Productivity loss in the workforce: associations with health, work demands, and individual characteristics.
Decreased productivity at work is an important consequence of the presence of health problems at work. The study population consisted of 2,252 workers in 24 different companies in The Netherlands in 2005-2006 (response 56%). Self-reported loss of productivity on the previous workday was measured on a 10-point numerical rating scale by the Quantity and Quality method. Logistic regression analysis was used to explore the associations between work demands, health problems, individual characteristics, and lifestyle factors with the occurrence of productivity loss. About 45% of the workers reported some degree of productivity loss on the previous workday, with an average loss of 11%. Moderate and severe functional limitations due to health problems (OR = 1.28 and 1.63, respectively) and lack of control at work (OR = 1.36) were associated with productivity loss at work with population attributable fractions of 7%, 6%, and 16%, respectively. Productivity losses at work frequently occur due to health problems and subsequent impairments, and lack of control over the pace and planning of work. This will substantially contribute to indirect costs of health problems among workers.


Effect of affective temperament on outcome of rotator cuff surgery.
Although numerous risk factors have been described, the effects of temperament, which is defined as a risk factor for certain disorders, on the outcome of patients undergoing rotator cuff surgery have not been investigated. We investigated whether a relationship exists between affective temperament and the outcome of patients undergoing rotator cuff surgery. The outcomes of 176 patients undergoing rotator cuff surgery were examined using the Oxford and Constant questionnaires as well as visual analog scale values preoperatively and postoperatively. Inclusion criteria were defined as 1) dissatisfaction with pain despite 6 months of nonoperative treatment; 2) rotator cuff defects with full-thickness, small- to large-sized defects; 3) presence of a single dominant temperament or nondominant temperament; 4) no history of a diagnosed psychiatric disorder; and 5) a minimum of greater than 1 year of follow-up after surgery. Exclusion criteria were 1) other comorbid shoulder pathology; 2) irreparable or partial rotator cuff rupture; 3) grade 3 retractions; 4) grade 3-4 fatty infiltration; 5) other comorbid diseases such as diabetes, thyroid disorders, or inflammatory diseases; 6) history of shoulder surgery; 7) infection of the shoulder joint; 8) neurologic deficit in muscles around the shoulder; 9) two or more dominant temperaments; and 10) history of acromioclavicular joint resection and/or biceps tenodesis with cuff repair. All patient temperaments were evaluated according to the Temperament Evaluation of Memphis, Pisa, Paris and San Diego auto questionnaire version. The mean follow-up time was 45.5 months. The outcomes of patients with depressive temperament were worse than of patients with a nondominant temperament. This situation was observed both preoperatively and postoperatively. However, a similar relationship between nondominant and anxious temperament groups was observed only postoperatively. We noticed that depressive and anxious temperaments had a negative effect on patient outcomes after rotator cuff surgery; however, nondominant temperaments had a positive effect on patient outcomes. Level III; Retrospective Comparative Study.


Associations between HLA and immune responses in individuals with chronic schistosomiasis japonica.
The association of an HLA specificity with low or high immune responsiveness to Schistosoma japonicum antigen (Sj) was demonstrated among individuals who had previously been exposed to S. japonicum infection. The frequency of HLA-Aw24 specificity among low responders in the IgG antibody response determined by the enzyme-linked immunosorbent assay (ELISA) was higher than that among high responders. Significant association between HLA-B7 and high responsiveness was observed in the IgE antibody response. The frequency of HLA-Bw52-Dw12 was also found to increase among individuals with higher levels of total serum IgE. These results suggest that antibody responses to Sj are regulated by an immune response (Ir) gene(s) linked to the major histocompatibility complex (MHC), although a possibility of the presence of non-MHC-linked Ir genes is not excluded. Serum IgE levels may also be controlled by a gene(s) linked to the MHC.


Chronic depth electrodes study of one case of bitemporal epilepsy due to glial tumour. Some physiopathological considerations.
The authors describe a seventeen-years-old girl suffering from partial seizures with complex symptomatology. The neuroradiological studies demonstrated a slow-growing glial tumour seated deeply in the right temporo-occipital region. Scalp EEG demonstrated a bilateral asynchronous temporal focus without definite lateralization. Chronic depth electrodes recording allowed identification of a primary epileptogenic area in the right rhinencephalic structures. Radiofrequency lesions performed in the right amygdala and anterior third of right Ammon's horn abolished the seizures at ten months follow up.


Synthesis and NKT cell stimulating properties of fluorophore- and biotin-appended 6"-amino-6"-deoxy-galactosylceramides.
Alpha-galactosylceramides are potent stimulators of human T cells. Stimulation occurs through binding of the glycolipids by CD1d, presentation to T cells, and formation of a CD1d-glycolipid-T cell receptor complex. To facilitate the elucidation of the structural features of glycolipids necessary for T cell stimulation, alpha-galactosylceramides have been prepared with small molecules appended at the C6 position of the sugar. The appended molecules do not significantly influence the abilities of the glycolipids to stimulate T cells. [reaction: see text]


Structural identification of (1→6)-α-d-glucan, a key responsible for the health benefits of longan, and evaluation of anticancer activity.
Longan is a delicious subtropical fruit with great health-beneficial effects. It has been utilized for disease prevention and health care since ancient age. To explore the chemicals responsible for the health benefits, water-soluble polysaccharides were extracted from longan flesh in this work. A pure polysaccharide (LPS1) was obtained through column purification. Analysis by gas chromatography showed LPS1 was a homopolysaccharide of glucose with glycosidic linkage of →6)-d-Glc-(1→. Nuclear magnetic resonance (NMR) spectra indicated that the configuration of anomeric carbon in glucose residual was α-form. The polysaccharide structure was further confirmed to be (1→6)-α-d-glucan by chemcial shift of C6. The molecular weight of LPS1 was calculated to be 108 kDa, which had 661 glucose residuals. Anticancer assay showed that LPS1 had anticancer activity against the growth of HepG2 cells to a certain extent. However, it did not show any cytotoxicity against MCF-7 breast cancer cells.


A single nucleotide substitution at the rib2 locus of the yeast mitochondrial gene for 21S rRNA confers resistance to erythromycin and cold-sensitive ribosome assembly.
We have studied a mutation (cs23) in the mitochondrial gene for 21S rRNA that affects the peptidyl transferase center of the ribosome and conditionally blocks the assembly of the 54S ribosomal subunit. Strains carrying this mutation are resistant to erythromycin and cold-sensitive for growth on nonfermentable carbon sources (Singh et al. 1978) Mitochondria isolated from mutant cells grown on glucose at 20 degrees C, the nonpermissive temperature, were depleted of the 54S subunit and instead contained a novel 45S ribosomal particle. After mutant cells were shifted from 20 degrees C to 32 degrees C, 54S subunits were assembled, apparently from the 45S particles and pre-existing ribosomal proteins. DNA sequencing revealed that the mutant phenotype is a consequence of a C to A transversion at position 3993 of the 21S rRNA gene. Previously, C to U and C to G mutations have been identified at the same position in the 21S rRNA sequence. This position corresponds to C-2611 in the E. coli 23S RNA, a nucleotide that appears to be conserved in the large rRNA of all erythromycin-sensitive ribosomes.


Swallowed dentures: Two cases and a review.
Denture ingestion or aspiration is a problem requiring awareness of different specialists including dentists, surgeons, otolaryngologists, anesthesiologists etc. in terms of prevention, early diagnosis and adequate treatment. Complications of swallowed dentures include hollow viscus necrosis, perforation, penetration to neighbor organs leading to fistulae, bleeding and obstruction. First case is a 54-year-old female who accidentally swallowed retractable one-tooth denture during fall about 22 h before admission and clinical manifestation of acute small bowel obstruction developed. The patient underwent laparotomy, enterotomy with retrieval of the foreign body. The second case is a 31-year-old male who accidentally ingested fixed one-tooth prosthesis while eating which impacted in the ileocaecal valve. During the preparation to colonoscopy the denture spontaneously passed out with stools. Denture ingestion is more common among patients with psychoneurologic deficit, alcohol and drug abusers. Among healthy and younger population denture ingestion is rare. Both reported patients are not elder. Thus dislodgement of removable or fixed dentures is another risk factor of denture ingestion. Most common site of denture impaction is esophagus; small bowel impaction is rare. Moreover, in most reported cases, small bowel impaction of ingested dentures leads to small bowel perforation. In our first case the complication of denture ingestion appeared to be bowel obstruction what is even rarer. Fixed dentures can be accidentally ingested as well as removable dentures. Denture loosening leads to accidental denture ingestion. Patients with denture loosening should be recommended to visit dentist as soon as possible.


The influence of social evaluation on cerebral cortical activity and motor performance: a study of "Real-Life" competition.
Motor performance in a social evaluative environment was examined in participants (N = 19) who completed a pistol shooting task under both performance-alone (PA) and competitive (C) conditions. Electroencephalographic (EEG), autonomic, and psychoendocrine activity were recorded in addition to kinematic measures of the aiming behavior. State anxiety, heart rate, and cortisol were modestly elevated during C and accompanied by relative desynchrony of high-alpha power, increased cortico-cortical communication between motor and non-motor regions, and degradation of the fluency of aiming trajectory, but maintenance of performance outcome (i.e., score). The findings reveal that performance in a complex social-evaluative environment characterized by competition results in elevated cortical activity beyond that essentially required for motor performance that translated as less efficient motor behavior.


Safe use of meropenem in a patient with a possible nonimmediate allergy to imipenem.
Strong data are lacking on the cross-reactivity between individual carbapenems. We describe a 48-year-old woman with ventilator-associated Pseudomonas aeruginosa pneumonia who received an 8-day course of imipenem-cilastatin and experienced a delayed (i.e., nonimmediate) hypersensitivity reaction, evidenced by an extensive erythematous macular morbilliform rash and an increased eosinophil count. Eight days after completion of therapy, the pneumonia returned, and it was decided to avoid using imipenem-cilastatin; she was administered a 14-day course of meropenem. To our knowledge, this is the first report of a nonimmediate hypersensitivity reaction to imipenem-cilastatin without cross-reactivity to meropenem. This suggests that if carbapenem therapy is unavoidable, meropenem may be cautiously administered in patients with a known allergy to imipenem-cilastatin.


