related molecular mechanisms were explored. The peptide-encoding potential of SNHG6 was predicted by FuncPEP and getorf databases and validated by western blot assay. Cell viability was tested by cell counting kit-8 assay. Cell migratory ability was examined by wound healing and transwell migration assays. Protein levels of genes were measured by western blot assay. Prediction analysis suggested that SNHG6 had the potential peptide-coding ability and multiple open-reading frames (ORFs). Western blot validated that SNHG6 ORF#1 and ORF#2 could translate into short peptides. SNHG6 ORF#2 overexpression facilitated cell migration and epithelial-mesenchymal transition (EMT) in hESCs and hEECs, while these effects were abrogated by transforming growth factor-beta (TGF-β)/SMAD signaling inhibitor GW788388. Moreover, GW788388 inhibited the increase of p-SMAD2 and p-SMAD3 levels induced by SNHG6 ORF#2 in hESCs. SNHG6 ORF#2-encoded peptide did not influence endometrial stromal and epithelial cell viability. LncRNA SNHG6 ORF#1 and ORF#2 could translate into small peptides and SNHG6 ORF#2 overexpression promoted cell migration and EMT by activating the TGF-β/SMAD pathway in hESCs and hEECs, suggesting the potential roles of SNHG6-encoded peptides in the development of endometrial stromal and epithelial cells and related gynecological diseases.


Identification of animal species by protein radioimmunoassay of bone fragments and bloodstained stone tools.
In forensics and archaeology, it is important to distinguish human from animal remains and to identify animal species from fragmentary bones and bloodstains. We report blind tests in which a protein radioimmunoassay (pRIA) was used to identify the species of six bone fragments lacking morphological specificity and 43 bloodstained lithic tools, knapped experimentally and soaked in blood of known animal and human origin. The submitters of the bone fragments and the bloodstained tools each listed a number of possible species, from which the testers selected the best match with the pRIA results. All six bone fragments were correctly identified: three humans, a deer, a dog, and a cow. Forty-three tools were stained with blood from a wide variety of species including ungulates, carnivores, a fish, and a bird. On 40 of these 43, at least one species (or blood-free control) was identified correctly. Some of the tools were stained with blood of two different species. A mixture of sheep and musk ox blood was correctly identified; in several other mixtures, only a single species was detected. Two tools with human blood and one with human sweat were correctly reported as human. There was a single false positive (one of three controls reported as weakly bovine) and no false negatives. We conclude that the pRIA technique shows a high degree of accuracy in discriminating human from animal bone fragments and bloodstains and in identifying animal species.


Curcumin inhibits the migration and invasion of mouse hepatoma Hca-F cells through down-regulating caveolin-1 expression and epidermal growth factor receptor signaling.
Mouse hepatoma cellular carinoma cell line (Hca-F) cells have highly invasive and lymphatic metastasis potential in vitro and in vivo. Curcumin (diferuloylmethane) is an active component of the spice turmeric and has a diversity of antitumor activities. However, there is no available information to address the effects of curcumin on migration and invasion of mouse hepatoma Hca-F cells. In this study, we found that curcumin exerted a concentration- and time-dependent inhibitory effect on the migration and invasion of Hca-F cells in vitro. Curcumin inhibited the expression of the tumor promoter caveolin-1 (Cav-1) in Hca-F cells. Up-regulation of Cav-1 expression by pcDNA3.1/Cav-1 plasmid was able to reverse the curcumin-induced antimigration and anti-invasion effects in vitro. Curcumin down-regulated the expression of cluster of differntiation (CD)147, matrix metalloproteinase 2, and matrix metalloproteinase 9 and inhibited the phosphorylation of epidermal growth factor receptor (EGFR), the phosphoinositilde 3-kinase (PI3K)/protein kinase B (Akt), p38 mitogen-activated protein kinase (MAPK), and p44/42MAPK in Hca-F cells. Taken together, our findings suggest that curcumin can suppress the migratory and invasive ability of mouse hepatoma Hca-F cells, and this action is mediated through a novel mechanism involving inactivation of Cav-1 and EGFR signaling pathways.


Limbal stem cell deficiency and ocular phenotype in ectrodactyly-ectodermal dysplasia-clefting syndrome caused by p63 mutations.
To describe the ocular phenotype in patients with ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (MIM#604292) and to determine the pathogenic basis of visual morbidity. Retrospective case series. Nineteen families (23 patients) affected by EEC syndrome from the United Kingdom, Ireland, and Italy. General medical examination to fulfill the diagnostic criteria for EEC syndrome and determine the phenotypic severity. Mutational analysis of p63 was performed by polymerase chain reaction-based bidirectional Sanger sequencing. All patients with EEC syndrome underwent a complete ophthalmic examination and ocular surface assessment. Limbal stem cell deficiency (LSCD) was diagnosed clinically on the basis of corneal conjunctivalization and anatomy of the limbal palisades of Vogt. Impression cytology using immunofluorescent antibodies was performed in 1 individual. Histologic and immunohistochemical analyses were performed on a corneal button and corneal pannus from 2 EEC patients. The EEC syndrome phenotypic severity (EEC score), best-corrected Snellen visual acuity (decimal fraction), slit-lamp biomicroscopy, tear function index, tear breakup time, LSCD, p63 DNA sequence variants, impression cytology, and corneal histopathology. Eleven heterozygous missense mutations in the DNA binding domain of p63 were identified in all patients with EEC syndrome. All patients had ocular involvement and the commonest was an anomaly of the meibomian glands and lacrimal drainage system defects. The major cause of visual morbidity was progressive LSCD, which was detected in 61% (14/23). Limbal stem cell deficiency was related to advancing age and caused a progressive keratopathy, resulting in a dense vascularized corneal pannus, and eventually leading to visual impairment. Histologic analysis and impression cytology confirmed LSCD. Heterozygous p63 mutations cause the EEC syndrome and result in visual impairment owing to progressive LSCD. There was no relationship of limbal stem cell failure with the severity of EEC syndrome, as classified by the EEC score, or the underlying molecular defect in p63. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Influence of long-term inundation and nutrient addition on denitrification in sandy wetland sediments from Poyang Lake, a large shallow subtropical lake in China.
Wetlands at aquatic/terrestrial transition zones may play an important role in nitrogen removal due to the denitrification during inundation events. In this study, air-dried sandy sediment cores from Poyang Lake's wetlands were continuously inundated in the laboratory to investigate the rate, efficiency, and pattern of denitrification at the sediment-water interface (SWI). Denitrification rates responded to inundation in three stages: an adaptive period, a rapid growth period, and a stable period. The average denitrification rates during these stages were 52.62 ± 11.33 μmol N2 m-2 h-1, 115.74 ± 58.40 μmol N2 m-2 h-1 and 187.74 ± 16.44 μmol N2 m-2 h-1, respectively. Multiple regression analysis showed that inundation duration was the most important factor controlling denitrification rates at the SWI rather than nitrate concentrations, which were also positively correlated with denitrification rates. Changes in water content, oxidation-reduction potential (Eh), and pH in the surface sediments, which were consequences of inundation, significantly influenced the denitrification rate (p < 0.05). The N2O/(N2O + N2) flux ratio in denitrification production varied from 1.61% during the adaptive period to 0.03% in the stable period, suggesting that continuous inundation of sediments in aquatic-terrestrial transition zones of Poyang Lake could decrease the proportion of greenhouse gases (N2O). Since inputs of bioavailable nitrogen and phosphorus to Poyang Lake have increased in recent decades, the influence of elevated nutrients on denitrification under continuous inundation were also evaluated by simulation experiments. The results showed that increased nitrate or phosphate loading stimulate denitrification rates in sandy sediments during the inundation process. The addition of nitrate plus phosphate showed a stronger influence on denitrification than single nutrient additions. This study facilitates understanding of the influence of continuous inundation and elevated nutrients on denitrification in sandy sediments in aquatic/terrestrial transition zones.


