Postoperative tomographic assessment of veneer bone grafting with implant placement in the maxillary anterior region.
Various ridge augmentation and sinus lift procedures were performed in severely resorbed alveolar crests of a maxilla to provide some volume for implant treatment. It was reported that the outcome of maxillary sinus lift procedures was evaluated with conventional tomography or computerized tomography, and that grafted bone around implants markedly progressed in resorption, particularly at the implant apex. However, veneer bone grafting with implant placement has not been evaluated after treatment with imaging techniques. Therefore, the purpose of this study was to assess veneer bone grafting after maxillary anterior implant treatment. Seven patients with a mean age of 24 years, with implants placed in the maxillary anterior region with or without autogenous veneer bone grafting were postoperatively examined using conventional tomography. On tomograms, the ratio of bone-to-implant contact and the area of bone were measured in labial bones with bone grafts, and they were compared with the values without bone grafts. In cases with bone grafting, the average ratio of bone-to-implant contact was 63.6%, whereas 81.8% was formed in cases without bone grafting. The average area of bone was 12.9 mm and 23.4 mm in patients with and without bone grafting, respectively. No significant difference was found between the implants with and without bone grafts. Resorbed labial bone was observed in the maxillary anterior region with and without veneer bone grafting.


Cochlear Implant in cochlear Hypoplasia type 4 with Chiari Malformation- Case Report.
Cochlear hypoplasia type IV is a rare cochlear malformation with hypoplastic middle and apical turns while basal turn develops normally, it often coexist with other genetic mutations. We present a case of 4 year old with chiari malformation type 1 along with bilateral Cochlear hypoplasia type IV who underwent cochlear implantation.


Laser-induced changes of in vitro erythrocyte sedimentation rate.
The study of the effects of low-level laser (LLL) radiation on blood is important for elucidating the mechanisms behind the interaction of LLL radiation and biologic tissues. Different therapy methods that involve blood irradiation have been developed and used for clinical purposes with beneficial effects. The aim of this study was to compare the effects of different irradiation protocols using a diode-pumped solid-state LLL (λ = 405 nm) on samples of human blood by measuring the erythrocyte sedimentation rate (ESR). Human blood samples were obtained through venipuncture into tubes containing EDTA as an anticoagulant. Every sample was divided into two equal aliquots to be used as an irradiated sample and a non-irradiated control sample. The irradiated aliquot was subjected to a laser beam with a wavelength of 405 nm and an energy density of 72 J/cm2. The radiation source had a fixed irradiance of 30 mW/cm2. The ESR change was observed for three different experimental protocols: irradiated whole blood, irradiated red blood cells (RBCs) samples re-suspended in non-irradiated blood plasma, and non-irradiated RBCs re-suspended in irradiated blood plasma. The ESR values were measured after laser irradiation and compared with the non-irradiated control samples. Irradiated blood plasma in which non-radiated RBCs were re-suspended was found to result in the largest ESR decrease for healthy human RBCs, 51%, when compared with RBCs re-suspended in non-irradiated blood plasma. The decrease in ESR induced by LLL irradiation of the plasma alone was likely related to changes in the plasma composition and an increase in the erythrocyte zeta potential upon re-suspension of the RBCs in the irradiated blood plasma.


Assessment of neuropsychological changes in patients with arteriovenous malformation (AVM) after radiosurgery.
The purpose of this study was to investigate neuropsychological effects of radiosurgery in patients with cerebral arteriovenous malformation (AVM), with special focus on attention and memory. This report describes the study setup and presents the first results during a follow-up of up to 1 year. Seventy-nine patients were studied before, acutely after radiosurgery, and during the regular follow-up (subacute phase: Weeks 6-12, chronic phase: Months 6-12). Radiosurgery was performed using a modified linear accelerator (minimum doses to the target volume: 15-22 Gy, median 20 Gy). Estimated whole brain dose was 0.5 to 2 Gy. Neuropsychological testing included assessment of general intelligence (Wechsler Adult Intelligence Scale), attention (modified Trail-Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine) and memory (Rey Auditory Verbal Learning Test, Benton Visual Retention Test). During follow-up, alternate test versions were used. Neuropsychological deficits were defined as a test score of at least one standard deviation (SD) below the mean of the normal distribution. The pretherapeutic evaluation revealed marked deviations from the normal population; 24% had deficits in intelligence (range 23-31% in different subtests), attention (35%, 23-59%) and memory (48%, 31-61%). The overall percentage of aberrant results was reduced by 12% (memory) to 14% (attention) in the chronic phase up to 12 months after therapy. The improvement in test scores was significant (p < 0.05) in 3 of 4 subtests of attention functions. The acute tolerance of radiosurgery seems to be very good in these patients, showing no relevant increase in number of patients with neuropsychological deficits. Although the long-term follow-up needs to be further increased, our data indicate a tendency to slight improvement in the overall neuropsychological performance of AVM patients in the chronic phase after radiosurgery.


A study of the user's perception of economic value in nursing visits to primary care by the method of contingent valuation.
The identification of the attribution of economic value that users of a health system assign to a health service could be useful in planning these services. The method of contingent valuation can provide information about the user's perception of value in monetary terms, and therefore comparable between services of a very different nature. This study attempts to extract the economic value that the subject, user of primary care nursing services in a public health system, attributes to this service by the method of contingent valuation, based on the perspectives of Willingness to Pay (WTP) and Willingness to Accept [Compensation] (WTA). This is an economic study with a transversal design. The contingent valuation method will be used to estimate the user's willingness to pay (WTP) for the care received from the primary care nurse and the willingness to accept [compensation] (WTA), were this service eliminated. A survey that meets the requisites of the contingent valuation method will be constructed and pilot-tested. Subsequently, 600 interviews will be performed with subjects chosen by systematic randomized sampling from among those who visit nursing at twenty health centers with different socioeconomic characteristics in the Community of Madrid. The characteristics of the subject and of the care received that can explain the variations in WTP, WTA and in the WTP/WTA ratio expressed will be studied. A theoretical validation of contingent valuation will be performed constructing two explanatory multivariate mixed models in which the dependent variable will be WTP, and the WTP/WTA relationship, respectively. The identification of the attribution of economic value to a health service that does not have a direct price at the time of use, such as a visit to primary care nursing, and the definition of a profile of "loss aversion" in reference to the service evaluated, can be relevant elements in planning, enabling incorporating patient preferences to health policy decision-making.


