Intra-individual comparison of image quality of the coronary arteries between photon-counting detector and energy-integrating detector CT systems.
To intra-individually compare the objective and subjective image quality of coronary computed tomography angiography (CCTA) between photon-counting detector CT (PCD-CT) and energy-integrating detector CT (EID-CT). Consecutive patients undergoing clinically indicated CCTA on an EID-CT system were prospectively enrolled for a research CCTA performed on a PCD-CT system within 30 days. Polychromatic images were reconstructed for both EID- and PCD-CT, while virtual monoenergetic images (VMI) were generated at 40, 45, 50, 55, 60 and 70 keV for PCD-CT. Two blinded readers calculated contrast-to-noise ratio (CNR) for each major coronary artery and rated image noise, vessel attenuation, vessel sharpness, and overall quality on a 1-5 Likert scale. Patients were then stratified by body mass index (BMI) [high (>30 kg/m2) vs low (<30 kg/m2)] for subgroup analysis. A total of 20 patients (67.5 ± 9.0 years, 75% male) were included in the study. Compared with EID-CT, coronary artery CNR values from PCD-CT monoenergetic and polychromatic reconstructions were all significantly higher than CNR values from EID-CT, with incrementally greater differences in obese subjects (all p < 0.008). Subjective image noise and sharpness were also significantly higher for all VMI reconstructions compared to EID-CT (all p < 0.008). All subjective scores were significantly higher for 55, 60, and 70 keV PCD-CT than EID-CT values (all p < 0.05). The improved objective and subjective image quality of PCD-CT compared to EID-CT may provide better visualization of the coronary arteries for a wide array of patients, especially those with a high BMI.


Ultraviolet-induced dimerization of non-adjacent pyrimidines. A potential mechanism for the targeted -1 frameshift mutation.
The DNA photoproduct responsible for the ultraviolet (u.v.)-induced targeted -1 frameshift mutation is unknown. Based on mutagenesis studies by others, we surmised that this lesion might be found in high abundance in single-stranded DNA. u.v. irradiation of the single-stranded alternating copolymer poly[d(G-T)] yielded a photoproduct that was characterized in detail. It consists of a thymine-thymine cyclobutane dimer of predominantly cis-syn configuration occurring between non-adjacent thymidyl residues on the same strand. Its formation is strongly inhibited in double-stranded DNA. A similar u.v. photoproduct was obtained in higher yield from the polypyrimidine alternating copolymer poly[d(C-T)] under conditions in which it is single-stranded. It is proposed that replication across the unrepaired photoproduct: (formula; see text) is the cause of the targeted u.v.-induced -1 frameshift mutation.


Specializations of the outer mitochondrial membrane during oocyte development.
A coating of electron dense material is present on the cytoplasmic surface of outer mitochondrial membranes in medium-sized hamster oocytes. The coating is not present at earlier or later stages of oocyte development. Its possible relationship to the synthesis and transport of mitochondrial protein is discussed. Associations between endoplasmic reticulum, ribosomes, glycogen and the outer mitochondrial membrane are also described and discussed.


Advances in quality control: mouse embryo morphokinetics are sensitive markers of in vitro stress.
Can time-lapse analysis of cell division timings [morphokinetics (MK)] in mouse embryos detect toxins at concentrations that do not affect blastocyst formation? An MK algorithm enhances assay sensitivity while providing results 24-48 h sooner than the traditional mouse embryo assay (MEA). Current quality control testing methodology is sensitive but further improvements are needed to assure optimal culture conditions. MKs of embryo development may detect small variations in culture conditions. Cross sectional-control versus treatment. Mouse embryo development kinetics of 466 embryos were analyzed according to exposure to various concentrations of toxins and toxic mineral oil. Cryopreserved 1-cell embryos from F1 hybrid mice were cultured with cumene hydroperoxide (CH) (0, 2, 4, 6 and 8 µM) and Triton X-100 (TX-100; 0, 0.0008, 0.0012, 0.0016 and 0.002%). Using the Embryoscope, time-lapse images were obtained every 20 min for 120 h in seven focal planes. End-points were timing and pattern of cell division and embryo development. The blastocyst rate (BR) was defined as the percentage of embryos that developed to the expanded blastocyst stage within 96 h. BR was not affected for embryos cultured in the three lowest concentrations of CH and the four lowest concentrations of TX-100. In contrast, a unique MK model detected all concentrations tested (P < 0.05). The MK model identified toxicity in two lots of toxic mineral oil that did not affect BR (P < 0.05). A limited number of toxins were used so that the results may not apply to all potential embryo toxins. A larger sample size may also demonstrate other statistically significant developmental kinetic parameters. MKs in mouse embryos are a sensitive and efficient method for quality control testing of in vitro culture conditions. BR, the end-point of traditional quality control assays, did not detect sublethal concentrations of toxins in the culture milieu in our study. This study demonstrates that temporal variation at key developmental stages reflects the quality of the culture environment. An MEA that incorporates MK will provide enhanced sensitivity and faster turn-around times.


Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model.
We previously demonstrated angiotensin converting enzymes (ACE) over-expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I) treatment reduced colitis severity in this model. However, ACE-I has not been tested in more immunologically relevant colitis models. We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model. Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg for 21 days. Prednisolone (PSL) with or without enalaprilat were used as therapeutic, comparative groups. All groups were compared to a placebo treated group. Outcome measures were clinical course, histology, abundance of pro-inflammatory cytokines/chemokines, and epithelial barrier function. Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL: 85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups showed significantly better histological scores versus placebo mice. ACE-I and the PSL groups significantly reduced several pro-inflammatory cytokines versus placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I groups. Blood pressure was not affected in ACE-I treated mice compared to placebo mice. ACE-I was effective in reducing severity of colitis in an IL-10-/- model. The addition of prednisolone minimally augmented this effect. The findings suggest that appropriately dosed ACE-I with or without steroids may be a new therapeutic agent for colitis.


From unexpected reactions to a new family of ionic co-crystals: the case of barbituric acid with alkali bromides and caesium iodide.
Pressing solid barbituric acid with KBr to prepare samples for IR spectroscopy leads to the formation of an ionic co-crystal, in which the co-former is a classical ionic salt; co-crystal formation is also obtained with the other alkali bromides (LiBr, NaBr, RbBr and CsBr) and with caesium iodide. The simultaneous presence of alkali and halide ions affects the dissolution properties of barbituric acid in water.


Fatty acid composition of erythrocyte membrane lipid obtained from children suffering from kwashiorkor and marasmus.
The fatty acid composition of erythrocyte membrane (EM) lipids obtained from normal, kwashiorkor, and marasmic children was analyzed by gas chromatography. The proportion of palmitic acid (16:0) was lower and of oleic acid (18:1) higher in the kwashiorkor group than in the control group. The marasmic group showed lower proportions of eicosatrienoic acid (20:3) and arachidonic acid (20:4) and a higher proportion of oleic acid (18:1) than the control group. A significant difference was found between the marasmic and kwashiorkor groups with respect to arachidonic acid (20:4), which showed a lower proportion in the former group than the latter. The ratio of arachidonic acid to linoleic acid (20:4/18:2) was markedly lower in the marasmic group than the control group, suggesting a possible impairment in the conversion of linoleic acid to arachidonic acid in marasmic children. The ratio of unsaturated fatty acids to saturated fatty acids was markedly elevated in the kwashiorkor group over that of control group, indicating increased fluidity of EM in kwashiorkor. It is suggested that the altered membrane fatty acid composition reflects deranged lipid metabolism and affects the physical and physiological properties of EM and could contribute to changes in the activities of several red blood cell membrane-bound enzymes reported earlier in kwashiorkor children.


Light-emitting diodes: whether an efficient source of light for indoor plants?
Availability of sufficient light for growth optimization of plants in greenhouse environment during winter is a major challenge, as light during winter is significantly lower than that in the summer. The most commonly used artificial light sources (e.g., metal halide lamps, high pressure sodium lamps, and high fluorescent lamps) are of low quality and inefficient. Therefore, better options should be developed for sustaining agricultural food production during low levels of solar radiation. In recent advances, light-emitting diodes (LEDs) have remarkable potential as supplemental source of light for promoting plant growth. LEDs are novel and versatile source of light with cool emitting surface, wavelength specificity, and low electric power requirement. In the present study, we provided a contemporary synthesis of existing evidence along with our hypothetical concepts to clarify how LED approach could be an efficient and cost-effective source of light for plant growth and development especially in closed production system. In comparative analysis of common artificial vs. LED lighting, we revealed that spectral quality of LEDs can have vivid effects on plant morphogenesis and anatomy. We also discussed the influence of different colors of LEDs on growth performance of plants and provided the cost benefit analysis of using LEDs compared with other traditional sources. Overall, we hope that this article will be of great worth in future due to its practical implications as well as research directions.


Optimization of the nutritional constituents for ergosterol peroxide production by Paecilomyces cicadae based on the uniform design and mathematical model.
we optimized medium components for the production of ergosterol peroxide (EP) by Paecilomyces cicadae based on a mono-factor experiment, a uniform design, and a non-linear regression analysis. The maximum EP yield achieved was 256 μg/L, which was increased by 5 folds compared with that before the optimization. Structured Monod model, Andrews model, Contois model, and Aibe model were developed to describe the effects of viscosity inhibition, substrate, and production on biomass growth. The results showed that the Monod model could predict biomass growth, and the effects of viscosity and substrate on the EP concentration were significantly higher compared with the effect of production. The addition of water and glycerol could decrease the viscosity inhibition and glycerol inhibition, and further increase the EP yield. The newly developed structured model was demonstrated for batch growth of P. cicadae.