A vector that expresses VP28 of WSSV can protect red swamp crayfish from white spot disease.
White spot disease caused by white spot syndrome virus (WSSV) leads to devastating losses in shrimp farming. The WSSV envelope protein VP28, can be used as subunit vaccines that can efficiently protect shrimp against WSSV disease. However, the function of the envelope protein VP19 was not confirmed, some researches found that VP19 could protect shrimp against WSSV, and other reports found it no any protection. To detect the functions of VP28 and VP19 and find a method to prevent this disease in red swamp crayfish Procambarus clarkii, we constructed the plasmid vectors pIevp28 and pIevp19, which contains the ie1 promoter and coding region of vp28 or vp19 of WSSV, respectively. The results of quantitative real-time PCR and western blot showed that the injected vectors could transcribe corresponding mRNAs and translate to the protein VP28 or VP19 in the crayfish. The vp28 or vp19 signal was detected on the third day post injection, and maintained its expression for 30days. The mortality of the crayfish with pIevp28 showed obvious decline compared with the controls (pIe and PBS injection). However, pIevp19 seems did not affect the mortality of the crayfish compared with the controls. Furthermore, only VP28 was found tightly bound to the host haemocytes under immunocytochemistry. The results suggest that the VP28 protein might protect shrimp from the virus through competitive inhibition. We also found that oral administration of Escherichia coli with pIevp28 could protect crayfish from white spot disease, but the E. coli with pIevp19 was not. Therefore, we think that oral administration of bacteria with pIevp28 is a potentially easy therapeutic way against white spot disease in aquaculture.


Therapeutic leukocyte reduction for acute and chronic myeloid leukemias: A 4-year experience from an oncology center in India.
Hyperleukocytosis (HL) and leukostasis seen in myeloid leukemias are a medical emergency. We present a case series of ten such patients in a 4-year period. Sixteen therapeutic leukocyte reduction (TLR) were done in ten cases along with other supportive measures. The American Society for Apheresis supports the routine implementation of TLR in cases of HL secondary to myeloid leukemias with signs of leukostasis. The procedures were performed on the intermittent flow cell separator after discussion with the treating physician about patient's condition. Clinical, demographic, analytical, and technical variables were reviewed retrospectively and the patients were followed up at the end of 4 years. Descriptive analysis was performed for all variables, and relationships between quantitative variables and categorical variables were determined by applying the Student's t-test. The mean age of presentation was 34 years. Priapism was the most common symptom followed by respiratory distress and neurological disturbances. After an average of 1.6 TLR procedures, the mean leukocyte count reduction achieved was 39.9% along with symptomatic relief. The mean survival at 4-year follow-up was 12.8 months and the overall mortality was 20%. Acute myeloid leukemia patients presented with lower mean platelet counts compared to chronic myeloid leukemia patients; however, the platelet loss in the final product was minimized. TLR is a safe and effective therapy for leukoreduction in hematological malignancies in our experience.


Fat not so bad? The role of ketone bodies and ketogenic diet in the treatment of endothelial dysfunction and hypertension.
The ketogenic diet (KD), a high-fat, low-carbohydrate dietary approach that is based on the induction of extensive ketone bodies (KB) metabolism, is recently receiving a lot of attention due to its application as effective intervention for multiple metabolic disorders including cardiovascular diseases. Despite its already established clinical use, especially in the treatment of drug-resistant epilepsy, GLUT1 deficiency syndromes and, in selected cases, obesity; the systemic impact of is not yet fully understood. Here, we discuss the evidence for and against the application of ketogenic diets, or ketone bodies precursors, in the etiology of hypertension and endothelial cells dysfunction. We attempt to identify the benefits and potential risks of chronic use of the ketogenic diet, also considering the molecular effects that KB exerts at multiple levels.


Norepinephrine regulation of fetal heart rate: multiple mechanisms of action.
Norepinephrine was infused intravenously for 30 minutes into chronically catheterized sheep fetuses averaging 133 days' gestation. At infusion rates of 3.9, 12, and 39 micrograms/min, heart rate initially decreased as much as 40 bpm and then gradually increased to 50 bpm above the control value by the end of the infusion. Thereafter, heart rate increased further, and by the end of a 30-minute recovery period, heart rate was still 66 bpm above the control value. In fetuses pretreated with either a ganglionic blocker or a parasympathetic blocker, norepinephrine caused a large and sustained rise in heart rate by 124 bpm, which declined rapidly when the infusion was terminated. These results suggest that circulating norepinephrine affects fetal heart rate by several mechanisms: a baroreceptor-mediated suppression, a direct stimulation by norepinephrine, a gradual weakening of the vagal and an increase in cardiac sensitivity to sympathetic stimulation. In addition, there appears to be a long-term positive correlation between fetal heart rate and circulating norepinephrine levels.


The impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian cysts: a prospective clinical study of 191 patients.
To investigate the impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian cysts and the possible mechanisms. A prospective study. Obstetrics and Gynecology Department of a university hospital. 191 patients with benign ovarian cysts undergoing ovarian cystectomy. Laparoscopic ovarian cystectomy using bipolar or ultrasonic scalpel electrocoagulation and laparotomic ovarian cystectomy using sutures after the excision of ovarian cysts. Follicle-stimulating hormone (FSH) assay and transvaginal ultrasound evaluating basal antral follicle number, mean ovarian diameter, and ovarian stromal blood flow velocity at day 3 of menstrual cycles 1, 3, 6, and 12 after surgery. When comparing the bipolar group and ultrasonic scalpel group with the suture group, a statistically significant increase of the mean FSH value was found in bilateral-cyst patients at 1-, 3-, 6-, and 12-month follow-up evaluations and in unilateral-cyst patients at the 1-month follow-up evaluation. Statistically significant decreases of basal antral follicle number and mean ovarian diameter were found during the 3-, 6-, 12-month follow-up evaluations as well as statistically significant decreases of peak systolic velocity at all of the follow-up evaluations. Electrocoagulation after laparoscopic excision of ovarian cysts is associated with a statistically significant reduction in ovarian reserve, which is partly a consequence of the damage to the ovarian vascular system.


A Missed Nasopharyngeal Foreign Body.
Nasopharyngeal foreign bodies are exteremely rare and early diagnosis and prompt removal is of paramount importance. A 31 years old woman presented with serous otitis media and nasal stiffness. After imaging and nasal endoscopy a missed chicken bone was removed from the nasopharynx. She had a previous history of foreign body ingestion with an unsuccessful esophageal endoscopy 5 years ago. Although rare, we should evaluate the whole upper aerodigestive tract in the endoscopy for foreign body swallowing.


Parental bonding and bulimic psychopathology: the mediating role of mistrust/abuse beliefs.
To determine whether the previously reported relationship between parental bonding and bulimic psychopathology is mediated by the development of unhealthy core beliefs. One hundred and two nonclinical women completed the Parental Bonding Instrument, the short form of the Young Schema Questionnaire, and the Bulimic Investigatory Test, Edinburgh. Mistrust/abuse beliefs were found to be a partial mediator in the relationship between paternal overprotection and the severity of bulimic attitudes. The findings suggest that the development of mistrust/abuse beliefs is important in determining the effect that paternal overprotection has on bulimic attitudes.


Calcitonin gene-related peptide promotes the wound healing of human bronchial epithelial cells via PKC and MAPK pathways.
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendritic cell function, stimulate proliferation of alveolar epithelial cells and mediate lung injury in mice. In this study, we investigated the effect of CGRP on the wound healing of human bronchial epithelial cells (HBECs) in vitro. The results showed that CGRP accelerated the recovery of wound area of monolayer HBECs in a dose-dependent manner. CGRP inhibited the lipopolysaccharide-induced apoptosis in HBECs. The percentage of S phase and G2/M phase was increased in HBECs after CGRP treatment. CGRP upregulated the expression of Ki67 in a dose-dependent manner. Some pathway inhibitors were used to investigate the signal pathway in which CGRP was involved. We found out that PKC pathway inhibitor (H-7) and MAPK pathway inhibitor (PD98059) could partially attenuate the effect of CGRP, which indicated that CGRP might promote the wound healing of HBECs via PKC and/or MAPK dependent pathway by accelerating migration and proliferation, and inhibiting apoptosis.


