Preparation of biochar by simultaneous carbonization, magnetization and activation for norfloxacin removal in water.
Activated magnetic biochar (AMB) was prepared with corn stalks, reed stalks, and willow branches by simultaneous carbonization, magnetization, and activation, and used for norfloxacin removal in water. The exploration results showed that the zeta potential was positively charged at pH 2-10. These prepared activated magnetic biochars have a large specific surface area (>700m2·g-1) and pore volume (>0.3cm3·g-1). The quasi-second-order kinetic adsorption equation could better describe the adsorption of NOR on AMB. The Langmuir isotherm showed the better fitting results on AMB. The AMB showed the strong adsorption of NOR, and the saturated adsorption capacity of corn activated magnetic biochar was the highest, 7.6249mg·g-1. The adsorption of NOR on AMB was a spontaneous endothermic process. The effect of pH on the adsorption behaviors of NOR on AMB was not obvious, and AMB had a good adsorption effect on NOR in a wide pH range.


Salt impregnation of implant materials.
Implant infection and peri-implantitis are recurrent and serious complications in implantology. Antibiotic treatment of infected implants in bone is complicated because of limited vascularization of the surrounding tissue on the one hand, and biofilm formation on the implant surface on the other. Therefore, contamination of the implant surface has to be prevented. For this purpose we developed a method of coating Ti6Al4V samples with NaCl in order to reduce the water activity on the sample surface. The resulting NaCl-coated surfaces showed good biocompatibility with osteoblastlike cells and resulted in a significant reduction of bacterial strains. The presented surface modification is hence a promising method to reduce bacterially induced implant failure.


Ni Flower/MXene-Melamine Foam Derived 3D Magnetic/Conductive Networks for Ultra-Efficient Microwave Absorption and Infrared Stealth.
The development of multifunctional and efficient electromagnetic wave absorbing materials is a challenging research hotspot. Here, the magnetized Ni flower/MXene hybrids are successfully assembled on the surface of melamine foam (MF) through electrostatic self-assembly and dip-coating adsorption process, realizing the integration of microwave absorption, infrared stealth, and flame retardant. Remarkably, the Ni/MXene-MF achieves a minimum reflection loss (RLmin) of - 62.7 dB with a corresponding effective absorption bandwidth (EAB) of 6.24 GHz at 2 mm and an EAB of 6.88 GHz at 1.8 mm. Strong electromagnetic wave absorption is attributed to the three-dimensional magnetic/conductive networks, which provided excellent impedance matching, dielectric loss, magnetic loss, interface polarization, and multiple attenuations. In addition, the Ni/MXene-MF endows low density, excellent heat insulation, infrared stealth, and flame-retardant functions. This work provided a new development strategy for the design of multifunctional and efficient electromagnetic wave absorbing materials.


Design, synthesis and SAR of new-di-substituted pyridopyrimidines as ATP-competitive dual PI3Kα/mTOR inhibitors.
PI3Kα/mTOR ATP-competitive inhibitors are considered as one of the promising molecularly targeted cancer therapeutics. Based on lead compound A from the literature, two similar series of 2-substituted-4-morpholino-pyrido[3,2-d]pyrimidine and pyrido[2,3-d]pyrimidine analogs were designed and synthesized as PI3Kα/mTOR dual inhibitors. Interestingly, most of the series gave excellent inhibition for both enzymes with IC50 values ranging from single to double digit nM. Unlike many PI3Kα/mTOR dual inhibitors, our compounds displayed selectivity for PI3Kα. Based on its potent enzyme inhibitory activity, selectivity for PI3Kα and good therapeutic index in 2D cell culture viability assays, compound 4h was chosen to be evaluated in 3D culture for its IC50 against MCF7 breast cancer cells as well as for docking studies with both enzymes.


New HLA DNA polymorphisms associated with autoimmune diseases.
Certain class II determinants of the human histocompatibility locus antigens (HLA) have been implicated in the aetiology of several autoimmune diseases, including rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM). HLA-Dw4 was the first HLA determinant found to be significantly increased in RA patients compared with controls, while Dw4 and Dw3 were found to be significantly increased in IDDM patients. When the HLA-DR system was defined, RA patients were found to have an increased frequency of DR4 and IDDM patients an increased incidence of both DR4 and DR3 compared with controls. As the HLA-Dw specificities are narrower than the serologically defined DR specificities, it was of specific interest to the present study that Dw4, Dw10, Dw13, Dw14, Dw15 and DKT2 are included in DR4. We describe here new restriction fragment length polymorphisms (RFLPs) and, together with the newly described serologically defined DQ specificity TA10, test their prevalence and associations in controls and diseased patients. We find that the newly characterized DNA bands are present at a much higher frequency in RA and IDDM patients than in controls. These findings may lead to a greater understanding of the pathogenesis of such diseases.


Cadmium toxicity mediated by the inhibition of SLC2A4 expression in human proximal Tubule cells.
Cadmium (Cd) is an environmental contaminant that causes renal toxicity. We have previously demonstrated that Cd induces renal toxicity by altering transcriptional activities. In this study, we show that Cd markedly inhibited the activity of transcription factor MEF2A in HK-2 human proximal tubule cells, which generated significant cytotoxicity in the cells. This reduction in the nuclear levels of MEF2A protein may be involved in the Cd-induced inhibition of MEF2A activity. We also demonstrate that one of the glucose transporters, GLUT4, was downregulated not only by Cd treatment but also by MEF2A knockdown. Knockdown of SLC2A4, encoding GLUT4, eliminated both cell viability and Cd toxicity. Cd treatment or SLC2A4 deficiency reduced the cellular concentration of glucose. Therefore, the suppression of SLC2A4 expression, which mediates the reduction in cellular glucose, is involved in Cd toxicity. The Cd toxicity induced by the reduction in GLUT4 may be associated with a reduction of cellular ATP levels in HK-2 cells. The levels of Slc2a4 mRNA in the kidney of mice exposed to Cd for 6 or 12 months were significantly lower than those in the control group. These results demonstrate that Cd exerts its cytotoxicity through the suppression in SLC2A4 expression and the subsequent inhibition of MEF2A transcriptional activity. Cd-induced suppression of SLC2A4 expression also reduces cellular ATP levels, partly by reducing glucose levels. This study suggests that the glucose transporter plays an important role in the renal toxicity of Cd, and provides a crucial breakthrough in our understanding of the mechanism of Cd toxicity.


No effects of rhythmic visual stimulation on target discrimination: An online alpha entrainment experiment.
Previous research established that rhythmic sensory stimulation can affect subsequent stimulus perception, possibly through 'entrainment' of oscillations in the brain. Alpha frequency is a natural target for visual entrainment, because fluctuations in posterior alpha oscillations have been linked to visual target detection or discrimination. On the other hand, alpha oscillations also relate to attentional mechanisms, such as attentional orienting or selection. Previous visual alpha entrainment studies focused on differential processing of targets presented in-phase with the preceding rhythmic stimulation relative to out-of-phase targets (an 'SOA effect'), putatively related to the phase of entrained neuronal alpha oscillations. Fewer studies probed the consequences of rhythmic alpha stimulation for attention mechanisms related to alpha power. Here, we asked whether alpha stimulation of one hemifield has similar effects on reaction times as we see for increased alpha synchronization in magneto/electroencephalography (M/EEG) studies (i.e., more alpha means impaired processing and functional inhibition). We implemented a task inspired by attention studies, assessing reaction times to ipsilateral vs. contralateral visual targets, with and without concurrent presentation of distractors. Yet, in place of any attention cues, we presented a rhythmic, vs. arrhythmic, alpha-frequency train of visual flashes to one hemifield, in a large sample size (N = 115) in an online experiment. We found clear evidence that flash train rhythmicity did not impact task performance. We also found that the spatial congruence between the unilateral flash train and the subsequent visual target did impact response times but only in the presence of contralateral distractor stimuli. We discuss implications, limitations and future directions.


Spatial distributions, source apportionment and ecological risk of SVOCs in water and sediment from Xijiang River, Pearl River Delta.
Xijiang River is an important drinking water source in Guangxi Province, China. Along the Xijiang River and surrounding tributary, the pollution profile of three important groups of semi-volatile organic compounds, including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and phthalate esters (PAEs), was analyzed. Relatively low levels of PAHs (64-3.7 × 102 ng L-1) and OCPs (16-70 ng L-1), but high levels of PAEs (7.9 × 102-6.8 × 103 ng L-1) occurred in the water. Comparatively, low levels of OCPs (39-1.8 × 102 ng g-1) and PAEs (21-81 ng g-1), but high levels of PAHs (41-1.1 × 103 ng g-1) were found in sediment. Principal component analyses for source identification indicated petroleum-derived residues or coal and biomass combustion, and vehicular emission was the main sources for PAHs. The OCPs sources of each category were almost independent, whereas the new input of HCHs and p,p'-DDTs probably existed in some areas. PAEs were mainly originated from personal care products of urban sewage, plastic and other industrial sources. Ecological risk through the risk quotient analysis indicated a small or significant potential adverse effect on fish, daphnia and green algae. Nevertheless, the integrated risk of all pollutants should be taken into account in future study.


Bone marrow stem cells added to a hydroxyapatite scaffold result in better outcomes after surgical treatment of intertrochanteric hip fractures.
Intertrochanteric hip fractures occur in the proximal femur. They are very common in the elderly and are responsible for high rates of morbidity and mortality. The authors hypothesized that adding an autologous bone marrow stem cells concentrate (ABMC) to a hydroxyapatite scaffold and placing it in the fracture site would improve the outcome after surgical fixation of intertrochanteric hip fractures. 30 patients were randomly selected and divided into 2 groups of 15 patients, to receive either the scaffold enriched with the ABMC (Group A) during the surgical procedure, or fracture fixation alone (Group B). There was a statistically significant difference in favor of group A at days 30, 60, and 90 for Harris Hip Scores (HHS), at days 30 and 60 for VAS pain scales, for bedridden period and time taken to start partial and total weight bearing (P < 0.05). These results show a significant benefit of adding a bone marrow enriched scaffold to surgical fixation in intertrochanteric hip fractures, which can significantly reduce the associated morbidity and mortality rates. Bone marrow stem cells added to a hydroxyapatite scaffold result in better outcomes after surgical treatment of intertrochanteric hip fractures.