Radial astrocytes and ependymocytes in the spinal cord of the adult toad (Bufo bufo L.). An immunohistochemical and ultrastructural study.
Immunohistochemical and ultrastructural techniques have been used to demonstrate glial fibrillary acidic protein (GFAP) immuno-positive cells in the adult toad spinal cord. Two types of GFAP-immunoreactive cells were observed: ependymocytes and radial astrocytes. GFAP-positive ependymocytes were scarce and contained the immunoreactive product in their processes. They showed intermediate filaments in the basal pole and in their processes when studied with the electron microscope. These immuno-positive ependymocytes represent the tanycytic form of ependymal cells because their processes ended at the subpial zone. The radial astrocytes showed a more intensive immunoreactive product in somata and processes when they were located far away from the ependymal layer. Cell bodies and processes were also associated with blood vessels, but most of the processes ended at the subpial zone forming a continuous subpial glia limitans. The GFAP-positive processes, which form this subpial glia limitans in the toad spinal cord, belong to both tancytic ependymocytes and radial astrocytes, whose somata are located in the grey matter. These findings lead us to suggest that both types of GFAP-immunopositive cells might be the functional equivalents of mammalian astrocytes.


Germination and establishment of Sahelian rangeland species : II. Effects of water availability.
In order to understand the vegetation dynamics of Sahelian rangelands, the effects of water availability on germination were investigated under controlled conditions in climate rooms. Mixtures of seeds from species that occur in the same habitats but have different seed characteristics were exposed to different watering treatments. Responses to the treatments in the climate room were comparable to those observed in the field situation. However, induction time was generally some-what longer, and in some cases the germination rate was lower. The size, frequency, and timing of showers decisively influenced the ratio between the proportions of the various species among the seedlings that established. In general, conditions were favourable for fast germinating species with rainfall patterns without serious intermittent periods of drought, whereas the conditions became favourable for the slower germinating species after dry periods had eliminated the seedlings of the fast germinating species. Large differences in drought resistance were found among seedlings of different species. This causes more differentiation in establishment of species. Seed losses during the pre-emergence phase were also important. These losses can be very high, especially for the fastest germinating species. The dynamics observed in field situations could be explained on the basis of germination characteristics and drought resistance.


Roles of hydrophobicity and charge distribution of cationic antimicrobial peptides in peptide-membrane interactions.
Cationic antimicrobial peptides (CAPs) occur as important innate immunity agents in many organisms, including humans, and offer a viable alternative to conventional antibiotics, as they physically disrupt the bacterial membranes, leading to membrane lysis and eventually cell death. In this work, we studied the biophysical and microbiological characteristics of designed CAPs varying in hydrophobicity levels and charge distributions by a variety of biophysical and biochemical approaches, including in-tandem atomic force microscopy, attenuated total reflection-FTIR, CD spectroscopy, and SDS-PAGE. Peptide structural properties were correlated with their membrane-disruptive abilities and antimicrobial activities. In bacterial lipid model membranes, a time-dependent increase in aggregated β-strand-type structure in CAPs with relatively high hydrophobicity (such as KKKKKKALFALWLAFLA-NH(2)) was essentially absent in CAPs with lower hydrophobicity (such as KKKKKKAAFAAWAAFAA-NH(2)). Redistribution of positive charges by placing three Lys residues at both termini while maintaining identical sequences minimized self-aggregation above the dimer level. Peptides containing four Leu residues were destructive to mammalian model membranes, whereas those with corresponding Ala residues were not. This finding was mirrored in hemolysis studies in human erythrocytes, where Ala-only peptides displayed virtually no hemolysis up to 320 μM, but the four-Leu peptides induced 40-80% hemolysis at the same concentration range. All peptides studied displayed strong antimicrobial activity against Pseudomonas aeruginosa (minimum inhibitory concentrations of 4-32 μM). The overall findings suggest optimum routes to balancing peptide hydrophobicity and charge distribution that allow efficient penetration and disruption of the bacterial membranes without damage to mammalian (host) membranes.


Milk fever in dairy cows: a review of pathophysiology and control principles.
The periparturient or transition period of 4 weeks before and 4 weeks after calving is characterised by a greatly increased risk of disease. Hypocalcaemia around calving is a risk factor for many of these diseases and is an indirect risk factor for increased culling. The incidence of clinical hypocalcaemia (milk fever) in the field generally ranges from 0-10%, but may exceed 25% of cows calving. In research trials conducted on milk fever the incidence has approached 80% of cows calving. Homeostasis of calcium (Ca) is regulated by calcitonin, parathyroid hormone and 1,25(OH)(2) vitamin D(3). Age increases the risk of milk fever by approximately 9% per lactation. Control of milk fever has revolved around stimulation of homeostatic mechanisms through feeding a pre-calving diet low in Ca. More recently, the role of the dietary cation anion difference (DCAD) in the prevention of Ca disorders has been examined, both by field research and meta-analysis. The most appropriate form of the DCAD equation has been contentious, but recent meta-analyses have shown that the equation (Na(+)+K(+))-(Cl(-)+S(2-)) is most effective for predicting milk fever risk. Decreased risk of milk fever is linear with DCAD, whereas the effect of DCAD on urinary pH is curvilinear. A pivotal role of providing dietary magnesium (Mg) before calving has been confirmed by meta-analysis, and a quadratic effect of Ca on milk fever risk was found with a peak occurring with dietary levels of 1.1-1.3% of dry matter. Risks of milk fever increase with increased dietary phosphorus (P) fed pre-calving and with increasing days of exposure to a pre-calving diet. Meta-analysis has revealed that the important roles of dietary Ca, Mg and P, as well as the duration of exposure to the pre-calving diet in milk fever control strategies are independent of DCAD. Studies on the effect of exposure to well designed pre-calving diets have shown that substantial improvements in production, reproduction and animal health can be made but further examination of the influence of the period of exposure to different diets is warranted.


Occurrence of trace elements in print paper products: Non-carcinogenic risk assessment through dermal exposure.
Over time, the risk assessment of dermal exposure to pollutants in print paper products has received considerable attention. Most studies have focused on organic pollutants, especially bisphenol A (BPA). However, little is known about the levels of trace elements in print paper products, despite the knowledge that these elements are components of printing inks and toners. This study was aimed at determining the concentrations of trace elements in 5 types of paper products, namely bulletins, magazines, special events program booklets, handbills, and newspapers. The average daily intake (ADI) of each element was subsequently estimated through dermal exposure to the papers. The detection frequency of the elements of interest was high (nearly 100%) in most paper products, with the exception of chromium, whose detection was low. In contrast, Ag was not detected in any sample. The levels of the elements in the paper products were low and comparable to those found in other personal and consumer products with the potential for skin contact. The range values of estimated ADIs were 1.70-3.90E-08, 2.30-18.2E-10, 2.60-16.4E-09, 3.65-5.75E-08, 1.29-4.38E-08, 6.23-15.6E-10, 1.51-2.80E-10, 1.43-9.16E-09, 0.00-9.47E-09, and 4.68-220E-08 mg/kg bw/day for Mn, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Fe respectively. These values were well below the dermal standard reference doses (RfD) for each element. The present results indicate that dermal exposure to trace elements from print paper products was low and does not pose significant risks for toxic (non-carcinogenic) effects on humans.


Duration and Degree of Weight Gain and Incident Diabetes in Younger Versus Middle-Aged Black and White Adults: ARIC, CARDIA, and the Framingham Heart Study.
To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults. We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: ≥30 and <45 years; middle-aged: ≥45 and <60 years) and examined for incident diabetes (median follow-up 9 years). Duration and degree of gain in BMI were calculated as "BMI-years" above one's baseline BMI. Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BMI and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 (P = 0.02) and 1.02 (P = 0.39), respectively (P for interaction by age-group = 0.047), and in whites were 1.35 (P < 0.001) and 1.11 (P < 0.001), respectively (P for interaction by age-group = 0.008). Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain.


Reevaluating the role of the medial prefrontal cortex in delay eyeblink conditioning.
It has been proposed that the medial prefrontal cortex (mPFC) is not necessary for delay eyeblink conditioning (DEC). Here, we investigated the involvement of the mPFC in DEC with a soft or loud tone as the conditioned stimulus (CS) by using electrolytic lesions or muscimol inactivation of guinea pig mPFC. Interestingly, when a soft tone was used as a CS, electrolytic lesions of the mPFC significantly retarded acquisition of the conditioned response (CR), and muscimol infusions into mPFC distinctly inhibited the acquisition and expression of CR, but had no significant effect on consolidation of well-learned CR. In contrast, both electrolytic lesions and muscimol inactivation of mPFC produced no significant deficits in the CR when a loud tone was used as the CS, or in the unconditioned response (UR) when a soft or loud tone was used as the CS. These results demonstrate that the mPFC is essential for the DEC with the soft tone CS but not for the DEC with the loud tone CS.


Recent advances in protein methylation: enzymatic methylation of nucleic acid binding proteins.
Heterogeneous nuclear RNP protein A1, one of the major proteins in hnRNP particle (precursor for mRNA), is known to be posttranslationally arginine-methylated in vivo on residues 193, 205, 217 and 224 within the RGG box, the motif postulated to be an RNA binding domain. Possible effect of NG-arginine methyl-modification in the interaction of protein A1 to nucleic acid was investigated. The recombinant hnRNP protein A1 was in vitro methylated by the purified nuclear protein/histone-specific protein methylase I (S-adenosylmethionine:protein-arginine N-methyltransferase) stoichiometrically and the relative binding affinity of the methylated and the unmethylated protein A1 to nucleic acid was compared: Differences in their binding properties to ssDNA-cellulose, pI values and trypsin sensitivities in the presence and absence of MS2-RNA all indicate that the binding property of hnRNP protein A1 to single-stranded nucleic acid has been significantly reduced subsequent to the methylation. These results suggest that posttranslational methyl group insertion to the arginine residue reduces protein-RNA interaction, perhaps due to interference of H-bonding between guanidino nitrogen arginine and phosphate RNA.