Flexor digitorum longus tendon harvest length utilising a limited operative exposure: A cadaveric study.
Flexor digitorum longus (FDL) is a commonly used donor tendon for transfer to substitute for a dysfunctional tibialis posterior in the management of adult acquired flatfoot deformity. The tendon transfer is attached to the navicular bone via a drill hole. Interference-fit screws are an alternative means of securing a transferred tendon allowing for a shorter length of graft and less extensive dissection. The aim of this cadaveric study was to investigate the length of FDL tendon harvest required for transfer and to determine if this length of tendon can be obtained without formal dissection to the Knot of Henry. The FDL tendon was exposed in 8 cadaveric specimens via a medial hindfoot incision. The tendon was divided proximal to the Knot of Henry. The lengths of the skin incisions and the length of the FDL tendon harvest were measured. No specialist tendon harvesting instruments were used. The average length of the skin incision was 9.0cm (95% confidence intervals 8.0-10.0cm). The average length of the harvested FDL tendon was 6.7cm (95% confidence intervals 6.4-7.0cm). This study demonstrates that the FDL tendon can be safely and adequately harvested via a limited exposure. The average length of FDL tendon harvest via this approach compares favourably with other descriptions of approaches. This shorter graft length is more than adequate, allowing at least 2cm for fixation by interference screw to a tunnel in the navicular bone.


Sphaerularia vespae sp. nov. (Nematoda, Tylenchomorpha, Sphaerularioidea), an endoparasite of a common Japanese hornet, Vespa simillima Smith (Insecta, Hymenoptera, Vespidae).
Sphaerularia vespae sp. nov., an endoparasite of a common Japanese hornet, Vespa simillima is described from Hokkaido, Japan, and its molecular sequence profiles are given. This newly discovered nematode appears to belong to the genus Sphaerularia, judging from its characteristic parasitic form, the uterium, which looks like a sausage with many verrucae on its surface. Sphaerularia vespae sp. nov. is distinguished from S. bombi, the only other nominal species of the genus, by the morphology of the male bursa, female tail, and anterior end of parasitic juveniles. SSU, ITS, and D2D3 (LSU) DNA sequences were determined for S. vespae sp. nov. and compared with those from related nematodes obtained from the GenBank database. The sequences from S. vespae sp. nov. were close to those of S. bombi and several another tylenchid entomoparasitic nematodes. Sphaerularia vespae sp. nov. parasitizes overwintering gynes of the hornet and practically sterilizes them, as S. bombi does for bumblebee gynes.


Histamine affects release and biosynthesis of opioid peptides primarily via H1-receptors in bovine chromaffin cells.
Histamine is a potent secretagogue for opioid pentapeptides (Met- and Leu-enkephalin) in adrenal chromaffin cells in vitro. This effect is dependent on extracellular Ca2+ and is reduced by Ca2+ channel blockers such as Co2+, D 600, and nifedipine. Moreover, histamine also produced a profound compensatory increase in cellular peptide content after 48 h of exposure, most likely caused by a four- to fivefold increase in the mRNA levels coding for the proenkephalin A precursor. All the histamine-induced effects (acute release, changes in peptide cell content, proenkephalin A mRNA levels) are antagonized by the H1-receptor antagonist, clemastine, whereas the H2-receptor antagonists, ranitidine and cimetidine, were less effective (approximately 20% inhibition).


Integrated care delivery and health care seeking by chronically-ill patients - a case-control study of rural Henan province, China.
This study examined the impact of an Integrated Care Delivery intervention on health care seeking and outcomes for chronically-ill patients in Henan province, China. A case-control study was carried out in six health care organizations from two counties in Henan province, China. 371 patients aged 50 years or over with hypertension or diabetes who visited either community health centers or hospitals in the Intervention or Control Counties were systematically selected and surveyed on health care seeking behavior, quality of care, and pathway of care for their major chronic condition. Bivariate analyses were performed to compare quality and value of care indicators between patients from the Intervention and Control Counties. Multivariate analyses were used to confirm these associations after controlling for patients' demographic and health characteristics. Patients in both the Intervention and Control Counties chose their current health care providers primarily out of concern for quality of care (provider expertise and adequate medical equipment) and patient-centered care. Compared with the patients from the Control County, those from the Intervention County performed significantly better on almost all the quality and value of care indicators even after controlling for patients' demographic and health characteristics. Significant associations between types of health care facilities and quality as well as value of care were also observed. The study showed that the Integrated Care Delivery Model was critical in guiding patients' health care seeking behavior and associated with improved accessibility, continuity, coordination and comprehensiveness of care, as well as reducing health inequities and mitigating disparities for older patients with chronic conditions.


MicroRNA expression analysis: techniques suitable for studies of intercellular and extracellular microRNAs.
MicroRNAs, the class of small ribo-regulators, have been implicated in the regulation of a range of different biological processes, including development and differentiation, proliferation, and cell death. Only for a small fraction of identified microRNAs has a function been elucidated; therefore, a great deal of research remains to be performed to fully understand the role and implications of microRNAs.This chapter discusses protocols for the isolation of microRNAs, reverse transcription, PCR, and large scale profiling using TaqMan low density miRNA arrays for analysis of microRNA expression levels.


[The effect of high-heeled shoes on the venous pressure of the legs (author's transl)].
The influence of high-heeled shoes on the venous pressure in the lower limbs is studied. In a test series on an exercise band subjects with high heels showed a significantly smaller drop in pressure than subjects wearing flat shoes.


Inhibitory effects of synthetic somatostatin receptor subtype 4 agonists on acute and chronic airway inflammation and hyperreactivity in the mouse.
Somatostatin released from activated capsaicin-sensitive afferents of the lung inhibits inflammation and related bronchial hyperreactivity presumably via somatostatin 4 receptors (sst(4)). The aim of this study was to examine the effects of TT-232, a heptapeptide sst(4)/sst(1) receptor agonist and J-2156, a high affinity sst(4) receptor-selective peptidomimetic agonist in airway inflammation models. Acute pneumonitis was evoked by intranasal lipopolysaccharide 24 h before measurement. Chronic inflammation was induced by ovalbumin inhalation on days 28, 29 and 30 after i.p. sensitization on days 1 and 14. Semiquantitative histopathological scoring was based on perivascular/peribronchial oedema, neutrophil/macrophage infiltration, goblet cell hyperplasia in the acute model and eosinophil infiltration, mucosal oedema, mucus production and epithelial cell damage in chronic inflammation. Myeloperoxidase activity of the lung was measured spectrophotometrically to quantify granulocyte accumulation and the broncoalveolar lavage fluid was analysed by flow cytometry. Carbachol-induced bronchoconstriction was assessed by unrestrained whole body plethysmography and its calculated indicator, enhanced pause (Penh) was determined. TT-232 and J-2156 induced similar inhibition on granulocyte recruitment and histopathological changes in both models, although macrophage infiltration in LPS-induced inflammation was unaltered by either compounds. Both agonists diminished inflammatory airway hyperresponsiveness. Since their single administration after the development of the inflammatory reactions also inhibited carbachol-induced bronchoconstriction, somatostatin sst(4) receptor activation on bronchial smooth muscle cells is likely to be involved in their anti-hyperreactivity effect. These results suggest that stable, somatostatin sst(4) receptor-selective agonists could be potential candidates for the development of a completely novel group of anti-inflammatory drugs for the treatment of airway inflammation and hyperresponsiveness.