Near-infrared spectroscopy assessment following exercise training in patients with intermittent claudication and in untrained healthy participants.
Selected near-infrared spectroscopy (NIRS) parameters were assessed in healthy untrained participants and in peripheral arterial disease (PAD) trained patients to evaluate their usefulness in rehabilitative outcome. Forty-five PAD and 15 healthy participants were studied at entry and at 34 ± 2 weeks. Healthy participants performed their usual activities. Patients with PAD performed 2 home-based programs: structured at prescribed pace (S-pre, n = 31) and unstructured at free pace (U-free, n = 14). We measured ankle-brachial index (ABI), NIRS calf oxygen consumption at rest, NIRS dynamic muscle perfusion during an incremental test, and walking capacity. In all patients with PAD the NIRS parameters significantly increased approaching the stable values of untrained healthy participants. Among PAD, only S-pre group showed significant improvements in hemodynamic, functional, and NIRS parameters with selective adaptations in the worse legs. The assessment of NIRS parameters, that were found stable without training in healthy and modified in PAD only following structured training, might outline the local exercise-induced adaptations.


Do elevated levels of abdominal visceral adipose tissue contribute to age-related differences in plasma lipoprotein concentrations in men?
Age-related differences in body fat and more specifically in the accumulation of abdominal visceral adipose tissue were examined as a potential covariate for the alteration in the plasma lipoprotein profile found with aging. For that purpose, results from 79 young adults (aged 24.5 +/- 4.0 years) were compared to 61 middle-aged men (54.7 +/- 6.4 years). Younger men had significantly lower body fat mass and abdominal visceral adipose tissue area measured by computed tomography than middle-aged men (P < 0.0001). Plasma cholesterol, triglyceride, apolipoprotein (apo) B, low density lipoprotein (LDL)-cholesterol and LDL apo B levels, as well as the ratio of plasma cholesterol to high density lipoprotein (HDL)-cholesterol were all significantly lower in younger men as compared to middle-aged men (P < 0.0001). The comparison of younger men to middle-aged men with comparable levels of abdominal visceral fat and total body fat eliminated the age-related differences in plasma triglyceride and in the ratio of plasma cholesterol to HDL-cholesterol, whereas the difference in plasma apolipoprotein B levels, although still significant, was largely reduced. Age-related differences in plasma cholesterol and in LDL-cholesterol levels were still observed after this matching procedure and the differences between age-groups were essentially of similar magnitude than before pairing. In summary, these results suggest that the deterioration of plasma lipoprotein profile observed in middle-aged men as compared to young adult men is partly mediated by concomitant increases in total body fat and abdominal visceral adipose tissue. However, other factors related to the aging process appear to be involved, particularly for the age-related increase in plasma LDL-cholesterol.


α-D-Glucose as a non-radioactive MRS tracer for metabolic studies of the brain.
Changes in brain glucose metabolism occur in many neurological disorders as well as during aging. Most studies on the uptake of glucose in the brain use positron emission tomography, which requires injection of a radioactive tracer. Our study shows that ultra-high-field 1H-MRS can be used to measure α-D-glucose at 5.22 ppm in vivo, and the α-D-glucose can be used as a radiation-free tracer in the human brain.


Stabilization strategies of a general nonlinear car-following model with varying reaction-time delay of the drivers.
In this paper, the stabilization strategies of a general nonlinear car-following model with reaction-time delay of the drivers are investigated. The reaction-time delay of the driver is time varying and bounded. By using the Lyapunov stability theory, the sufficient condition for the existence of the state feedback control strategy for the stability of the car-following model is given in the form of linear matrix inequality, under which the traffic jam can be well suppressed with respect to the varying reaction-time delay. Moreover, by considering the external disturbance for the running cars, the robust state feedback control strategy is designed, which ensures robust stability and a smaller prescribed H∞ disturbance attenuation level for the traffic flow. Numerical examples are given to illustrate the effectiveness of the proposed methods.


Developmental increases in the inwardly-rectifying K+ current of embryonic chick ventricular myocytes.
Whole-cell and single-channel inwardly-rectifying K+ currents (IK1) of early (3-day-old) and late (17-day-old) embryonic chick ventricular myocytes were compared to ascertain whether there are developmental changes in the properties of this conductance. The magnitude of the IK1 conductance in the early myocytes was small, but it was increased about five-fold in the older embryonic myocytes. It was found that the density of inwardly-rectifying K+ channels was greater (in the surface membrane) of the 17-day than in the 3-day embryonic myocyte. In addition, the single channel conductance for 17-day myocytes was several-fold larger than for the 3-day myocytes. These results suggest that cardiac inward rectifier channels may not only proliferate in number, but may also undergo structural alterations during development.


A novel CD28 mRNA variant and simultaneous presence of various CD28 mRNA isoforms in human T lymphocytes.
The primary transcript of the human CD28 gene in T lymphocytes, encoding for a costimulatory molecule, is known to undergo alternative splicing, and different small sets of variant isoforms have been reported. This report presents the novel simultaneous presence of eight different mRNA isoforms, all observed together in normal human T cells; this is an interesting finding in the study of CD28 mRNA structural variants. A similar pattern was found in a total of four individuals. In addition, we also report the occurence and sequence of a new CD28 mRNA isoform, one of the above eight, which is a novel variant generated by the use of a new combination of splice donor and acceptor sites.


Phosphorylation of the calmodulin-dependent protein phosphatase by protein kinase C.
The calmodulin-dependent protein phosphatase was shown to be phosphorylated by the Ca2+, phospholipid-dependent protein kinase (protein kinase C). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the 61 kDa catalytic subunit was phosphorylated. Phosphorylation by protein kinase C was stimulated up to 15-fold by addition of phosphatidyl-L-serine and between 0.5 to 1.0 mole of phosphate was incorporated per mole of phosphatase. It is possible that protein kinase C is involved in the regulation of the calmodulin-dependent protein phosphatase via this novel phosphorylation of the enzyme.


Modulating photoswitch performance with halogen, coordinative and hydrogen bonding: a comparison of relative bond strengths.
The behavior of an enediyne photoswitch is modulated with halogen bonding, coordinative bonding and hydrogen bonding. Through NMR and computational studies we demonstrate that the relative strength of the secondary bonding directly influences the rate of photoisomerization and the photostationary state.


Tumor Cell Extrinsic Synaptogyrin 3 Expression as a Diagnostic and Prognostic Biomarker in Head and Neck Cancer.
Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV) yet biomarkers for stratifying oropharyngeal head and neck squamous cell carcinoma (HNSC) patient risk are limited. We used immunogenomics to identify differentially expressed genes in immune cells of HPV(+) and HPV(-) squamous carcinomas. Candidate genes were tested in clinical specimens using both quantitative RT-PCR and IHC and validated by IHC using the Carolina Head and Neck Cancer Study (CHANCE) tissue microarray of HNSC cases. We performed multiplex immunofluorescent staining to confirm expression within the immune cells of HPV(+) tumors, receiver operating characteristic (ROC) curve analyses, and assessed survival outcomes. The neuronal gene Synaptogyrin-3 (SYNGR3) is robustly expressed in immune cells of HPV(+) squamous cancers. Multiplex immunostaining and single cell RNA-seq analyses confirmed SYNGR3 expression in T cells, but also unexpectedly in B cells of HPV(+) tumors. ROC curve analyses revealed that combining SYNGR3 and p16 provides more sensitivity and specificity for HPV detection compared to p16 IHC alone. SYNGR3-high HNSC patients have significantly better prognosis with five-year OS and DSS rates of 60% and 71%, respectively. Moreover, combining p16 localization and SYNGR3 expression can further risk stratify HPV(+) patients such that high cytoplasmic, low nuclear p16 do significantly worse (Hazard Ratio, 8.6; P = 0.032) compared to patients with high cytoplasmic, high nuclear p16. SYNGR3 expression in T and B cells is associated with HPV status and enhanced survival outcomes of HNSC patients.


The price of emergency contraception in the United States: what is the cost-effectiveness of ulipristal acetate versus single-dose levonorgestrel?
Ulipristal acetate (UPA) is a novel form of emergency contraception (EC) that appears to be more effective than the prevailing method, single-dose levonorgestrel (LNG). This study examines the cost-efficacy of UPA compared with LNG. A decision-analytic model was developed to compare the cost-effectiveness of UPA versus LNG in preventing unintended pregnancy when taken within 120 h of unprotected intercourse. Univariate and bivariate sensitivity analyses, as well as Monte Carlo simulation and threshold analyses, were performed. Utilizing UPA instead of LNG would result in 37,589 fewer unintended pregnancies per 4,176,572 estimated US annual EC uses (UPA 54,295 pregnancies; LNG 91,884 pregnancies) and a societal savings of $116.3 million annually. Cost-effectiveness acceptability curve analyses suggest a 96% probability that UPA is more cost-effective at a willingness to pay $100,000 per quality-adjusted life year. UPA is cost-effective in preventing unintended pregnancy after unprotected intercourse. Efforts should be promoted to increase access to UPA.


The effect of humeral version on teres minor muscle moment arm, length, and impingement in reverse shoulder arthroplasty during activities of daily living.
External rotation can be compromised after reverse total shoulder arthroplasty (RTSA). A functional teres minor (TM) is relatively common in patients with posterosuperior tears of the rotator cuff, and its function should be enhanced for better postoperative results. The aim of this study was to investigate how the version of humeral fixation can affect the TM rotational moment arm and muscle length as well as impingement after RTSA. A 3-dimensional shoulder model was used to describe RTSA. Four humeral fixation versions were tested: +20°, 0°, -20°, and -40° (+, anteverted; -, retroverted). TM rotational moment arm and length as well as impingement-free range of motion were calculated for a set of 3 simple clinical motions: (1) scapula plane abduction (0°-150°); (2) internal/external rotation with the arm in adduction; and (3) internal/external rotation with the arm in abduction. Six common activities of daily living were also evaluated. An anteverted fixation maximized TM moment arms, but it also resulted in very short muscle length (compared with normal) and increased inferior impingement. In contrast, 40° humeral retroversion resulted in the longest TM muscle length, but it also showed the smallest moment arms and increased anterior impingement in some of the activities of daily living. Even if TM external rotation moment arm is higher in RTSA than in a normal shoulder, the decreased length could impair its force generation. The 0° and 20° retroversion was the optimum compromise between sufficient TM length and moment arm with minimum impingement.


Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis.
Inhibition of glycogen synthase kinase (GSK)-3 and the consequent activation of the Wnt/β-catenin signaling pathway have been reported to increase bone volume. To develop a novel pharmacotherapy for injured bone, we investigated whether GSK-3 inhibitor was effective in promoting bone formation. In in vitro experiments, we examined the effects of GSK-3 inhibitors LiCl and SB216763 on osteoblastogenesis of mesenchymal progenitor C3H10T1/2 cells and osteoclastogenesis of osteoclast precursor RAW-D cells. Both inhibitors promoted osteoblast differentiation, assessed by alkaline phosphatase activity and calcium deposition, stimulating the Wnt/β-catenin signaling pathway and thereby inducing Runx2. On the other hand, the GSK-3 inhibitors suppressed osteoclast differentiation, assessed by tartrate-resistant acid phosphatase staining and number of nuclei in the cells, reducing NFATc1 expression independently of the Wnt/β-catenin signaling pathway. In subsequently performed in vivo studies, we examined the effect of locally administered Li2CO3 on the recovery from a partial defect made on the rat tibia. Computerized tomography and bone histomorphometry showed that Li2CO3 accelerated bone regeneration in defect lesion with increased lamellar bone ratio compared with the controls. These results suggested that local application of lithium (or other GSK-3 inhibitors) might effectively facilitate recovery from bone injury by promoting osteoblastogenesis and inhibiting osteoclastogenesis.


Quantification of phenolic compounds in vegetable oils by mixed-mode solid-phase extraction isotope chemical labeling coupled with UHPLC-MS/MS.
In the present work, a rapid, accurate and cost-effective method has been developed for the simultaneous quantification of phenolic compounds in oil using mixed-mode solid-phase extraction (SPE) coupled with chemical labeling UHPLC-MS/MS. Mix-mode SPE weak cation cartridges were selected to enrich and purify phenolic compounds in oil, and hydroxyl moiety was dansylation as stable-isotope internal standard. The major parameters that affected the extraction and chemical labeling efficiency were investigated, and the method was fully validated. The limit of quantifications and the limit of detections were 0.002 µg kg-1 ~ 0.10 µg kg-1 and 0.006 µg kg-1 ~ 0.30 µg kg-1, respectively. The recoveries were 61.2% ~ 129.3% with intra-day and inter-day precision less than 12%. The results for 38 rapeseed oils revealed that 14 phenolic compounds, including canolol, phenolic acids, phenolic alcohols, tyrosol and vanillin from trace levels to relatively high content.


An outer membrane enzyme encoded by Salmonella typhimurium lpxR that removes the 3'-acyloxyacyl moiety of lipid A.
The Salmonella and related bacteria modify the structure of the lipid A portion of their lipopolysaccharide in response to environmental stimuli. Some lipid A modifications are required for virulence and resistance to cationic antimicrobial peptides. We now demonstrate that membranes of Salmonella typhimurium contain a novel hydrolase that removes the 3'-acyloxyacyl residue of lipid A in the presence of 5 mM Ca2+. We have identified the gene encoding the S. typhimurium lipid A 3'-O-deacylase, designated lpxR, by screening an ordered S. typhimurium genomic DNA library, harbored in Escherichia coli K-12, for expression of Ca2+-dependent 3'-O-deacylase activity in membranes. LpxR is synthesized with an N-terminal type I signal peptide and is localized to the outer membrane. Mass spectrometry was used to confirm the position of lipid A deacylation in vitro and the release of the intact 3'-acyloxyacyl group. Heterologous expression of lpxR in the E. coli K-12 W3110, which lacks lpxR, resulted in production of significant amounts of 3'-O-deacylated lipid A in growing cultures. Orthologues of LpxR are present in the genomes of E. coli O157:H7, Yersinia enterocolitica, Helicobacter pylori, and Vibrio cholerae. The function of LpxR is unknown, but it could play a role in pathogenesis because it might modulate the cytokine response of an infected animal.


Asymmetry of the C2 pars interarticularis: a clinical anatomical study with relevance to screw placement.
Potential asymmetries of the C2 posterior elements pose a problem for the spine surgeon seeking to make the best choice for spinal stabilization while reducing morbidity. A digital caliper was used to measure the pars interarticularis height and length on left and right sides of 25 adult C2 vertebrae. The pars interarticularis was defined as the bone between the posterior most aspect of the superior articular process and the anterior most aspect of the inferior articular process of C2. Also, the C2 vertebrae from 49 patients were scanned by CT. Parasagittal images were reviewed and using the same definitions as were used for the skeletal specimens, the length and the height of the C2 pars interarticularis from both the left and right sides were measured using CT. The image slices were acquired at 3 mm intervals. The pars interarticularis height was determined on sagittal CT reconstruction, while the pars interarticularis length was calculated on the basis of the axial images. The lengths and the heights of the left and right pars interarticularis were compared using CTs of patients and skeletal specimens. No significant differences were found in the length and height measurements of the CT images on both sides. However, in the skeletal specimens, the left and right pars interarticularis did not differ significantly in length but differed significantly in height (p = 0.003). The mean height of the left pars interarticularis was approximately two times larger than the right in the skeletal specimens. Absolute differences were calculated between the side with the greater length and height and the side with the lesser length and height irrespective of their left-right orientations. For CT measurements, most differences in length and height between the greater pars interarticularis and lesser pars interarticularis occurred between 0 and 1 mm with each successive disparity interval yielding lower numbers. Skeletal measurements revealed a similar length disparity distribution to the CT measurements. However, height measurements in the skeletal specimens varied widely. Eight pars interarticularis specimens demonstrated a height difference between 0 and 1 mm. No dry bone pars interarticularis specimens demonstrated a height difference between 1 and 2 mm. The pars interarticularis of nine specimens demonstrated a height difference between 2 and 3 mm. Two demonstrated a height difference between 3 and 4 mm. Four demonstrated a height difference between 4 and 5 mm and two demonstrated a height difference greater than 5 mm. The greater pars interarticularis lengths and heights were combined and compared to their lesser counterparts on CT and skeletal measurements. In all measurements of this type, significant differences were found in the pars interarticularis length and height, whether measured through CT or via digital calipers. Asymmetry between the left and right C2 pars interarticularis as shown in the present study can alter surgical planning. Therefore, knowledge of this anatomical finding might be useful to spine surgeons.


Effects of hypoxia on muscle capillarity in rats.
Capillary density, fiber cross-sectional area, capillary/fiber ratio and fiber composition were determined in gastrocnemius and diaphragm muscles of laboratory rats following five weeks at 350 Torr ambient pressure. Growth rates of hypoxic rats were lower than normoxic controls, but the periods of sacrifice were adjusted to achieve similar body masses for the two groups. Hypoxic rats had significantly higher hematocrits and heart masses, characteristic of acclimation to hypoxia. However, capillary/fiber ratios in gastrocnemius and diaphragm were similar for hypoxic and normoxic rats suggesting that hypoxia did not stimulate capillarity in either muscle. In diaphragm, but not gastrocnemius, diffusion distances were significantly shorter in hypoxic rats than in controls. We conclude that the differences in diffusion distances represent an important secondary effect of hypoxia on the diaphragm associated with changes in demands on ventilation in response to low oxygen pressures.


The enantiomers of SK&F 83566, a new selective D-1 dopamine antagonist, stereospecifically block stereotyped behaviour induced by apomorphine and by the selective D-2 agonist RU 24213.
The non-selective dopamine receptor agonist apomorphine and the selective D-2 receptor agonist RU24213 each induced a typical syndrome of stereotyped behaviour characterised by sniffing and locomotion. The syndrome and its associated behaviours induced by each agonist were dose-dependently antagonised by pretreatment with the R- but not with the S-enantiomer of the benzazepine SK&F 83566. R- but not S-SK&F 83566 stereoselectively blocks D-1 receptors with high affinity, while the enantiomers have a very weak affinity for D-2 receptors which shows negligible stereoselectivity. Therefore, enantioselective blockade of brain D-1 receptors appears able to influence the expression of behaviours initiated by D-2 receptor stimulation.


The role of sex guilt in the relationship between culture and women's sexual desire.
A large body of literature demonstrates that East Asian women report lower sexual desire than Caucasian women. Although most studies have explained these differences by referring to general culture-linked differences in sexual conservatism, none have examined the potential role of specific constructs such as sex guilt. The goals of the current study were to examine the supposition that sexual conservatism mediates the relationship between culture and sexual desire, and to explore the potential mediating role of sex guilt in the link between culture and sexual desire. Caucasian (n = 105) and East Asian (n = 137) female university students completed questionnaires online. Caucasian women reported significantly higher levels of sexual desire, significantly lower levels of sexual conservatism, and significantly less sex guilt. In the entire sample, sexual conservatism and sex guilt separately mediated the relationship between ethnicity and sexual desire such that women with more sex guilt and those who were more sexually conservative reported lower sexual desire. Among the East Asian women, sex guilt, but not sexual conservatism, mediated the relationship between mainstream acculturation (degree of westernization) and sexual desire such that women with more sex guilt reported lower sexual desire. These findings suggest that sex guilt may be one mechanism by which ethnic groups differ in sexual desire.