Local administration of (15 S)-15-methyl PGF2 alpha for management of hypotonic post-partum hemorrhage.
Local (uterine) injection of (15 S)-15-methyl prostaglandin F2 alpha was highly effective as first-aid treatment for hypotonic post-partum hemorrhage and only 2% of the 50 treated patients required surgical intervention for such hemorrhage. Systemic side-effects did not occur, and besides the procedure is extremely simple as well as painless.


Characterization of calcium efflux by osteoblasts derived from long bone periosteum.
Inside-out vesicles were prepared from the plasma membrane of osteoblasts which had been isolated from the periosteum of 2-3-week-old chicken tibia and cultured for 6-8 days. Calcium uptake was initiated by adding 0.4 mM ATP and detected as a reduction in fluorescence from the reaction medium using the Ca(2+)-specific fluoroprobe, fluo-3. The reaction medium contained ouabain (1 mM) to block Na+, K(+)-ATPase activity and oligomycin (20 micrograms/ml) to block mitochondrial activity. Thapsigargin (5 microM) had little effect, indicating that contributions to Ca2+ uptake by endoplasmic reticulum derived microsomes were minimal. The Ca2+ uptake rate was 9.9 +/- 2.3 nmol/mg protein/min. Trifluoperazine (0.1 mM), which impairs the capacity of calmodulin to activate Ca(2+)-ATPase, substantially inhibited transport, as did quercetin (10 mM) and vanadate (10 microM), inhibitors of Ca(2+)-ATPases. This study has shown the presence of an outwardly directed, calmodulin-sensitive calcium transport system in the primary osteoblast plasma membrane. The pumping rate is substantially less than rates found in the intestine, a tissue which is involved in massive transport of Ca2+, but is similar to rates found in many other tissues. It is concluded that the enzyme does not support calcium translocation to sites of mineralization.


A new cell line based coculture system for skin sensitisation testing in one single assay using T cells, aryl hydrocarbon receptor knockout, and co-inhibitory blockage.
Established in vitro assays for regulatory testing of skin sensitisation partly suffer from only moderate sensitivity, specificity, and predictivity when testing specific groups of chemicals. This may be due to limited biomarker response in vitro in cell types that interact as crucial players of in vivo skin sensitisation pathogenesis. Here, we propose a molecular approach to overcome this limitation. In our model, we apply genome editing and blocking of immunoregulatory molecules to increase the range of biomarker modulation by sensitising chemicals. To this end, aryl hydrocarbon receptor (AhR) knockout was done by CRISPR/Cas9 technology in THP-1 cells and combined with Programmed Cell Death-Ligand (PD-L)1 blockade. AhR-knockout THP-1 in coculture with HaCaT keratinocytes showed increased CD54 expression compared to wild type cells after stimulation with 10 µmol/L dinitrochlorobenzene (DNCB) that was further enhanced by anti-PD-L1. After stimulation of AhR-knockout THP-1 with 200 µmol/L mercaptobenzothiazol or 10 µmol/L DNCB, cocultivated Jurkat T cells significantly increased expression of T cell receptor-associated CD3. No such increase was detected after prior treatment of THP-1 with 150 µmol/L of irritant sodium lauryl sulphate. Additionally, higher levels of inflammatory cytokines MIP-3α, MIP-1β, TNF-α, and IL-8 were found in supernatants of enhanced loose-fit co-culture based sensitisation assay (eLCSA) after substance treatment. Hence, eLCSA allowed to discriminate between sensitisers and non-sensitisers. Thus, inhibition of immunoinhibitory pathway signalling by combining AhR knockout and PD-L1 antibody blockage into an assay involving main acting cell types in skin sensitisation may increase sensitivity and specificity of such assays and allow potency derivation.


Ligustrazine derivatives. Part 4: design, synthesis, and biological evaluation of novel ligustrazine-based stilbene derivatives as potential cardiovascular agents.
A series of novel stilbene derivatives containing ligustrazinyl moiety was designed, synthesized, and assayed for their protective effects on damaged endothelial cells. The results showed that most ligustrazinyl stilbene derivatives exhibited high protective effects on the human umbilical vascular endothelial cells (HUVECs) damaged by hydrogen peroxide in comparison with Ligustrazine. The stilbene derivatives A6, A9, A11, A21, A24, A25, and A27 exhibited high potency with low EC(50) values ranged from 0.0249 μm to 0.0898 mm. Compound A27 displayed EC(50) 0.0249 μm, which is 30,000 times higher than that of Ligustrazine, presenting a most promising lead for further investigation. Structure-activity relationships were briefly discussed.


Changes in lymphocytes following mercury administration in mice. Observations under fluorescence microscopy.
Lymphocytes were stained with vital stain acridine orange. The number of lysosomes per lymphocyte was calculated using "score" test. It should be emphasized that the present paper has proved the reliability of the fluorescence microscopy method of identification of lysosomes in the lymphocytes from peripheral blood, employed for studing the toxic effect of metals.


Effect of suicidal loss on bereaved individuals' suicidal ideation: Structural equation model using attitudes towards suicide scale and moderation effect of interest in news media.
Exposure to suicidal death may cause trauma and change the bereaved family/friends' attitudes towards suicide and increase their suicide-related behavior. We aimed to examine the life-time prevalence of loss experience among the general population of South Korea, the relationship between attitudes towards suicide and suicidal intensity, and the moderation effect of interest in news media. After analyzing 2973 structured interviews, we hypothesized structural equation model and conducted a moderation analysis. A total of 10.1% (n = 301) respondents had experienced the suicide of acquaintances. Acceptive attitudes such as "suicide as right" and "suicide as normal-common" were higher in the "experienced" group. All fit indices of the hypothesized model were satisfied, and experience of suicidal loss was positively associated with both acceptive attitudes and suicidal intensity. "Suicide as normal-common" positively affected suicidal intensity, but "suicide as right" was not significant. "Interest in news media" significantly moderated the relationship between loss experience and suicidal intensity. Since our study was cross-sectional design, further longitudinal studies are needed to draw casual inferences between factors. We used the at home interview method, which might have resulted underestimated experience of suicidal loss. Our findings showed that experiencing suicide death of any acquaintances could increase individual's acceptance of suicide and also increase the risk of suicide. Frequent exposure to suicide-related news amplified their risk of suicide. To reduce the suicide risk behavior, targeted intervention with those bereaved by suicide and restriction of media reports on suicide news will be needed as prevention strategies.


[Derivatisation methods in gas chromatographic analysis. application in the toxicological field (author's transl)].
Derivatisation methods are described, which can be used in gas chromatography of drugs in the forensic toxicological usage. Especially acetylation, silylation and methylation can be performed quite simply and fast. Several procedures for these reactions are compliled from the literature.


Ophthalmologic screening in 25 consecutive geriatric psychiatric inpatient admissions.
In the aging process, people are at increasing risk of visual abnormalities such as cataracts, glaucoma, age-related macular degeneration, and other retinal defects. This holds true for geriatric psychiatric patients as well. These ophthalmic problems may increase risk of falls or increase the comorbidity from dementing processes and depression. Geriatric patients presenting for psychiatric treatment may also be misdiagnosed or under-diagnosed as a result of these visual problems. This quality assurance review of 25 consecutive geriatric psychiatric inpatients demonstrated discrepancies between chart documentation and actual ophthalmologic pathology present in the patients. Doing a simple but complete ophthalmologic screening as part of the general physical examination on admission to an inpatient psychiatric unit can identify those patients who will need more in depth examination of their eyes and promote more accurate differential diagnoses for the patients.


Bacterial quality of groundwater downgradient of onsite wastewater disposal systems and the influence on eastern Long Island's embayments.
Onsite wastewater disposal systems (OWDS) can introduce bacterial and chemical contaminants, via groundwater, into aquifers and adjacent waterways. We evaluated the concentration of fecal indicator bacteria (FIB) and antibiotic resistant bacteria (ARB) in the shallow groundwater of Eastern Long Island, New York, downgradient of OWDS using cultivation approaches and analysis of 16 S rRNA genes. While FIB and ARB were detected in 80% and 67% of groundwater samples, respectively, concentrations were low, suggesting that, at least at the time of sampling, groundwater was not a large-scale source of fecal bacterial contamination to adjacent embayments. ARB isolates did not include common fecal associated genera and the concentration of FIB and ARB did not correlate well with the concentration of pharmaceutical contaminants, suggesting that bacterial contaminants were poorly linked to OWDS discharge. Concentrations of FIB in the studied embayments were significantly greater in nearshore compared to mid-channel environments, suggesting that land-based sources are likely to be the major contributors of bacterial contamination.


Dose reconstruction for plutonium-239 intakes at the Rocky Flats Plant.
The Rocky Flats (RF) Plant was a weapons manufacturing facility that operated from the early 1950s to 1989. Its primary missions were the production of plutonium (Pu) pits for thermonuclear weapons and the processing of retired weapons for Pu recovery. The purpose of this study was to estimate radiation doses to a cohort of 4499 RF workers from an intake of 239Pu, the primary plutonium isotope handled at the site. The latest biokinetic models of the International Commission on Radiological Protection, or site-specific variations of those models, were used to estimate 239Pu intakes for each worker based on model fits to bioassay data often coupled with lung measurements. Urinary excretion and lung retention data for most 239Pu intakes could be fit reasonably well by a mixture of Pu dioxide and moderately soluble material. For some workers, better fits were obtained by application of other absorption types including Type S, 239Pu nitrate, or pure 239Pu dioxide, or by assuming intake via a wound. The lungs typically received the highest tissue doses, with fifty-year committed equivalent doses in the range of 0.5-1 Sv for 275 workers, 1-5 Sv for 115 workers, and greater than 5 Sv for 12 workers. RF was a unique site regarding a large number of lung measurements available for determining the appropriate absorption types for inhaled material. This provided higher confidence in reconstructed 239Pu doses than is generally gained from urinary data alone.