Fungus-specific SSR markers in the Antarctic lichens Usnea antarctica and U. aurantiacoatra (Parmeliaceae, Ascomycota).
Usnea antarctica and U. aurantiacoatra (Parmeliaceae) are common lichens in the maritime Antarctic. These species share the same habitats on King George Island (South Shetland Islands, Antarctica) and are distinguishable based on reproductive strategies. We developed 23 fungus-specific simple sequence repeat (SSR) markers that cross-amplify between the two species. We used a low-coverage genome-skimming approach on one sample of each species to identify SSR repeats in the two species. Primers were designed for 3-4-bp repeats, and only the loci common to both species were selected for further analyses. Seventy-seven samples of the two species were selected to assess fungal specificity, genetic variability, and linkage of the markers. In addition, we tested cross-amplification in other Usnea species. The 23 newly designed SSR markers are suitable for population genetic and phylogeographic studies of Usnea species.


A comparison of live and formalised leptospiral microscopic agglutination test.
The sensitivity and reliability of a formalised leptospiral antigen battery was compared with a smaller battery of live leptospiral antigens with 152 human sera positive for leptospirosis. There was good concurrence of results between the formalised and live antigens, however the live battery did fail to detect some positive sera where the antibody level was low. The formalised antigens were more sensitive than the live (P less than 0.001) and more reliable in the detection of early leptospiral infection, but the live antigens were more specific in the determination of probable infecting serogroup.


Smoking among adults in Germany.
Smoking poses a considerable health risk and is the leading cause of premature death. Germany has implemented numerous measures (such as tax increases, protection of non-smokers, and cigarette warning labels) to reduce the population's tobacco consumption. According to the GEDA 2014/15-EHIS survey, 20.8% of women and 27.0% of men aged 18 and over smoke at least occasionally. For both genders, the share of smokers is highest among the younger age groups. Among women and men with higher levels of education, smoking is far less common than among those with lower levels of education. Since 2003, the share of smokers in the adult population has decreased. Compared to other European countries, and in spite of making considerable progress in tobacco prevention policy, Germany still has great potential for improvement in many areas, such as bans on tobacco adverts and tobacco taxation.


Effect of imatinib on oral wound healing after extraction: A rare case report.
Proper tissue repair and healing after oral surgery are vital to achieve optimal outcomes. Certain medications may interfere with wound healing, but this debilitating adverse drug reaction is often not reported in the literature. It is unknown whether imatinib (Gleevec; Novartis Pharmaceuticals) interferes with gingival healing after oral surgery. A 58-year-old man with a dislodged crown and core buildup of tooth no. 19 sought treatment at a prosthodontic clinic. After examination, the patient consented to extraction, ridge preservation, and future implant placement. He had previous surgical resection of a gastrointestinal stromal tumor and was taking 400 mg of imatinib daily. After extraction and ridge preservation, delayed soft-tissue healing and loss of the coronal portion of bone graft were observed at 8 weeks after surgery. Delayed wound healing was observed again after revision surgery. After imatinib therapy was paused, the adverse effect subsided and the wound healed properly. On the basis of causality assessment and clinical judgment, the authors determined that imatinib was the probable cause of this adverse drug reaction. To their best knowledge, this is the first report of delayed gingival healing after oral surgery secondary to imatinib. Dental practitioners should consider the possibility of impaired healing among their patients taking imatinib, especially before procedures that damage gingival tissue, although this adverse drug reaction is not reported in the drug's package insert. Consult with the patient's oncologist is advised before dental manipulations; temporary discontinuation (or dose reductions) of imatinib may be warranted until wounded tissue heals properly.


[Mean osteoplastic surface in zones of plexiform neo-osteogenesis compared with mean osteoplastic surface measured on the fetal bone].
In some pathologic cases, areas of woven bone can be observed in and around human adult bones. This plexiform neo-osteogenesis looks like fetal bone. The mean osteoplastic surface was quantified in these different kinds of bony tissues. The formation of this plexiform neo-osteogenesis is discussed.


Phosphorylation of DPE2 at S786 partially regulates starch degradation.
In plants, transitory starch is synthetized during the day and degraded at night to provide the continuous carbon needed for growth and development. Starch metabolism is highly coordinated, as the starch degradation rate must be coupled to the amount of starch synthetized during the day. Maltose is one of the chloroplastic products obtained from starch degradation, and maltose is exported to the cytosol where disproportionating enzyme-2 (DPE2) is responsible for its metabolism. The amount of DPE2 remained unchanged throughout the day, but its activity notably increased at the end of the day (7 p.m.), suggesting that posttranslational modification drives the mechanism underlying the regulatory activity of this enzyme. Sucrose nonfermenting-related kinase-1 (SnRK1), a protein kinase that controls the activity of several metabolic enzymes, was able to interact and phosphorylate DPE2 at three different residues localized in the α-glucanotransferase domain. This phosphorylation acts as a positive regulator of DPE2, increasing its activity. Complementation of dpe2-deficient mutants with the wild-type (WT) and S786A forms of DPE2 showed that the nonphosphorylated form of DPE2 only partially restored starch degradation, suggesting that phosphorylation at S786 is involved in enzyme regulation.


Practical isolation of polygodial from Tasmannia lanceolata: a viable scaffold for synthesis.
Polygodial, a valuable sesquiterpene dialdehyde featuring an epimerizable stereocenter was efficiently extracted and isolated in gram-scale quantities (3.3% w/w) from Tasmannia lanceolata (Tasmanian native pepper) via a recently developed rapid pressurised hot water extraction (PHWE) technique that utilises an unmodified household espresso machine. This method was compared to the maceration of T. lanceolata under a range of conditions. Polygodial was used to achieve semi-syntheses of closely related sesquiterpene natural products drimendiol, (-)-drimenol, (+)-euryfuran, and some non-natural derivatives.