Preoperative glucose in surgical oncology patient is not associated with postoperative outcomes after adjustment for frailty.
Observational studies have shown associations between even small elevations in preoperative glucose and poorer outcomes, including increased length of stay (LOS) and higher mortality. This has led to calls for aggressive glycemic control in the preoperative period, including delay of treatment until glucose is reduced. However, it is not known whether there is a direct causal effect of blood glucose or whether adverse outcomes result from overall poorer health in patients with higher glucose. Analysis was performed using a retrospective database of patients aged 65 and older who underwent cancer surgery. The last measured preoperative glucose was the exposure variable. The primary outcome was extended LOS (>4 days). Secondary outcomes included mortality, acute kidney injury (AKI), major postoperative complications during the admission period, and readmission within 30 days. The primary analysis was a logistic regression with prespecified covariates: age, sex, surgical service, and the Memorial Sloan Kettering-Frailty Index. In an exploratory analysis, lasso regression was used to select covariates from a list of 4160 candidate variables. This study included 3796 patients with a median preoperative glucose of 104 mg/dL (interquartile range: 93-125). Higher preoperative glucose was univariately associated with increased odds of LOS > 4 days (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.22-1.73), with similar results for AKI, readmission, and mortality. Adjustment for confounders eliminated these associations for LOS (OR: 0.97 [95% CI: 0.80-1.18]) and attenuated all other glucose-outcome associations. Lasso regression gave comparable results to the primary analysis. Using the upper bound of the respective 95% confidence interval, we estimated that, at best, successful reduction of elevated preoperative glucose would reduce the risk of LOS > 4 days, 30-day major complication, and 30-day mortality by 4%, 0.5%, and 1.3%, respectively. Poor outcomes following cancer surgery in older adults with elevated glucose are most likely related to poorer overall health in these patients rather than a direct causal effect of glucose. Aggressive glycemic management in the preoperative period has very limited potential benefits and is therefore unwarranted.


French adaptation of the PO-Bado short form, an interview-based expert rating scale for distress screening.
Basic Documentation for Psycho-Oncology (PO-Bado) is a hetero-assessment and psychosocial burden documentation tool for cancer patient caregivers (across all types and stages). Recently, the psychometric properties of the standard 12-item version of PO-Bado were published. However, the standard version is relatively time-consuming for the caregivers. Here, we developed and examined psychometric properties of a French short-form of PO-Bado (PO-Bado-FSF) with seven items derived from the validated standard version. One hundred and twenty-one cancer patients (M age = 58.4 years, SD = 13.9 years; 68.6% were women) participated in this study during a supportive care following the first diagnosis of cancer or a relapse. All patients completed the Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), in addition to the PO-Bado-FSF. PO-Bado-FSF scores exhibit sound psychometric qualities such as internal consistency, test-retest reliability, inter-rater reliability, and scalability (i.e. Mokken's scalability coefficients); all items loaded significantly on the single CFA factor and yielded coefficients 0.40 or higher. The results of this study highlight the value of using PO-Bado-FSF to identify psychological distress in cancer patients in research and practice. PO-Bado-FSF presents good psychometric properties and is less time-consuming than the standard version.


Limited proteolysis and photoaffinity labeling with 8-azido-ATP of fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase.
Limited proteolysis and photoaffinity labeling of fructose-6-P,2-kinase and fructose-2,6-bisphosphatase were studied. Proteolysis by trypsin proceeds in two stages in which the first cleavage yields a product, Mr about 53,000, which has lost 90% of fructose-6-P,2-kinase, but retains nearly 80% of fructose-2,6-bisphosphatase. Further digestion of this product yields a second cleavage product, Mr about 50,000, which is completely devoid of the kinase and most of the phosphatase activities. These results indicate that fructose-6-P,2-kinase resides only in the original ("native") enzyme (Mr = 55,000), but fructose-2,6-bisphosphatase activity is present in both the native enzyme and the cleavage product(s). All three activities of fructose-6-P,2-kinase including the forward, the reverse, and ATP-ADP exchange activities are lost to the same degree by the mild proteolysis. Ki of fructose-6-P for fructose-2,6-bisphosphatase is not altered by the proteolysis. Partial protection against the proteolysis is provided by ATP, fructose-6-P, and fructose-2,6-P2. When the tryptic digestion of fructose-6-P,2-kinase:fructose-2,6-bisphosphatase was performed before and after phosphorylation of the enzyme by cAMP-dependent protein kinase, both the first and the second cleavage products contained the phosphorylation site. 8-Azido-ATP serves as a substrate for fructose-6-P,2-kinase with a Km of about 1 mM. Exposure of the enzyme-8-azido-ATP complex results in covalent incorporation (0.7 mol/mol of subunit) and 90% inactivation of fructose-6-P,2-kinase without loss of fructose 2,6-bisphosphatase. When the native and the first cleavage product of tryptic digestion were photoaffinity labeled with [alpha-32P]8-azido-ATP, the radiolabel occurred only in the native enzyme. These results provide evidence in support of, although not conclusive, the idea that the active sites of this bifunctional enzyme are different and located in two distinct sites.


"Viologen" dendrimers as antiviral agents: the effect of charge number and distance.
A series of "viologen" derivatives (4,4'-bipyridinium salts) carrying between 1 and 90 charges per molecule have been prepared and investigated for their activity against human immunodeficiency virus (HIV), herpes simplex virus (HSV), vesicular stomatitis, Punta Toro virus, Sindbis virus, Reovirus, and respiratory syncytial viruses. In general, most of the compounds showed good activities against HIV-1 (strain III(B)). In particular, compound 36 exhibited the highest in vitro activity and selectivity index against HIV-1 (strain III(B)) (EC(50) = 0.26 +/- 0.08 microM, SI = 75.7) in MT-4 cells. The results imply that the antiviral activity requires an optimal number and distance of the positive charges.


Prioritization of cancer driver gene with prize-collecting steiner tree by introducing an edge weighted strategy in the personalized gene interaction network.
Cancer is a heterogeneous disease in which tumor genes cooperate as well as adapt and evolve to the changing conditions for individual patients. It is a meaningful task to discover the personalized cancer driver genes that can provide diagnosis and target drug for individual patients. However, most of existing methods mainly ranks potential personalized cancer driver genes by considering the patient-specific nodes information on the gene/protein interaction network. These methods ignore the personalized edge weight information in gene interaction network, leading to false positive results. In this work, we presented a novel algorithm (called PDGPCS) to predict the Personalized cancer Driver Genes based on the Prize-Collecting Steiner tree model by considering the personalized edge weight information. PDGPCS first constructs the personalized weighted gene interaction network by integrating the personalized gene expression data and prior known gene/protein interaction network knowledge. Then the gene mutation data and pathway data are integrated to quantify the impact of each mutant gene on every dysregulated pathway with the prize-collecting Steiner tree model. Finally, according to the mutant gene's aggregated impact score on all dysregulated pathways, the mutant genes are ranked for prioritizing the personalized cancer driver genes. Experimental results on four TCGA cancer datasets show that PDGPCS has better performance than other personalized driver gene prediction methods. In addition, we verified that the personalized edge weight of gene interaction network can improve the prediction performance. PDGPCS can more accurately identify the personalized driver genes and takes a step further toward personalized medicine and treatment. The source code of PDGPCS can be freely downloaded from https://github.com/NWPU-903PR/PDGPCS .


[Examination of the stability of medically unexplained symptoms and somatoform disorders over time within the context of different diagnostic concepts].
The aim of this study was to determine and to compare the stability of medically unexplained symptoms and somatoform disorders within the context of different diagnostic concepts (SSI4/6, DSM-IV, DSM-V). In a 2-stage follow-up study, 620 consecutive patients were first of all screened using the PHQ-15 questionnaire. In the second stage, 308 selected persons were then interviewed in detail. 12 months later, 89,9% of participants could be interviewed again. Medically unexplained symptoms and somatoform disorders showed weak stability coefficients. In regard to Complex Somatic Symptom Disorder (DSM-V), the prevalence rates were smaller than expected. Within a year, they declined drastically. The instability of Complex Somatic Symptom Disorder should be taken into account when revising somatoform disorder for DSM-V. In order to improve stability, the time criterion should be extended by the duration of mental preoccupation with the ailments.


Expandable stents: unique devices and clinical uses.
The use of stents throughout the gastrointestinal tract has evolved over the past century. The evolution of endoscopic ultrasound and significant improvements in stent design are key factors that have allowed endoscopists to drive the use of stents in gastroenterology into new directions. Endoscopic creativity remains crucial in the evolution of any new endoscopic technology. Finally, the use of multidisciplinary teams, including endoscopists, radiologists, and surgeons, allows for the exchange of ideas and procedural planning necessary for successful innovation.


Effective adsorption of methylene blue by biodegradable superabsorbent cassava starch-based hydrogel.
Superabsorbent hydrogels were synthesized from cassava starch (CS) and polyacrylamide (PAM) via radical polymerization. Scanning electron microscope revealed the porous structure of the hydrogels. Pore size was smaller at higher CS contents. Hydrogel containing 50 wt% CS (CS50) showed excellent water absorbency of >8000%, which was much greater than that of CS0 (pure PAM) hydrogel. This CS50 hydrogel removed >85% of methylene blue (MB) in <10 h with the greatest adsorption capacity of 2000 mg MB/g. The experimental results fitted the Freundlich and pseudo-second order models. After 4 cycles of use, the hydrogel could still remove >50% of MB in solution. Interestingly, the hydrogels were photodegradable and biodegradable. Buried in soil, the CS50 hydrogel was 80% degraded within 30 days whereas pure PAM was only 22% degraded.


Nerve suture and grafting to restore the extratemporal facial nerve.
A concept for dealing with extratemporal lesions of the facial nerve is based on cadaver studies performed by Meissl. In spite of plexiform arrangement and fiber exchange, areas and fascicle groups can be differentiated within the cross section of the facial nerve which contain a great percentage of the fibers supplying a certain muscle group. An attempt should be made to unite the corresponding parts by direct coaptation, or, if nerve defect exists, by nerve grafts.