Enhancing substance abuse treatment evaluations: examining mediators and moderators of treatment effects.
This article considers ways in which the basic, comparative approach to evaluating treatment for substance abuse is sometimes enhanced. The general strategy has been to make treatment evaluation projects explanatory by embedding them in a theoretical framework. Using either a theory of the treatment process or of patient-treatment matching guide, the typical approaches for enhancing comparative treatment evaluations are to identify either mediators or moderators of treatment effects. In addition to addressing the basic question of "Does the treatment work or not work?" one can also ask in more explanatory evaluations: "How or why does the treatment work or not work?" and/or "For whom do treatments work or not work?" Variations of these questions that can be addressed in treatment process and patient-treatment interaction effect analyses are discussed. Particular attention is given to explaining (identifying mediators of) patient-treatment interaction effects. Some advantages of making treatment evaluations more explanatory are discussed.


Tankyrase Activity in Organs and Tissues of Mice.
Tankyrase, one of the NAD+ ADP-ribosyltransferases, is a target for drugs developed for their anticancer and other pharmacological activities. We designed an assay for estimation of the inhibition or activation of the enzyme in preclinical studies. In mice, the highest specific activity of tankyrase was observed in thymus, spleen, pancreas, and bone marrow. In murine liver, tankyrase is active in ontogenesis and during reparative regeneration; however, the basal activity is hardly detectable in normal liver and most of other organs of adult animals. We suggest that tankyrase is a part of the tissue growth and repair machinery, while its age-dependent inhibition, when an organism stops growing, turns on phenoptosis.


Quantitative determination of tolazoline in human serum by high performance liquid chromatography.
A micro high performance liquid chromatography assay is reported for the measurement of tolazoline in newborn infants. Pharmacokinetic data are presented for a single infant receiving tolazoline therapy. Tolazoline and the internal standard, clonidine, are extracted from alkaline serum into butylchloride/isopropanol (95/5). The organic layer is then back extracted with 50 mM phosphoric acid. A portion of the phosphoric acid layer is injected onto a 15-cm CN-bonded phase column. A mobile phase consisting of acetonitrile and phosphate buffer (pH 3) is used to elute tolazoline and the internal standard in less than 5 min. The effluent is monitored with a fixed wavelength detector at 214 nm. Using 50 microliters of serum, concentrations as low as 0.25 mg/L can be routinely determined with a coefficient of variation (CV) of 7.2%. However, when a 100-microliters sample is used, and the injection volume increased, a concentration of 0.05 mg/L can be routinely monitored with a CV of 1.2%. Interference from other drugs that are often used concurrently with tolazoline therapy was not observed.


An S-glutathiomimetic Provides Structural Insights into Stromal Interaction Molecule-1 Regulation.
Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca2+) sensing protein that regulates store-operated calcium entry (SOCE). In SOCE, STIM1 activates Orai1-composed Ca2+ channels in the plasma membrane (PM) after ER stored Ca2+ depletion. S-Glutathionylation of STIM1 at Cys56 evokes constitutive SOCE in DT40 cells; however, the structural and biophysical mechanisms underlying the regulation of STIM1 by this modification are poorly defined. By establishing a protocol for site-specific STIM1 S-glutathionylation using reduced glutathione and diamide, we have revealed that modification of STIM1 at either Cys49 or Cys56 induces thermodynamic destabilization and conformational changes that result in increased solvent-exposed hydrophobicity. Further, S-glutathionylation or point-mutation of Cys56 reduces Ca2+ binding affinity, as measured by intrinsic fluorescence and far-UV circular dichroism spectroscopies. Solution NMR showed S-glutathionylated-induced perturbations in STIM1 are localized to the α1 helix of the canonical EF-hand, the α3 and α4 helices of the non-canonical EF-hand and α6 and α8 helices of the SAM domain. Finally, we designed an S-glutathiomimetic mutation that strongly recapitulates the structural, biophysical and functional effects within the STIM1 luminal domain and we envision to be another tool for understanding the effects of protein S-glutathionylation in vitro, in cellulo and in vivo.


The neural hypothesis of muscular dystrophy. A review of recent experimental evidence with particular reference to the Duchenne form.
Recent observations are considered to provide further evidence for an abnormality involving motoneurones in DMD. The dystrophic process appears to take place in two stages of which the first occurs during early embryonic life. This stage is thought to involve faulty inductive actions of the neural tube upon mesoderm and upon itself. The neural consequences vary among individuals and are manifested as mental retardation; EEG abnormalities and losses of functioning motor units. While the first two abnormalities are non-progressive, a further loss of motor units, associated with striking reductions in the numbers of excitable muscle fibers, takes place in trunk and large limb muscles at 9--12 years. The latter process, the cause of which is uncertain, constitutes the second stage of DMD.


Identifying social mechanisms for the prevention of adolescent drinking and driving.
This study identifies social mechanisms that might help prevent youth from being involved in driving under the influence of alcohol (DUI) and riding with drinking drivers (RWDD). Data collected through telephone surveys with 1534 adolescents and young adults aged 15-20 years (mean=17.6, S.D.=1.6) in California, USA, were analyzed. Structural equation modeling analyses showed that DUI and RWDD were strongly related to drinking in unstructured situations, modeling of DUI by peers and parents, and perceived peer approval or disapproval of DUI. DUI outcome expectancies were indirectly related to DUI and RWDD through situational drinking. Parental monitoring and DUI law enforcement were also indirectly related to DUI and RWDD through DUI expectancies and other mechanisms. The findings, overall, suggest that parental influence remains important even through late adolescence. Parental monitoring, in particular, might help to reduce unstructured socializing with peers, drinking, and affiliation with peers who engage in DUI. Parental monitoring may also foster beliefs about the risks of DUI. Conversely, parents' own DUI behavior may normalize drinking and DUI behaviors, thus countering monitoring efforts.


Epidemiology of Untreated Psychoses in 3 Diverse Settings in the Global South: The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II).
Less than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the world. To compare demographic and clinical profiles of cohorts of cases and rates of untreated psychoses (proxy for incidence) across and within 3 economically and socially diverse settings in the Global South. Two hypotheses were tested: (1) demographic and clinical profiles of cases with an untreated psychotic disorder vary across setting and (2) rates of untreated psychotic disorders vary across and within setting by clinical and demographic group. The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II) comprises incidence, case-control, and cohort studies of untreated psychoses in catchment areas in 3 countries in the Global South: Kancheepuram District, India; Ibadan, Nigeria; and northern Trinidad. Participants were individuals with an untreated psychotic disorder. This incidence study was conducted from May 1, 2018, to July 31, 2020. In each setting, comprehensive systems were implemented to identify and assess all individuals with an untreated psychosis during a 2-year period. Data were analyzed from January 1 to May 1, 2022. The presence of an untreated psychotic disorder, assessed using the Schedules for Clinical Assessment in Neuropsychiatry, which incorporate the Present State Examination. Identified were a total of 1038 cases, including 64 through leakage studies (Kancheepuram: 268; median [IQR] age, 42 [33-50] years; 154 women [57.5%]; 114 men [42.5%]; Ibadan: 196; median [IQR] age, 34 [26-41] years; 93 women [47.4%]; 103 men [52.6%]; Trinidad: 574; median [IQR] age, 30 [23-40] years; 235 women [40.9%]; 339 men [59.1%]). Marked variations were found across and within settings in the sex, age, and clinical profiles of cases (eg, lower percentage of men, older age at onset, longer duration of psychosis, and lower percentage of affective psychosis in Kancheepuram compared with Ibadan and Trinidad) and in rates of untreated psychosis. Age- and sex-standardized rates of untreated psychoses were approximately 3 times higher in Trinidad (59.1/100 000 person-years; 95% CI, 54.2-64.0) compared with Kancheepuram (20.7/100 000 person-years; 95% CI, 18.2-23.2) and Ibadan (14.4/100 000 person-years; 95% CI, 12.3-16.5). In Trinidad, rates were approximately 2 times higher in the African Trinidadian population (85.4/100 000 person-years; 95% CI, 76.0-94.9) compared with the Indian Trinidadian (43.9/100 000 person-years; 95% CI, 35.7-52.2) and mixed populations (50.7/100 000 person-years; 95% CI, 42.0-59.5). This analysis adds to research that suggests that core aspects of psychosis vary by historic, economic, and social context, with far-reaching implications for understanding and treatment of psychoses globally.


Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro.
We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (K(m)) of 5.25 (SD 1.2) micromol.l(-1). Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (K(i)) of 12.4 (95% CI 4.65-20.06) micromol.l(-1). Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a K(i) of 94.3 (95% CI 55.01-133.5) micromol.l(-1). Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro.


Electron transfer and electrocatalytics of cytochrome c and horseradish peroxidase on DNA modified electrode.
A bio-interphase composed of DNA, cytochrome c (Cyt c) and horseradish peroxidase (HRP) was developed by layer-by-layer assembling Cyt c, DNA and Cyt c-HRP on biocompatible 11-mercaptoundecanoic acid--6-mercapto-1-hexanol modified gold electrode. The new bio-interphase was used as a model system to mimic the electron transfer and electrocatalytic performance of two proteins in living organisms. Results showed that the electron transfer rate at bi-protein bio-interphase was faster than those at the single protein bio-interphase, indicating a synergistic interaction between the two proteins occurred in the electron transfer. Moreover, the mixed proteins modified electrode exhibited good electrocatalytic response to reduction of hydrogen peroxide (H₂O₂) and oxygen (O₂), suggesting that it could be used as a sensor for H₂O₂ and O₂ detection. The properties of the bio-interphase, together with the bioelectrocatalytic activity, could make it useful in the development of bioelectronic devices, and investigation of electrochemistry of other heme proteins at functional interphase. It would also provide a new strategy for further study on the electron transfer of other multi-proteins in a bio-interphase and the development of biosensors.


TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation.
It has been reported that deletion of tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2, TIPE2) facilitates the activation of T-cell receptors. However, the role of TIPE2 in T-cell-mediated acute transplant rejection remains unclear. To illustrate the underlying cellular mechanisms, we transplanted BALB/c hearts into C57BL/6 wild-type (WT) or C57BL/6 mice deficient for TIPE2 (TIPE2-/-) and found that TIPE2-/- recipient mice showed significantly prolonged survival of heart allografts and suppressed maturation of CD11c+ dendritic cells (DCs), which largely abolished the activation and proliferation of alloreactive T cells and their cytotoxic activity. TIPE2-/- DCs increased CD4+CD25+Foxp3+CD127- regulatory T cells (Tregs)generation, likely by inhibiting DCs maturation and CD80 and CD86 expression. Administration of anti-CD25 abolished the allograft survival induced by TIPE2 deficiency. Moreover, TIPE2 deficiency increased IL-10 production in T cells and in recipient serum and allografts. Mechanistic studies revealed that TIPE2-/- restrained the maturation of DCs via inhibition of PI3K/AKT phosphorylation during alloantigen stimulation. Taken together, TIPE2 deficiency in recipient mice inhibited acute rejection by increasing Tregs generated by immature DCs. Thus, TIPE2 could be a therapeutic target for suppressing rejection in organ transplantation.


Role of substrate binding forces in exchange-only transport systems: I. Transition-state theory.
An analysis of transition-state models for exchange-only transport shows that substrate binding forces, carrier conformational changes, and coupled substrate flow are interrelated. For a system to catalyze exchange but not net transport, addition of the substrate must convert the carrier from an immobile to a mobile form. The reduction in the energy barrier to movement is necessarily paid for out of the intrinsic binding energy between the substrate and the transport site, and is dependent on the formation of two different types of complex: a loose complex initially and a tight complex in the transition state in carrier movement. Hence the site should at first be incompletely organized for optimal binding but, following a conformational change, complementary to the substrate structure in the transition state. The conformational change, which may involve the whole protein, would be induced by cooperative interactions between the substrate and several groups within the site, involving a chelate effect. The tightness of coupling, i.e., the ratio of exchange to net transport, is directly proportional to the increased binding energy in the transition state, a relationship which allows the virtual substrate dissociation constant in the transition state to be calculated from experimental rate and half-saturation constants. Because the transition state is present in minute amount, strong bonding here does not enhance the substrate's affinity, and specificity may, therefore, be expressed in maximum exchange rates alone. However, where substrates largely convert the carrier to a transport intermediate whose mobility is the same with all substrates, specificity is also expressed in affinity. Hence the expression of substrate specificity provides evidence on the translocation mechanism.


Ensemble approaches for improving HLA class I-peptide binding prediction.
Accurately predicting peptides binding to major histocompatibility complex (MHC) I molecules is of great importance to immunologists for elucidating the underlying mechanism of immune recognition and facilitating the design of peptide-based vaccine. Various computational methods have been developed for MHC I-peptide binding prediction, and several of them are reported to achieve high accuracy in recent evaluation on benchmark datasets. For attending the machine learning in immunology competition (MLIC) in prediction of human leukocyte antigen (HLA)-binding peptides, we (FudanCS) have made use of ensemble approaches to further improve the prediction performance by integrating the outputs of several leading predictors. Two ensemble approaches, PM and AvgTanh, have been implemented for attending MLIC. AvgTanh and PM achieved the fourth and the seventh out of all 20 submissions in MLIC in terms of the average AUC. In addition, AvgTanh was awarded the winner in the category of HLA-A*0101 of 9-mer. Overall, the competition results validate the effectiveness of ensemble approaches.


LD50 determination: objections to the method of Beccari as modified by Molinengo.
The efficiency of the method of Beccari as modified by Molinengo is compared with the sequential technique of Dixon and Mood. It is concluded that the sequential technique is less constrained, gives estimates that are less disperse and is simpler to analyze statistically than the regression of Beccari-Molinengo. Both techniques are comparable in the number of animals required, as well as in the time invested in each assay.


Ramp-rate dependent external work during ramp-load release in cardiac muscle.
When the load of frog cardiac muscle was decreased linearly from the maximum force to the resting force (ramp-load release), the muscle shortened with various velocities calculated from the instantaneous lengths, which showed the instantaneous force-velocity relationship. These velocities increased with the increase of the ramp rate. To study these dependency of ramp rate, the parameters obtained from Huxley model in 1957 during quick load-release were fixed throughout the calculations, but even if the shortening of the series elastic component (SEC) was taken into account, the model did not seem to explain these velocities. If the ramp rate was reduced, velocities were more decreased as expected, especially at smaller load, which suggested that the cross-bridges should bear some extra load. Thus the internal load was added in calculation. The velocities in the modified model well explained those measured even the ramp rate varied widely, especially in higher force. At lower force, the calculated velocities increased rapidly than those measured, mainly due to the shortening of SEC which were calculated from the initial shortening of quick release. On the force-sarcomere length plane, the calculated sum-force (internal-plus external-load) was almost linearly decreased versus length with the initial slope of 2.66 (mean). Adding the original dependency (= 1), the value of 3.66 was similar to 3.5 in skeletal muscle. The external work during the ramp-load release was also calculated and decreased with the increase of ramp rate, and showed the peak or plateau, which suggested the existence of optimal work.


Functional outcome of inpatient rehabilitation in persons with brain tumors.
To document functional outcome in persons with brain tumors undergoing inpatient rehabilitation and to compare outcomes with a group of traumatically brain injured patients. Retrospective, descriptive, and case-matched. A free-standing inpatient brain injury rehabilitation unit. Forty consecutive patients with a variety of tumor types (40% were either glioblastoma multiforme or meningioma) and a mean age of 53.1 (SD 15.4) years. Sixty percent were men, 25% had recurrent tumors, and 15% had metastatic disease. Also, 40 patients with traumatic brain injury (TBI) matched for age, gender, and admission functional status. Change in Functional Independence Measure (FIM) scores, length of rehabilitation stay (LOS), and discharge disposition. The mean LOS for the tumor group was 17.8 (SD 9.9) days, mean FIM gain was 25.4 (SD 20.1) points, and 82.5% were discharged home. No demographic or tumor characteristic was statistically significant in predicting functional outcome at discharge, but greater gains were seen for persons with the diagnosis of meningioma, those with left-sided cerebral lesions, and those not receiving radiation therapy. TBI patients made statistically significant greater gains in total FIM change (34.6 vs 25.4), self-care (12.3 vs 8.5), and social cognition (5.2 vs 3.6). However, FIM efficiency and LOS were not statistically different between the TBI and tumor groups (1.9 vs 1.5 FIM points/day and 22.1 vs 17.8 days, respectively). Daily functional gains made by persons with brain tumor undergoing rehabilitation were similar to those made by a group of persons with TBI matched by age, gender, and admission functional status. Further research should use larger samples and address the impact of psychosocial and team factors on LOS and discharge disposition.