Prognostic value of preoperative C-reactive protein concentration and white cell count in acute extremity ischaemia.
To find out if the C-reactive protein (CRP) concentration and the white cell count (WCC) are of any prognostic value in patients with acute extremity ischaemia. Retrospective study. Tampere University Hospital and Jyväskylä Central Hospital, Finland. 129 patients with acute extremity ischaemia. Preoperative CRP concentration, white cell count, packed cell volume, serum creatinine concentration, major amputation and death. The median (range) CRP concentration was 50.0 (3-271) mg/l in the 28 patients who underwent major amputation or died (group 1) and 11.0 (1.175) mg/l in the 65 patients who survived with viable limbs (group 2) (p = 0.007). The median (range) WCC was 13.1 (5.9-42.0) x 10(9)/l in group 1 (30 patients) and 9.5 (2.2-23.9) x 10(9)/l in group 2 (79 patients) (p < 0.001). The cut-off point of 20 mg/l for CRP and 11.0 x 10(9)/l for WCC had negative predictive values of 0.83 and 0.85 for amputation and mortality, respectively. Preoperative CRP concentration and WCC correlated with limb salvage and mortality in patients with acute extremity ischaemia.


Autofluorescence imaging in the differential diagnosis of optic disc melanocytoma.
Optic disc melanocytoma (ODM) is a benign tumour that usually occurs on or adjacent to the optic nerve head. The aim of the study was to evaluate fundus autofluorescence (FAF) imaging as a diagnostic tool in ODM. Retrospective comparative case series study of six patients with ODM and a comparing group of four patients with juxtapapillary choroidal nevus (JCN) and four with juxtapapillary uveal melanoma (JUM). Clinical examination was supplemented with ultrasound B-scan examination and spectral-domain optical coherence tomography. FAF images were obtained with the 532-nm laser (Optomap P200Tx) from all patients. Clinical examination in the ODM group revealed a dome-shaped, darkly pigmented tumour on or adjacent to the optic disc in all patients, with a mean tumour basal dimension 1.4 mm and mean tumour thickness by ultrasonography of 1.0 mm. FAF revealed a totally hypofluorescent mass with sharply demarcated, feathery edges. No hyperfluorescent changes due to orange pigment or subretinal fluid were seen. In contrast, patients with JCN and JUM manifested focal hyperfluorescence as well as larger hyperfluorescent areas at the tumour and its borders. Fundus autofluorescence imaging is a non-invasive adjuvant tool in the differential diagnosis of ODM characterized by lack of hyperfluorescence compared to JCN and JUM.


Correction: High-throughput cell focusing and separation via acoustofluidic tweezers.
Correction for 'High-throughput cell focusing and separation via acoustofluidic tweezers' by Mengxi Wu et al., Lab Chip, 2018, 18, 3003-3010, DOI: .


Multiomic profiling of the acute stress response in the mouse hippocampus.
The acute stress response mobilizes energy to meet situational demands and re-establish homeostasis. However, the underlying molecular cascades are unclear. Here, we use a brief swim exposure to trigger an acute stress response in mice, which transiently increases anxiety, without leading to lasting maladaptive changes. Using multiomic profiling, such as proteomics, phospho-proteomics, bulk mRNA-, single-nuclei mRNA-, small RNA-, and TRAP-sequencing, we characterize the acute stress-induced molecular events in the mouse hippocampus over time. Our results show the complexity and specificity of the response to acute stress, highlighting both the widespread changes in protein phosphorylation and gene transcription, and tightly regulated protein translation. The observed molecular events resolve efficiently within four hours after initiation of stress. We include an interactive app to explore the data, providing a molecular resource that can help us understand how acute stress impacts brain function in response to stress.


A label-free luminescent assay for tyrosinase activity monitoring and inhibitor screening with responsive lanthanide coordination polymer nanoparticles.
In this work, a label-free, selective, and sensitive luminescent sensing platform was established for tyrosinase (TYR) activity monitoring and its inhibitor screening using one kind of lanthanide coordination polymer nanoparticles AMP-Tb/Ag+. By taking advantage of the specific binding and redox properties of Ag+ incorporated into the AMP-Tb network and dopamine (DA) as the product of the model substrate tyramine, the enzymatic reaction and the signal change of the sensing platform was effectively linked. The cooperative effect of a weakened energy transfer from AMP to Tb3+ by altering the electronic structure of Ag+ and an efficient photoinduced election transfer (PET) process caused by dopaquinone facilitated the luminescence quenching of Tb3+. Thus, this luminescent sensing platform could be employed for quantitative evaluation of TYR activity. There was a good linear range for TYR activity from 0.08 to 0.20 U mL-1 with a low detection limit of 0.004 U mL-1. Furthermore, this assay was successfully applied to accurate determination of TYR activity in human serum samples and efficient screening of TYR inhibitors. Considering unique spectral characteristics of lanthanides along with operation simplicity and superior analytical performance, this sensing platform is very promising in clinical diagnosis and drugs screening for TYR-associated diseases.


Mini-winkler extractor and pitfall trap as complementary methods to sample formicidae.
The aim of the present study was to evaluate the use of mini-Winkler extractor and pitfall traps as appropriate and complementary methods to sample ant communities in the phytophysiognomy mosaic in the Poconé Pantanal region, state of Mato Grosso, Brasil. Seven units were studied for landscape, located within a 25 km(2) collection area, formed by thirty 250-m transects, at 1-km intervals in a 5 × 5 km area. Five collection points were marked in each transect at 50-m intervals, totaling 150 points. A collection was made at each sampling point with mini-Winkler extractor and pitfall traps. Using the mini-Winkler extractor, 1,088 individuals were collected distributed in 20 genera and 55 species, with Solenopsis invicta Buren and Pheidole (gr. biconstricta) sp.1 as the most frequent ants. Using pitfall traps, 2,726 individuals distributed in 24 genera and 48 species were sampled and Dorymyrmex (gr. pyramicus) sp.1 and Pheidole (gr. biconstricta) sp.1 were the most frequent species. A significant difference between the methods was observed in measured species number. The Principal coordinates analysis discriminated two species groups exclusively sampled by the mini-Winkler extractor and another by the pitfall methods. Therefore, it was concluded that these methods were complementary for ant diversity inventories in the Poconé Pantanal region.


Stroke in two children with Mycoplasma pneumoniae infection. A causal or casual relationship?
We report on 2 children who had a stroke biologically related to Mycoplasma pneumoniae infection. Invasion of the central nervous system and an immune mechanism represent 2 pathogenesis pathways. Prompt macrolide therapy does not prevent stroke, but immediate and aggressive immunosuppressive treatment seems to help recovery.


[Smoking cessation support among persons in situation of precariousness].
Underprivileged people smoke more frequently, present with a more severe smoking profile and stop less often than wealthier smokers. They can have difficulties to afford smoking cessation treatments as the French medical insurance coverage system requires smokers to pay it in advance with a later reimbursement. The objective of this study was to compare the characteristics, treatment plans and cessation rates of smokers from disadvantaged population in comparison with smokers in wealthier condition. Study population concerned smokers received for a first visit in the smoking cessation service at Georges-Pompidou European Hospital (Paris, France) in 2013. The EPICES score was used to define precariousness. The national file of smoking cessation consultation (CDT) was completed and the nicotine replacement therapy (NRT) prescriptions were detailed, as treatment could be given for free to precarious smokers on a weekly basis. Data were registered in CDTnet, the French national database of smoking cessation services. Precarious smokers (36.8%) presented with a more severe smoking profile and suffered more often from psychiatric disorders than wealthier smokers. They benefited most often from a combination NRT with patch and oral forms. The followed-up precarious smokers attended a greater number of consultations (4.7 against 3.4) and, if they were less often abstainers (22.2% against 41.3%), they were able to significantly reduce their consumption. Precarious smokers adhere to structured care with aid for access to TSN with a positive consequent impact on consumption.


Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an A1 adenosine receptor agonist.
Adenosine, via interaction with A1 adenosine receptors, increases insulin sensitivity and inhibits lipolysis in adipocytes. To investigate regulation of this system, adipocytes were incubated for up to 72 h with the nonmetabolizable adenosine receptor agonist, N6-phenylisopropyl adenosine (PIA). Adenosine receptors were measured by the binding of 125I-hydroxyphenylisopropyl adenosine to membranes. PIA down-regulated adenosine receptors, decreasing the number of binding sites with no change in affinity. Adipocytes were incubated for 48 h without or with 100 nM PIA to down-regulate the A1 receptors by approximately 60%. The cells were washed, and lipolysis and glucose transport were assessed. The ability of PIA to inhibit lipolysis was markedly attenuated in the down-regulated cells. Furthermore, the EC50 of insulin was increased approximately 3-fold in the PIA-treated cells. 125I-Insulin binding to the PIA-treated cells was unchanged, demonstrating that the decreased insulin sensitivity is not due to decreased insulin receptor binding. Pertussis toxin catalyzed ADP-ribosylation of a 41-kDa protein thought to be the alpha-subunit of Gi. This 41-kDa protein was decreased in membranes from cells treated with PIA, with a maximal 50% loss. This suggests that Gi is down-regulated and that loss of both the A1 adenosine receptor and Gi are involved in the metabolic changes observed after PIA treatment.


Silent Gastroesophageal Reflux Disease in Patients with Morbid Obesity Prior to Primary Metabolic Surgery.
Long-term follow-up after sleeve gastrectomy (SG) revealed a high incidence of gastroesophageal reflux disease (GERD) frequently caused by preoperative silent pathologic reflux. We aimed to evaluate prevalence and phenotypes of GERD in asymptomatic patients with morbid obesity prior to metabolic surgery according to modern objective testing. Prospective collection of data including consecutive patients with morbid obesity (body mass index (BMI) ≥ 35 kg/m2) prior to metabolic surgery was applied for this study between 2014 and 2019. Patients underwent clinical examinations, endoscopy, pH metry, and high-resolution manometry and were analyzed according to the Lyon consensus. Of 1379 patients undergoing metabolic surgery, 177 (12.8%, females = 105) asymptomatic individuals with a median age of 42.6 (33.8; 51.6) years and a median BMI of 44.6 (41.3; 50.8) kg/m2 completed objective testing and were included during the study period. GERD was diagnosed in 55 (31.1%), whereas criteria of borderline GERD were met in another 78 (44.1%). GERD was mediated by a structural defective lower esophageal sphincter (p = 0.004) and highlighted by acidic (p = 0.004) and non-acidic (p = 0.022) reflux episodes. Esophageal motility disorders were diagnosed in 35.6% (n = 63) of individuals with a novel hypercontractile disorder found in 7.9% (n = 14) of patients. GERD affects a majority of asymptomatic patients with morbid obesity prior to primary bariatric surgery. Future longitudinal trials will have to reveal the clinical significance of esophageal motility disorders in patients with morbid obesity.