The rectum of Oxaea flavescens (Andrenidae) has a specialized structure among bees.
The rectum of the bee Oxaea flavescens contains six hollow rectal papillae, in contrast to rectal pads found in others Hymenoptera. The rectal epithelium is formed by cubical cells with structural specializations for fluid transport, such as apical plasma membrane invaginations, endocytic vesicles, scalariform junctions, wide extracellular space and double-membrane vesicles. Globular-shaped cells form the rectal papillae with surface plasma membrane invaginations that vary from small depressions to very large sinuses. The cell-cell contact is narrow, exhibiting extensive regions with scalariform junction, while cytoplasmic free ribosome-like material is prominent. These ultrastructural features are discussed in relation to their role in excretion in this bee.


Systematic review: incidence of abdominal/pelvic surgery amongst patients using tegaserod in randomized controlled trials.
In the USA, tegaserod is contraindicated in patients with a history of bowel obstruction, abdominal adhesions or symptomatic gall-bladder disease due to a non-significant difference in abdominal surgery between tegaserod-using and placebo-using patients in Phase III trials. To calculate the incidence of abdominal and pelvic surgery in tegaserod-using and placebo-using patients in randomized controlled trials and to assess the possible association between medication and surgery, using pre-specified criteria in a blind adjudication procedure. Primary study selection criteria included: (i) randomized controlled trial; (ii) comparison of tegaserod vs. placebo; and (iii) results reporting the incidence of abdominal and pelvic surgery. A panel of experts in epidemiology and functional bowel disorders reviewed the history of each patient who underwent surgery. Experts were blind with regard to whether patients used tegaserod or placebo. Using pre-specified criteria, experts rated the likelihood of an association between medication use and surgery. Thirteen randomized controlled trials (n =9857 patients) met the primary study selection criteria. No significant difference in the incidence of abdominal/pelvic surgery was identified between tegaserod-using and placebo-using patients: pelvic surgery, 0.16% vs. 0.19% (P = 0.80); abdominal surgery (non-cholecystectomy), 0.15% vs. 0.19% (P = 0.61); cholecystectomy, 0.13% vs. 0.03% (P = 0.17); total abdominal/pelvic surgery, 0.44% vs. 0.41% (P = 1.00). Post-adjudication, there was no significant difference in the incidence of abdominal/pelvic surgery between tegaserod-using and placebo-using patients. Data from randomized controlled trials demonstrate a similar incidence of abdominal/pelvic surgery in tegaserod-using and placebo-using patients.


Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.
In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 μm in C1, -108.8 μm in C2, -100.6 μm in C3, and -89.5 μm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.


Preparation of poly (A)-binding proteins from endoplasmic reticulum-containing subfractions of rat liver cells and their use in mRNA purification.
Approximately 2% of the proteins solubilised from rat liver microsomes or rapidly sedimenting endoplasmic reticulum (RS-ER) adsorbed to poly(A)-Sepharose. The adsorption appeared to be selective for a few proteins, and proteins of different apparent molecular weights adsorbed from RS-ER and the microsomes. The proteins from RS-ER with affinity for poly(A) were coupled to Sepharose and used for the purification of mRNA from rabbit mammary glands. A portion of the RNA wihich did not adsorb to poly(U)-Sepharose adsorbed to protein-Sepharose and was active in a cell-free protein synthesis system.


Making chronic pain count: empirical support for the ICD-11 classification of chronic pain.
The purpose is to review the evidence that has been collected with regard to the new classification of chronic pain. In 2022, the World Health Assembly endorsed the 11 th revision of the International Classification of Diseases and Related Health Problems (ICD-11), and with it a new classification of chronic pain. The evidence from the formative field testing indicated that the categories were clearly delineated and the coverage of chronic pain excellent (<3% in remainder categories). Official WHO field tests showed that the classification works well within the technical parameters WHO classifications must conform to and outperformed the ICD-10 diagnoses in all respects. International field tests, in which clinicians diagnosed consecutive patients in settings of medium and high resources, showed substantial interrater reliability (κ = 0.596 to κ = 0.783) for the diagnoses and the clinicians rated their clinical utility as very high. Studies using complete hospital records demonstrated that with the information they contain, retrospective coding of the new diagnoses is possible and provides much more meaningful information than the ICD-10 diagnoses. The evidence supports the use of the new classification and highlights its informational gains - using it will contribute to making chronic pain count in many contexts.


Genetic and molecular understanding of host rice resistance and Nilaparvata lugens adaptation.
The variability of brown planthopper (BPH) populations and diversity of the host rice germplasm provide an ideal model for exploring the genetic and molecular basis of insect-plant interactions. During the long-term evolutionary arms race, complicated feeding and defense strategies have developed in BPH and rice. Nine major BPH resistance genes have been cloned and the exploration of BPH resistance genes medicated mechanism against BPH shed a light on the molecular basis of the rice-BPH interaction. This short review provides an update on our current understanding of the genetic and molecular mechanism for rice resistance and BPH adaptation. Understanding the interactions between BPH and rice will provide novel insights for sustainable control of this pest.


A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair.
The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.


Effects of weight loss on epicardial adipose tissue thickness and its relationship between serum soluble CD40 ligand levels in obese men.
Epicardial adipose tissue (EAT) induces activated inflammatory cells secreting cytokines, including soluble CD40 ligand (sCD40L). In turn, the serum sCD40L can trigger inflammatory responses. We examined the reduction of EAT in response to weight loss (WL) and its relationship with alterations in sCD40L in obese men. We prospectively provided dietary education and exercise intervention for 3 months for 32 non-diabetic obese men with metabolic syndrome. Twenty-five age-matched healthy men served as controls. Circulating sCD40L was measured, and EAT thickness (EATt) was determined by magnetic resonance imaging before and after WL. EATt was increased in the obese individuals, but there were no significant differences in baseline serum sCD40L levels between the 2 groups. Serum concentrations of sCD40L were higher in individuals with high right atrioventricular groove (RAVG)-EATt. EATt was reduced significantly in individuals who completed the weight-loss program. In addition, a positive correlation was shown between changes in sCD40L and RAVG-EATt. Multiple linear regression analysis showed the change in sCD40L to be independently associated with the change in RAVG-EATt. WL can significantly reduce epicardial fat thickness, and the reduced EATt after WL may provide a beneficial reduction in circulating levels of sCD40L in obese males.


Presence of interferon and anti-interferon in patients with systemic lupus erythematosus.
Sera from 61 patients with systemic lupus erythematosus (SLE) were serially screened over a period of at least 2 years for IFN and anti-IFN antibodies. IFN concentrations were measured both with a cytopathic effect assay and a more sensitive radioimmunoassay. Of the patients 15% (9/61) had IFN in their serum at one or more occasions as measured in the bioassay (greater than or equal to 6 IU/ml); employing a RIA (greater than or equal to 1 IU/ml) 28% (17/61) of the patients studied were positive for IFN-alpha. Fifteen patients had a measurable interferonemia over 2-16 months; only two patients had detectable IFN in their serum at only one occasion. In five patients, hourly and daily variations of the IFN titer as measured by RIA were found to amount to less than 80%. The IFN activity found in these sera was characterized as IFN-alpha by means of acid stability, cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous and heterologous antisera. IFN antibodies were quantified with a neutralization bioassay, an ELISA, and a radioimmunoassay. Of the 61 patients 5% (3) possessed high titers of anti-IFN antibodies which persisted over 2 years. The IFN-alpha antibody positive patients had an inactive form of the disease over years without visceral involvement but decreased serum complement levels (C4, C3, CH50) and repeated episodes of Quincke-like edema.


Pediatric flexible bronchoscopy under conscious sedation: nursing considerations for preparation and monitoring.
Flexible bronchoscopy provides a powerful tool to evaluate pulmonary abnormalities in the pediatric population. Nursing involvement may range from age-appropriate preparation of the patient and family to administration of conscious sedation agents. Meticulous nursing assessment of the child, family, and environment facilitates identifying and meeting client needs related to flexible bronchoscopy. Preparation of the physical environment as well as physiological and psychological preparation of the child increase the likelihood of a positive experience. By increasing their familiarity with the procedure, sedation strategies, and monitoring standards, nurses increase the probability of safe and successful flexible bronchoscopic evaluations.


SegPC-2021: A challenge & dataset on segmentation of Multiple Myeloma plasma cells from microscopic images.
Multiple Myeloma (MM) is an emerging ailment of global concern. Its diagnosis at the early stages is critical for recovery. Therefore, efforts are underway to produce digital pathology tools with human-level intelligence that are efficient, scalable, accessible, and cost-effective. Following the trend, a medical imaging challenge on "Segmentation of Multiple Myeloma Plasma Cells in Microscopic Images (SegPC-2021)" was organized at the IEEE International Symposium on Biomedical Imaging (ISBI), 2021, France. The challenge addressed the problem of cell segmentation in microscopic images captured from the slides prepared from the bone marrow aspirate of patients diagnosed with Multiple Myeloma. The challenge released a total of 775 images with 690 and 85 images of sizes 2040×1536 and 1920×2560 pixels, respectively, captured from two different (microscope and camera) setups. The participants had to segment the plasma cells with a separate label on each cell's nucleus and cytoplasm. This problem comprises many challenges, including a reduced color contrast between the cytoplasm and the background, and the clustering of cells with a feeble boundary separation of individual cells. To our knowledge, the SegPC-2021 challenge dataset is the largest publicly available annotated data on plasma cell segmentation in MM so far. The challenge targets a semi-automated tool to ensure the supervision of medical experts. It was conducted for a span of five months, from November 2020 to April 2021. Initially, the data was shared with 696 people from 52 teams, of which 41 teams submitted the results of their models on the evaluation portal in the validation phase. Similarly, 20 teams qualified for the last round, of which 16 teams submitted the results in the final test phase. All the top-5 teams employed DL-based approaches, and the best mIoU obtained on the final test set of 277 microscopic images was 0.9389. All these five models have been analyzed and discussed in detail. This challenge task is a step towards the target of creating an automated MM diagnostic tool.