Gradual potentiation of isometric muscle force during constant electrical stimulation.
An investigation was carried out into how stimulation frequency and stimulation history affect the potentiation of muscle force during 20s of constant stimulation of the two knee extensors in isometric conditions. Stimulation frequency significantly affected the potentiation pattern: low-frequency (2.5-10 Hz) stimulation showed a reduction and subsequent enhancement of force, and high-frequency (14.3-25 Hz) stimulation showed only enhancement of force. The degree of enhancement in force and time-to-peak decreased with the stimulation frequency. Whereas 40 Hz conditioning stimulation enhanced the muscle force, 14 Hz stimulation after 10s of rest induced little force enhancement (8% in both muscles). When the frequency of the conditioning stimulation was 14 Hz and the main 14 Hz stimulation was applied after 50s of rest, the initial force at the main stimulation was similar to the final force value of the conditioning stimulation (above 90% similarity). The potentiated twitch force slowly decayed during rest, with an average time constant of 2.4 min. These observations indicate that muscle potentiation depends on the stimulation frequency and stimulation history, and therefore a computer model of potentiation can play an important role in predicting muscle force and body movement induced by electrical stimulation.


Genotyping of Candida albicans isolated from animals using 25S ribosomal DNA and ALT repeats polymorphism in repetitive sequence.
Candida albicans is the most prevalent Candida species isolated from animals. Candidiasis can be systemic in animals or may affect a single organ, such as the mouth, urinary tract, and skin. The aim of the present study was to determine the genetic diversity of C. albicans isolated from different animals and investigate the presence of a relationship between host specificity and genetic typing of C. albicans. For the purpose of the study, DNA extraction was performed on 27 clinical isolates of C. albicans obtained from animals. Subsequently, they were subjected to 25S ribosomal DNA amplification and ALT repeats in repetitive sequences (RPSs). The minimum inhibitory concentrations of fluconazole, ketoconazole, clotrimazole, nystatin, amphotericin B, and caspofungin were determined using the microdilution method based on the Clinical and Laboratory Standards Institute M27-S4 standard. Out of 27 C. albicans strains, 11, 6, 5, and 5 cases were recognized as genotypes A (40.8%), E (22.2%), B (18.5%), and C (18.5%), respectively, through amplification using AS-I, which revealed 17 different types of C. albicans. By combining the two typing methods, 27 C. albicans strains were finally divided into 22 genotypes. Different genotypes showed genetic diversity among the C. albicans strains isolated from animal sources. The results revealed no special genotype relationship according to the host, anatomical source of isolation, and antifungal susceptibility.


Energy balance and reproductive performance in rabbit does.
The mortality and the culling rates of females are very high in rabbit breeding. In many cases, the dead or culled females show low reproductive performances and poor body conditions. Energy deficit leads to body mobilization and reduced reproductive performance. Consequently, energy balance and lifespan are closely linked. Two in vivo methods to estimate body composition were recently validated for rabbit does. Ultrasounds and TOBEC methods permitted the evaluation of the changes in energy balance and their relationship to reproductive performance of females. Influence of intrinsic (parity, litter size, genetic line, ...) and extrinsic (reproduction rhythm, temperature, ...) factors on the energetic balance of females are discussed. Energy deficit and depletion of body stores occurring during lactation lead to a decrease in reproductive performance and the physiological mechanisms implicated in these effects were presented. Interest and limitations of several strategies to reduce the body energy deficit in reproducing does and to improve their fertility and thus lifespan are discussed: rearing, feeding, management, genetic selection. A multi-facetted approach, combining these various strategies seems to be required to meet these objectives.


[Bacteriuria].
Bacteriuria remains the most important sign of urinary tract infection. A standardization of the diagnosis and treatment of urinary tract infection requires a standard period of urine collection (4 hours), the correct collection of specimens, the determination of the number of bacteria by appropriate media (dipslide) and of urinary leucocytes. Test strips cannot replace the microscopy of the sediment. The therapeutic consequences result from the localization of the infection, the duration of treatment of cystitis is 1 to 4 days, of pyelonephritis 10 to 14 days.


Pulmonary actinomycosis simulating a bronchial neoplasm.
We report a case of pulmonary actinomycosis, stimulating a bronchial neoplasm, in which serological tests for actinomycosis were positive.


Role of calcium antagonists as initial pharmacologic monotherapy for systemic hypertension in patients over 60 years of age.
Hypertension is most prevalent in older patients and is associated with increasing morbidity and mortality with age. The ability of antihypertensive treatment to reduce these complications in the elderly is now well established. However, several aspects of the treatment of hypertension are being evaluated. In particular, there is a growing trend to avoid individualizing the choice of medication. This is of particular concern in older patients who may differ in the pathophysiology of their hypertension, in their accompanying medical conditions, and in how they may respond to antihypertensive drugs. In addition, elderly hypertensives are often taking a number of medications in addition to antihypertensive drugs. This, along with the fact that the elderly often metabolize drugs more slowly, makes this group particularly susceptible to drug-drug interactions and pharmacologically induced toxic side effects. Considering these points, it appears that the calcium channel blockers are attractive antihypertensive agents for the elderly population.


Recruitment and retention of economically underserved women to a cervical cancer prevention trial.
This review contrasts the planned and actual recruitment and retention efforts for a cervical cancer prevention study within a predominantly underserved population. Recruitment was a primary obstacle to trial progression and multiple strategies to improve recruitment were implemented to meet objectives. The actual recruitment strategies were expansion to five geographically distinct clinical sites, use of nurse practitioners focused primarily on patient issues, extremely flexible study hours and location, honorariums, support for transportation and child care, and creativity in maintaining contact with study participants. With these strategies, 90% of eligible patients consented to participate in the study.


Perioperative myocardial infarction in a patient with metabolic syndrome.
We report on the case of a 19-year-old Hispanic male with metabolic syndrome who developed a myocardial infarction after an uneventful appendectomy. To our knowledge, this is the first published report of a young adult with metabolic syndrome suffering a major cardiac event after a simple abdominal surgical procedure. It raises the question as to how to prevent such complications in the future.


The Utility and Potential of Mathematical Models in Predicting Fibrinolytic Outcomes.
The enzymatic degradation of blood clots, fibrinolysis, is an important part of a healthy hemostatic system. If intrinsic fibrinolysis is ineffective, thrombolysis - the clinically-induced enzymatic degradation of blood clots - may be necessary to treat life-threatening conditions. In this review we discuss recent models of fibrinolysis and thrombolysis, and open questions that could be resolved through modeling and modeling-experimental collaboration. In particular, we focus on 2- and 3-dimensional models that can be used to study effects of fibrin network structure and realistic blood vessel geometries on the phenomena underlying lytic outcomes. Significant open questions such as the role of clot contraction, network and inherent fiber tension, and fibrinolytic inhibitors in lysis could benefit from mathematical models aimed at understanding the underlying biological mechanisms.


Ability of Patient-Reported Outcomes to Characterize Patient Acceptable Symptom State (PASS) After Attending a Primary Care Physical Therapist and Medical Doctor Collaborative Service: A Cross-Sectional Study.
To determine if the Patient-Reported Outcome Measurement Information System (PROMIS) physical function, pain interference, self-efficacy, and global rating of normal function (GRNF) scales are able to accurately characterize a patient's acceptable symptom state (PASS). A cross-sectional analysis, using receiver operator curves and chi-square analysis to explore criteria to determine thresholds (80% and 95% sensitivity/specificity) for PASS that are applicable to PROMIS and GRNF scales. Phone survey after primary care. Patients (N=94) attending primary care for musculoskeletal problems. Not applicable. Accuracy and proportion of patients classified as PASS Yes or No. Receiver operator curve analysis showed significant area under the curve (AUC) values for each PROMIS scale (AUC>.72) and the GRNF rating (AUC=.74). Identified PROMIS thresholds suggested PASS was achieved when scores were at or slightly worse than the US population average. A score of ≥7 and ≤4 characterized patients that were PASS Yes and No, respectively, on the GRNF rating. A moderate (80%) specificity/sensitivity criteria yielded 72.3%-73.5% accuracy for a majority of participants (>69.9%). This analysis suggests the PROMIS and GRNF scales are able to characterize PASS status with moderate accuracy (∼70%) for a large portion of patients (∼70%). New to this study is the association of self-efficacy with PASS status. PROMIS scales at or slightly worse than the US population average characterized PASS status.