Exceeding expectations after perinatal risks for poor development: associations in term- and preterm-born preschoolers.
To define parenting/social characteristics associated with better-than-expected cognitive and motor outcomes in preschoolers at similar perinatal biological risk-level including various gestational ages at birth (GA) and perinatal complications. Prospective cohort study (n = 87) of children at four years, median GA 29 weeks (IQR 26, 38). Assessments included Differential Ability Scales, Movement Assessment Battery, parenting styles, and social risk scores. Perinatal risk factors were weighted based on regression models for each outcome; individual calculated risk scores became predictors to extract standardized residuals from the mean (>1 SD above mean = better-than-expected). Mixed-effect regressions examined associations between positive adaptation and parenting/social factors. Perinatal risk scores explained 21-53% outcome variability. Children across all GA displayed positive adaptation. Children of parents with higher authoritarian scores had higher odds of better-than-expected outcomes (OR 1.17, p = 0.0002). Parental structure may promote positive adaptation at preschool age in children with perinatal risk factors for poor development, including extreme prematurity.


HSPB8 facilitates prostate cancer progression via activating the JAK/STAT3 signaling pathway.
Prostate cancer (PC) is a clinically and biologically heterogeneous disease that lacks effective treatment. Heat shock protein B8 (HSPB8) is an important factor in the progression of various types of cancer. However, the clinical significance and biological role of HSPB8 in PC are still unclear. In this study, we determined HSPB8 expression in PC tissues by immunohistochemical staining and explored the in vitro functions of HSPB8 using HSPB8 knockdown DU145 and LNcap PC cell lines. The in vivo effect of HSPB8 was explored by a subcutaneous xenograft mice model. The human phospho-kinase array and signal transducer and activator of transcription (STAT) 3 activator were utilized to explore the potential mechanism of HSPB8-induced PC progression. As a result, we found that HSPB8 was abundantly expressed in PC tissues and cell lines. HSPB8 knockdown inhibited cell proliferation and migration, promoted apoptosis and cycle repression, as well as weakened tumorigenesis ability. Mechanistically, we demonstrated that HSPB8 facilitates the malignant phenotypes of PC by activating the Janus kinase/STAT3 signaling pathway. These results proposed that HSPB8 seems to be an attractive therapeutic target for PC patients.


Selective formation of homo- and heterobivalent peptidomimetics.
Methodology is presented for assembling fluorescently labeled bivalent molecules from monovalent constituents, without side chain protection or coupling agents. To illustrate the procedure, a series of bivalent peptidomimetics directed toward the Trk receptors were prepared and screened via fluorescent activated cell sorting scan assays.


"Just how graphic are graphic novels?" An examination of aggression portrayals in manga and associations with aggressive behavior in adolescents.
Manga, a type of graphic novel, represent a widely popular literary genre worldwide and are one of the fastest growing areas of the publishing arena aimed at adolescents in the United States. However, to our knowledge, there has been almost no empirical research examining content or effects of reading manga. This article consists of 2 studies. Study 1 represents a content analysis of aggressive behavior in best-selling manga aimed at adolescents. Results revealed that aggression was common and was often portrayed in ways that may influence subsequent behavior. Study 2 examined the relationship between reading manga and aggressive behavior in 223 adolescents. Manga readers were more physically aggressive than non-manga readers and also reported more peer relationships with lonely individuals and smaller groups. In addition, reading manga with particularly high levels of aggression was associated with physical aggression even after controlling for media violence exposure in other media. Implications regarding these findings are discussed.


A systematic review on the efficiency of cerium-impregnated activated carbons for the removal of gas-phase, elemental mercury from flue gas.
In the present systematic review, we aimed to collect and analyze all the relevant evidence on the efficiency of cerium-impregnated versus virgin-activated carbons (ACs) for the removal of gas-phase elemental mercury (Hg0) from the flue gas of coal-fired power plants and to assess the effect of different calcination and operational parameters on their efficiency. A total of eight relevant papers (out of 1193 hits produced by the search) met the eligibility criteria and were included in the study. Results indicated that the Hg0 adsorption capacity of cerium-impregnated ACs is significantly higher than that of virgin ACs, depending highly on the impregnation and operational parameters. It was noticed that although cerium-impregnated ACs possessed smaller surface areas and pore volumes, their Hg0 removal efficiencies were still higher than their virgin counterparts. An increased Hg0 removal efficiency was in general found by increasing the operational adsorption temperature as high as 150-170 °C. Studies also indicated that NO, SO2, and HCl have promoting impacts on the Hg0 removal efficiency of Ce-impregnated ACs, while H2O has an inhibitory effect.


Definition and classification of cancer: monothetic or polythetic?
Since the microbiological revolution, most infectious diseases have been defined and classified according to an etiologic criterion, i.e. the identification of single, external "necessary" causes (for example, Mycobacterium for tuberculosis). This is not the case with cancer. Not only external "necessary" causes of cancer have not been identified, but also the morphological classification cannot be based on univocal criteria. Although "neoplasia" and "anaplasia" appear to be universal attributes of cancer, these events are only quantitative. Neoplastic growth can be fast or slow (development may take weeks or years), and tissue pathologies are difficult to detect from normal tissue in some cancers but are obvious in others. Common special properties of anaplasia appear to be concealed in the wide range of morphologies. In the absence of a coherent morphological definition, and of external necessary causes (such as bacteria for infectious diseases), a mechanistic definition could be adopted. However, unless molecular biology discovers specific mechanistic steps in carcinogenesis, which indicate the existence of "necessary" events in carcinogenesis, we cannot adopt a univocal (monothetic) definition of cancer. The alternative is to use a polythetic definition, according to Wittgenstein's model of a "long rope twisted together out of many shorter fibres."


Methods of dynamic spectral analysis by self-exciting autoregressive moving average models and their application to analysing biosignals.
Dynamic methods in the spectral domain are necessary to analyse biological signals because of the frequently nonstationary character of the signals. The paper presents an adaptive procedure of fitting time-dependent ARMA models to nonstationary signals, which is suitable for on-line calculations. The properties of the model parameter estimations are examined, and in the stationary case are compared with the results of convergent estimation methods. On this basis time-varying spectral parameters with high temporal and spectral resolution are calculated, and the possibility of their application is shown in EEG analysis and laser-Doppler-flowmetry.


Spectroscopic (FT-IR, FT-Raman, UV absorption, 1H and 13C NMR) and theoretical (in B3LYP/6-311++G** level) studies on alkali metal salts of caffeic acid.
The effect of some metals on the electronic system of benzoic and nicotinic acids has recently been investigated by IR, Raman and UV spectroscopy [1-3]. Benzoic and nicotinic acids are regarded model systems representing a wide group of aromatic ligands which are incorporated into enzymes. In this work the FT-IR (in solid state and in solution), FT-Raman, UV absorption and (1)H and (13)C NMR spectra of caffeic acid (3,4-dihydroxycinnamic acid) and its salts with lithium, sodium, potassium, rubidium and caesium were registered, assigned and analyzed. The effect of alkali metals on the electronic system of ligands was discussed. Studies of differences in the number and position of bands from the IR, Raman, UV absorption spectra and chemical shifts from NMR spectra allowed to conclude on the distribution of electronic charge in the molecules, the delocalization energy of π electrons and the reactivity of ligands in metal complexes. Optimized geometrical structures of studied compounds were calculated by B3LYP method using 6-311++G** basis set. Bond lengths, angles and dipole moments for the optimized structures of caffeic acid and lithium, sodium, potassium caffeinates were also calculated. The theoretical wavenumbers and intensities of IR spectra were obtained. The calculated parameters were compared to the experimental characteristics of investigated compounds. Microbial activity of studied compounds was tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris.


Comparison of Conventional and Cone-Beam CT for Monitoring and Assessing Pulmonary Microwave Ablation in a Porcine Model.
To compare cone-beam computed tomography (CT) with conventional CT for assessing the growth and postprocedural appearance of pulmonary microwave ablation zones. A total of 17 microwave ablations were performed in porcine lung in vivo by applying 65 W for 5 minutes through a single 17-gauge antenna. Either CT (n = 8) or CBCT (n = 9) was used for guidance and ablation zone monitoring at 1-minute intervals. Postprocedural noncontrast images were acquired with both modalities. Three independent readers measured the length, width, cross-sectional area, and circularity of the ablation zones on gross tissue samples and CT and cone-beam CT images. The measurements were compared via linear mixed-effects models for postprocedural appearance and with a polynomial mixed effects model for ablation zone growth curves. On postprocedural images, the differences between cone-beam CT and CT in mean length (3.84 vs 3.86 cm; Δ = -0.02; P = .70), width (2.61 vs 2.56 cm; Δ = 0.06; P = .46), area (7.84 vs 7.65 cm2; Δ = 0.19; P = .35), and circularity (0.85 vs 0.85; Δ = 0.01; P = .62) were not statistically significant after accounting for intersubject and interrater variability. Also, there was no significant difference between CT and cone-beam CT growth curves of the ablation zones during monitoring in terms of length (pInt. = 1.00; pLin.Slope = 0.52; pQuad.Slope = 0.69); width (pInt. = 0.83; pLin.Slope = 0.98; pQuad.Slope = 0.79), area (pInt. = 0.47; pLin.Slope = 0.27; pQuad.Slope = 0.57), or circularity (pInt. = 0.54; pLin.Slope = 0.74; pQuad.Slope = 0.80). Both CT and cone-beam CT overestimated gross pathologic observations of ablation length, width, and area (P < .001 for all). Cone-beam CT was similar to conventional CT when assessing the growth, final size, and shape of pulmonary microwave ablation zones and may be useful for monitoring and evaluating microwave ablations in the lung.