FTIR and FT-Raman spectra and DFT vibrational analysis of phosphorus-containing dendrons.
FTIR and FT-Raman spectra of four generations of phosphorus-containing dendrons with terminal aldehyde or PCl groups have been recorded and analyzed. Their spectral patterns are determined by the ratio T/R (T, the number of terminal groups; R, the number of repeated units). Bands assigned to the core, repeated units and terminal groups were separated by the difference spectroscopy method. The optimized geometry, frequencies and intensity of IR bands of G(1v) generation dendron with terminal aldehyde groups were obtained by the density functional theory (DFT). It was found that the internal skeleton of molecules exists in a single stable conformation with planar O-C(6)H(4)-CHN-N(CH(3))-P(S) fragments, but terminal groups may adopt the t,g,g- and t,-g,g-rotational isomers. The t,-g,g-conformer is 0.74 kcal/mol less stable compared to the t,g,g-conformer. The bond length and bond angles obtained by DFT show the best agreement with experimental data. Relying on DFT calculations a complete assignment of vibrations is proposed for different parts of the studied dendrons. The calculated frequencies and intensity of IR bands of the t,g,g- and t,-g,g-conformers of G(1v) are found to be in reasonable agreement with the experimental results. The most reactive site in dendron is the core function and vinyl group is preferred for nucleophilic attack. In dendrimer the most reactive are the terminal groups.


Caspase-3-like proteases and 6-hydroxydopamine induced neuronal cell death.
Neurotoxicity induced by 6-hydroxydopamine (6-OHDA) is believed to be due, in part, to the production of reactive oxygen species (ROS) and/or an inhibition of mitochondrial function. However, little is known about the ensuing intracellular events which ultimately result in cell death. Here we show that exposure to relatively low concentrations of 6-OHDA induces apoptosis of cerebellar granule neurons (CGN). 6-OHDA-induced apoptosis of CGN is associated with activation of a caspase-3-like protease. Western blots of cytosolic extracts from 6-OHDA-treated CGN reveal a translocation of cytochrome c from mitochondria to the cytosol, which precedes activation of the protease detected by Ac-DEVD-pNA. DNA laddering can be blocked by caspase inhibitors zVAD-FMK and Ac-DEVD-CHO, however cell death can only be attenuated for a short time period in the presence of these inhibitors. Our data suggest that 6-OHDA-induced apoptosis of CGN involves activation of a caspase-3-like protease. In contrast to the neurotoxicity induced by MPP+, however, the peptide inhibitors zVAD-FMK and Ac-DEVD-CHO can only attenuate early neuronal death induced by 6-OHDA. At later time points, neuronal death lacking DNA laddering occurs even in the presence of the peptide inhibitor zVAD-FMK or Ac-DEVD-CHO.


Disposition of sulfonamides in food-producing animals IV: Pharmacokinetics of sulfamethazine in cattle following administration of an intravenous dose and three oral dosage forms.
The plasma and urine data obtained following intravenous administration of sulfamethazine to cattle were fit to a one-compartment pharmacokinetic model with a half-life of elimination of 9 hr and a volume of distribution of 0.35 liter/kg. Sulfamethazine was eliminated by excretion of unchanged sulfamethazine (18%) into urine and by formation of three metabolites subsequently excreted into urine. Sulfamethazine also was administered as a solution, a rapid-release bolus, and a sustained-release bolus. The change in the urinary metabolic pattern with different routes of administration suggested that first-pass metabolism was occurring during the absorption process. The absorption half-life was 6 hr. The absorption process for the two solid boluses kinetically appeared to include a dissolution step.


Distribution and frequency of thin-capped fibroatheromas and ruptured plaques in the entire culprit coronary artery in patients with acute coronary syndrome as determined by optical coherence tomography.
The aim of this study was to investigate the distribution and frequency of thin-capped fibroatheromas (TCFAs) within the entire length of culprit coronary arteries in patients with acute coronary syndrome. Our population was drawn from 43 consecutive patients with acute coronary syndrome (with or without ST-segment elevation) who underwent optical coherence tomography to visualize the entire culprit coronary artery using a nonocclusive optical coherence tomographic technique. Patients were categorized divided into a TCFA group or a no-TCFA group on the basis of the optical coherence tomographic findings. There were no differences in baseline characteristics or angiographic findings between the 2 groups. High-sensitive C-reactive protein in the TCFA group was significantly higher than in the no-TCFA group (median 3.3 mg/L, interquartile 3.1, vs 1.7 mg/L, interquartile 2.2, p = 0.03). Plaque rupture was found in 28 patients (65%) and multiple plaque ruptures in 5 patients (12%). Optical coherence tomogram revealed 21 TCFAs in 18 patients (42%). Multiple TCFAs were found in the same vessel in 3 patients (7%). The distribution of TCFAs in the right coronary arteries of our subject population was relatively even (proximal 2 [12%], mid 5 [29%], distal 3 [18%], p = 0.42), whereas TCFAs in the left anterior descending artery were common in proximal sites (proximal 6 [27%], mid 2 [9%], distal 0, p = 0.018). In conclusion, the use of optical coherence tomography to look for TCFAs and identify their distribution when combined with C-reactive protein may contribute to forming a strategy for preventing impending coronary events.


Cerebrospinal fluid creatine kinase isoenzyme BB levels do not predict the clinical outcome in patients unconscious following cardiac resuscitation.
It has recently been claimed that an increase in creatine kinase isoenzyme BB(CK-BB) in cerebrospinal fluid (CSF) is well correlated with the cerebral outcome in patients resuscitated after cardiac arrest. Twenty-one such patients consecutively admitted from outside this hospital participated in the study. The patients were divided into two groups: 6 survivors and 15 nonsurvivors. The median CSF-CK-BB value was 5 U/L among nonsurvivors and below detection limit among survivors (NS). However, the predictive value of a positive test is limited, since only 6 of 15 nonsurvivors (40%) had an increase in CSF-CK-BB (predictive value of positive test = 67%). The predictive value of a negative test is limited, since 3 of 6 survivors (50%) showed no rise in CSF-CK-BB (predictive value of negative test = 25%). No relationship between cerebral dysfunction and CSF-CK-BB values was revealed. Thus, CSF-CK-BB does not predict the clinical outcome in patients resuscitated after cardiac arrest.


Novel thermodynamic mechanisms of co-conditioning with polymeric aluminum chloride and polyacrylamide for improved sludge dewatering: A paradigm shift in the field.
This study investigated the combined effects of polymeric aluminum chloride (PAC) and polyacrylamide (PAM) on sludge dewatering, aiming to unveil underlying mechanisms. Co-conditioning with 15 mg g-1 PAC and 1 mg g-1 PAM achieved optimal dewatering, reducing specific filtration resistance (SFR) of co-conditioned sludge to 4.38 × 1012 m-1kg-1, a mere 48.1% of raw sludge's SFR. Compared with the CST of raw sludge (36.45 s), sludge sample can be significantly reduced to 17.7 s. Characterization tests showed enhanced neutralization and agglomeration in co-conditioned sludge. Theoretical calculations revealed elimination of interaction energy barriers between sludge particles post co-conditioning, converting sludge surface from hydrophilic (3.03 mJ m-2) to hydrophobic (-46.20 mJ m-2), facilitating spontaneous agglomeration. Findings explain improved dewatering performance. Based on Flory-Huggins lattice theory, connection between polymer structure and SFR was established. Raw sludge formation triggered significant change in chemical potential, increasing bound water retention capacity and SFR. In contrast, co-conditioned sludge exhibited thinnest gel layer, reducing SFR and significantly improving dewatering. These findings represent a paradigm shift, shedding new light on fundamental thermodynamic mechanisms of sludge dewatering with different chemical conditioning.