Scanning electron microscopy and atom probe tomography characterization of laser powder bed fusion precipitation strengthening nickel-based superalloy.
Atom probe tomography (APT) was utilized to supplement scanning electron microscopy (SEM) characterization of a precipitation strengthening nickel-based superalloy, Alloy 247LC, processed by laser powder bed fusion (L-PBF). It was observed that the material in the as-built condition had a relatively high strength. Using both SEM and APT, it was concluded that the high strength was not attributed to the typical precipitation strengthening effect of γ'. In the absence of γ' it could be reasonably inferred that the numerous black dots observed in the cells/grains with SEM were dislocations and as such should be contributing significantly to the strengthening. Thus, the current investigation demonstrated that relatively high strengthening can be attained in L-PBF even in the absence of precipitated γ'. Even though γ' was not precipitated, the APT analysis displayed a nanometer scale partitioning of Cr that could be contributing to the strengthening. After heat-treatment, γ' was precipitated and it demonstrated the expected high strengthening behavior. Al, Ta and Ti partitioned to γ'. The strong partitioning of Ta in γ' is indicative that the element, together with Al and Ti, was contributing to the strain-age cracking occurring during heat-treatment. Cr, Mo and Co partitioned to the matrix γ phase. Hf, Ta, Ti and W were found in the carbides corroborating previous reports that they are MC.


Vegetative anatomy and micromorphology of Salvia divinorum (Lamiaceae) from Mexico, combined with chromatographic analysis of salvinorin A.
Salvia divinorum--a species traditionally cultivated in Oaxaca, Mexico--possesses hallucinogenic properties. It is legally recognized as a controlled substance and prohibited in many countries. The proper identification of the plant, both in fresh and dried forms, is an important issue in crime-prevention campaigns. This paper provides a thorough anatomical description of leaves, petioles, and stems of S. divinorum. Detailed investigation of foliar trichomes was performed and illustrated. In addition, chromatographic analyses, including TLC and HPLC, were applied to fresh and dried plant material, together with the standard reference salvinorin A. A comprehensive identification method for S. divinorum based on a thorough anatomical examination is proposed, combined with chemical analysis for proper plant recognition.


Photodynamic therapy upregulates expression of Mac-1 and generation of leukotriene B(4) by human polymorphonuclear leukocytes.
This study investigated the expression of Mac-1 (CD11b/CD18) and generation of leukotriene B(4) (LTB(4)) by polymorphonuclear leukocytes (PMNs) in response to Mono-L-aspartyl chlorine 6 (NPe6) mediated photodynamic therapy (PDT). PDT was carried out using a laser diode at a light dose of 10 J/cm(2) and wavelength of 664 nm. Expression of Mac-1 was significantly increased about 3-fold by PDT compared with that of Npe6 exposure. The increase in the expression of Mac-1 was not inhibited by 5-lipoxygenase inhibitor (AA861). On the other hand, generation of LTB(4) by PMNs was increased by incubation with NPe6 alone and further promoted by PDT and that was significantly inhibited by AA861. These results suggest that PDT can induce PMNs to express extensively Mac-1 and generate a certain amount of LTB(4) that may play an important cytocidal role in the treatment of oral cancer.


Studies on lipid and carbohydrate metabolism during surface-induced deep hypothermia with circulatory arrest for open-heart surgery.
Plasma lipids, blood glucose, plasma insulin (IRI) and serum dopamine-beta-hydroxylase (DBH) were measured in 30 subjects undergoing surface-induced deep hypothermia with circulatory arrest for open-heart surgery. Non-esterified fatty acid (NEFA) in the plasma rapidly increased at the lowest temperature (23 degrees C) reached and other lipids in the plasma decreased during the cooling period. An increase of NEFA and a decrease of triglyceride have been attributed to the action of lipoprotein lipase activity stimulated by heparin. It is also likely that the decrease of other lipids and beta-lipoprotein in the plasma results from the transient hypofunction of the liver due to hypothermia. Blood glucose increased during the cooling period, while plasma insulin showed no significant change. Serum DBH reflecting catecholamine also showed no significant change during the cooling or rewarming periods. Therefore, hyperglycemia in hypothermic open-heart surgery may result from the decrease of peripheral utilization of glucose and from the inhibition of insulin secretion due to the transient pancreatic hypofunction.


[Prevention and nutrition related illnesses. Obesity, diabetes mellitus].
Faced with the obesity epidemic there is need for therapy as well as public health strategies for health promotion and obesity prevention. Both strategies add to each other, none should be done in isolation. Obesity is not only an individual problem. It is also a problem of our society. We are now an overweight society, which is on the way to a fat society. There is urgent need for a national public health strategy for population wide prevention of overweight and obesity. Health authorities as well as politicians are asked to support public health strategies creating a supportive environment for making healthy choices the easier choices.


Glucose solution intake in the rat: the specificity of postingestive satiety.
Hungry rats were permitted to drink a concentrated glucose solution to 'satiety', as indicated by (1) cessation of drinking, (2) the appearance of behaviors correlated with satiety (grooming and exploring followed by resting), and (3) refusal to drink appreciable further quantities when access to the solution was prolonged. Yet such rats returned to vigorous and prolonged feeding when offered laboratory pellets, powered chow, or even glucose itself in powered form. "Satiety" for a glucose solution does not reflect a generalized suppression of hunger or of a specific carbohydrate hunger. Its properties are more specific than existing theories of energy intake regulation would lead us to suppose.


Cytotoxic action of diethanolamine oleate on Ehrlich exudative carcinoma in mice, compared with the action of polyoxyethylene sorbitan mono-oleate (Tween 80).
The salt of oleic acid and diethanolamine, and polyoxyethylene sorbitan mono-oleate inhibited growth of Ehrlich exudative carcinoma in mice.


Nodal Metastasis Count and Oncologic Outcomes in Head and Neck Cancer: A Secondary Analysis of NRG/RTOG 9501, NRG/RTOG 0234, and EORTC 22931.
A better understanding of the relationship between the spread of head and neck squamous cell carcinoma (HNSCC) to regional lymph nodes (LNs) and the frequency and manner of treatment failure should help design better treatment intensification strategies. In this study, we evaluated the relationship between recurrence patterns, mortality, and number of pathologically positive (+) LNs in HNSCC in 3 prospective randomized controlled trials. We performed a secondary analysis of 947 patients with HNSCC enrolled in RTOG 9501 (n = 410), RTOG 0234 (n = 203), and EORTC 22931 (n = 334) undergoing surgery and postoperative radiation ± systemic therapy. Multivariable models were constructed for overall survival (OS), disease-free survival (DFS), locoregional relapse (LRR), and distant metastases (DM). Restricted cubic splines were used to model the nonlinear relationship between +LN number and outcomes. In multivariable analysis, OS and DFS decreased with each +LN without plateau, most pronounced up to 5 +LNs (OS: hazard ratio [HR], 1.21 per +LN; 95% confidence interval [CI], 1.10-1.34; P < .001; DFS: HR per +LN, 1.19; 95% CI, 1.08-1.30; P < .001) and more gradually beyond this (OS: HR per +LN, 1.02; 95% CI, 1.01-1.06; P < .001; DFS: HR per +LN, 1.04; 95% CI, 1.02-1.06; P < .001). In contrast to LRR risk, which increased sharply up to 5 +LNs (HR per +LN, 1.28; 95% CI, 1.10-1.50; P < .001) but plateaued beyond this (HR per +LN, 1.00; 95% CI, 0.96-1.04; P = .98), DM risk increased continuously with increasing +LNs (≤5 +LNs: HR per +LN, 1.10; 95% CI, 1.01-1.20; P = .04; >5 +LNs: HR per +LN, 1.05; 95% CI, 1.02-1.08; P = .003). In high-risk resected HNSCC, increased mortality was associated with increased +LN count. LRR and DM risk both increased in parallel up to 5 +LNs, but only DM continued to increase for further +LN increases. These differing recurrence patterns can help inform design of future treatments.