Characterization of two anti-DNA antibodies bearing distinct idiotypes. Correlation with clinical manifestations.
Spontaneous idiotype shift of anti-DNA antibodies in systemic lupus erythematosus was shown to be associated with changes in the clinical manifestations of the disease. Characterization of two anti-DNA antibody preparations from the same lupus patient showed that lupus nephritis was associated with antibodies showing higher specific antigen-binding activity and avidity to DNA and presenting more cationic quality upon isoelectric focusing and Western blot analysis than the ones found in patients without renal involvement. Lupus cerebritis was associated with anti-DNA antibodies with different idiotypic characteristics not shared by anti-DNA antibodies present in lupus nephritis. Lupus cerebritis anti-DNA antibodies had less specific antigen-binding activity and avidity to DNA and did not show cationic quality. Idiotypic and immunochemical changes of anti-DNA antibodies in lupus may be associated with various clinical manifestations.


Inversion 19 and isochromosome short arm 17 or 18.
A case of inversion 19 and isochromosome short arm 17 or 18 has been studied, and the possibility of an increased risk of nondisjunction in persons with certain chromosome inversions is discussed.


Children's skepticism: developmental and individual differences in children's ability to detect and explain distorted claims.
The current study examined some key developmental and individual differences in how elementary school-aged children evaluate sources of information. A sample of 130 children ages 6 to 9 years participated in a task designed to measure children's understanding of ways that claims can be distorted (i.e., biased decisions, skewed self-reports, and misleading persuasive claims). Children also completed several individual difference measures, including a brief intelligence task and an advanced social cognition measure (interpretive theory of mind). Overall, older children were less trusting and better than younger children at explaining the reasons to doubt sources that might provide distorted claims. Crucially, the results also suggest that beyond age, both general intelligence and advanced social cognitive skills play roles in children's ability to understand when and why they must doubt sources of distortion.


Ultrastructural identification of corticotropes of the fetal rat. In-vivo and in-vitro immunocytochemistry.
Corticotropes of rat fetuses aged 16, 18 and 21 days were localized by the indirect antibody-enzyme method on semithin sections of the pituitary. The development of the ultrastructure of these cells was observed on consecutive ultrathin sections. In comparison with previous data our present results show that identification of a fetal cell type cannot be based entirely on morphological criteria. The structural peculiarities of corticotropes obtained from studies in vivo are compared with those observed in cells maintained in vitro.


Passive biaxial mechanical properties of the rat bladder wall after spinal cord injury.
Changes in the mechanical properties of the bladder wall after spinal cord injury can alter bladder compliance and wall tension, leading to changes in afferent nerve activity and to abnormal reflex mechanisms. To our knowledge we report the first application of biaxial mechanical testing to the normal bladder wall and demonstrate how these properties change after spinal cord injury. Whole bladders were harvested from mature female Sprague-Dawley rats weighing 250 to 300 gm. Test group animals underwent complete spinal cord transection at the T9 to T10 level and normal animals comprised the control group. The bladders were cut open longitudinally, the trigone and apex were removed and the remaining tissue was trimmed to a square of 9 to 13 mm. per side. Mechanical properties of the tissue sample were tested using planar biaxial testing, in which a stress was applied in the circumferential and longitudinal (base-apex) directions, and resulting axial strains were measured. In normal and spinal cord injured rats bladder wall tissue demonstrated isotropic mechanical behavior when equal stress levels were applied in anatomical directions. However, under nonequi-biaxial loading bladder specimens were not truly isotropic but displayed anisotropic-like behavior. Spinal cord injured tissues were consistently more compliant than normal controls. Biaxial mechanical testing can detect differences in normal control and hypertrophied rat bladders 10 and 14 days after spinal cord injury. These changes represent an important component of the bladder response to spinal cord injury.


[ASA - from cardiovascular to cancer prevention].
Cardiovascular disease and cancer are the leading causes of morbidity and mortality worldwide. Low-dose ASA has been shown to effectively prevent about one fifth of atherothrombotic vascular complications in patients with previous myocardial infarction, peripheral arterial occlusive disease (PAOD), or stroke 2. In secondary prevention, the benefits of antiplatelet therapy substantially exceed its risk 2. By contrast, recommendations for the use of ASA in primary prevention are still a matter of controversy. The aim of this article is to review the current evidence for the efficacy of low-dose ASA in primary and secondary prevention of cardiovascular diseases as well as to discuss its potential additional chemopreventive action.


Anti-phospholipid antibodies in serum from patients with Guillain-Barré syndrome.
The Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy related to autoimmunity. However, no conclusive etiological concept has yet been found. We examined the variation in autoantibodies to lipids in serum of GBS patients in response to the course of the disease but investigated titer modifications during treatment with gamma-globulin. Prospective clinical study in a 14-bed general ICU. Nine patients with GBS and nine controls were included in the study. Four blood samples were obtained before and after treatment. Serum samples, diluted 1:60, were tested by enzyme-linked immunosorbent assay for IgM, IgA, and IgG antibodies to phosphatidylcholine, phosphatidylinositol, cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine, sphingomyelin, and gangliosides. Anti-phospholipid antibodies of the IgM, IgA, and IgG families were detected in all GBS patients but in none of the controls. Phosphatidylinositol, cardiolipin, phosphatidylcholine, and phosphatidic acid were the main antigens. All patients developed anti-phosphatidylinositol antibodies of the IgM family and anti-cardiolipin antibodies of the IgA and IgG families. A decrease in the level of anti-phospholipid autoantibodies was observed after 1 day of treatment with gamma-globulin. Two days after ending gamma-globulin administration the IgG antibodies increased again. Our findings suggest that in GBS there is an extensive immune reaction, which is altered after gamma-globulin treatment. Anti-cardiolipin and anti-phosphatidylinositol antibodies could be useful markers for the response to treatment.


Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor.
Leishmanolysin, the Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the pathogenesis and virulence of Leishmania major, targeted gene replacement was used to delete the entire 20 kb region containing all seven leishmanolysin genes (gp63 genes 1-7). The resulting L. major leishmanolysin deficient mutants showed normal development inside the sand fly vector, however, promastigotes recovered from sand flies or from culture showed an increase in sensitivity to complement-mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic differences could be significantly improved by expression of a cloned leishmanolysin gene. These results demonstrate that leishmanolysin is a vital virulence factor in Leishmania pathogenesis.


Fifty years of recurring struggles with recurrent laryngeal neuropathy.
Recurrent laryngeal neuropathy appears to be a simple problem that should have a simple solution, yet the complexity and dynamic nature of laryngeal function is underappreciated. This review highlights the challenges and accomplishments that work towards that greater understanding of what is necessary to find a successful solution.


Protocol design for randomized clinical trial to compare underwater cold snare polypectomy to conventional cold snare polypectomy for non-pedunculated colon polyps of size 5-10 mm (COLDWATER study).
Colorectal cancer is internationally the third leading cause of death from a malignant disease. The aim of screening colonoscopy in adults > 45 years of age is early diagnosis and treatment of precancerous polyps. Endoscopic polyp removal (polypectomy) can be achieved with various techniques depending on the size, morphology, and location of the polyp. According to current guidelines, small non-pedunculated polyps should be removed with a cold snare after the colorectal lumen has been insufflated with air (conventional cold snare polypectomy).In recent years, several studies have described the benefits of water aided colonoscopy, as well as the safety and efficacy of underwater cold snare polypectomy for large colon polyps. However, there are insufficient data on conventional and underwater techniques for small polyps, the most commonly diagnosed colorectal polyps. We have designed a prospective randomized double-blind clinical trial to compare the safety and efficacy of conventional and underwater cold snare polypectomy for non-pedunculated polyps 5-10 mm in size. A total of 398 polyps will be randomized. Randomization will be carried out using the random numbers method of Microsoft Excel 2016. The primary endpoint is the muscularis mucosa resection rate. Secondary endpoints are the depth and percentage of R0 excisions, complications, and the recurrence rate at follow-up endoscopy 6-12 months after polypectomy. We hypothesize underwater polypectomy will result in a higher muscularis mucosa resection rate. The results of our study will provide useful data for the development of guidelines in polypectomy techniques for non-pedunculated polyps 5-10 mm in size. Clinicaltrials.gov, NCT05273697.


Pseudouridylation of U(35) in the anticodon of Arabidopsis thaliana pre-tRNA(Tyr) depends on length rather than structure of an intron.
In order to establish the structure and sequence requirements for pseudouridine (Psi(35)) biosynthesis in Arabidopsis thaliana tRNA(Tyr) five mutants of nuclear pre-tRNA(Tyr) have been prepared and analyzed: DeltaI-tRNA(Tyr) transcript depleted of an intron, and 5UI, 7UI, 9UI and 12UI transcripts containing tracts of five, seven, nine and 12 U residues, respectively, instead of the wild type tRNA(Tyr) intron. The in vitro transcripts were incubated in a lupin seed extract containing Psi(35) synthase activity, and those containing an artificial intron composed of 12 or nine U residues turned out to be good substrates for Psi(35) synthase. The transcript with an intron composed of seven uridine residues was pseudouridylated up to 40%, whereas the remaining two were not pseudouridylated at all. The secondary structures of all transcripts were determined using enzymatic and chemical probes: S(1), V(1), T(1), A, P(1) and Pb(2+). All mutant pre-tRNAs show similar structural features: their anticodon arm contains a five base pair stem and a large loop which consists of five natural tRNA(Tyr) AC loop nucleotides to which five, seven, nine and 12 U residues are added. As the structure of the wild type pre-tRNA(Tyr) is different we propose that the role of its intron in the process of U(35) pseudouridylation is simply to expand the anticodon region to the required critical length.


Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner.
Defects in nucleic acid metabolizing enzymes can lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing type I interferon-driven inflammatory diseases. In these pathophysiological conditions, activation of the DNA sensor cGAS and IFN production are linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways. Here, we show that low-level chronic DNA damage in mice lacking the Aicardi-Goutières syndrome gene SAMHD1 reduced tumor-free survival when crossed to a p53-deficient, but not to a DNA mismatch repair-deficient background. Increased DNA damage did not result in higher levels of type I interferon. Instead, we found that the chronic interferon response in SAMHD1-deficient mice was driven by the MDA5/MAVS pathway but required functional priming through the cGAS/STING pathway. Our work positions cGAS/STING upstream of tonic IFN signaling in Samhd1-deficient mice and highlights an important role of the pathway in physiological and pathophysiological innate immune priming.


Older Patients with Acute Myeloid Leukemia Deserve Individualized Treatment.
Treatment of elderly patients with acute myeloid leukemia is a known challenge for hematologists due to patient diversity, heterogeneous disease biology, and a rapidly evolving treatment landscape. Here, we highlight the importance of determining fitness, review the latest therapeutic developments, and discuss clinical scenarios to provide guidance on individualized treatment for older AML patients. Several factors, like age, performance status, and comorbidities, play a role in fitness and are associated with outcome. Comorbidity scoring systems and geriatric assessments are tools to help physicians select the most appropriate treatment for each patient. The addition of venetoclax, targeted therapy with IDH1/2 and FLT3 inhibitors, and enhanced formulas of existing drugs like CPX-351 and oral azacitidine have improved responses and outcomes. New drugs and combination therapies have increased the therapeutic options for elderly AML patients but determination of fitness and disease biology is essential to select patient-tailored treatments.


The value of pre-symptomatic genetic risk assessment for age-related macular degeneration: the Moran AMD Genetic Testing Assessment (MAGENTA) study-a study protocol for a randomized controlled trial.
Age-related macular degeneration (AMD) is an irreversible blinding eye condition with complex genetic and environmental etiologies. Genetic testing for AMD for previously identified multiple-risk single nucleotide polymorphisms can help determine an individual's future susceptibility. However, such testing has been discouraged until evidence shows that providing such information to symptomatic or pre-symptomatic individuals will alter their disease course. Therefore, we designed this study to investigate whether knowledge of AMD risk could stimulate the adoption of a healthier lifestyle that could lower the incidence of AMD later in life. We hypothesize that pre-symptomatic individuals informed of a high genetic risk of AMD are more likely to make quantifiable, positive lifestyle changes relative to participants informed of lower genetic risk or randomized to deferred disclosure of genetic testing results. The Moran AMD Genetic Testing Assessment (MAGENTA) study is a phase 2, single-center, prospective, double-masked, randomized controlled trial conducted at the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Participants are randomized by a 3:1 allocation ratio to immediate and deferred disclosure groups and followed for 12 months. Skin, ocular, and serum carotenoid status, as well as nutritional and social surveys, are assessed at study visits. Skin carotenoid assessment is by resonance Raman spectroscopy and reflectance spectroscopy, ocular carotenoids are measured with Heidelberg Spectralis autofluorescence imaging and fluorescence lifetime imaging ophthalmoscopy (FLIO), and serum carotenoids are quantified using high-performance liquid chromatography. The primary outcome evaluates changes in skin carotenoid status in response to genetic risk disclosure. The secondary outcomes examine changes in ocular and serum carotenoid status in response to genetic risk disclosure. Also, we will correlate AMD genetic risk with baseline ocular and systemic carotenoid status and FLIO. MAGENTA will provide much-needed evidence on whether pre-symptomatic testing for AMD risk can lead to quantifiable long-term changes in behavior and lifestyle associated with a lower incidence of AMD later in life. Findings from the MAGENTA trial will facilitate the design of a future larger, longer-term, multicenter phase 3 trial that could feature subgroup analysis, expanded measures of lifestyle modification, and potential active nutritional interventions. ClinicalTrials.gov NCT05265624 . Registered on March 3, 2022.


Climate has contributed to population diversification of Daphnia galeata across Eurasia.
Climate is a fundamental abiotic factor that plays a key role in driving the evolution, distribution and population diversification of species. However, there have been few investigations of genomic signatures of adaptation to local climatic conditions in cladocerans. Here, we have provided the first high-quality chromosome-level genome assembly (~143 Mb, scaffold N50 12.6 Mb) of the waterflea, Daphnia galeata, and investigated genomic variation in 22 populations from Central Europe and Eastern China. Our ecological-niche models suggested that the historic distribution of D. galeata in Eurasia was significantly affected by Quaternary climate fluctuations. We detected pronounced genomic and morphometric divergences between European and Chinese D. galeata populations. Such divergences could be partly explained by genomic signatures of thermal adaptation to distinct climate regimes: a set of candidate single-nucleotide polymorphisms (SNPs) potentially associated with climate were detected. These SNPs were in genes significantly enriched in the Gene ontology terms "determination of adult lifespan" and "translation repressor activity", and especially, mthl5 and SOD1 involved in the IIS pathway, and EIF4EBP2 involved in the target of the rapamycin signalling pathway. Our study indicates that certain alleles might be associated with particular temperature regimes, playing a functional role in shaping the population structure of D. galeata at a large geographical scale. These results highlight the potential role of molecular variation in the response to climate variation, in the context of global climate change.


Inhibition of induction of adaptive response by o-vanillin in Escherichia coli B.
Mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were strongly enhanced in the presence of o-vanillin in E. coli B. The enhancement was also observed in uvrA, umuC, recA, polA, or alkB mutants. This effect was lower in an alkA mutant, but was restored in an alkA umuC double mutant. By contrast, the enhancing effect was almost blocked in an ada and ada umuC double mutant. It was necessary to add simultaneously MNNG and o-vanillin to the growth medium. Further investigations were conducted on the induction of ada and umuC genes using ada'-lacZ' and umuC'-lacZ' plasmids. o-Vanillin suppressed the induction of the ada gene by MNNG treatment, but not that of the umuC gene. In fact expression of the umuC gene was induced by lower concentrations of MNNG in the presence of o-vanillin. The results suggest that o-vanillin inhibits induction of the adaptive response, and consequently, the MNNG-induced mutation frequency is increased due to unrepaired O6-methylguanine.


Adsorption of naphthalene polycyclic aromatic hydrocarbon from wastewater by a green magnetic composite based on chitosan and graphene oxide.
A green magnetic composite mCS/GO was synthesized using water hyacinth extract, as a reducing agent, and proanthocyanidin, as a crosslinking agent, for the adsorption of naphthalene from effluents. The green composite was evaluated using different characterization techniques to determine its thermal (TG/DTG), structural (BET, XPS and FTIR), crystallographic (XRD), and textural (SEM) properties in natura and post-adsorption. The results obtained through a central composite design (CCD) experiment indicated that the initial concentration of NAP and the adsorbent dosage are significant for the adsorption capacity. The adsorption assays indicated that physisorption, through π-π and hydrophobic interactions, were the main mechanism involved in the NAP adsorption. However, the adjustment to the PSO and Freundlich models, obtained through kinetic and equilibrium studies, indicated that chemisorption also influences the adsorptive process. The thermodynamic study indicated physisorption as the mechanism responsible for the NAP adsorption. Also, the adsorbent has high affinity for the adsorbate and the process is spontaneous and endothermic. The maximum adsorption capacity (qmax) of the green mCS/GO was 334.37 mg g-1 at 20 °C. Furthermore, the green mCS/GO was effectively regenerated with methanol and reused for five consecutive cycles, the percentage of NAP recovery went from approximately 91 to 75% after the fifth cycle. The green composite was also applied in the adsorption of NAP from river water samples, aiming to evaluate the feasibility of the method in real applications. The adsorption efficiency was approximately 70%. From what we know, this it is the first time that a green adsorbent was recycled after the polycyclic aromatic hydrocarbon (PAHs) adsorption process.


The two-component stomach: effects of meal particle size on fundal and antral emptying.
Using a dual-headed gamma camera and a standardized egg test meal labeled with 99mTc-sulfur colloid, the quantitative emptying of the total, proximal and distal stomach in five normal subjects was characterized. The same egg meal was given to the volunteers in 3 different forms: homogenized, and as 2.5 mm and 5.0 mm cubes on 3 separate occasions for a total of 15 studies. For the total stomach emptying, the lag phase and half emptying time (T1/2) obtained using a power exponential model were significantly shorter for the homogenized test meal than for the 2.5 mm and 5.0 mm cubed egg particles; the lag phases were 29 +/- 19 min (mean +/- SD) vs 55 +/- 26 (P less than 0.05) and 64 +/- 24 min (P less than 0.01), the T1/2's were 71 +/- 30 min vs 91 +/- 26 (P less than 0.05) and 104 +/- 30 min (P less than 0.05), respectively. For the proximal stomach, no statistically significant difference was observed among the 3 test meals; the T1/2s for the homogenized, 2.5 mm and 5.0 mm cubed meals were 65 +/- 26 min, 53 +/- 18 min and 64 +/- 20 min, respectively. For the distal stomach, both the peak activity (%) and time to peak activity (min) were significantly higher for the 2.5 mm cubes (43%, 54 min) and the 5.0 mm cubes (38%, 60 min) than for the homogenized eggs (16.4%, 30 min) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Cord blood banking - bio-objects on the borderlands between community and immunity.
Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.


Factors to consider during anesthesia in patients undergoing preemptive kidney transplantation: a propensity-score matched analysis.
International guidelines have recommended preemptive kidney transplantation (KT) as the preferred approach, advocating for transplantation before the initiation of dialysis. This approach is advantageous for graft and patient survival by avoiding dialysis-related complications. However, recipients of preemptive KT may undergo anesthesia without the opportunity to optimize volume status or correct metabolic disturbances associated with end-stage renal disease. In these regard, we aimed to investigate the anesthetic events that occur more frequently during preemptive KT compared to nonpreemptive KT. This is a single-center retrospective study. Of the 672 patients who underwent Living donor KT (LDKT), 388 of 519 who underwent nonpreemptive KT were matched with 153 of 153 who underwent preemptive KT using propensity score based on preoperative covariates. The primary outcome was intraoperative hypotension defined as area under the threshold (AUT), with a threshold set at a mean arterial blood pressure below 70 mmHg. The secondary outcomes were intraoperative metabolic acidosis estimated by base excess and serum bicarbonate, electrolyte imbalance, the use of inotropes or vasopressors, intraoperative transfusion, immediate graft function evaluated by the nadir creatinine, and re-operation due to bleeding. After propensity score matching, we analyzed 388 and 153 patients in non-preemptive and preemptive groups. The multivariable analysis revealed the AUT of the preemptive group to be significantly greater than that of the nonpreemptive group (mean ± standard deviation, 29.7 ± 61.5 and 14.5 ± 37.7, respectively, P = 0.007). Metabolic acidosis was more severe in the preemptive group compared to the nonpreemptive group. The differences in the nadir creatinine value and times to nadir creatinine were statistically significant, but clinically insignificant. Intraoperative hypotension and metabolic acidosis occurred more frequently in the preemptive group during LDKT. These findings highlight the need for anesthesiologists to be prepared and vigilant in managing these events during surgery.