Tree kernel-based protein-protein interaction extraction from biomedical literature.
There is a surge of research interest in protein-protein interaction (PPI) extraction from biomedical literature. While most of the state-of-the-art PPI extraction systems focus on dependency-based structured information, the rich structured information inherent in constituent parse trees has not been extensively explored for PPI extraction. In this paper, we propose a novel approach to tree kernel-based PPI extraction, where the tree representation generated from a constituent syntactic parser is further refined using the shortest dependency path between two proteins derived from a dependency parser. Specifically, all the constituent tree nodes associated with the nodes on the shortest dependency path are kept intact, while other nodes are removed safely to make the constituent tree concise and precise for PPI extraction. Compared with previously used constituent tree setups, our dependency-motivated constituent tree setup achieves the best results across five commonly used PPI corpora. Moreover, our tree kernel-based method outperforms other single kernel-based ones and performs comparably with some multiple kernel ones on the most commonly tested AIMed corpus.


Down-regulation of cyclin-dependent kinase-4 and MAPK through estrogen receptor mediated cell cycle arrest in human breast cancer induced by gold nanoparticle tagged toxin protein NKCT1.
The aim of this study was to determine whether gold nanoparticles conjugated cytotoxic protein NKCT1 (GNP-NKCT1) acted through the estrogen receptor mediated pathway in MCF-7 cells and to establish the MAPK and PI3k/Akt signal transduction pathway. Apoptosis was done by flow cytometry. BrdU incorporation and nuclear proliferating antigen was measured by flow cytometry. Wound healing assay along with matrigel chamber invasion and migration was done. Expression of MMP9 was checked by flow cytometry and also by gelatin zymography. To analyze the regulation of signaling protein, western blot was done. MTT assay was done to evaluate the ligand receptor pathway using the estrogen receptor negative cell line (MDA-MB-231) for inhibitor effects. Treatment of GNP-NKCT1 (3.9 μg/ml) exhibited 38.04% early apoptosis and 4.29% late apoptotic cell. GNP-NKCT1 significantly inhibited both cell migration and invasion with suppressed expression of MMP9. In addition, treatment of cultured human breast cancer MCF7 cells with GNP-NKCT1 reversely suppressed the incorporation of BrdU, with reduced expression of Ki-67. The western blot analysis showed that GNP-NKCT1 arrested cell cycle progression through upregulation of the kinase inhibitor protein p21 and inactivation of G1-cylin dependent kinase (CDK4). GNP-NKCT1 suppressed nuclear translocation of nuclear factor kappa B (NF-κB) and also abrogated the phosphorylation of p38 mitogen activated protein kinase (MAPK), phosphatidylinositide-3-kinase (PI3k), Akt and extracellular regulated kinase (ERK1/2). MTT assay indicated that GNP-NKCT1 reduced proliferation in the estrogen receptor induced ER negative breast cancer cell line (MDA-MB-231). Addition of, ER inhibitor (tamoxifen) and PI3K inhibitor (wortmannin) to cells resulted in reduced expression of Ki-67 and MMP-9. The data suggested that GNP-NKCT1 induced MCF7 cell inhibition may occur through estrogen receptor pathway via inactivation of CDK4 and inactivation of PI3K/Akt, ERK1/2 and p38 MAPK signaling pathway with inhibitory effects on NF-κB, reducing the activity of MMP9. This result provides a new mechanism to explain the role of gold nanoparticles conjugated NKCT1 as a potent anti-metastatic agent in MCF7 cells.


Differential expression of astrocytic connexins in a mouse model of prenatal alcohol exposure.
Maternal alcohol consumption during gestation can cause serious injury to the fetus, and may result in a range of physiological and behavioral impairments, including increased seizure susceptibility, that are collectively termed fetal alcohol spectrum disorder (FASD). The cellular mechanisms underlying increased seizure susceptibility in FASD are not well understood, but could involve altered excitatory coupling of neuronal populations mediated by gap junction proteins. We utilized a mouse model of the prenatal alcohol exposure (PAE) to study the expression pattern of connexin (Cx) major components of gap junctions, and pannexin proteins, which form membrane channels, in the brain of 2-3weeks old PAE and control postnatal offspring. PAE during the first trimester-equivalent period of pregnancy in mice resulted in significant up-regulation of Cx30 mRNA and Cx30 total protein in the hippocampus of PAE animals compared to age-matched controls. Surface level expression of both dimeric and monomeric Cx30 were also found to be significantly up-regulated in both hippocampus and cerebral cortex of PAE animals compared to age-matched controls. On the membrane surface, the fast migrating form of Cx43 was found to be up-regulated in the hippocampus of PAE mice. However, we did not see any up-regulation of the phosphorylated forms of Cx43 on the membrane surface. These results indicate that the expression and processing of astrocytic connexins (Cx30, Cx43) are up-regulated in the brain of PAE offspring, and these changes could play a role in the cerebral hyperexcitability observed in these animals.


Examination of Hacking and Blunt Force Skeletal Trauma.
Hacking trauma is prevalent in forensic cases involving genocide and dismemberment, but research into the identification of this type of trauma is lacking. The present study examines characteristics of hacking and blunt force skeletal trauma in order to determine if there is a point at which blunt force trauma becomes distinguishable from hacking trauma. Ten implements with a range of blade angles (i.e., the striking surface of the implement) were used in conjunction with a controlled-force hacking device to impact 100 limb bones of white-tailed deer (Odocoileus virginianus). Observations of the trauma included the occurrence and degree of fragmentation, the entrance widths of the impacts, and composite scores of six hacking characteristics, especially the distinctive V-shaped kerf. ANOVA tests and regression analyses were used to assess the relationships between these characteristics and the blade angles. A significant relationship (p-value = 0.011) was found between the composite hacking scores and the blade angles, indicating that blunt force and hacking trauma can be distinguished. The entrance widths of the impacts exhibited a significant relationship with the blade angles (p-value = 0.037). There was also a significant relationship between the visibility of a V-shaped kerf in the bones (p-value = 0.003), with visibility decreasing around the 60° blade angle. These data should assist in establishing guidelines to differentiate hacking and blunt force skeletal trauma in cases where the implement is on a spectrum between sharp and blunt.