Increased oxidative stress condition found in different stages of HIV disease in patients undergoing antiretroviral therapy in Umuahia (Nigeria).
Effective diagnostic tools for management of HIV disease progression in Sub-Saharan Africa is inadequate considering the endemic nature of the infection in the region. To elucidate the clinical implication of oxidative stress (measured as Malondialdehyde, MDA) as additional biomarker of HIV disease progression and its implication in HIV clinical management. A total of 250 individuals were recruited for the study. FACScan cytometry and spectrophotometric methods were employed in assessing T-lymphocytes (CD3, CD4, CD8) and MDA respectively. MDA concentration increased significantly (P < 0.05) in highly active antiretroviral therapy (HAART) subjects by 12.72% in category 1, 9.75% in III and in category II (4.63%) on comparison with non-HAART subjects. In subjects taking HAART, 22.2%, 56.3%, and 22.2% were found to be in category I, II and III, respectively, with a corresponding non-HAART values of 15.6%, 45.6% and 38.9%. However, Spearman's rank correlation (P < 0.001) statistics of MDA and HIV categories showed a negative correlation in all the categories (I, II and III). These findings suggest that MDA may be an additional clinical factor in assessing progression of HIV disease; however, necessary fortification of regimen with antioxidant may help reduce the high MDA concentration in the disease progression of the infection.


AE-TPGG: a novel autoencoder-based approach for single-cell RNA-seq data imputation and dimensionality reduction.
Single-cell RNA sequencing (scRNA-seq) technology has become an effective tool for high-throughout transcriptomic study, which circumvents the averaging artifacts corresponding to bulk RNA-seq technology, yielding new perspectives on the cellular diversity of potential superficially homogeneous populations. Although various sequencing techniques have decreased the amplification bias and improved capture efficiency caused by the low amount of starting material, the technical noise and biological variation are inevitably introduced into experimental process, resulting in high dropout events, which greatly hinder the downstream analysis. Considering the bimodal expression pattern and the right-skewed characteristic existed in normalized scRNA-seq data, we propose a customized autoencoder based on a two-part-generalized-gamma distribution (AE-TPGG) for scRNA-seq data analysis, which takes mixed discrete-continuous random variables of scRNA-seq data into account using a two-part model and utilizes the generalized gamma (GG) distribution, for fitting the positive and right-skewed continuous data. The adopted autoencoder enables AE-TPGG to captures the inherent relationship between genes. In addition to the ability of achieving low-dimensional representation, the AE-TPGG model also provides a denoised imputation according to statistical characteristic of gene expression. Results on real datasets demonstrate that our proposed model is competitive to current imputation methods and ameliorates a diverse set of typical scRNA-seq data analyses. Supplementary material is available in the online version of this article at 10.1007/s11704-022-2011-y.


Early gestational profiling of oxidative stress and angiogenic growth mediators as predictive, preventive and personalised (3P) medical approach to identify suboptimal health pregnant mothers likely to develop preeclampsia.
Pregnant women, particularly in developing countries are facing a huge burden of preeclampsia (PE) leading to high morbidity and mortality rates. This is due to delayed diagnosis and unrecognised early targeted preventive measures. Adapting innovative solutions via shifting from delayed to early diagnosis of PE in the context of predictive diagnosis, targeted prevention and personalisation of medical care (PPPM/3 PM) is essential. The subjective assessment of suboptimal health status (SHS) and objective biomarkers of oxidative stress (OS) and angiogenic growth mediators (AGMs) could be used as new PPPM approach for PE; however, these factors have only been studied in isolation with no data on their combine assessment. This study profiled early gestational biomarkers of OS and AGMs as 3 PM approach to identify SHS pregnant mothers likely to develop PE specifically, early-onset PE (EO-PE) and late-onset PE (LO-PE). A prospective cohort of 593 singleton normotensive pregnant (NTN-P) women were recruited at 10-20th (visit 1) and followed from 21 weeks gestation until the time of PE diagnosis and delivery. At visit 1, SHS was assessed using SHS questionnaire-25 (SHSQ-25) and women were classified as SHS and optimal health status (OHS). Biomarkers of OS (8-hydroxy-2-deoxyguanosine [8-OHdG], 8-epi-prostaglansinF2alpha [8-epi-PGF2α] and total antioxidant capacity [TAC]) and AGMs (vascular endothelial growth factor [VEGF-A], soluble Fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF] and soluble endoglin [sEng]) were measured at visit 1 and time of PE diagnosis. Of the 593 mothers, 498 (248 SHS and 250 OHS) returned for delivery and were included in the final analysis. Fifty-six, 97 and 95 of the 248 SHS mothers developed EO-PE, LO-PE and NTN-P respectively, versus 14 EO-PE, 30 LO-PE and 206 NTN-P among the 250 OHS mothers. At the 10-20th week gestation, unbalanced levels of OS and AGMs were observed among SHS women who developed EO-PE than LO-PE compared to NTN-P women (p < 0.0001). The combined ratios of OS and AGMs, mainly the levels of 8-OHdG/PIGF ratio at 10-20th week gestation yielded the best area under the curve (AUC) and highest relative risk (RR) for predicting SHS-pregnant women who developed EO-PE (AUC = 0.93; RR = 6.5; p < 0.0001) and LO-PE (AUC = 0.88, RR = 4.4; p < 0.0001), as well as for OHS-pregnant women who developed EO-PE (AUC = 0.89, RR = 5.6; p < 0.0001) and LO-PE (AUC = 0.85; RR = 5.1; p < 0.0001). Unlike OHS pregnant women, SHS pregnant women have high incidence of PE coupled with unbalanced levels of OS and AGMs at 10-20 weeks gestation. Combining early gestational profiling of OS and AGMs created an avenue for early differentiation of PE subtypes in the context of 3 PM care for mothers at high risk of PE.


Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum depressive symptoms in a small population based sample.
The decrease of maternal docosahexaenoic (DHA) status during pregnancy has been associated with postpartum depression, especially in women with a low intake of DHA. Since the DHA intake in the Netherlands is low, we investigated whether supplementation of low doses of DHA or DHA plus arachidonic acid (AA) during pregnancy and lactation could prevent depressive symptoms and sleep disturbances in this period. Women were supplemented daily with placebo, DHA (220 mg) or DHA+AA (220 mg each) from week 16 of pregnancy till three months postpartum. Fatty acid analyses were performed in the available plasma samples at 16 and 36 weeks of pregnancy. Depressive symptoms were measured in weeks 16 and 36 of pregnancy and six weeks postpartum using EPDS and within one week postpartum using a blues questionnaire. 119 women completed the study. The average frequency of fish intake was low, 0.94 times per week, and did not differ between the groups. The supplementation groups did not differ in mean EPDS scores or changes in EPDS scores, nor in incidence or severity of postpartum blues. Red blood cell DHA, AA and DHA/AA ratio did not correlate with EPDS or blues scores. Indices of sleep quality did not differ between the groups. Supplementation of 220 mg/day DHA or DHA+AA (220 mg/day each) does not prevent peri-partum depressive symptoms, in a population based sample with low background DHA intake. ISRCTN Register nr. ISRCTN58176213.


John Peever.
Interview with John Peever, who studies the brain mechanisms that control REM sleep and how their dysfunction underlies sleep disorders at the University of Toronto.


A longitudinal study of nurses' career choices: The importance of career expectations on employment in care of older people.
To investigate how undergraduate nursing students' career expectations relate to their career choices, particularly employment in care of older people, in the first 10 years of nurses' careers. Due to an increasing demand for nurses, it is important to understand nurses' career choices over the course of their careers. A quantitative longitudinal study of 445 undergraduate nursing students based on a questionnaire survey and register data. Data were analysed by multinomial logistic regression analyses. The questionnaire was distributed to all undergraduate nursing students in 2001-2003 in their final study semester at four universities in Norway (N = 445) to collect the students' career expectations. Register data on clinical fields for the first 10 years after graduation were merged into the survey in 2014 (Statistics Norway). With exception of the very first years after graduation, care of older people is the most common field for undergraduate nurses to enter for a career. This choice can be understood in light of nurses' career expectations. Among newly educated nurses, the choice to work in care of older people (rather than general hospital care) correlates with expectations of achieving a management position. Ten years after graduation, the likelihood of working in care of older people rather correlates with nurses' expectations of part-time work. The likelihood of moving into care of older people increases with time in nursing careers and relates to nurses' career expectations such as achieving a leadership position and working part-time.


Calcium efflux and histamine secretion from rat peritoneal mast cells.
Purified rat peritoneal mast cells rapidly accumulated 45calcium from the external medium. The uptake was essentially unaffected by lanthanide ions but was almost totally prevented by metabolic inhibitors. Cells preloaded with 45calcium showed a steady efflux of the cation on transfer to a medium lacking the isotope. The efflux was unaffected by metabolic inhibitors but was totally dependent on extracellular sodium ions. These results indicate the operation of a sodium-calcium exchange mechanism for the extrusion of the divalent cation. Antigenic or pharmacologic stimulation of the mast cell led to a temporary suppression of calcium efflux during the period in which histamine release occurred. This effect was potentiated by phosphatidylserine and high concentrations of the lipid inhibited basal efflux. These results suggest that activation of the mast cell leads to an inhibition of calcium extrusion, thereby potentiating the induced rise in the intracellular concentration of the cation and thus augmenting the secretory response.


Direct enhancement of intercomponent interactions in polyrotaxane and its pronounced effects on glass state properties.
Strong interactions between the host cyclodextrin and the threading guest polymer were introduced by selective modifications to the polymer of a polybutadine-based polyrotaxane. The changes in the intercomponent interactions influenced the mobility of the threading polymer that was confined in the glassy host framework, resulting in different mechanical properties.