Comparison of the mutagenicity of amsacrine with that of a new clinical analogue, CI-921.
The mutagenicity of CI-921, the 4-methyl-5-(N-methyl)carboxamide derivative of the clinical antileukaemia agent, amsacrine, has been assessed using both bacterial and mammalian cells. CI-921 is distinguished from amsacrine in its high activity against some experimental tumours and is currently undergoing phase I clinical trial. Like 9-aminoacridine and amsacrine, CI-921 is mutagenic to the Salmonella typhimurium frameshift tester strain TA1537, but shows no sign of inducing base pair changes in strain TA100. In Chinese hamster cell culture, however, it differs from 9-aminoacridine in causing extensive chromosomal aberrations and an increase in mutations at the hypoxanthine-guanine phosphoribosyltransferase locus. It induces the formation of tightly packed and multilayered colonies in treated cultures of C3H/10T1/2 cells, but its action differs from that of benzo[a]pyrene, which induces type III fibroblastic multilayered colonies. Side-by-side comparison of the mutagenic properties of CI-921 and amsacrine showed no substantial differences at similar toxicity, suggesting that the increased lipophilicity and DNA-binding affinity of CI-921, which are thought to contribute to its increased antitumour activity, do not concomitantly increase the efficiency of in vitro mutagenesis or cell transformation.


Update on the Impact of Depot Medroxyprogesterone Acetate on Vaginal Mucosal Endpoints and Relevance to Sexually Transmitted Infections.
The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although DMPA-IM provides reliable contraception, potential effects on the female genital tract (FGT) mucosa have raised concern, including risk of HIV infection. This review summarises and compares evidence from observational cohort studies and the randomised Evidence for Contraceptive Options in HIV Outcomes (ECHO) Trial. Although previous observational studies found women using DMPA-IM had higher abundance of bacterial vaginosis (BV)-associated bacteria, increased inflammation, increased cervicovaginal HIV target cell density, and epithelial barrier damage, sub-studies of the ECHO Trial found no adverse changes in vaginal microbiome, inflammation, proteome, transcriptome, and risk of viral and bacterial STIs, other than an increase in Th17-like cells. Randomised data suggest that DMPA-IM use does not adversely change mucosal endpoints associated with acquisition of infections. These findings support the safe use of DMPA-IM in women at high risk of acquiring STIs, including HIV.


Cerebrovascular response to intracranial hypertension.
Pial arterial and venous calibre changes during intracranial hypertension were studied in 11 cats under barbiturate- and nitrous oxide-anaesthesia by using a closed cranial window technique and multichannel videoangiometry. Intracranial pressure was elevated from a normal mean level of 6.4 mm Hg by cisternal infusion of mock CSF in steps to 20, 30, 40, 50 mm Hg and finally to the level of systolic pressure. Pial arteries dilated significantly, small ones more than large ones, by 42 +/- 5.6% and 33 +/- 3%, respectively at ICP 50. With a further elevation of ICP up to systolic pressure, dilatation diminished to 28 +/- 10% in small, and to near resting calibres in large arteries. Pial veins remained unreactive on the average. Grouping into veins smaller and larger than 100 microns of resting size revealed, however, minor though statistically significant 5-10% dilatation of small, and a 5-10% diminution of large veins. Blood flow stopped, when cerebral perfusion pressure was zero, however, neither arteries nor veins collapsed. The present data support the hypothesis that CBF during acute elevation of CSF pressure depends on perfusion pressure rather than local vascular compression.


Rehabilitation after lower limb amputation: a comparative study of above-knee, through-knee and Gritti-Stokes amputations.
A study of 169 unilateral amputees under three Disablement Services Centres was performed. The study comprised 88 above-knee, 54 through-knee and 27 Gritti-Stokes amputations. Satisfactory rehabilitation occurred in 33 per cent of above-knee, 62 per cent of through-knee and 44 per cent of Gritti-Stokes patients (56 per cent overall). The better rehabilitation of through-knee versus above-knee amputees (P less than 0.02) was also found in a group of patients matched for comparable age and duration of amputation as well as in a group of age-matched vascular amputees. Through-knee amputees relied significantly less on wheelchairs than above-knee (P = 0.016) and Gritti-Stokes (P = 0.05) amputees. The prosthesis used for the through-knee and Gritti-Stokes amputations was considered unsightly in 50 per cent of cases (versus 31 per cent for the above-knee prosthesis). The superior rehabilitation with through-knee amputations should prompt us to improve both our technique for this amputation and the prostheses currently available. A through-knee amputation should be performed in preference to an above-knee amputation in the case where either is surgically possible, and a below-knee amputation not feasible.


Synthesis and structure-activity relationships of novel substituted 8-amino, 8-thio, and 1,8-pyrazole congeners of antitubercular rifamycin S and rifampin.
A series of rifamycin S and rifampin analogues incorporating substituted 8-amino, 8-thio, and 1,8-pyrazole substituents has been synthesized. The compounds were made by activation of the C-8 phenol as a sulfonate ester, followed by displacement with selected nitrogen and sulfur nucleophiles. The analogues were screened in assays to quantify their antitubercular activity under both aerobic and anaerobic conditions, and for inhibition of wild-type Mycobacterium tuberculosis (MTB) RNAP and rifamycin-resistant MTB RNAP (S450L) via an in vitro rolling circle transcription assay. Additionally, the MIC(90) values were determined for these analogues against Escherichia coli strains. Although none of the analogues displayed superior enzymatic or microbiological activity to their parent scaffolds, the results are consistent with the Rif C-8 hydroxyl acting as a hydrogen bond acceptor with S450 and that Rif resistance in the S450L mutant is due to loss of this hydrogen bond. Representative analogues were also evaluated in the human pregnane X receptor (PXR) activation assay.


A case of gastrojejunal rupture.
Rupture of the stomach, duodenum and jejunum are well-recognized complications of non-penetrating abdominal trauma. This case is thought to be the first recorded injury of its kind.


RNA decay machines: deadenylation by the Ccr4-not and Pan2-Pan3 complexes.
Shortening and removal of the 3' poly(A) tail of mature mRNA by poly(A)-specific 3' exonucleases (deadenylases) is the initial and often rate-limiting step in mRNA degradation. The majority of cytoplasmic deadenylase activity is associated with the Ccr4-Not and Pan2-Pan3 complexes. Two distinct catalytic subunits, Caf1/Pop2 and Ccr4, are associated with the Ccr4-Not complex, whereas the Pan2 enzymatic subunit forms a stable complex with Pan3. In this review, we discuss the composition and activity of these two deadenylases. In addition, we comment on generic and specific mechanisms of recruitment of Ccr4-Not and Pan2-Pan3 to mRNAs. Finally, we discuss specialised and redundant functions of the deadenylases and review the importance of Ccr4-Not subunits in the regulation of physiological processes. This article is part of a Special Issue entitled: RNA Decay mechanisms.


The Utility of Chlorhexidine Cloth Use for the Prevention of Surgical Site Infections in Total Hip Arthroplasty and Surgical as well as Basic Science Applications: A Meta-Analysis and Systematic Review.
Skin antisepsis, such as ready-to-use, no-rinse, 2% chlorhexidine-impregnated cloths, is one of the fundamental cornerstones for reducing periprosthetic infections after primary lower extremity total joint arthroplasties. This systematic review presents background material concerning the problem and methods to deal with and then describes the use of chlorhexidine cloth prophylaxis related to various surgical applications. The authors found an almost universal benefit of the cloths. In the meta-analysis, the total pooled effect showed a reduction in infection rates. The use of chlorhexidine cloths is appropriate for prophylaxis for knee arthroplasty, hip arthroplasty, and a variety of other surgeries.