Unleashing the photocatalytic potential of a noble-metal-free heteroleptic copper complex-based nanomaterial for an enhanced aza-Henry reaction.
In this work, we fabricated a versatile and noble metal free copper-based heterogeneous photocatalyst, representing a green shift away from precious group metals such as Ir, Ru, Pt, which have been widely utilized as photocatalysts. The successfully synthesized and characterized copper photocatalyst was employed to establish a cross dehydrogenative coupling via C-H activation between tertiary amines and carbon nucleophiles. The highly efficient copper-based photocatalyst was characterized by numerous physico-chemical techniques, which confirmed its successful formation as well as its high activity. Inductively coupled plasma (ICP-OES) analysis revealed that the composite Cu@Xantphos@ASMNPs had a very high loading of 0.423 mmol g-1 of copper. The magnetic Cu@Xantphos@ASMNPs were utilized as a potential heterogeneous photocatalyst for the very facile and regioselective conversion of aryl tetrahydroqinoline to the respective nitroalkyl aryl tetrahydroisoquinoline in high yield using air as an oxidant and methanol as a green solvent with irradiation with visible light under mild reaction conditions. Additionally, the catalyst shows exceptional chemical stability and reusability without any agglomeration even after several cycles of use, which is one of the key features of this material, rendering it a potential candidate from economic and environmental perspectives.


Opposing roles for dopamine D2 and D3 receptors on neurotensin mRNA expression in nucleus accumbens.
Using in situ hybridization histochemistry in rat nucleus accumbens, we show that the dopamine D3 receptor mRNA is expressed in the ventromedial part of the shell subdivision, where its gross distribution matches that of neurotensin mRNA. In addition, hybridization studies at the cellular level show that a large fraction of the neurotensin neurons co-express the D3 receptor mRNA in this restricted area. In contrast, the dopamine D2 receptor mRNA is expressed mainly in the core and marginally in the shell, at the level of the cone. In rats treated by haloperidol and sulpiride, two D2-like receptor antagonists, but not by SCH 23390, a D1-like receptor antagonist, proneurotensin mRNA was increased in the D2 receptor mRNA-rich areas but decreased in the D3 receptor mRNA-rich areas. This suggests that the D2 and D3 receptors control neurotensin mRNA expression negatively and positively, respectively.


The difficult management of anaphylaxis in the elderly.
In this article, an overview of the main characteristics of the anaphylaxis in the elderly, a subset of the population with particular clinical and physiological features that might influence the presentation and management of this entity, is performed. Life expectancy of the population is increasing and so is the prevalence of allergic diseases in the elderly, including anaphylaxis. Older people present higher risk of fatalities after anaphylaxis, and some comorbidities and pharmacological treatments they may use might also increase that risk. Recognition of the main triggers, the risk factors, and the wide variety of presenting symptoms of anaphylaxis is therefore helpful in its management, as well as a prompt initiation of the treatment and a complete follow-up.


A property of face representation at the categorical level.
Face processing is unique to human beings and is likely to have special neuronal properties. We studied one of these properties, categorical representation of the face in perception processing (perception) and in memory recall processing (imagery), using the face and building stimuli. The same building-selective areas showed categorical selectivity in imagery as well as in perception, but face-selective areas did not. The selective areas to face stimuli in perception were completely different from those in imagery. This indicates that conceptual category selectivity in top-down processing is based on schemes different from that in bottom-up processing in the case of face processing. This may explain an aspect of specialized processing mechanisms of the face.


Potential impacts of SARS-CoV-2 on parathyroid: current advances and trends.
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection affects several important organs including endocrine glands. Experimental studies demonstrated that the virus exploits the ACE2, a transmembrane glycoprotein on the cell surface as a receptor for cellular entry. This entry process is exclusively facilitated by other intracellular protein molecules such as TMPRSS2, furin, NRP1, and NRP2. Recent findings documented the involvement of the SARS-CoV-2 in inducing various parathyroid disorders including hypoparathyroidism and hypocalcemia, which received significant attention. This review extensively describes rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various parathyroid disorders due to SARS-CoV-2 infection particularly parathyroid malfunction in COVID-19 cases, and post-COVID-19 conditions. Further, it presents the expression level of various molecules such as ACE2, TMPRSS2, furin, NRP1, and NRP2 in the parathyroid cells that facilitate the SARS-CoV-2 entry into the cell, and discusses the possible mechanism of parathyroid gland infection. Besides, it explores parathyroid malfunction in COVID-19 vaccine-administered cases. It also explains the possible long-COVID-19 effect on parathyroid and post-COVID-19 management of parathyroid. A complete understanding of the mechanisms of SARS-CoV-2-triggered pathogenesis in parathyroid dysfunctions may curtail treatment options and aid in the management of SARS-CoV-2-infected cases.


Efficacy of chemotherapies for unresectable extramammary Paget disease: a single-centre retrospective study.
Extramammary Paget disease (EMPD) is a cutaneous neoplasm that can metastasize to the lymph nodes and distant organs, resulting in a poor prognosis. For unresectable distant metastases of EMPD, no consensus has been reached regarding optimal chemotherapy owing to a lack of data. To evaluate the efficacy of three regimens: docetaxel (DTX) monotherapy; combination therapy with 5-fluorouracil, epirubicin, carboplatin, vincristine and mitomycin C (FECOM); and tegafur (S-1) monotherapy. This single-centre retrospective study included 32 patients diagnosed with unresectable EMPD and treated with chemotherapy between 2002 and 2022 at the National Cancer Center Hospital in Japan. Patient characteristics, responses to treatment and survival data were evaluated for each of the first-line therapies. Among the 17 patients who received DTX monotherapy, the response rate (RR) and disease control rate (DCR) were 47% and 77%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 12.3 months [95% confidence interval (CI) 6.1-26.6] and 19.2 months (95% CI 8.5-not reached), respectively. Among the 11 patients who received combination FECOM chemotherapy, the RR and DCR were 55% and 64%, respectively. The median PFS and OS were 6.8 months (95% CI 3.5-not reached) and 13.4 months (95% CI 8.6-21.3), respectively. Among the four patients who received S-1 monotherapy, the RR and DCR were 0% and 25%, respectively. The median PFS and OS were 5.4 months (95% CI 2.3-not reached) and 12.5 (95% CI 2.3-not reached) months, respectively. Further investigations with prospective analysis are required to confirm these findings.