Ethnoracial differences in workplace drug testing and policies on positive drug tests in the United States.
Drug testing is widely implemented as a work-based prevention strategy for employee substance use. However, it has raised concerns about its potential use as a punitive measure in the workplace where racialized/ethnic workers are over-represented. This study examines the rates of exposure to workplace drug testing among ethnoracial workers in the United States and the potential differences in the employers' responses to positive test results. A nationally-representative sample of 121,988 employed adults was examined using the 2015-2019 National Survey on Drug Use and Health data. The rates of exposure to workplace drug testing were estimated separately for ethnoracial workers. Then we used multinomial logistic regression to test differences in employers' responses to the first positive drug test results across ethnoracial subgroups. Since 2002, Black workers reported 15-20% points higher rates of having a workplace drug testing policy than Hispanic or White workers. When tested positive for drug use, Black and Hispanic workers were more likely to be fired than White workers. When tested positive, Black workers were more likely to be referred to treatment/counseling services while Hispanic workers were less likely to be referred compared to White workers. Black workers' disproportionate exposure to drug testing and punitive responses in the workplace may potentially place individuals with substance use problems out of the workforce, limiting their access to treatment/other resources available via their workplaces. Also, Hispanic workers' limited accessibility to treatment and counseling services when tested positive for drug use requires attention to address unmet needs.


Impact of hierarchical water dipole orderings on the dynamics of aqueous salt solutions.
Ions exhibit highly ion-specific complex behaviours when solvated in water, which remains a mystery despite the fundamental importance of ion solvation in nature, science, and technology. Here we explain these ion-specific properties by the ion-induced hierarchical dipolar, translational, and bond-orientational orderings of ion hydration shell under the competition between ion-water electrostatic interactions and inter-water hydrogen bonding. We first characterise this competition by a new length λHB(q), explaining the ion-specific effects on solution dynamics. Then, by continuously tuning ion size and charge, we find that the bond-orientational order of the ion hydration shell highly develops for specific ion size and charge combinations. This ordering drastically stabilises the hydration shell; its degree changes the water residence time around ions by 11 orders of magnitude for main-group ions. These findings are fundamental to ionic processes in aqueous solutions, providing a physical principle for electrolyte design and application.


Dissecting Chemical Composition and Cardioprotective Effects of Fuzhengkangfu Decoction against Doxorubicin-Induced Cardiotoxicity by LC-MS and Bioinformatics Approaches.
Cardiotoxicity of doxorubicin (DOX) has gained increasing attention in clinical application. Fuzhengkangfu (FZK) decoction, a traditional Chinese herbal formula of replenishing Qi strengthening spleen, has been used to treat various cardiovascular diseases. However, the chemical composition, the protective effects of FZK, and the underlying mechanisms are yet unclear. In this study, an high-performance liquid chromatography-mass spectrometry (HPLC-MS) analytical method was established for the structural identification of constituents in FZK extracts. Target prediction and enrichment analysis of the identified ingredients were performed. The cell viability was measured via (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT) assay. The protective effects of FZK on cell survival, mitochondrial membrane potential, intracellular calcium homeostasis, and cell apoptosis were detected. The level of relevant proteins was measured by Western blot. The effect of FZK on the antitumor activity of DOX was evaluated in HeLa cells. A total of 42 major chemical constituents were identified in FZK extracts by HPLC-MS. A comprehensive target prediction of these constituents retrieved 46 pathways, of which several key pathways were related to mitochondrial dysfunction, including metabolic pathways and calcium signaling pathways. Furthermore, FZK ameliorated DOX-induced H9C2 cell apoptosis and increased the Bcl-2/Bax ratio. Also, it moderated the loss of mitochondrial membrane potential and reduced the intracellular calcium overload, which are the major targets of DOX-induced injury. These results confirmed that FZK ameliorates DOX-induced cardiotoxicity via antiapoptotic and mitochondrial protection but does not affect the antitumor activity of DOX.


Bifunctional resin-ZVI composites for effective removal of arsenite through simultaneous adsorption and oxidation.
Bifunctional resin-supported nanosized zero-valent iron (N-S-ZVI) composite was developed by combining the oxidation properties of nZVI/O2 with adsorption features of iron oxides and anion-exchange resin N-S. In batch culture experiments, N-S and the N-S-ZVI composite were examined for As(III) and As(V). The results reveal that ZVI in the composite played a key role in enhancing As(III) removal. The N-S-ZVI composites could oxidize more toxic As(III) to less toxic As(V) with high efficiency under ambient conditions without the need of noble metals. At the same time, the oxidized As(V) could be effectively removed by adsorption onto the surface of composites. The mechanisms for the oxidation of As(III) to As(V) and the simultaneous removal of As(V) are proposed. In order to investigate the potential performance of N-S-ZVI in practical use, the effects of solution pH and coexisting anions on arsenite removal and on fixed-bed column treatment of simulated waters were studied. All the results indicated that the bifunctional composites have a great potential for As(III) removal from contaminated waters.


Degradation of 2-chlorobenzoic and 2,5-dichlorobenzoic acids in pure culture by Pseudomonas stutzeri.
A strain of Pseudomonas stutzeri KS25 utilizing 2-chlorobenzoic and 2,5-dichlorobenzoic acids as the sole carbon and energy source was isolated from polychlorophenol-contaminated soil and sewage, using the method of enrichment cultures. This strain was also able to grow on 2-fluoro-, 2-iodo-, 2-bromo- and 2,5-dihydroxybenzoate, but did not utilize 3-, 4-chloro-, 2,4- and 2,6-dichlorobenzoates as the sole carbon and energy source, however, it cometabolized 3-chloro-, 2,4- and 2,6-dichlorobenzoates, but not 4-chlorobenzoate. The yield of released chlorine during utilization of 2-chloro- and 2,5-dichlorobenzoates amounted to 100% of the theoretical. The concentration of 2-chloro- and 2,5-dichlorobenzoates, not substantially inhibiting the isolated microorganism, was within the range 0.25-0.5 and 2.5-3.0 g/L, respectively.


Self-Assembled Polymeric Materials: Design, Morphology, and Functional-Oriented Applications.
This Review focuses on the current research advances of the synthesis of various amphiphilic block copolymers (ABCs), such as conventional ABCs and newly presented polyprodrug amphiphiles, and the development of corresponding self-assemblies in selective solvents driven by the intermolecular interactions, like noncovalent hydrophobic interactions, π-π interactions, and hydrogen bonds, between ABCs or preformed small polymeric nanoparticles. The design of these assemblies is systematically introduced, and the diverse examples concerning the unique assembly structures along with the fast development of their exclusive properties and various applications in different fields are discussed. Possible perspectives on the existential challenges and glorious future are elucidated finally. It is hoped that this Review will provide a convenient way for readers to motivate more evolutional innovative concepts and methods to design next generation of novel polymeric nanoassemblies, and fill the gap between material design and practical applications.


Pleuro-pulmonary endometriosis and pulmonary ectopic deciduosis: a clinicopathologic and immunohistochemical study of 10 cases with emphasis on diagnostic pitfalls.
The clinical and pathological features of nine cases of pleuro-pulmonary endometriosis and the first case of pulmonary ectopic deciduosis are presented. The patients were all women between the ages of 27 and 74 years (median, 36 years) who presented with symptoms of catamenial pleural pain, shortness of breath, hemoptysis, or radiographically detected lung masses. Clinically, six patients were multiparous, one patient had pelvic endometriosis, and four patients had undergone prior pelvic surgical procedures, including dilatation and curettage. Radiographically, eight patients had pulmonary infiltrates or nodules, and four patients had pneumothorax. Three cases involved the visceral pleura and one case the parietal pleura. The other six cases, including the single case of ectopic deciduosis, involved the lung parenchyma. Histologically, the single or multifocal lesions were well circumscribed or infiltrative, nodular, cystic, or nodulo-cystic, and showed the characteristic features of proliferative or secretory endometrium with numerous mullerian metaplastic changes. Mucin stains were negative in five cases of endometriosis and in the single case of ectopic deciduosis. Immunohistochemical studies were performed in these same six cases using antibodies to epithelial, mesenchymal, vascular, and neuroendocrine markers. The glandular epithelium was decorated with antibodies to pan-cytokeratin, CK7, BER-EP4, ER, and PR, whereas the stromal cells showed positive staining for vimentin, actin, smooth muscle actin, desmin, ER, and PR. Follow-up information obtained in seven patients showed all women without recurrences after 1 to 20 years. The current study highlights the importance of recognizing intrathoracic endometriosis and ectopic deciduosis and properly assessing small biopsy specimens to avoid a misdiagnosis of malignancy.