Linking ADHD and ASD Symptomatology with Social Impairment: The Role of Emotion Dysregulation.
Children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often experience social impairments. These children also frequently struggle with emotion regulation, and extant literature suggests that emotion dysregulation predicts social impairment in both clinical and neurotypical populations. However, the evidence base linking ADHD/ASD with social impairment comes primarily from samples meeting full diagnostic criteria for ADHD and/or ASD despite evidence that both syndromes reflect extreme ends of natural continuums that are normally distributed across the general population. To our knowledge, the present study is the first to concurrently examine unique and overlapping relations among ADHD/ASD symptoms, emotion regulation, and social difficulties using multi-informant measures (parent, teacher) with a clinically-evaluated sample of 108 children ages 8-13 (40 girls; 66% White/Non-Hispanic) with and without clinically-elevated ASD and ADHD symptoms and other common clinical disorders. Bias-corrected, bootstrapped conditional effects modeling revealed that ADHD-inattentive (β=-0.23) and ASD-social communication (β=-0.20) symptoms predicted social impairment directly, whereas ADHD-hyperactive/impulsive (β=-0.06) and ASD-restricted/repetitive behavior/interests (β=-0.06) symptoms predicted social impairment only via their shared associations with emotion dysregulation. Sensitivity analyses revealed that most relations were robust to control for item overlap across measures. In contrast, only the ADHD-inattention/social impairment link was robust to control for mono-informant bias, highlighting the importance of multi-informant methods and the potential for different determinants of social functioning across settings. Overall, this study implicates emotion regulation skills and all four ADHD/ASD symptom clusters as potential influences on children's social functioning, albeit with a more nuanced and potentially setting-specific pattern than suggested by prior work.


Enantioseparation of organic acids of pharmaceutical interest using eremomycin as a chiral selector.
Strong adsorption of eremomycin on the fused-silica capillary wall was used for separation of enantiomers by CE. The capillary with adsorbed chiral selector was shown to be easily prepared and has reproducible properties. The effect of the chiral selector concentration, pH and composition of the BGE, and applied voltage on enantioseparation of acidic compounds, such as profens and aromatic carboxylic acids, was investigated. Two native α-amino acids, aspartic acid and glutamic acid, were enantioseparated. Fourteen tested compounds (including amino acids) were baseline resolved. Good selectivity of separation (α>1.09) was achieved. The migration order of ibuprofen and ketoprofen enantiomers was determined. The procedures were proposed for the analysis of flurbiprofen and warfarin in pharmaceuticals. Linearity was achieved in the concentration range of 4.0×10(-5)-2.0×10(-3) M for flurbiprofen and 3.2×10(-6)-4.9×10(-6) M for warfarin. The detection limits were found to be about 1×10(-5) M for flurbiprofen and 1×10(-6) M for warfarin.


Efficacy of the Orally Disintegrating Strip Sildenafil for the Treatment of Erectile Dysfunction: A Prospective, Randomized Trial.
Phosphodiesterase 5 inhibitors are the predominant treatment option for erectile dysfunction. This study evaluates the efficacy and safety of sildenafil orally disintegrating strips for the treatment of erectile dysfunction. One hundred twenty erectile dysfunction patients were enrolled in a prospective, randomized, controlled crossover study and allocated into 2 groups of 60 participants. Patients were either treated with sildenafil strips or tablets for 8 weeks after which they crossed over into the alternate treatment formulation for another 8 weeks following a 4-week wash-out period. Each participant was assessed 8 times throughout the study period and their formulation preference registered at the end of the study. Changes in the abridged International Index of Erectile Function (IIEF-5) score and Erection Hardness Score (EHS) resulting from sildenafil orally disintegrating strip or tablet treatments were the primary end points, with differences in onset of action, duration of action, and incidence of adverse events between the 2 formulations included as secondary end points. Both sildenafil formulations were effective in treating patients with erectile dysfunction. There was significant improvement of erectile function in term of IIEF-5 score and EHS from both formulations. The number and type of adverse events were also comparable. Likewise, there were no statistically significant differences between the earliest onset of action times and longest duration of action times. However, the results showed a 7.1-minute earlier onset of action time for orally disintegrating strips that may be considered as clinically meaningful by some patients. Sildenafil orally disintegrating strips are a safe and effective alternative to the conventional tablet formulation for the treatment of erectile dysfunction. Sangkum P, Sirisopana K, Matang W, et al. Efficacy of the Orally Disintegrating Strip Sildenafil for the Treatment of Erectile Dysfunction: A Prospective, Randomized Trial. Sex Med 2021;9:100453.


Factorial validity of a substance-use stigma scale in methamphetamine-using adults in China.
Despite the large number of individuals who use substances of abuse and the stigma of such behaviors in China, scales have not been developed and validated for assessing substance-use stigma. Given its importance for targeting interventions, the aim of the present study was to validate a Chinese substance-use stigma measure including three dimensions of substance-use-disorder-related stigma (personal stigma, perceived stigma and social distance) by modifying a pre-existing scale measuring mental illness-related stigma and social distance. A convenience sample of eight-hundred-and-twelve individuals with substance abuse (aged 18-68 years) from different drug rehabilitation centers completed a self-reported survey including their demographics and drug use, and the stigma and social distance scales. The adapted, translated from English to Chinese, and back-translated scales were an 18-items stigma scale including personal stigma and perceived stigma subscales and a 5-items one domain social distance scale. Confirmatory factor analysis and multigroup confirmatory factor analysis tested factorial validity and measurement invariance of the scales, respectively. For the stigma scale, by deleting one low correlation dimension (named "weak-not-sick"), personal stigma and perceived stigma showed acceptable fit indices and internal consistency with two dimensions (named "dangerous/unpredictable" and "social discrimination"), separately. The social distance scale showed good fit indices and internal consistency as a separate facet of stigma-related substance-use problems. Invariance of the model across drug-rehabilitation centers was found. The Chinese substance-use stigma scale may serve as a valuable tool for better understanding substance-use stigma among adults in China who abuse substances.


Application of deep reinforcement learning for spike sorting under multi-class imbalance.
Spike sorting is the basis for analyzing spike firing patterns encoded in high-dimensional information spaces. With the fact that high-density microelectrode arrays record multiple neurons simultaneously, the data collected often suffers from two problems: a few overlapping spikes and different neuronal firing rates, which both belong to the multi-class imbalance problem. Since deep reinforcement learning (DRL) assign targeted attention to categories through reward functions, we propose ImbSorter to implement spike sorting under multi-class imbalance. We describe spike sorting as a Markov sequence decision and construct a dynamic reward function (DRF) to improve the sensitivity of the agent to minor classes based on the inter-class imbalance ratios. The agent is eventually guided by the optimal strategy to classify spikes. We consider the Wave_Clus dataset, which contains overlapping spikes and diverse noise levels, and the macaque dataset, which has a multi-scale imbalance. ImbSorter is compared with classical DRL architectures, traditional machine learning algorithms, and advanced overlapping spike sorting techniques on these two above datasets. ImbSorter obtained improved results on the Macro_F1. The results show ImbSorter has a promising ability to resist overlapping and noise interference. It has high stability and promising performance in processing spikes with different degrees of skewed distribution.


Cultural and educational influences on pain of childbirth.
This study investigated the effects of sociocultural family of origin and educational level on the verbal ratings of pain and pain behavior during childbirth for 83 women. Coping style and extroversion were also measured. It was found that all women rated the pain of childbirth as high. Overall, women from a Middle-Eastern compared with a Western background gave higher ratings of pain and showed more pain behavior. This was found especially for Middle-Eastern women of a low educational background. Overall, low compared with high educational level resulted in higher ratings of pain and more pain behavior. No differences were obtained as a function of extroversion. Middle-Eastern and Western women did not differ in coping style. However, women who had higher monitoring scores rated the pain as less even through no differences were obtained for pain behavior. Sociocultural group of origin as well as other relevant reference groups, such as educational level, are important in determining pain perception and behavior. Combining this information with coping style could lead to an instructional intervention for preparing women for childbirth.


A handheld electronic device with the potential to detect lung cancer biomarkers from exhaled breath.
Lung cancer is the leading cause of cancer death in the United States. It has the lowest 5-year survival rate among the most common cancers and therefore, early diagnosis is critical to improve the survival rate. In this paper, a new handheld electronic device is proposed to detect nine lung cancer biomarkers in the exhaled breath. An electrochemical gas sensor was produced through deposition of a thin layer of graphene and Prussian blue on a chromium-modified silicon substrate. Selective binding of the analyte was formed by molecular imprinting polymer (MIP). Subsequent polymerization and removal of the analyte yielded a layer of a conductive polymer on top of the sensor containing molecularly imprinted cavities selective for the target molecule. The sensors were tested over 1-20 parts per trillion (ppt) level of concentration while the sensor resistance has been monitored as the sensors react to the analyte by resistance change. Pentane sensor was also tested for selectivity. A printed circuit board was designed to measure the resistance of each sensor and send the data to a developed application in smartphone through Bluetooth. This handheld device has the potential to be used as a diagnostic method in the near future.


Isolation of Kell-active protein from the red cell membrane.
Kell blood-group-active protein has been isolated by labeling red cell surface proteins with 125I, sensitizing intact cells with anti-K1, anti-K2, anti-K7, or anti-K22, solubilizing the cell membranes, isolating immune complexes, and separating their components by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Each antibody separated a protein of approximately 93,000 daltons. Periodic-acid Schiff (PAS) staining of Kell protein showed that it was glycosylated. When separated under non-reducing conditions, Kell protein had different SDS-PAGE characteristics with protein bands of approximately 85,000 daltons and 115,000 daltons. This suggests that in the red cell membrane Kell protein is complexed with other proteins. Quantitative experiments made with anti-K7, anti-K22, and a mixture of anti-K7 and anti-K22 indicate that both antigen specificities are present in the same molecule. These biochemical data support serological studies which indicate that K22 is part of the Kell system.