A conceptual framework to understand the role of built environment on traffic safety.
Many U.S. cities have adopted the Vision Zero strategy with the specific goal of eliminating traffic-related deaths and injuries. To achieve this ambitious goal, safety professionals have increasingly called for the development of a safe systems approach to traffic safety. This approach calls for examining the macrolevel risk factors that may lead road users to engage in errors that result in crashes. This study explores the relationship between built environment variables and crash frequency, paying specific attention to the environmental mediating factors, such as traffic exposure, traffic conflicts, and network-level speed characteristics. Three years (2011-2013) of crash data from Mecklenburg County, North Carolina, were used to model crash frequency on surface streets as a function of built environment variables at the census block group level. Separate models were developed for total and KAB crashes (i.e., crashes resulting in fatalities (K), incapacitating injuries (A), or non-incapacitating injuries (B)) using the conditional autoregressive modeling approach to account for unobserved heterogeneity and spatial autocorrelation present in data. Built environment variables that are found to have positive associations with both total and KAB crash frequencies include population, vehicle miles traveled, big box stores, intersections, and bus stops. On the other hand, the number of total and KAB crashes tend to be lower in census block groups with a higher proportion of two-lane roads and a higher proportion of roads with posted speed limits of 35 mph or less. This study demonstrates the plausible mechanism of how the built environment influences traffic safety. The variables found to be significant are all policy-relevant variables that can be manipulated to improve traffic safety. Practical Applications: The study findings will shape transportation planning and policy level decisions in designing the built environment for safer travels.


Cyberchondria levels in women with human papilloma virus.
To investigate the level of cyberchondria in patients with high-risk human papilloma virus (HPV) positivity. One hundred and forty women who applied to our clinic between July 2020 and September 2020 and were diagnosed with high-risk HPV positivity or abnormal uterine bleeding (AUB) were included in the study. The Cyberchondria Severity Scale (CSS) was administered face-to-face to the participants. CSS and subscales scores of both groups of patients were evaluated and compared. The mean score of the patients on the CSS was 78.54 ± 22.09 and the patients with AUB and HPV(+) was 67.43 ± 19.87 and 84.16 ± 21.08, respectively. The mean subscale scores were as follows, compulsion 13.89 ± 6.49, distress 20.07 ± 7.54, excessiveness 22.40 ± 8.18, reassurance 15.07 ± 6.56, and mistrust of medical professionals 7.26 ± 3.62. The mean scores of the CSS and subscales except for the mistrust of medical professional subscale were higher in patients who were HPV-positive than in other patients. Women with HPV have higher levels of cyberchondria. Medical professionals can reduce this anxiety by giving information to patients.


Neuronal calcium sensor 1 (NCS1) promotes motility and metastatic spread of breast cancer cells in vitro and in vivo.
Increased levels of the calcium-binding protein neuronal calcium sensor 1 (NCS1) predict an unfavorable patient outcome in several aggressive cancers, including breast and liver tumors. Previous studies suggest that NCS1 overexpression facilitates metastatic spread of these cancers. To investigate this hypothesis, we explored the effects of NCS1 overexpression on cell proliferation, survival, and migration patterns in vitro in 2- and 3-dimensional (2/3-D). Furthermore, we translated our results into an in vivo mouse xenograft model. Cell-based proliferation assays were used to demonstrate the effects of overexpression of NCS1 on growth rates. In vitro colony formation and wound healing experiments were performed and 3-D migration dynamics were studied using collagen gels. Nude mice were injected with breast cancer cells to monitor NCS1-dependent metastasis formation over time. We observed that increased NCS1 levels do not change cellular growth rates, but do significantly increase 2- and 3-D migration dynamics in vitro. Likewise, NCS1-overexpressing cells have an increased capacity to form distant metastases and demonstrate better survival and less necrosis in vivo. We found that NCS1 preferentially localizes to the leading edge of cells and overexpression increases the motility of cancer cells. Furthermore, this phenotype is correlated with an increased number of metastases in a xenograft model. These results lay the foundation for exploring the relevance of an NCS1-mediated pathway as a metastatic biomarker and as a target for pharmacologic interventions.-Apasu, J. E., Schuette, D., LaRanger, R., Steinle, J. A., Nguyen, L. D., Grosshans, H. K., Zhang, M., Cai, W. L., Yan, Q., Robert, M. E., Mak, M., Ehrlich, B. E. Neuronal calcium sensor 1 (NCS1) promotes motility and metastatic spread of breast cancer cells in vitro and in vivo.


Short-term biochar application induced variations in C and N mineralization in a compost-amended tropical soil.
To mitigate food shortage due to global warming, developing sustainable management practices to stabilize soil organic matter (SOM) and sequester more carbon (C) in the cultivated soils is necessary, particularly in subtropical and tropical areas. A short-term (56 days) incubation experiment was conducted to evaluate the influences of rice husk biochar (RHB) and manure compost (MC) application on C mineralization and nitrogen (N) immobilization in a sandy loam soil. The RHB was separately incorporated into the soil at application rates of 2 and 4% (w/w) either with or without 1% (w/w) compost. Our results displayed that macroaggregates (≥2 mm) were obviously increased by 11% in soil amended with RHB + MC at the end of incubation. In addition, the experimental results presented that the C mineralization of the soil rapidly increased during the first week of incubation. However, the co-application of compost with biochar (RHB + MC) revealed that CO2 emission was significantly decreased by 13-20% compared to the soil with only MC. In addition, the mineralized N in the soil was lower in RHB + MC-amended soil simultaneously than only MC-amended soil, indicating that biochar addition induced N immobilization. The physical protection of compost by its occlusion into aggregates or adsorption on surface of RHB as proved by the micromorphological observation was the main reason for lower C and N mineralization in soil amended with RHB + MC. Overall results revealed that RHB + MC treatment can decrease the decomposition of compost and sequester more C in the tropical agricultural soils.


Sociocultural factors affecting drive for muscularity among male college students in Malaysia.
Compared with females, little research on muscularity and the sociocultural influences on this domain has been conducted with males in non-Western societies. The current study explored these sociocultural predictors of drive for muscularity among Malaysian male college students, specifically in terms of ethnicity and exposure to media (i.e., Internet and social media). In total, 166 male college students from two universities in Kuala Lumpur were asked to rate the questionnaires as to muscularity-oriented attitudes and behaviours. Multivariable general linear model analyses revealed that being Chinese was a strong predictor of muscularity-oriented attitudes and behaviours. In addition, modern media, particularly, Internet use and the number of followers on Instagram, was found to significantly predict males' drive for muscularity. Overall findings suggest that males of particular ethnic groups may be at higher risk for negative body image compared to the other ethnic populations and modern media use may accelerate drive for muscularity, which may also in turn place males at higher risk for excess muscularity-oriented thoughts and behaviours.


Dietary-Physical Activity Patterns in the Health Context of Older Polish Adults: The 'ABC of Healthy Eating' Project.
The study aimed to analyze the dietary-physical activity patterns (D-PAPs) in the health context of Polish people aged 60+ years. A total of 418 respondents across Poland were recruited; however, the final analysis included 361 women and men aged 60-89 years old. D-PAPs were derived using a principal component analysis (PCA); input variables were the frequency of consumption of 10 food groups and physical activity. Finally, three D-PAPs were identified: 'Pro-healthy eating and more-active', 'Sweets, fried foods and sweetened beverages', and 'Juices, fish and sweetened beverages'. We developed the Functional Limitations Score (FLS) using the Mini Nutritional Assessment (MNA®). A logistic regression was applied to verify the association between the D-PAPs and health-condition outcomes. Older adults were more likely to adhere to the upper tertile of the 'Pro-healthy eating and more-active' pattern, with good/better self-reported health status in comparison with their peers (OR = 1.86) or with good/very good self-assessed appetite (OR = 2.56), while this was less likely for older adults with malnutrition risk (OR = 0.37) or with a decrease in food intake (OR = 0.46). Subjects with a decrease in food intake (OR = 0.43), who declared a recent weight loss (OR = 0.49), or older adults in the upper tertile of the FLS (OR = 0.34) were less likely to adhere to the upper tertile of the 'Sweets, fried foods and sweetened beverages' pattern. The decrease in food intake due to a loss of appetite or chewing or swallowing difficulties was inversely associated with the 'Pro-healthy eating and more-active' pattern characterized by a relatively high frequency of consumption of vegetables, fruit, water, dairy, and grains and a high physical activity. In the interest of the good nutritional status and health of older adults, special attention should be paid to removing limitations in meal consumption, including improved appetite.


The Need for Epistemological Vigilance : (Commentary to the Target Article "Psychology: A Giant With Feet of Clay", Zagaria, Andò & Zennaro).
The analysis and proposal of Zagaria, Andò and Zennaro are suggestive, but the essential question is not raised: the need for scientific research to be explicitly based on an epistemological reflection that takes into account the specificity of psychology. In the first and second parts of my comment, I will justify the need for epistemological reflection in psychology, and in the third part, I will analyze, by means of an example, why the option of adopting the principles of evolutionary psychology does not guarantee greater theoretical coherence.


Bioassay of Some Indigenous Entomopathogens for Controlling Rhynchophorus ferrugineus, Olivier in Saudi Arabia.
Background and Objective: The red palm weevil is a dangerous date palm pests that cannot be controlled with chemical pesticides only. As a result of the justified concerns of the negative use of synthetic insecticides on human health and the environment. So on, candidate eco-friendly micro-organisms isolated from KSA agri-ecosystems were evaluated in controlling RPW. Materials and Methods: Some indigenous entomopathogenic fungi and bacteria were isolated from naturally infected RPW larvae and adults and evaluated as alternative control methods. Results: The infection of RPW larvae with entomopathogenic fungi and bacteria under natural conditions was higher than in adults. Beauveria bassiana was the most prevalent followed by Aspergillus sp., Metarhizium anisopliae, Mucor sp., Cladosporium chlorocephalum. In contrast, both Bacillus thuringiensis and Bacillus popilliae formed 73.9 and 26.1%, respectively. From the 7th day, mortalities (%) increased gradually and recorded the highest mortalities with 21st days after treatment and recorded 93.33, 66.70, 53.36, 46.69 and 60.00% when treated with B. bassiana, M. anisopliae, C. chlorosphalum, Mucor sp. and Aspergillus sp., respectively. Conclusion: Although there was evidence indicating midgut damage and feeding inhibition among larvae that survived the treatments, instead of lower activity of B. thuringiensis against R. ferrugineus immature stages may refer to that, Both species of Bacillus were more virulent as the days 15-21 post-treatment.