Comparison of the effects of exercise and cold pressor test on the vasomotor response of normal and atherosclerotic coronary arteries and their relation to the flow-mediated mechanism.
This study was designed to assess the vasomotor response of coronary arteries to exercise and the cold pressor test, and its relationships with the endothelium-mediated dependent mechanism. Twenty-two patients were entered in the study. Group I was composed of 12 patients with a total cholesterol level < 200 mg/dl associated with angiographically smooth, normal coronary arteries. Group 2 consisted of 10 patients with both a cholesterol level > 240 mg/dl and angiographic luminal irregularities of the left anterior descending coronary artery. Coronary blood flow was assessed by a 0.018-inch tip guidewire during Doppler ultrasonography, and analysis of the coronary arterial dimension of the midportion of the left anterior descending coronary artery was performed by quantitative coronary angiography. Catecholamine concentrations were assessed at the different stages of the protocol. The rate-pressure product increased during both the cold pressure test and exercise (p < 0.001). Coronary blood flow velocity increased during the cold pressor and exercise tests by 24.5 +/- 10% and 72 +/- 42%, respectively (p < 0.001), and by 127 +/- 62% (p < 0.0001) after administration of papaverine. In group 1, the cold pressor test had a more pronounced vasodilating effect on epicardial coronary arteries (+11.2 +/- 16%) compared with group 2 (-2 +/- 9%, p < 0.05). Similarly, exercise had a vasodilating action in group 1 (11.3 +/- 15%) compared with group 2 (-1.9 +/- 8%, p < 0.05). Both responses were highly correlated (r = 0.92, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Poly-3-hydroxybutyrate production by Azotobacter chroococcum.
Thirty-seven soil isolates and mutants of Azotobacter chroococcum tested for poly-3-hydroxybutyrate (PHB) production using Sudan black B staining method were found to be positive. One mutant showed a higher number of PHB-producing cells and maximum number of granules per cell. Using 2% glucose and 15 mmol/L ammonium acetate, PHB production was found to be maximum at 36 and 48 h of growth under submerged cultivation and under stationary cultivation, respectively. PHB production was found to be higher on sucrose and commercial sugar (as carbon sources) as compared to glucose and mannitol. As commercial sugar is cheaper than sucrose it was selected as carbon source for PHB production, that being found to be maximum at 1% concentration. Inorganic nitrogen sources seemed to have no stimulatory effect on the production of PHB. However, ammonium acetate (15 mmol/L) was found to be best for PHB production. Peptone (0.2%) gave a better yield of PHB under both growth conditions. Using all optimized conditions, PHB production was studied in ten selected strains. Two of them were found to be best PHB producers under both growth conditions, one producing 621 and 740 micrograms/g dry mass under submerged cultivation and under stationary cultivation, respectively, while the second one produced 589 and 733 micrograms/g.


Self-control training with maltreating parents.
Seeking a method of intervention based on research about correlates of child maltreatment, the authors find that small-group, short-term training in self-control and child management skills gives parents the tools to better handle family stress and develop supportive social networks.


Isolation of a gene encoding a mitochondrial HSP70 protein from Schizosaccharomyces pombe.
We have isolated cDNA and genomic clones encoding a mitochondrial HSP70 protein from Schizosaccharomyces pombe. Nucleotide sequence analysis indicates that the encoded protein is homologous to the HSP70s of other organisms. The highest degree of amino acid conservation is with the proteins encoded by the Escherichia coli dnaK gene, the SSC1 gene of Saccharomyces cerevisiae and the MTP70 gene of Trypanosoma cruzi, the latter two having recently been shown to be located in the mitochondria. Western-blot analysis with immunoglobulin G raised against a peptide corresponding to the C terminus of the SSP1 protein indicates a 70-kDa protein which is associated with the mitochondria.


Combining the oxygen sensor based respirometry and 16S rRNA amplicon sequencing for the analysis of microbiota in commercial mince products.
In this study, rapid respirometric microbial testing was combined with 16S rRNA amplicon sequencing, to assess the composition of microbiota in a total of 64 samples of commercial beef, turkey, lamb and pork mince. The O2 sensor-based respirometry system, while producing the anticipated total aerobic viable counts (TVC) data and patterns for most samples, also revealed unusual (linear) respiration profiles for some samples, mostly lamb and pork mince. The TVC values for beef mince, produced by respirometry and calculated using the available calibration equation, correlated well with the conventional plate counting method, ISO 4833-1:2013, 2013, while for the other species the correlation was less good. These effects, not observed in previous studies employing various food matrices, require further investigation. Using the same samples (crude homogenates) as in respirometry, the whole microbiome was also analysed by 16S rRNA amplicon sequencing for each mince-type. The sequencing showed an overall decrease in alpha diversity over shelf-life, with lamb and pork mince maintaining a proportion of rare taxa. Some taxa exhibited significant changes in abundance over shelf-life and after the respirometric analysis, with beef mince exhibiting a decrease in aerobic bacteria and an increase in facultative anaerobes. Beta diversity was also seen to depend on mince-type. Thus, the combined use of respirometry and sequencing techniques shows promise as a useful and unique analytical approach for food quality and safety evaluation, However, more data points and in-depth analysis are required to back up the findings of this initial study.


Preservation of cerebral blood flow responses to hypoxia and arterial pressure alterations in hyperammonemic rats.
Acute hyperammonemia causes cerebral edema, elevated intracranial pressure and loss of cerebral blood flow (CBF) responsivity to CO2. Inhibition of glutamine synthetase prevents these abnormalities. If the loss of CO2 responsivity is secondary to the mechanical effects of edema, one would anticipate loss of responsivity to other physiological stimuli, such as hypoxia and changes in mean arterial blood pressure (MABP). To test this possibility, pentobarbital-anesthetized rats were subjected to either hypoxic hypoxia (PaO2 approximately 30 mm Hg), hemorrhagic hypotension (MABP approximately 70 and 50 mm Hg), or phenylephrine-induced hypertension (MABP approximately 125 and 145 mm Hg). CBF was measured with radiolabeled microspheres. Experimental groups received intravenous ammonium acetate (approximately 50 mumol min-1 kg-1) for 6 h to increase plasma ammonia to 500-600 microM. Control groups received sodium acetate plus HCl to prevent metabolic alkalosis. The increase in CBF during 10 min of hypoxia after 6 h of ammonium acetate infusion (84 +/- 19 to 259 +/- 52 ml min-1 100 g-1) was similar to that after sodium acetate infusion (105 +/- 20 to 265 +/- 76 ml min-1 100 g-1). Cortical glutamine concentration was elevated equivalently in hyperammonemic rats subjected to normoxia only or to 10 min of hypoxia. With severe hypotension, CBF was unchanged in both the ammonium (80 +/- 20 to 76 +/- 24 ml min-1 100 g-1) and the sodium (80 +/- 14 to 73 +/- 16 ml min-1 100 g-1) acetate groups. With moderate hypertension, CBF was unchanged. With the most severe hypertension, significant increases in CBF occurred in both groups, but there was no difference between groups. We conclude that hypoxic and autoregulatory responses are intact during acute hyperammonemia. The previously observed loss of CO2 responsivity is not the result of a generalized vasoparalysis to all physiological stimuli.


Effectiveness of negative pressure wound therapy/closed incision management in the prevention of post-surgical wound complications: a systematic review and meta-analysis.
The treatment of post-surgical wound complications, such as surgical site infections and surgical wound dehiscence, generates a significant burden for patients and healthcare systems. The effectiveness of negative pressure wound therapy has been under investigation but to date no systematic review has been published in relation to its effectiveness in the prevention of surgical wound complications. To identify the effectiveness of negative pressure wound therapy in the prevention of post-surgical wound complications in adults with a closed surgical incision compared to standard surgical dressings. Male and female adults who have had negative pressure wound therapy applied to their surgical incision following a procedure in one of the following areas: trauma, cardiothoracic, orthopedic, abdominal, or vascular surgery.The intervention of interest was the use of negative pressure wound therapy directly over an incision following a surgical procedure; the comparator was standard surgical dressings.Both experimental and epidemiological study designs, including randomized controlled trials, pseudo-randomized trials, quasi-experimental studies, before and after studies, prospective and retrospective cohort studies, case control studies, and analytical cross sectional studies were sought.The primary outcome was the occurrence of post-surgical wound infection or dehiscence as measured by the following: surgical site infections - superficial and deep; surgical wound dehiscence; wound pain; wound seroma; wound hematoma. Published and unpublished studies in English from 1990 to 2013 were identified by searching a variety of electronic databases. Reference lists of all papers selected for retrieval were then searched for additional studies. Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. Data were extracted from the included papers using a standardized data extraction tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. In addition to study results, the data extracted included details of the study population, setting, intervention and author's conclusion. Where appropriate, data were pooled using Comprehensive Meta-Analysis software. Meta-analyses were performed for three outcomes. In cases of heterogeneity between studies a narrative summary of results was undertaken. Eight studies were included in the review. Meta-analyses revealed a statistically significant difference in favor of the use of negative pressure wound therapy as compared to standard surgical dressings was found for surgical site infections. Conflicting results were found for wound dehiscence and seroma. Given the small number of studies, mostly retrospective comparative cohort in design, no definitive conclusions can be reached as to the effectiveness of the use of negative pressure wound therapy in the prevention of surgical wound complications. However, there was a demonstrated association between the use of negative pressure wound therapy and reduction in surgical site infection. Negative pressure wound therapy in preference to standard postoperative dressings, for example dry gauze, may be considered for closed surgical incisions in adults assessed as high-risk for surgical site infections. The focus of further research on this topic should be level one studies (randomized controlled trials) on patients identified as 'at risk' in the preoperative period.


Impacts of sludge retention time on sludge characteristics and membrane fouling in a submerged osmotic membrane bioreactor.
Sludge retention time (SRT) is a feasible method to alleviate the salt accumulation in the osmotic membrane bioreactor (OMBR) by discharging the waste activated sludge. In this study, effects of SRT on sludge characteristics and membrane fouling were investigated using a submerged OMBR under two SRTs of 10 and 15d. The results showed that the lower SRT was helpful for alleviating the salt accumulation and flux decline. Besides that, the removal of NH3-N was significantly influenced by SRT. SRT also had a strong effect on soluble microbial products (SMP) and microbial activity due to the variation of salinity. Microbial diversity analysis indicated that the high salinity environment in the OMBR significantly affected the microbial communities. The flux decline in the OMBR was mainly attributed to the reduced driving force resulting from the salt accumulation, and the reversible fouling was the dominant forward osmosis (FO) membrane fouling in the OMBR.