Disease surveillance and nonprescription medication sales can predict increases in poison exposure.
Real-time Outbreak and Disease Surveillance (RODS) is a national real-time syndromic surveillance system that classifies hospital registration chief complaints into one of seven syndromic categories. The National Retail Data Monitor (NRDM) is a public health surveillance tool that is designed to collect and analyze the daily sales of 18 categories of nonprescription medications. The goal of RODS and NRDM is to provide early warning of disease outbreaks, such as biological terrorism. The purpose of this study was to determine whether peak syndromic activity and the consequential purchase of nonprescription medications could predict an increase in poisoning exposures involving NRDM-monitored medications. Data from the RODS and NRDM databases were plotted graphically to portray activity that occurred during 2003. Data from a regional poison information center electronic medical record system that involved all human exposure calls related to NRDM monitored medications in 2003 were extracted and graphed. Analysis included comparisons between the data sets. Poison center exposure volume correlated predictably and simultaneously with the peak activity in both the RODS and NRDM databases. There was no delay between the onset of an influenza outbreak in December 2003, the sale of nonprescription palliative mediations, and the increase in poison center exposure call volume. Increased availability of and access to nonprescription medications resulted in more poisoning exposure calls. Real-time surveillance using other databases can help to forecast poison center activity. This knowledge allows the poison center to provide anticipatory guidance to the residents of its region.


Intracellular transport and processing of lysosomal cathepsin H.
Intracellular transport and processing of lysosomal cathepsin H was investigated in the subcellular fractions of rat liver by pulse-labeling experiments with [35S]methionine in vivo. A newly synthesized procathepsin H with a molecular weight of 41 kDa first appeared in the rough microsomal fraction at 10 min postinjection of label. This procathepsin H moved from the microsomal fraction to the Golgi subfractions at 30 min. Then a processed single-chain form with 28 kDa appeared in the lysosomal fraction at 60 min and persisted as the predominant form after 180 min. These results suggest that the propeptide-processing of procathepsin H indeed takes place in lysosomes in the course of intracellular transport from endoplasmic reticulum via Golgi complex to lysosomes.


[Cerebellar metastasis from ovarian carcinoma. A case report].
This report presents an unusual case of 40-year-old woman with complete locoregional remission of ovarian carcinoma, presented with a single cerebellar metastasis. Surgical excision of the cerebellar lesion, followed by brain irradiation, resulted in complete resolution of her symptoms.


Acanthamoeba keratitis after photorefractive keratectomy.
A 37-year-old women developed severe suppurative keratitis immediately after having photorefractive keratectomy in her left eye. The keratitis was unresponsive to intensive topical antibiotic agents and topical and systemic steroids. Although the differential diagnosis included nonmicrobial and fungal keratitis, the clinical course and confocal microscopy suggested, and subsequent histopathologic examination confirmed, a diagnosis of Acanthamoeba keratitis. The amebic contamination probably resulted from exposure of the deepithelialized cornea to contaminated freshwater in a northern Wisconsin marsh. This case emphasizes the importance of encouraging patients with epithelial defects and bandage soft contact lenses to avoid exposure to contaminated freshwater until reepithelialization is complete.


DKPNet41: Directed knight pattern network-based cough sound classification model for automatic disease diagnosis.
Cough-based disease detection is a hot research topic for machine learning, and much research has been published on the automatic detection of Covid-19. However, these studies are useful for the diagnosis of different diseases. In this work, we collected a new and large (n=642 subjects) cough sound dataset comprising four diagnostic categories: 'Covid-19', 'heart failure', 'acute asthma', and 'healthy', and used it to train, validate, and test a novel model designed for automatic detection. The model consists of four main components: novel feature generation based on a specifically directed knight pattern (DKP), signal decomposition using four pooling methods, feature selection using iterative neighborhood analysis (INCA), and classification using the k-nearest neighbor (kNN) classifier with ten-fold cross-validation. Multilevel multiple pooling decomposition combined with DKP yielded 41 feature vectors (40 extracted plus one original cough sound). From these, the ten best feature vectors were selected. Based on each vector's misclassification rate, redundant feature vectors were eliminated and then merged. The merged vector's most informative features automatically selected using INCA were input to a standard kNN classifier. The model, called DKPNet41, attained a high accuracy of 99.39% for cough sound-based multiclass classification of the four categories. The results obtained in the study showed that the DKPNet41 model automatically and efficiently classifies cough sounds for disease diagnosis.


Gelatinases impart susceptibility to high-fat diet-induced obesity in mice.
Gelatinases play a role in adipose and muscle hypertrophy and could be involved in tissue remodeling in response to high-fat diet (HFD) intake. This study tested potential roles of gelatinases (matrix metalloproteinses-2 and -9 [MMP-2 and -9]) in relationship to an antigrowth factor [myostatin (MSTN)] known to be dysregulated in relation to HFD-induced obesity (HFDIO) propensity. In vitro and ex vivo analyses demonstrated that MMP-9 increased mature MSTN levels, indicating a potential role of gelatinases in MSTN activation in vivo. HFD intake resulted in increased body weight and circulating blood glucose values in C57BL/6J and MMP-9 null mice, with no changes observed in SWR/J mice. HFD intake attenuated MMP-9 and MMP-2 mRNA levels in SWR/J mice while elevating MMP-2 levels in skeletal muscle in C57BL/6J mice. In MMP-9 null mice, the effects of HFD intake were muted. Consistent with changes in mRNA levels, HFD intake increased MMP-9 activity in muscle tissue of C57BL/6J mice, demonstrating a strong relationship between HFDIO susceptibility and local MMP regulation. Overall, resistance to HFDIO appears to correspond to low MMP-9 and MSTN levels, suggesting a role of MMP-9 in MSTN activation in local tissue responses to HFD intake.


Trace Determination of Iron in Real Waters and Fruit Juice Samples Using Rapid Method: Optimized Dispersive Liquid-Liquid Microextraction with Synthesized Nontoxic Chelating Agent.
The purpose of this research was to optimize a new method for preconcentration and determination of trace iron concentrations in aqueous solutions. For this purpose, a newly synthesized ligand, 3-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl) benzoic acid (3-OH-3-MOPBA), was used in the dispersive liquid-liquid microextraction (DLLME) method coupled with UV-vis spectroscopy. The experiments considering input variables of extractant volume, disperser volume, salt concentration, and pH were designed with the aid of central composite design (CCD). The results were analyzed using response surface methodology (RSM). The limit of detection (LOD) was found to be 4.0 μg L-1 under the optimized conditions. A calibration curve with a good linearity (R2 = 0.9986) was obtained over the concentration range of 15-800 μg L-1. The relative standard deviations (RSD) were found to be around 2.1% (n = 7). The main advantages of the developed method are simple application, environment friendly, short time, and low cost which makes this method to be applied routinely for measuring iron in various water samples.


AF-1 a novel regulator of the redox equilibrium during aging.
Multicellular organisms generally undergo qualitative changes within time that are associated with progressive degeneration of biological functions, increased susceptibility to diseases, and increased probability to die within a given time period (aging). One of the major factors contributing to aging is accumulation of oxidative damage. We show that Aging Factor-1 (AF-1) negatively influences the redox balance during aging. AF-1 expression is greatly enhanced in various human cell types of aged individuals which leads to decreased stress resistance towards oxidative damage. We used Drosophila melanogaster as an in vivo model system. Functional knockdown of AF-1 in Drosophila melanogaster reveals a gender-specific effect on lifespan. Whereas female flies show a prolonged healthy lifespan, males show no difference (or even a shortened lifespan). Altogether our data suggest AF-1 expression during aging to be a mechanism that affects healthy aging and age-related stress resistance depending on the gender of the fly.