Estimating the indirect prevalence of female genital mutilation/cutting in Switzerland.
We updated the indirect estimates for women and girls living with Female Genital Mutilation Cutting (FGM/C) in Switzerland, using data from the Swiss Federal Statistical Office of migrant women and girls born in one of the 30 high-prevalence FGM/C countries that are currently living in Switzerland. We used Yoder and Van Baelen's "Extrapolation of FGM/C Countries' Prevalence Data" method, where we applied DHS and MICS prevalence figures from the 30 countries where FGM/C is practiced, and applied them to the immigrant women and girls living in Switzerland from the same 30 countries. In 2010, the estimated number of women and girls living with or at risk of FGM/C in Switzerland was 9059, whereas in 2018, we estimated that 21,706 women and girls were living with or at risk of FGM/C. Over the past decade, there have been significant increases in the number of estimated women and girls living with or at risk of FGM/C in Switzerland due to the increase in the total number of women and girls originally coming form the countries where the practice of FGM/C is traditional.


Effects of androgen supplementation therapy on partial androgen deficiency in the aging male: a preliminary study.
To assess the responses of a symptom complex related to partial androgen deficiency in the aging male (PADAM) to androgen supplementation. Eighty-six men from five hospitals in Beijing aged 50-70 years with symptoms related to PADAM received oral testosterone undecanoate for 2 months, and the effects of the therapy were evaluated. After treatment, the symptom scores were significantly improved (all p < 0.001). Serum levels of luteinizing hormone and follicle stimulating hormone were suppressed, and free testosterone and albumin-bound testosterone levels were elevated. However, they were not significantly different from the pretreatment values. Waist/hip ratio and blood pressure were markedly decreased, but no changes were found in serum levels of total cholesterol, triglyceride, albumin and prostate specific antigen. Two months of treatment with oral testosterone undecanoate clearly improved the symptoms related to PADAM. No statistical relationship was found between symptom improvement and androgen levels. Androgen therapy for 2 months was beneficial to the waist/hip ratio and blood pressure, and no harm was done to the prostate gland or lipid metabolism.


Polyvinyl alcohol/starch-based film incorporated with grape skin anthocyanins and metal-organic framework crystals for colorimetric monitoring of pork freshness.
An intelligent film for the visual monitoring of pork freshness was developed using degradable polyvinyl alcohol (PVA)/starch (PS) to immobilize the chromogenic agent of anthocyanins and the volatile amine collector of metal-organic frameworks (MOFs). The indicative property of grape skin anthocyanins (GSAs) was verified using the UV-vis spectra, corresponding to multi-color changing in a pH range of 2-12. Interestingly, the introduction of MIL-101 crystals in the PS/GSAs film significantly increased the specific surface area (approximately 10 times) of the film, the superior volatile amine enrichment capability of MIL-101 enabling the film to detect freshness with a high degree of sensitivity. Moreover, the as-prepared film exhibited good antibacterial properties attributed to MIL-101, which help maintain the freshness of the pork. Owing to these advantages, the PS-GSAs/MIL-101 film was tested to real-timely monitor pork freshness in package, the results were further confirmed basis the total volatile basic nitrogen values.


Umbu Fruit Peel as Source of Antioxidant, Antimicrobial and α-Amylase Inhibitor Compounds.
Herein, the extraction of bioactive compounds from umbu fruit peel was optimized using thermal-assisted solid-liquid extraction. In parallel, antioxidant, antimicrobial, and inhibitory effects against α-amylase of optimized extract were also evaluated. The combination of operational conditions including the temperature (32-74 °C), ethanol concentration (13-97%), and solid/liquid ratio (1:10-1:60; w/v) was employed using a rotational central composite design for optimization. The extracts were evaluated for total phenolic compounds (TPC), total flavonoid compounds (TFC) and antioxidant capacity by ABTS•+, DPPH• and FRAP assays. The bioactive profile of the optimized extract was obtained by ultra-performance liquid chromatography coupled to quadrupole/time-of-flight mass spectrometry in electrospray ionization in both negative and positive modes. The statistically evaluated results showed that the optimal operational conditions for the recovery of bioactive compounds from umbu fruit peel included 74 °C, 37% ethanol, and a solid-liquid ratio of 1:38. Under these conditions, the obtained values were 1985 mg GAE/100 g, 1364 mg RE/100 g, 122 µmol TE/g, 174 µmol/TE g and 468 µmol Fe2+/g for TPC, TFC, ABTS•+, DPPH•, and FRAP assays, respectively. In addition, the optimized extract was effective against Gram-positive and Gram-negative bacteria (MBC ranged from 0.060 to 0.24 mg GAE/mL), as well as it was effective to inhibit α-amylase (IC50 value of 0.076 mg GAE/mL). The optimized extract showed to be mainly constituted by phenolic acids and flavonoids.


Patient counselling profile in a Finnish pharmacy.
The present study assessed the patient satisfaction on Finnish community pharmacy services with a special focus on patient counselling. Two different study methods were performed in one Finnish community pharmacy to clarify the patient counselling profile. In autumn 1996, 200 of local citizens were interviewed and a questionnaire has been filled by the pharmacists after counselled episodes. The patient opinion of counselling showed that counselling by pharmacists is beneficial for their medication. Furthermore, pharmacists seem to be more active with the patients receiving prescription drugs. According to our results pharmacists should adjust more counselling to every patients needs. Thus, pharmaceutical information and support of self-care were found to be important areas in patient counselling.


A case of tuberculosis-induced hemophagocytic lymphohistiocytosis in a patient under hemodialysis.
The insidious onset, but rapid progression of hemophagocytic lymphohistiocytosis is always a diagnostic challenge. Herein, we report the case involving a 58-year-old man with diabetes-related nephropathy on dialysis who presented with fever of unknown origin, pancytopenia, and splenomegaly. A bone marrow smear showed extensive hemophagocytosis and the pathology disclosed granulomatous inflammation with caseous necrosis, suggestive of tuberculosis. Sputum culture and polymerase chain reaction confirmed tuberculosis. The patient exhibited signs of multiple-organ failure that were not reversed with anti-tuberculous medications and corticosteroids. The case reminds us that this is an uncommon clinical scenario, and only a timely diagnosis with prompt treatment results in a favorable outcome.


Separation of CH4, H2S, N2 and CO2 gases using four types of nanoporous graphene cluster model: a quantum chemical investigation.
Nanoporous graphene is being regarded as a promising candidate for reliable gas separation and purification applications. In the present research, the permeation barrier, selectivity and all thermodynamic functions for passing of four different molecules including CH4, H2S, N2 and CO2 gases on four types of porous graphene which is doped by two, three and six nitrogen atoms using quantum mechanical modelling, based on the density functional theory, B97D, and cc-pVTZ basis set have been evaluated. We find that the permeation barrier of all studied gases especially carbon dioxide decreased by considering the functionalized porous graphene by two, three and six nitrogens-doped, respectively. The results of our study propose using a porous graphene sheet as highly efficient and highly selective membranes for gas separations.


A proteomic platform to identify off-target proteins associated with therapeutic modalities that induce protein degradation or gene silencing.
Novel modalities such as PROTAC and RNAi have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate the abundance of off-target proteins. First, we selected off-target proteins using genetics and pharmacology evidence. This process yielded 2813 proteins, which we refer to as the "selected off-target proteome" (SOTP). An iterative algorithm was then used to identify four human cell lines out of 932. The 4 cell lines collectively expressed ~ 80% of the SOTP based on transcriptome data. Second, we used mass spectrometry to quantify the intracellular and extracellular proteins from the selected cell lines. Among over 10,000 quantifiable proteins identified, 1828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing to the rational selection process developed and the label free LC-MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.


Knowledge, Attitude and Practices Towards Vocal Health Care Amongst Indian Carnatic Singers.
The knowledge, attitudes and practices of Indian Carnatic singers is a dimension that yet to be explored in detail. The aim of the current study was to explore these knowledge, attitudes, and practices amongst Indian Carnatic singers towards vocal health care. Cross-sectional online questionnaire-based study. A cross-sectional online questionnaire-based study design was used to explore the knowledge, attitudes, and practices of Indian Carnatic singers towards vocal health care. The study was conducted in two phases, phase I involved questionnaire development and validation while phase II involved collection of data and further analysis. One hundred trained self-identified Indian Carnatic singers participated in this study. These singers displayed good knowledge and positive attitudes towards vocal health care. A preference (73%) towards home remedies was noted as compared to seeking medical attention. The measures reported by the singers for maintaining good vocal health revealed use of several home remedies, vocal as well as non-vocal measures. The findings of the present study reveal the knowledge and attitude of Indian Carnatic singers towards vocal health care as well as highlight several interesting practices.


The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient.
HIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. From March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/μL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/μL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. Patients in low-CD4 group have lower proportion of CD3-CD56dimCD16+ NK cell subset, but have higher proportion of CD3-CD56-CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3-CD56-CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3-CD56-CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). There are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3-CD56-CD16+ NK cell subset before treatment is related with HAART efficacy.


Bullous pemphigoid anti-BP180-NC16A autoantibody reactivity in healthy individuals is associated with marked hypovitaminosis D and Th2-like cytokine predominance.
Autoimmune bullous disease autoantibodies, particularly including bullous pemphigoid (BP)-related anti-BP180-NC16A IgG, have been reported in a small subset of healthy individuals, but information about associated factors is lacking. We hypothesized that an abnormal status of immunomodulatory vitamin D could play a role in anti-BP180-NC16A autoantibody reactivity in healthy persons. In addition, we aimed to evaluate the cytokine profile associated with these autoantibodies. Plasma samples from 34 anti-BP180-NC16A IgG-reactive and 85 anti-BP180-NC16A IgG-negative healthy blood donors were tested for levels of 25-hydroxyvitamin D [25(OH)D] and a wide range of cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ, and TNF-α). We observed that anti-BP180-NC16A IgG-reactive healthy subjects had significantly lower plasma 25(OH)D levels and about a two-fold higher rate of vitamin D deficiency (< 20 ng/ml) compared to anti-BP180-NC16A IgG-negative healthy persons. In addition, anti-BP180-NC16A IgG-positive samples were characterized by significantly higher levels of IL-2, IL-5, IL-9, IL-10, and IL-13 which were, however, not significantly associated with the vitamin D levels. Our results indicate that healthy individuals with BP autoantibody reactivity share similarities with BP patients regarding the vitamin D status and cytokine profile (i.e., marked hypovitaminosis D and Th2 predominance), which may have pathophysiologic implications.