Effect of ethanol variation on the internal environment of sol-gel bulk and thin films with aging.
Sol-gel derived bulk and thin films were prepared from different compositions at low pH ( approximately 2.0) containing varying concentrations of ethanol from 15 to 60% at constant water (H(2)O)/tetraethyl-orthosilicate (TEOS) ratio (R=4). The fluorescence microscopic and spectroscopic measurements on fluorescent probe, Hoechst 33258 (H258) entrapped in these compositions were carried out at different days of storage to monitor the effects of concentration of ethanol on the internal environment of sol-gel materials. Fluorescence microscopic observations on sol-gel thin films, prepared by dip coating technique depicted uniform and cracked surface at withdrawal speed 1cm/min (high speed) and 0.1cm/min (low speed) respectively, which did not change during aging. Fluorescence spectral measurements showed emission maximum of H258 at approximately 535 nm in fresh sols at all concentrations of ethanol which depicted slight blue shift to 512 nm during aging in bulk. No such spectral shift has been observed in sol-gel thin films coated at high speed whereas thin films coated at low speed clearly showed an additional band at approximately 404 nm at 45 and 60% concentration of ethanol after about one month of storage. Analysis of the fluorescence lifetime data indicated single exponential decay (1.6-1.8 ns) in fresh sol and from third day onwards, invariably double exponential decay with a short (tau(1)) and a long (tau(2)) component were observed in sol-gel bulk with a dominant tau(1) at approximately 1.2 ns at all concentrations of ethanol. A double exponential decay consisting of a short component (tau(1)) at approximately 0.2 ns and a long component (tau(2)) at approximately 3.5 ns were observed at all ethanol concentrations in both fresh and aged sol-gel thin films. Further, distribution analysis of lifetimes of H258 showed two mean lifetimes with increased width in aged bulk and thin films. These results are likely to have strong implications in designing the internal environment for applications in biosensors.


Body size, duration of parental care, and the intrinsic rate of natural increase in eutherian and metatherian mammals.
The intrinsic rate of natural increase (r m), conception to weaning time (t cw), age of first reproduction (tmat), and components of fecundity were compared between ecologically similar groups of 42 metatherian (=marsupial) and 42 eutherian mammals. Marsupial t cw s average 50% longer than those of eutherians. Small marsupials (<400 g) mature later, and have lower and r ms than eutherians; large marsupials (>10,000 g) do not mature later but also have lower r ms. At body sizes of 1,000-3,500 g, marsupials and eutherians have similar t mat s and t cw s but marsupials have greater r ms. Marsupials compensate for their longer t cw s by a variety of methods including embryonic diapause, larger litter sizes, and short periods between weaning and maturity. Although the greatest similarities in marsupial and eutherian life histories are at body sizes of 1-5 kg, compensation for long t cw may be seen at any marsupial body size. Other ecological factors not withstanding, marsupial reproduction is neither inherently inferior to that of eutherians nor obviously more advantageous in unpredictable environs.


Memory, amnesia, and the issue of recovered memory: neurobiological aspects.
The main thesis of this article is that the debate about the credibility of "recovered memories"--reports by adults of recovered memories of childhood sexual abuse and trauma that were allegedly repressed for many years--can be usefully informed by considering the biological and behavioral facts and ideas about how memory works. Accordingly, the first section of this review describes current facts and ideas about the neurobiology and neuropsychology of memory and amnesia, including what parts of the brain are important for memory, distinctions between different memory systems in the brain, and the phenomena of infantile amnesia and source amnesia. The second section takes into account the information about the biological and behavioral bases of memory and addresses two questions about memory that have become a focus of debate in the recovered memory controversy, that is, whether memories for traumatic events change over time, and whether memories can be created for traumatic events that did not actually happen.


Distribution of cerebellar terminations and their relation to other afferent terminations in the ventral lateral thalamic region of the monkey.
The efferent projections of the deep cerebellar nuclei were studied and their fiber trajectories and thalamic termination zones described. The thalamic termination zones for the dentate, interposed and fastigial nuclei are identical and coincide with the cytoarchitectonically unique cell-sparse region of the ventral lateral complex. This region includes nuclei VPLo, VLc, VLps, X and extensions of these between the cell clusters of nucleus VLo. The inputs from dentate and interpositus are contralateral, dense, and their termination patterns extend continuously throughout all nuclear components of the cell-sparse zone. Interdigitation of these two inputs within the cell-sparse region is directly demonstrated. The fastigial input is more restricted but bilateral. Each of the deep cerebellar nuclei also projects to the central lateral nucleus of the intralaminar complex. The strong interconnection of the cell-sparse zone with cortical area 4 is confirmed. The patterns of retrogradely labeled thalamocortical cells and of anterogradely labeled corticothalamic terminations following cortical injections of horseradish peroxidase and of tritiated amino acids, extend continuously through the VPLo-VLc region and its extensions, but do not invade the posteriorly situated VPLc nucleus. Thalamic inputs from the dorsal column nuclei terminate independently within the morphologically distinct VPLc nucleus adjacent to the cell-sparse cerebellar terminal zone. The dorsal column-lemniscal terminations do not overlap the cerebellar terminations. The clear segregation of the two sets of terminations is demonstrated directly using an anterograde double labeling method. Spinothalamic terminations end in VPLc but extend into the cerebellar terminal zone. Another ascending input, from the vestibular nuclei, is also shown to terminate within the cell-sparse zone. Comparison with other studies implies that cerebellar, pallidal and substantia nigral inputs do not converge in the monkey thalamus and that the nuclei in which they terminate project to different cortical areas. The relation of these and of sensory influences ascending to motor cortex from the periphery are discussed.


Controlled release of brefeldin A from electrospun PEG-PLLA nanofibers and their in vitro antitumor activity against HepG2 cells.
In this work, PEG-PLLA electrospun fibers were developed as a new controlled release system for macrolide antibiotic drug brefeldin A (BFA). SEM and XRD analyses of the BFA-loaded PEG-PLLA fibers revealed that the average diameter of fibers was below 950 nm with smooth surfaces, and the drug was well incorporated into the fibers in amorphous form. The release profiles of BFA in PBS were measured by HPLC, demonstrating that the controlled release of BFA could be gained for long time. The in vitro antitumor activity against human liver carcinoma HepG2 cells of the fibers containing 3%, 6%, 9%, 12% and 15% BFA were examined by MTT method, and the results showed that cell growth inhibition rates at 72 h were 64%, 77%, 80%, 81% and 85%, respectively. These results strongly suggested that the BFA/PEG-PLLA fibers had an effect of controlled release of BFA and were suitable for postoperative chemotherapy of cancers.


Logistic regression model to estimate the risk of unbalanced offspring in reciprocal translocations.
The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are cytogenetic characteristics of the translocation, age and sex of the parental carrier, and potential viability of the gametes. The results obtained by the logistic model demonstrate the important role of certain variables such as the sex of the parental carrier and the R band length of the translocated segments. Within the group of lower risk (risk of viable unbalanced offspring less than 5%), 97% of the individuals are correctly classified with this model. For this group, the choice prenatal diagnosis can be best discussed by considering both the risk for viable unbalanced offspring and the risk of induced abortion following prenatal diagnosis.


Malignant migrating partial seizures in infancy.
The syndrome of malignant migrating partial seizures in infancy (MMPSI) was first reported in 1995, and is now included among the childhood epileptic syndromes in the revision proposal of the ILAE Commission on classification and terminology. The main clinical features are seizure onset in the first 6 months of life, occurrence of almost continuous migrating polymorphous focal seizures, associated with multifocal ictal EEG discharges, progressive deterioration of psychomotor development combined with frequent evolution of acquired microcephaly, and lack of a significant familial and etiological context. Eventually, children develop major axial hypotonia, pyramidal and extrapyramidal signs with athetotic movements and strabismus. Neuroradiological, biochemical, and genetic investigations thus far have note contributed to our knowledge about this syndrome. Etiology is still unknown, though it appears reasonable to suspect a genetic etiology for MMPSI; a channelopathy may be responsible for the age-dependent cortical neuronal hyperexcitability. Seizures are markedly drug resistant and outcome is generally severe. However, some patients may respond favourably to bromide, stiripentol associated with clonazepam, and, more recently, to levetiracetam. Vagus nerve stimulation and a ketogenic diet have been tried also but with poor or inconclusive results. Based on age at onset, MMPEI may be placed between early epileptic encephalopthies and infantile spasms.