ZmAGO18b negatively regulates maize resistance against southern leaf blight.
Here, we report that ZmAGO18b encoding an argonaute protein is a negative regulator of maize resistance against southern leaf blight. Southern leaf blight caused by fungal pathogen Cochliobolus heterostrophus is a destructive disease on maize throughout the world. Argonaute (AGO) proteins, key regulators in small RNA pathway, play important roles in plant defense. But whether they have function in maize resistance against C. heterostrophus is unknown. Association analysis between the nucleic variation of 18 ZmAGO loci with disease phenotype against C. heterostrophus was performed, and the ZmAGO18b locus was identified to be associated with resistance against C. heterostrophus. Overexpression of ZmAGO18b gene suppresses maize resistance against C. heterostrophus, and mutation of ZmAGO18b enhances maize resistance against C. heterostrophus. Further, we identified the resistant haplotype of ZmAGO18b by association analysis of natural variation in ZmAGO18b genomic DNA sequences with seedling resistance phenotypes against C. heterostrophus and confirmed the resistant haplotype is co-segregated with resistance phenotypes against C. heterostrophus in two F2 populations. In sum, this study reports that ZmAGO18b negatively regulates maize resistance against C. heterostrophus.


A new technique applying botulinum toxin in narrow and wide foreheads.
The use of botulinum toxin is becoming increasingly popular, and application details are being examined in an effort to achieve more satisfactory results with fewer side effects. In the forehead area, the main considerations are the effacement of forehead wrinkles to a desirable extent and the prevention of complications such as ptosis of the eyebrow and upper eyelid. The frontalis muscle necessitates chemodenervation by botulinum toxin at multiple points for the desired effect. The dimensions of foreheads, and thus the frontalis muscle, differ from patient to patient. The effectiveness and side effects change according to whether the forehead is narrow or a wide. Therefore, no single application technique is best for all patients. For this study, the glabella-hairline distance was measured in 90 healthy adults. Patients with a vertical forehead length exceeding 70 mm were regarded as having a wide forehead, and the botulinum toxin was applied in three vertical lines in two split doses. On the other hand, individuals with a vertical forehead length of less than 60 mm were regarded as having a narrow forehead, and the toxin was applied in two split doses in three horizontal lines. The authors have found that in cases of wide or narrow foreheads, the effectiveness of the toxin increased, whereas the side effects such as brow asymmetry and ptosis were not encountered. Thus, they recommend the use of this technique for patients with wide or narrow foreheads.


β2-AGONISTS IN CHILDHOOD ASTHMA.
β2-agonists reduce airflow limitation by improving airway diameter as a consequence of a direct action on airway smooth muscle. β;2-agonists can be broadly classified according to their duration of action: short-acting β2-agonists (SABAs), including albuterol, terbutaline and fenoterol, have pharmacodynamics half–lives between 2 and 6 h and long-acting β2-agonists (LABAs), including salmeterol and formoterol, require twice daily treatment. SABAs are often used "as needed" for asthma exacerbations and before exercise in the presence of exercise-induced bronchospasm. LABAs provide longer symptom control, which is a particularly useful feature for preventing night-time symptoms. There are two main LABAs, salmeterol and formoterol. This review focused on the recent data published on this topic.


Preparation and study of the antibacterial ability of graphene oxide-catechol hybrid polylactic acid nanofiber mats.
The functionalization of electrospun mats with antimicrobial nanomaterials is an attractive strategy when developing functional graphene oxide coating materials to prevent bacterial colonization on surfaces. In this study, we demonstrated a simple approach to produce antimicrobial electrospun mats by dip-coating a polylactic acid (PLA) nanofiber into a graphene oxide-catechol derivative. PLA was first electrospun to yield narrow-diameter polymeric nanofibers. We then modified the graphene oxide (GO) with a catechol derivative - dopamine methacrylamide monomer (DMA) - to synthesize a GO-DMA nanocomposite material which exhibited robust antimicrobial properties. The catechol groups promote the immobilization of graphene oxide onto the PLA nanofibers and possess strong antimicrobial properties. We therefore selected this functional group to modify GO. We dipped the GO-DMA onto the PLA nanofiber to produce the final functionalized electrospun mats. The PLA mats which were functionalized using the GO-DMA nanocomposite (PLA-GO-DMA) displayed antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Furthermore, we studied the biocompatibility of the mats by culturing the cell lines (HepG2, A549, and HUVEC-C) of PLA-GO-DMA among the nanofibers which exhibited excellent biocompatibility. These results collectively demonstrate the potential of PLA-GO-DMA nanofiber mats as antimicrobial biomaterials and provide fundamental information toward the establishment of future biomedical applications.


Cholinergic manipulation of motor disability and L-DOPA-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets.
Anti-cholinergic drugs are used in the treatment of Parkinson's disease (PD) and they can improve motor disability in some patients and may alter the expression of dyskinesia. We report the effects of anticholinergic and pro-cholinergic agents administered alone and combined with L-DOPA, on motor function in 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets. Administration of atropine to MPTP-treated marmosets, not previously exposed to L-DOPA, improved motor disability but this did not occur with other centrally acting anti-cholinergics. Motor disability was worsened by centrally acting pro-cholinergics. However, neither peripherally acting anti- nor pro-cholinergics produced any effect on motor disability or dyskinesia. In MPTP-treated marmosets previously primed with L-DOPA to exhibit dyskinesia, acute L-DOPA challenge induced both chorea and dystonia. In these animals, centrally acting anti-cholinergics including atropine and trihexyphenidyl reversed motor deficits, but induced chorea. Combined with L-DOPA, both centrally and peripherally acting anti-cholinergics reduced peak locomotor activity and produced more chorea than dystonia compared to L-DOPA alone. Centrally acting pro-cholinergics decreased locomotor activity, worsened motor disability and induced dystonia. Co-administered with L-DOPA, pro-cholinergics reduced locomotor activity and decreased chorea while increasing dystonia compared with L-DOPA alone. In conclusion, anti-cholinergics can increase chorea with and without L-DOPA but improve motor disability. Pro-cholinergics decrease the proportion of chorea when combined with L-DOPA, increase motor disability and antagonise L-DOPA's effectiveness. These data suggest that there may be a case for revisiting the use of anti-cholinergic drugs in the treatment of PD.


Management of early-onset neonatal sepsis differs in the north and south of Scandinavia.
This study compared the management and outcomes of early-onset neonatal sepsis (EONS) in two tertiary neonatal units in Denmark and Norway. We retrospectively studied all infants diagnosed with EONS between April 2010 and March 2013 and managed at Odense University Hospital, Denmark, and the University Hospital of North Norway, Norway. Clinical and laboratory data were collected from patient records. We identified 137 EONS cases in Denmark and 101 in Norway. There were 35 culture-confirmed EONS cases: 16% of the Danish cases and 13% of the Norwegian cases. Staphylococcus aureus was the most frequently detected pathogen in 11 cases (31%), followed by Group B streptococci in nine (26%) and Escherichia coli in six (17%). In 85% of the 238 cases, the empiric therapy comprised gentamicin and a beta-lactam, namely ampicillin in Denmark and benzylpenicillin in Norway. Patients with positive blood cultures had higher C-reactive protein levels than patients with negative blood cultures and higher sepsis-attributable mortality. Lumbar punctures were performed more frequently in Denmark. There were marginal differences in the management of EONS between units in Denmark and Norway, mainly in their choice of antibiotics and the use of lumbar punctures. Staphylococcus aureus was the most common pathogen.


Chemical enhancement of cisplatin cytotoxicity in a human ovarian and cervical cancer cell line.
While many advances have been made in the chemotherapy of gynecologic cancers, treatment failures remain a major clinical problem. A growing understanding of the mechanisms of tumor cell resistance to antineoplastic drugs provides a framework for the development of chemotherapy regimens containing agents capable of modulating tumor response. Using a short-term ATP bioluminescence assay we studied the ability of two methylxanthines (caffeine, pentoxifylline) and an inhibitor of ADP-ribosyl transferase (3-aminobenzamide) to enhance cisplatin cytotoxicity in gynecologic cancer cell lines. Our findings of significantly enhanced cisplatin-induced cytotoxicity with two different analysis techniques confirms the effectiveness of these agents. These results may have future clinical significance.


[Effects of adaptation to work in heat of rectal temperature evolution during recovery].
Evolution of rectal temperature (Tre) during recovery in different air temperatures was studied following different patterns of heat load before and after adaptation to work in heat (10 consecutive days). Three subjects have been exposed, after a 30 min rest period (Ta=28degrees C, Pwa=14 mb) to 4 heat loads, each producing 1 degreeC increase in Tre in approximatively 30 min (Co:Ta= 50 degrees C, Pwa = 60 mb, W = O watt; C1; 50 degrees C, 42 mb, 50 W on bicycle ergometer; C2;39 degrees C, 38 mb, 100 W and C3: 28 degrees C, 31 mb, 150 W). After of these heat loads, subjects were allowed to recover during 2 h at Ta = 28, 22 or 16 degrees C (Pwa = 14 mb). Results show that: (a) the cooler was the Ta, the faster was the recovery time; (b) before adaptation occurs, the evolution of Tre depended on the preceding heat load pattern; (c) the more intense was the work load, the more the adaptation reduced time for subsequent recovery. The interaction obtained between adaptation and intensity of preceding work load is discussed. The evolutions of leg skin temperatures suggest that a decreased local heat conductance (of inferior limbs) is associated with a local increase in external heat exchange. Adaptation to work in heat would take the form of a local re-adjustment of internal and external heat exchanges.


Dihydropyrimidine amidohydrolase is a zinc metalloenzyme.
Bovine liver dihydropyrimidine amidohydrolase (EC 188.8.131.52) has been subjected to atomic absorption analysis. Three different preparations of homogeneous enzyme indicated that the enzyme contains 4.3 +/- 0.3 g atoms of Zn2+ per mol of enzyme or 1.1 g atoms of Zn2+ per subunit. No Co2+, Mn2+, Mg2+ or Cd2+ was detected. Exhaustive dialysis against either o-phenanthroline or EDTA did not reduce enzyme activity; however, prolonged incubation with dipicolinic acid resulted in inactivation which can be reversed by either Zn2+ or Co2+ but not Mg2+.