Assessment of various auditory perceptual and cognitive skills.
Certain questions regarding auditory skills that are of interest to both researchers and clinicians are raised. These questions have been translated into procedures for assessment of various auditory abilities, resulting in a battery of standardized tests. The main categories of listening skills that are measured are selective attention, auditory discrimination, auditory memory and operations with sounds and/or symbols. The information derived from this battery is discussed in terms of implications for diagnosis and for educational and therapeutic intervention.


PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages.
Resolving-type macrophages prevent chronic inflammation by clearing apoptotic cells through efferocytosis. These macrophages are thought to rely mainly on oxidative phosphorylation, but emerging evidence suggests a possible link between efferocytosis and glycolysis. To gain further insight into this issue, we investigated molecular-cellular mechanisms involved in efferocytosis-induced macrophage glycolysis and its consequences. We found that efferocytosis promotes a transient increase in macrophage glycolysis that is dependent on rapid activation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), which distinguishes this process from glycolysis in pro-inflammatory macrophages. Mice transplanted with activation-defective PFKFB2 bone marrow and then subjected to dexamethasone-induced thymocyte apoptosis exhibit impaired thymic efferocytosis, increased thymic necrosis, and lower expression of the efferocytosis receptors MerTK and LRP1 on thymic macrophages compared with wild-type control mice. In vitro mechanistic studies revealed that glycolysis stimulated by the uptake of a first apoptotic cell promotes continual efferocytosis through lactate-mediated upregulation of MerTK and LRP1. Thus, efferocytosis-induced macrophage glycolysis represents a unique metabolic process that sustains continual efferocytosis in a lactate-dependent manner. The differentiation of this process from inflammatory macrophage glycolysis raises the possibility that it could be therapeutically enhanced to promote efferocytosis and resolution in chronic inflammatory diseases.


Allergen-specific IgG show distinct patterns in persistent and transient food allergy.
Immediate food-allergic reactions are IgE-mediated, but many individuals with detectable allergen-specific IgE do not react to the food. Allergen-specific IgG may interfere with allergen-IgE interaction and/or through intracellular inhibitory signalling to suppress mast cell and basophil response to food allergens. We aimed to understand the role of allergen-specific IgG in food allergy and natural tolerance. IgG and IgG isotypes specific to peanut, cow's milk and egg were measured using ImmunoCAP and ELISA respectively in samples of children with suspected food allergies. Expression of IgE and IgG and their receptors and expression of activation markers following allergen stimulation were measured on basophils and mast cells by flow cytometry, with and without blockade of FcγRIIα or FcγRIIβ receptors. The levels of peanut-specific IgG, IgG1, IgG2, IgG3 and IgG4 in ELISA were higher in peanut-allergic than in non-peanut-allergic children. No difference in allergen-specific IgG isotypes was observed between allergic and non-allergic children to milk or egg, except for milk-specific IgG4 that was higher in non-cow's milk-allergic than in cow's milk-allergic children. Basophils and LAD2 cells expressed IgG receptors, but IgG and IgA were not detected on the surface of either cell type and blocking FcγRIIα or FcγRIIβ did not modify basophil or mast cell activation in response to allergen in allergic or tolerant children. Allergen-specific IgG patterns were distinct in persistent (peanut) versus transient (milk and egg) food allergies. We found no evidence that FcγRIIα or FcγRIIβ receptors affect allergen-induced activation of mast cells and basophils in food allergy or natural tolerance.


Pleural disease in lymphangioleiomyomatosis.
Pleural disease is a common complication of lymphangioleiomyomatosis (LAM). The incidence and recurrence rates of secondary spontaneous pneumothorax in LAM are the highest among chronic pulmonary disorders. Most patients have at least one pneumothorax before LAM is diagnosed, and pneumothorax is often the sentinel event that leads to the diagnosis. Although early, definitive treatment for recurrent pneumothorax by pleurodesis is recommended, the failure rate for chemical and surgical approaches is high. Chylothorax occurs owing to obstruction of lymphatics by proliferating smooth muscle cells and often requires pleurodesis to control expanding and recurrent effusions. Because of the rarity of the LAM, few data exist on whether the occurrence of pleural complications in LAM accelerates functional decline or portends a worse prognosis.


Special Education Assessment: Practices That Support Eligibility and Intervention.
Federal special education requirements specify that information districts must gather and review during the process of finding a student eligible for special education and developing a student's Individualized Education Program (IEP). The purpose of this tutorial is to describe the federal requirements related to evaluation and assessment and to apply best practices in assessment to those expectations, thereby enhancing teams' ability to identify students' strengths and needs, determine eligibility for services, and create high-quality IEPs. This tutorial includes a detailed review of the Individuals with Disabilities Education Act (IDEA) statute and regulations and the U.S. Department of Education guidance related to evaluation, assessment, and IEP development. The tutorial also reflects on an analysis of existing data regarding the identification of students with speech-language impairment in one state and a narrative review of the current literature related to assessment and its role in intervention planning. The results indicate that the IDEA requires rigorous evaluation and assessment practices to determine eligibility (evaluation) and identify students' unique strengths and needs for intervention (assessment). By adhering to these requirements and employing evidence-based assessment practices, speech-language pathologists (SLPs) can be assured that they are gathering accurate and useful information. This information is fundamental to developing an IEP that will support students' acquisition of the knowledge and skills needed to progress in the general curriculum. This tutorial reviews federal requirements related to assessment and links these with best practices in assessment, to facilitate compliance with federal evaluation requirements and IEP development in a manner that meets the needs of all students. SLPs can rely on the IDEA for guidance in completing their special education evaluations and assessments, using this as a framework for employing evidence-based assessment practices.


Motivational interviewing integrated with social network counseling for female adolescents: a randomized pilot study in urban primary care.
This study tested the efficacy of a brief preventive intervention for substance use and associated risk behaviors among female adolescent patients of an urban primary care health clinic. We integrated an evidenced-based motivational interviewing (MI) approach with a social network component to develop a 20-minute session, a social network intervention delivered in an MI-consistent style. Female adolescents (N = 28) 14 to 18 years old were recruited, provided consent/assent, were screened, and were randomly assigned to the treatment or control (no treatment) condition. The sample was 82% African American and 18% mixed race, with 32% living below the U.S. poverty line. At 1-month follow-up, teens in the treatment condition reported less trouble due to alcohol use, less substance use before sexual intercourse, less social stress, less offers for marijuana use, and increased readiness to start counseling compared with the teens in the control condition. Results provide support for socially based brief interventions with at-risk urban adolescents.


Oxidative degradation of food dye E133 Brilliant Blue FCF Liquid chromatography-electrospray mass spectrometry identification of the degradation pathway.
This paper is devoted to the evaluation of the degradation pathway of the E133 Brilliant Blue FCF (C.I. 42090) that is largely used in the food industry. The degradation is studied in oxidation conditions obtained by addition of potassium persulfate at different persulfate to dye molar ratios under natural sunlight irradiation. The degradation pathway of the dye passes through a species coloured in dark blue and then gives rise to uncoloured species. Due to the low volatility and the poor thermal stability of the dye, reversed-phase liquid chromatography associated to mass spectrometry and tandom mass spectrometry was employed to follow the kinetics of degradation and identify some intermediates. The identification of organic species still present in the decoloured dye and the value of COD obtained in these conditions show evidence that complete decolorization does not correspond to complete mineralisation. No direct information of toxicity is available for the uncoloured degradation products but the further formation of aromatic amines can not be excluded.


Rapid field estimation of biochemical oxygen demand in a subtropical eutrophic urban lake with chlorophyll a fluorescence.
Development of a technique for rapid field estimation of biochemical oxygen demand (BOD) is necessary for cost-effective monitoring and management of urban lakes. While several studies reported the usefulness of laboratory tryptophan-like fluorescence technique in predicting 5-day BOD (BOD₅) of wastewater and leachates, little is known about the predictability of field chlorophyll fluorescence measurements for BOD of urban lake waters that are constantly exposed to the mixture of chemical compounds. This study was conducted to develop a numeric relationship between chlorophyll a fluorescence and BOD for a eutrophic urban lake that is widely representative of lake water conditions in the subtropical southern USA. From October 2012 to September 2013, in situ measurements at the studied lake were made every 2 weeks on chlorophyll a fluorescence and other water quality parameters including water temperature, pH, dissolved oxygen, and specific conductivity. Water samples were taken for 5-day BOD and 10-day BOD (BOD₁₀) analysis with and without incubation. The results showed a clear seasonal trend of both BOD measurements being high during the summer and low during the winter. There was a linear, positive relationship between chlorophyll a fluorescence and BOD, and the relationship appeared to be stronger with the 10-day BOD (r(2) = 0.83) than with the 5-day BOD (r(2) = 0.76). BOD dropped each day with declining chlorophyll a fluorescence, suggesting that die-off of phytoplankton has been the main consumption of oxygen in the studied lake. Ambient conditions such as rainfall and water temperature may have partially affected BOD variation.


Functional cytoplasmic domains of the Mac-1 integrin receptor in phorbol ester-treated U937 cells.
The integrin receptor Mac-1 regulates adherence and survival of activated tissue macrophages but the underlying molecular mechanisms are poorly understood. Phorbol ester-induced macrophagic differentiation in U937 cells leads to surface expression of Mac-1 and its activation as well. We have attempted to determine essential amino acids for these activities in the cytoplasmic regions of CD11b and CD18 subunits by deletion mutagenesis. There was complete correlation between adherence and survival. Those deletions that lead to loss of adherence and enhanced apoptosis are truncation of CD11b before the MSEGG sequence; CD18 internal deletion of either the membrane-proximal residues before the NPLF sequence or the NPLF sequence itself; CD18 truncation of the C-terminal residues after the NPLF sequence. Unexpectedly, when the NPLF sequence and the C-terminal residues were removed together by truncation, the adherent, antiapoptotic properties were restored. These results were discussed in terms of protein interaction with Mac-1 cytoplasmic regions.