Effect of proximity to females on integument damage caused by self-enurination in male goats.
In male goats, self-enurination (SE) is the downward turning of the head and shoulders while urinating onto the face and front legs. Although it provides important chemical cues to females, other males, and even self, it is a costly behavior that can create a range of problems including erythema, irritation, hair loss, and compromised skin. It was hypothesized that the extent of integument damage from SE on bucks' faces and front legs would be increased by housing bucks near females. Four bucks were housed with fence-line contact to females ("Near" bucks), and four bucks were housed without fence-line contact to females ("Far" bucks). Each buck was photographed every other week over an 18-wk period during the breeding season. During each imaging session, seven different photographic views were captured, and burn areas were quantified for each buck. Overall, more Near bucks had urine burn than Far bucks, and Near bucks developed urine burn earlier in the breeding season than did Far bucks. Housing bucks close to females increases the extent of integument damage from SE. These findings may help goat breeders develop management practices to improve animal well-being by minimizing urine burn injury to bucks.


Irreducible anteromedial radial head dislocation without fracture caused by transposed biceps tendon in an adult: A case report and literature review.
Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of right elbow reveals in a "semi-extended and pronated" elastic fixation position. Radiography and three-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.


Efficacy of quetiapine monotherapy for the treatment of depressive episodes in bipolar I disorder: a post hoc analysis of combined results from 2 double-blind, randomized, placebo-controlled studies.
To investigate the efficacy and tolerability of quetiapine monotherapy for the treatment of major depressive episodes in patients with bipolar I disorder, as a post hoc analysis of data from 2 large studies, the BipOLar DEpRession (BOLDER) I and II studies, which investigated the overall efficacy of quetiapine in both bipolar I and II disorder. A combined cohort of patients with depressive episodes in bipolar I disorder (DSM-IV criteria) (N = 694) from 2 nearly identical double-blind, randomized, placebo-controlled studies that each randomly assigned patients with bipolar I and II disorder to 8 weeks of treatment with quetiapine 300 or 600 mg/day or placebo was analyzed. The primary efficacy measure was change from baseline to end of treatment (week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores. In the combined cohort of patients with depressive episodes in bipolar I disorder from 2 studies, there were significantly greater clinical improvements in mean MADRS total scores among patients who received quetiapine compared with placebo from baseline to week 1 and through week 8 (at week 8: quetiapine 300 mg/day = -19.4; 600 mg/day = -19.6; placebo = -12.6; p < .001 for each dose), providing effect sizes of 0.78 and 0.80, respectively. Changes in MADRS were unrelated to reports of sedation and somnolence. The most common adverse events (AEs) with quetiapine were dry mouth, somnolence, sedation, dizziness, and constipation. Rates of withdrawal because of these AEs were relatively low. Quetiapine monotherapy (300 and 600 mg/day) is more effective than placebo and generally well tolerated for the treatment of depressive episodes in patients with bipolar I disorder.


Insulin stimulates GDP release from G proteins in the rat and human liver plasma membranes.
Plasma membranes (1-2 mg protein) prepared from the livers of adult male rats and human organ donors were incubated with 0.6 microM [alpha-32P] guanosine triphosphate (GTP) in an adenosine triphosphate (ATP)-regenerating buffer at 37 degrees C for 1 h; during this incubation, the [32P]GTP is hydrolyzed and the nucleotide that is predominantly bound to the membranes is [32P] guanosine diphosphate (GDP). [32P]GDP release from the liver membranes was proportional to the protein concentration and increased as a function of time. At 5 mM, Ca2+, Mg2+, Mn2+, and Zn2+ maximally inhibited GDP release by 80-90%, whereas, 5 mM Cu2+ maximally stimulated the reaction by 100%. Therefore, cations were not included in the buffer used in the GDP release step. One microM Gpp(NH)p (5'-guanylylimidodiphosphate), a nonhydrolyzable analog of GTP, maximally stimulated [32P]GDP release in the liver membranes by up to 30%. Although 10 nM Gpp(NH)p had no effect on GDP release, it appeared to stabilize the hormonal effect by blocking further GDP/GTP exchange. In the rat membranes, 1-100 nM glucagon (used as a positive control) stimulated [32P]GDP release by about 17% (P < .05); similarly, 0.1-100 nM insulin stimulated [32P]GDP release by 10-13% (P < .05). In the human membranes, 10 pM to 100 nM insulin stimulated [32P]GDP release by 7-10%. In the rat membranes, 10 nM insulin stimulated [32P]GDP release by 17 and 24% at 2 and 4 min, respectively (P < .05); in the human membranes, 10 nM insulin stimulated [32P]GDP release by about 9% at 2 and 4 min.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of enamel thickness and refractive index on human tooth colour.
To investigate the role of enamel thickness and refractive index (n) on tooth colour. The colour and enamel thickness of fifteen extracted human central incisors were determined according to CIELab colour scale using spectrophotometer (Crystaleye) and swept-source optical coherence tomography (SS-OCT), respectively. Subsequently, labial enamel was trimmed by approximately 100μm, and the colour and remaining enamel thickness were investigated again. This cycle was repeated until dentin appeared. Enamel blocks were prepared from the same teeth and their n were obtained using SS-OCT. Multiple regression analysis was performed to reveal any effects of enamel thickness and n on colour difference (ΔE00) and differences in colour parameters with CIELCh and CIELab colour scales. Multiple regression analysis revealed that enamel thickness (p=0.02) and n of enamel (p<0.001) were statistically significant predictors of ΔE00 after complete enamel trimming. The n was also a significant predictor of ΔH' (p=0.01). Enamel thickness and n were not statistically significant predictors of ΔL', ΔC', Δa* and Δb*. Enamel affected tooth colour, in which n was a statistically significant predictor for tooth colour change. Understanding the role of enamel in tooth colour could contribute to development of aesthetic restorative materials that mimic the colour of natural tooth with minimal reduction of the existing enamel.


Neuro-ophthalmologic dilemma: chronic optic neuritis?
A patient with an 8-month history of chronic progressive visual loss was referred to the Neuro-ophthalmology Consult Office of Washington University with a diagnosis of chronic optic neuritis. Previous diagnostic studies, including CAT scan, had been negative. Because chronic progressive visual loss is considered a hallmark of mass lesion, more vigorous investigation, including repeat CAT scans, was undertaken, leading to the diagnosis and removal of a 2 cm meningioma.


The influence of cimetidine versus ranitidine on doxepin pharmacokinetics.
The effect of cimetidine and ranitidine on doxepin pharmacokinetics was studied in 6 healthy volunteers. Each subject completed 3 study phases: Treatment A, 9 consecutive doses of 50 mg doxepin (once daily); Treatment B, same as Treatment A but co-administration of cimetidine 600 mg b.i.d. starting after the sixth doxepin dose and continuing until approximately 2 days following discontinuation of doxepin administration; Treatment C, identical to Treatment B but with ranitidine 150 mg b.i.d. instead of cimetidine. Unlike ranitidine, cimetidine co-administration resulted in a significant increase in steady state plasma levels of doxepin (4.7, 9.0 and 4.5 ng/ml during Treatments A, B and C respectively) but not desmethyldoxepin (4.1, 4.6 and 4.2 ng/ml during Treatments A, B and C respectively). Elimination half-lives of doxepin and desmethyldoxepin were prolonged by cimetidine co-administration (19.6 and 26.2 h respectively), but remained unchanged during the ranitidine treatment phase (13.3 and 18.4 h) as compared to the control phase i.e. Treatment A (13.2 and 19.0 h). These results show that cimetidine, unlike ranitidine, significantly inhibits the biotransformation of doxepin. This data has clinical implications when the co-administration of tricylic antidepressants and H2-receptor antagonists are indicated.


Host-membrane interacting interface of the SARS coronavirus envelope protein: Immense functional potential of C-terminal domain.
The Envelope (E) protein in SARS Coronavirus (CoV) is a small structural protein, incorporated as part of the envelope. A major fraction of the protein has been known to be associated with the host membranes, particularly organelles related to intracellular trafficking, prompting CoV packaging and propagation. Studies have elucidated the central hydrophobic transmembrane domain of the E protein being responsible for much of the viroporin activity in favor of the virus. However, newer insights into the organizational principles at the membranous compartments within the host cells suggest further complexity of the system. The lesser hydrophobic Carboxylic-terminal of the protein harbors interesting amino acid sequences- suggesting at the prevalence of membrane-directed amyloidogenic properties that remains mostly elusive. These highly conserved segments indicate at several potential membrane-associated functional roles that can redefine our comprehensive understanding of the protein. This should prompt further studies in designing and characterizing of effective targeted therapeutic measures.


Human physiological models of insomnia.
Despite the wide prevalence and important consequences of insomnia, remarkably little is known about its pathophysiology. Available models exist primarily in the psychological domain and derive from the demonstrated efficacy of behavioral treatment approaches to insomnia management. However, these models offer little specific prediction about the anatomic or physiological foundation of chronic primary insomnia. On the other hand, a growing body of data on the physiology of sleep supports a reasonably circumscribed overview of possible pathophysiological mechanisms, as well as the development of physiological models of insomnia to guide future research. As a pragmatic step, these models focus on primary insomnia, as opposed to comorbid insomnias, because the latter is by its nature a much more heterogeneous presentation, reflecting the effects of the distinct comorbid condition. Current understanding of the regulation of sleep and wakefulness in mammalian brain supports four broad candidate areas: 1) disruption of the sleep homeostat; 2) disruption of the circadian clock; 3) disruption of intrinsic systems responsible for the expression of sleep states; or 4) disruption (hyperactivity) of extrinsic systems capable of over-riding normal sleep-wake regulation. This review examines each of the four candidate pathophysiological mechanisms and the available data in support of each. While studies that directly test the viability of each model are not yet available, descriptive data on primary insomnia favor the involvement of dysfunctional extrinsic stress-response systems in the pathology of primary chronic insomnia.


Training to enhance walking in children with cerebral palsy: are we missing the window of opportunity?
The objective of this paper is to (1) identify from the literature a potential critical period for the maturation of the corticospinal tract (CST) and (2) report pilot data on an intensive, activity-based therapy applied during this period, in children with lesions to the CST. The best estimate of the CST critical period for the legs is when the child is younger than 2 years of age. Previous interventions for walking in children with CST damage were mainly applied after this age. Our preliminary results with training children younger than 2 years showed improvements in walking that exceeded all previous reports. Further, we refined techniques for measuring motor and sensory pathways to and from the legs, so that changes can be measured at this young age. Previous activity-based therapies may have been applied too late in development. A randomized controlled trial is now underway to determine if intensive leg therapy improves the outcome of children with early stroke.