Heart Rate Variability in Children and Adolescents with Autism, ADHD and Co-occurring Autism and ADHD, During Passive and Active Experimental Conditions.
Despite overlaps in clinical symptomatology, autism and ADHD may be associated with opposite autonomic arousal profiles which might partly explain altered cognitive and global functioning. We investigated autonomic arousal in 106 children/adolescents with autism, ADHD, co-occurring autism/ADHD, and neurotypical controls. Heart rate variability was recorded during resting-state, a 'passive' auditory oddball task and an 'active' response conflict task. Autistic children showed hyper-arousal during the active task, while those with ADHD showed hypo-arousal during resting-state and the passive task. Irrespective of diagnosis, children characterised by hyper-arousal showed more severe autistic symptomatology, increased anxiety and reduced global functioning than those displaying hypo-arousal, suggesting the importance of considering individual autonomic arousal profiles for differential diagnosis of autism/ADHD and when developing personalised interventions.


Pancreatitis in Children.
Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].


Parenteral nutrition, and fluid and electrolyte therapy.
The provision of fluid and electrolytes during parenteral nutrition can be a challenge in the malnourished child or the child with complicating illnesses. The practitioner using the basic concepts of maintenance and deficit therapy--in this case for calories--must adapt his or her therapy to the expansion of the intracellular as well as the extracellular fluid compartment. Impairment of other organ systems further complicates the ability to deliver therapy. Careful monitoring and individually tailored solution will provide adequate caloric fluid and electrolyte therapy during parenteral nutrition in children.


Towards defining and supporting pharmacists' professional role associated with traditional and complementary medicines - A systematic literature review.
A review conducted in 2015 reported community pharmacists are willing to adopt a professional role in counselling consumers about the appropriate and safe use of traditional and complementary medicines (T&CM) but faced multiple barriers in doing so; including the role being poorly defined. This current review aimed to update and extend these findings, by identifying studies published since 2015 that reported on pharmacists across any setting. Eligible studies published between January 01, 2016 and December 31, 2021 were identified across six databases (PubMed, Scopus, Web of Science, EMBASE, ScienceDirect and MEDLINE). A grounded theory approach was used to thematically synthesize the data extracted. A total 64 studies representing pharmacists across 30 countries were included for review. Study designs varied including cross-sectional surveys (n = 36), qualitative studies (n = 14), and pseudo-patient studies (n = 3). Eight studies reported on practice and/or bioethical responsibilities and 19 studies reported on factors that would enable pharmacists to fulfill these responsibilities, while 37 studies reported about both. These findings indicate research about pharmacists' responsibilities associated with T&CM is evolving from gap analysis towards research that is proactive in advocating for change in multiple areas. These findings can be used to inform a consensus discussion among pharmacists and key stakeholders regarding a set of professional responsibilities that would serve in the development of: a clearly defined role and associated practice standards, and competency requirements that inform educational learning objectives for inclusion in undergraduate, post-graduate and continuing professional pharmacy education.


Learning to walk with a wearable robot in 880 simple steps: a pilot study on motor adaptation.
Wearable robots have been shown to improve the efficiency of walking in diverse scenarios. However, it is unclear how much practice is needed to fully adapt to robotic assistance, and which neuromotor processes underly this adaptation. Familiarization strategies for novice users, robotic optimization techniques (e.g. human-in-the-loop), and meaningful comparative assessments depend on this understanding. To better understand the process of motor adaptation to robotic assistance, we analyzed the energy expenditure, gait kinematics, stride times, and muscle activities of eight naïve unimpaired participants across three 20-min sessions of robot-assisted walking. Experimental outcomes were analyzed with linear mixed effect models and statistical parametric mapping techniques. Most of the participants' kinematic and muscular adaptation occurred within the first minute of assisted walking. After ten minutes, or 880 steps, the energetic benefits of assistance were realized (an average of 5.1% (SD 2.4%) reduction in energy expenditure compared to unassisted walking). Motor adaptation was likely driven by the formation of an internal model for feedforward motor control as evidenced by the reduction of burst-like muscle activity at the cyclic end of robotic assistance and an increase in arm-swing asymmetry previously associated with increased cognitive load. Humans appear to adapt to walking assistance from a wearable robot over 880 steps by forming an internal model for feedforward control. The observed adaptation to the wearable robot is well-described by existing three-stage models that start from a cognitive stage, continue with an associative stage, and end in autonomous task execution. Trial registration Not applicable.


Experimental demonstration of topological effects in bianisotropic metamaterials.
Existence of robust edge states at interfaces of topologically dissimilar systems is one of the most fascinating manifestations of a novel nontrivial state of matter, a topological insulator. Such nontrivial states were originally predicted and discovered in condensed matter physics, but they find their counterparts in other fields of physics, including the physics of classical waves and electromagnetism. Here, we present the first experimental realization of a topological insulator for electromagnetic waves based on engineered bianisotropic metamaterials. By employing the near-field scanning technique, we demonstrate experimentally the topologically robust propagation of electromagnetic waves around sharp corners without backscattering effects.


Human experience of cetiedil, a new vasodilator with anticholinergic properties.
Cetiedil, a new vasodilating drug with anticholinergic properties, was shown to be metabolised very rapidly in man after intravenous and oral administration of the 14C-compound. Higher concentrations of labelled compound after oral than after intravenous administration at the same sampling time, and proportional differences in urinary excretion, suggest that metabolic handling of the drug differs depending on the route of administration. Experiments in which inhibition of saliva secretion was measured indicated that (an) active metabolite(s) probably was (were) responsible for the action of the drug. As an anticholinergic drug, cetiedil is at least 400 times weaker than atropine.


A review on muscle activation behaviour during gait in shallow water and deep-water running and surface electromyography procedures.
Surface electromyography (sEMG) can provide information on muscle activation patterns during gait. To characterize electromyographic activity during gait in shallow water and during deep-water running compare to on land and to review and analyse underwater surface-electromyographic (sEMG) procedures. Eight databases (MEDLINE, EMBASE, WEB OF SCIENCE, SPORT Discus, CINAHL, SCOPUS, SCIELO, and LILACS) were searched from their inception to the December of 2019. The selected studies had to be related to electromyographic analysis of gait in an aquatic environment. The studies that met the inclusion criteria were reviewed by two independent reviewers and divided into four groups. Ten studies met the inclusion criteria. Lower muscle activation was found with treadmill water walking compared to treadmill land walking. With deep-water running, the leg muscles (tibialis anterior and gastrocnemius lateralis) have lower muscle activation when compared to on land running, but the trunk and thigh muscles have higher activation. If gait is performed on an aquatic treadmill, the muscles assessed had lower muscle activation when compared to land. During deep-water running activities, lower activation of the distal leg muscles and a higher activation thigh muscles were found when compared to on land. Studies did not follow standard processes in sEMG procedures.


Isolation of an integrated provirus of Moloney murine leukemia virus with long terminal repeats in inverted orientation: integration utilizing two U3 sequences.
We have previously described the construction of a mutant of Moloney murine leukemia virus, in594-2, which carries a 2-base-pair insertion in the U5 region of the genome and is partially defective in forming the integrated proviral DNA. We have now recovered a cloned copy of an unusual provirus from rat cells infected with this mutant. The viral genome is flanked by long terminal repeats in inverted orientation, with U3 sequences joined to cellular DNA at both of the outer edges. In addition, the provirus is a recombinant, containing a segment of a VL30 element in inverted orientation in place of the Moloney murine leukemia virus env region. The recovery of this provirus indicates that two U3 regions can be used for viral integration and suggests that there may be no absolute requirement in the reaction for those U5 sequences outside the 13-base-pair inverted repeats.


Spontaneous long-term changes of corneal power and astigmatism after suture removal after penetrating keratoplasty using a regression model.
To assess the diagnosis-based spontaneous long-term changes in corneal power and refraction with a regression model in the all-sutures-out time period following non-mechanical penetrating keratoplasty (PK). Retrospective non-randomized clinical trial. setting: Clinical practice. study population: 147 eyes [47 Fuchs dystrophy (FD); 100 keratoconus (KC)] were studied after suture removal in this retrospective longitudinal study. main outcome measures: Zeiss keratometry [equivalent power (KEQ) and astigmatism (KAST)], corneal topography analysis [equivalent power (TEQ) and astigmatism (TAST)], and subjective refractometry [spherical equivalent (SEQ) and refractive cylinder (RAST)] were assessed in at least three up to 16 ophthalmologic examinations in the all-sutures-out time period. observation procedure: The time course of each target variable was analyzed in a longitudinal manner (time interval > or = 12 months) separately for each patient with a linear regression model. Post-keratoplasty follow-up ranged from 31 months to 10.3 years. In the linear regression model, the annual change in FD/KC showed an increase/a decrease in KEQ (0.29 +/- 0.50/-0.63 +/- 0.46 diopters, P = .02) and an increase/a decrease in TEQ (0.37 +/- 0.54/-0.69 +/- 0.49 diopters, P = .04) corresponding to a decrease/an increase in SEQ (-0.31 +/- 0.47/0.63 +/- 0.43 diopters, P = .02). KAST/TAST/RAST showed a minimal annual decrease (-0.06 +/- 0.41/-0.05 +/- 0.45/-0.06 +/- 0.41 diopters) in FD but an increase in KC (0.46 +/- 0.41/0.51 +/- 0.43/0.46 +/- 0.38 diopters) (P = .05/0.06/0.12). In the follow-up after post-keratoplasty suture removal, patients with FD/KC tend to develop a spontaneous myopic shift (steepening of the cornea)/hyperopic shift (flattening of the cornea). In contrast with those with FD, patients with KC should be counseled on the fact that astigmatism may increase again over time after suture removal.