Cyclical mood changes as in the premenstrual tension syndrome during sequential estrogen-progestagen postmenopausal replacement therapy.
The etiology of the cyclical mood changes seen in the premenstrual syndrome is still unknown. A close relation to the luteal phase has been shown. One of the differences between the follicular and the luteal phase is the higher plasma progesterone concentration during the luteal phase. The present investigation has been conducted to study the effect of exogenously administered estrogen/gestagen sequential postmenopausal replacement therapy on mood and physical signs. Twenty-two women requiring postmenopausal estrogen treatment were recruited and divided into two groups. Eleven women were given estradiol treatment only (Oestrogel creme 3 mg percutaneously/day) for 21 days with a subsequent break of 7 days. The other 11 women were in addition given progestagen (Lynestrenol, Orgametril 5 mg/day) during the last 11 days of treatment. The women were asked to keep a daily record of their mood, using a visual analogue scale earlier tested in women with premenstrual syndrome. They also kept a record of physical signs and sexual feelings. The records were kept for between one and 6 months. The group with estrogen treatment only did not show any cyclical worsening in mood or physical signs during the treatment. The women who in the latter stage of the estrogen treatment cycle also received progestagen, showed significant cyclicity in both moods and physical signs, with a maximum symptom degree during the final days of gestagen treatment. The negative mood change started 1-3 days after the progestagen was added to the treatment. The results suggest that progestagens are involved in the provocation of cyclical symptom changes seen in the premenstrual syndrome.


Intra-articular injection of morphine to the horse: establishment of an in vitro-in vivo relationship.
In the area of parenteral depots, a strong need exists for the development of suitable in vitro drug release models that might enable establishment of in vitro-in vivo relations (IVIVRs). The objective of this study was to investigate the possibility of establishing an IVIVR between morphine disappearance from the joint cavity and in vitro release data obtained employing the rotating dialysis cell model. In vitro release experiments were conducted using the rotating dialysis cell model. For establishment of an IVIVR, data from a previous study on pharmacokinetics of intra-articular (IA) morphine in horses with lipopolysaccharide-induced synovitis were used (Lindegaard et al., (2009). Vet Anaesth Analg, 37, 186-195). A rate constant of morphine disappearance from the donor phase of the in vitro model of 1.8 × 10(-2) min(-1) was calculated, independently of the different release media used. The in vivo synovial fluid disappearance rate constants were in the range of 1.0 × 10(-2)-1.7 × 10(-2) min(-1). An IVIVR (R(2) = 0.89) was established between the calculated disappearance data and the joint disappearance data. The results indicate that the IA fate of morphine administered in the form of a solution can be predicted from the in vitro release data obtained in the rotating dialysis cell model. Thus, this model might be a valuable tool in the establishment of IVIVRs after IA administration of drugs with similar properties.


Incidence and Risk Factors of Venous Thromboembolism Following Hepatectomy for Colorectal Metastases: A Population-Based Retrospective Cohort Study.
Incidence of venous thromboembolism (VTE) following hepatectomy for colorectal cancer (CRC) metastases is unclear. These patients may represent a vulnerable population due to increased tumour burden. We aim to identify the risk of VTE development in routine clinical practice among patients with resected CRC liver metastases, the associated risk factors, and its impact on survival. We conducted a population-based retrospective cohort study of Ontario patients undergoing hepatectomy for CRC metastases between 2002 and 2009 using linked universal healthcare databases. Multivariable logistic regression was used to estimate the association between patient characteristics and VTE risk at 30 and 90-days after surgery. Cox proportional-hazards regression was used to estimate the association between VTE and adjusted cancer specific (CSS) and overall survival (OS). 1310 patients were included with a mean age of 63 ± 11. 62% were male. 51% had one metastatic deposit. Major hepatectomy occurred in 64%. VTE occurred in 4% within 90 days of liver resection. Only longer length of stay was associated with VTE development (OR 6.88 (2.57-18.43), p <0.001 for 15-21 days versus 0-7 days). 38% of VTEs were diagnosed after discharge, comprising 1.52% of the total cohort. VTE was not associated with inferior CSS or OS. Risk of VTE development in this population is similar to those undergoing hepatectomy for other indications, and to the risk following other cancer site resections where post-operative extended VTE prophylaxis is currently recommended. The number of VTEs occurring after discharge suggests there may be a role for extended VTE prophylaxis.


No correlation between clinical symptoms and Blastocystis hominis in immunocompetent individuals.
Abstract Background and Aim: Previous reports regarding the clinical significance and pathogenicity of Blastocystis hominis have been contradictory. The aim of this study was to examine the association between Blastocystis and gastrointestinal symptoms in immunocompetent individuals. We monitored over 2800 healthy people for a period of 15 months, and took stool specimens during both asymptomatic periods and during periods of gastrointestinal symptoms. After exclusion of individuals who had simultaneous identification of other fecal pathogens, we compared the proportions of asymptomatic versus symptomatic individuals positive for Blastocystis and found no significant difference (P = 0.5). Symptom status did not correlate with parasite abundance. We found that some individuals were likely to have Blastocystis detected during both asymptomatic and symptomatic periods, possibly suggesting carriage of the organism. In conclusion, we found no correlation between clinical symptoms and the presence or absence of Blastocystis among this healthy cohort.


Association of Cystic Periventricular Leukomalacia and Postnatal Epilepsy in Very Preterm Infants.
Cystic periventricular leukomalacia (PVL) is the most common white matter injury and a common cause of cerebral palsy in preterm infants. Postnatal epilepsy may occur after cystic PVL, but their causal relationship remains uncertain. Our aim was to validate the contribution of cystic PVL to postnatal epilepsy in very preterm infants and demonstrate their seizure characteristics. This prospective cohort study enrolled 1,342 preterm infants (birth weight <1,500 g and gestational age <32 weeks) from 2003 to 2015. Cystic PVL was diagnosed by serial cerebral ultrasound, and other comorbidities were recorded during hospitalization. Neurological developments and consequences, including epilepsy, were serially accessed until the age of 5. A total of 976 preterm infants completed a 5-year neurological follow-up; 47 (4.8%) had cystic PVL. Preterm infants with cystic PVL were commonly associated with other comorbidities, including necrotizing enterocolitis stage III, neonatal seizures, and intraventricular hemorrhage during hospitalization. At age 5, 14 of the 47 (29.8%) preterm infants with cystic PVL had postnatal epilepsy. After adjusting for gender, gestational age, and three common comorbidities, cystic PVL was an independent risk factor for postnatal epilepsy (adjust OR: 16.2; 95% CI: 6.8-38.4; p < 0.001). Postnatal epilepsy after cystic PVL was commonly the generalized type (13 of 14, 92.9%), not intractable and most occurred after 1 year of age. Cystic PVL would independently lead to postnatal epilepsy. Preterm infants with cystic PVL are at risk of postnatal epilepsy after age 1 in addition to cerebral palsy.


Rapid and sensitive identification of omicron by variant-specific PCR and nanopore sequencing: paradigm for diagnostics of emerging SARS-CoV-2 variants.
On November 26, 2021, the World Health Organization classified B.1.1.529 as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC), named omicron. Spike-gene dropouts in conventional SARS-CoV-2 PCR systems have been reported over the last weeks as indirect diagnostic evidence for the identification of omicron. Here, we report the combination of PCRs specific for heavily mutated sites in the spike gene and nanopore-based full-length genome sequencing for the rapid and sensitive identification of the first four COVID-19 patients diagnosed in Germany to be infected with omicron on November 28, 2021. This study will assist the unambiguous laboratory-based diagnosis and global surveillance for this highly contagious VoC with an unprecedented degree of humoral immune escape. Moreover, we propose that specialized diagnostic laboratories should continuously update their assays for variant-specific PCRs in the spike gene of SARS-CoV-2 to readily detect and diagnose emerging variants of interest and VoCs. The combination with established nanopore sequencing procedures allows both the rapid confirmation by whole genome sequencing as well as the sensitive identification of newly emerging variants of this pandemic β-coronavirus in years to come.


Recent diarrhea is associated with elevated salivary IgG responses to Cryptosporidium in residents of an eastern Massachusetts community.
Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults. Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow-up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a time-resolved fluorometric immunoassay. Log-transformed assay results were regressed on age using penalized B-splines to account for the strong age-dependence of antibody reactions. Positive responses were defined as fluorescence values above the upper 99% prediction limit. Forty-seven (13.5%) individuals had diarrhea without concurrent respiratory symptoms during the 3-month-long follow-up; eight of them had these symptoms during the month prior to saliva sampling. Two individuals had positive IgG responses: an adult who had diarrhea during the prior month and a child who had episodes of diarrhea during each survey month (Fisher's exact test for an association between diarrhea and IgG response: p = 0.0005 for symptoms during the prior month and p = 0.02 for symptoms during the entire follow-up period). The child also had a positive IgA response, along with two asymptomatic individuals (an association between diarrhea and IgA was not significant). These results suggest that the salivary IgG specific to Cryptosporidium antigens warrants further evaluation as a potential indicator of recent infections.


Incremental learning of feature space and classifier for face recognition.
We have proposed a new approach to pattern recognition in which not only a classifier but also a feature space of input variables is learned incrementally. In this paper, an extended version of Incremental Principal Component Analysis (IPCA) and Resource Allocating Network with Long-Term Memory (RAN-LTM) are effectively combined to implement this idea. Since IPCA updates a feature space incrementally by rotating the eigen-axes and increasing the dimensions, the inputs of a neural classifier must also change in their values and the number of input variables. To solve this problem, we derive an approximation of the update formula for memory items, which correspond to representative training samples stored in the long-term memory of RAN-LTM. With these memory items, RAN-LTM is efficiently reconstructed and retrained to adapt to the evolution of the feature space. This function is incorporated into our face recognition system. In the experiments, the proposed incremental learning model is evaluated over a self-compiled video clip of 24 persons. The experimental results show that the incremental learning of a feature space is very effective to enhance the generalization performance of a neural classifier in a realistic face recognition task.