Meige syndrome: a rare form of cranial dystonia that was treated successfully with botulinum toxin.
Meige syndrome, a rare form of cranial dystonia, is characterised by bilateral involuntary activity of facial and perioral muscles combined with blepharospasms. A case of a 15-year-old boy with Meige syndrome who was managed with injection of botulinum toxin is presented.


Sexually dimorphic behavioral and brain asymmetries in neonatal rats: effects of prenatal alcohol exposure.
Behavioral and neuroanatomical asymmetries were assessed in 3-day-old male and female rat pups chosen from litters whose dams had received one of 3 prenatal treatments: 35% ethanol-derived calories, pair-fed control, or lab chow control. Behavioral laterality was assessed by observing the preferred tail bias on postnatal (PN) day 1. On PN day 3, brains were sectioned and morphometric analyses conducted for total brain volume, left and right neocortical volumes, and left and right hippocampal volumes. Prenatal alcohol exposure altered the population proportions of left, right and neutral tail biases in male pups on PN day 1. Female pups were affected by both prenatal alcohol exposure and maternal undernutrition/stress of pair-feeding. Prenatal alcohol exposure decreased body weight and total brain volume, but increased the brain volume/body weight ratio compared to both control groups. Prenatal alcohol exposure also reduced the volumes of the hippocampus and neocortex, with the greatest proportional reduction found in the volume of the anterior neocortex. A left-right anterior neocortical asymmetry was observed, with tail bias, prenatal treatment and sex all significant factors. Alcohol-exposed males showed a 'feminized' asymmetry. These results demonstrate that a sexually dimorphic cerebral asymmetry can be detected at birth in rats; this asymmetry appears to be related to a postural position bias. The reversal of normal interhemispheric relations by prenatal alcohol exposure in male offspring suggested that the in utero hormonal milieu modulates the development of cerebral lateralization.


Congenital extrahepatic Portosystemic shunt with hypoplasia of the intrahepatic inferior vena cava: A rare case report.
Congenital portosystemic shunt (CPS) is a rare vascular anomaly resulting in diversion of splanchnic or portal blood into the systemic circulation. Other vascular malformations associated with this entity are uncommon. A 4-year-old female child with a diagnosis of acute viral hepatitis had an incidental finding of extrahepatic CPS on a Doppler abdominal ultrasound. Contrast-enhanced computed tomography showed a dilated portal vein having H-type side-to-side communication with a hypoplastic intrahepatic portion of the inferior vena cava and a prominent dilated azygos vein. There was retroaortic left renal vein drained into the IVC which was visualized in its entirety. Echocardiography findings were normal and the patient was discharged after symptomatic treatment that achieved improvement. With the expansion of abdominal imaging, incidental cases of CPS are increasingly being diagnosed in children. Although vascular malformations associated with CPS are rare, early diagnosis of cases helps avoid complications during shunt closure.


Guanylyl cyclase-activating proteins (GCAPs) are Ca2+/Mg2+ sensors: implications for photoreceptor guanylyl cyclase (RetGC) regulation in mammalian photoreceptors.
Guanylyl cyclase-activating proteins (GCAP) are EF-hand Ca(2+)-binding proteins that activate photoreceptor guanylyl cyclase (RetGC) in the absence of Ca(2+) and inhibit RetGC in a Ca(2+)-sensitive manner. The reported data for the RetGC inhibition by Ca(2+)/GCAPs in vitro are in disagreement with the free Ca(2+) levels found in mammalian photoreceptors (Woodruff, M. L., Sampath, A. P., Matthews, H. R., Krasnoperova, N. V., Lem, J., and Fain, G. L. (2002) J. Physiol. (Lond.) 542, 843-854). We have found that binding of Mg(2+) dramatically affects both Ca(2+)-dependent conformational changes in GCAP-1 and Ca(2+) sensitivity of RetGC regulation by GCAP-1 and GCAP-2. Lowering free Mg(2+) concentrations ([Mg](f)) from 5.0 mm to 0.5 mm decreases the free Ca(2+) concentration required for half-maximal inhibition of RetGC ([Ca]((1/2))) by recombinant GCAP-1 and GCAP-2 from 1.3 and 0.2 microm to 0.16 and 0.03 microm, respectively. A similar effect of Mg(2+) on Ca(2+) sensitivity of RetGC by endogenous GCAPs was observed in mouse retina. Analysis of the [Ca]((1/2)) changes as a function of [Mg](f) in mouse retina shows that the [Ca]((1/2)) becomes consistent with the range of 23-250 nm free Ca(2+) found in mouse photoreceptors only if the [Mg](f) in the photoreceptors is near 1 mm. Our data demonstrate that GCAPs are Ca(2+)/Mg(2+) sensor proteins. While Ca(2+) binding is essential for cyclase activation and inhibition, Mg(2+) binding to GCAPs is critical for setting the actual dynamic range of RetGC regulation by GCAPs at physiological levels of free Ca(2+).


In vivo effect of MPTP on monoamine oxidase activity in mouse striatum.
Striatal monoamine oxidase (MAO)-B, but not MAO-A, activity decreased in mice at 2 and 10 days and was back to control values at 20 and 30 days after systemic administration of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Striatal dopaminergic (DA) depletions were maximal at 2 days and were only partially reversed at 30 days post-treatment. In rats, unilateral kainic acid lesions increased MAO-B but not MAO-A activity probably due to reactive gliosis, but MPTP did not affect DA levels in control and kainic acid-lesioned striata. Findings support the importance of MAO-B in the toxicity of MPTP and suggest that resistance of rat DA neurons to the neurotoxin is probably not due to species differences in MAO-B activity.


Expression pattern analysis of SGF-3/POU-M1 in relation to sericin-1 gene expression in the silk gland.
Embryonic and larval expression patterns of the sericin-1 gene and its presumed transcription factor, SGF-3/POU-M1, in the silk gland were analyzed by in situ hybridization and immunohistochemistry. The sericin-1 transcripts were first detected at embryonic stage 26 in an increasing gradient pattern in the middle and posterior part of the middle silk gland (MSG), while at the same stage the SGF-3/POU-M1 was already present in the entire anterior silk gland (ASG) and in the MSG but with a decreasing gradient pattern. The latter expression pattern was consistently maintained through all larval stages, while the sericin-1 expression was detected during the feeding stages but disappeared at the molting stages. These observations suggest that, although the SGF-3/POU-M1 was proposed to be a positive transcription factor for the sericin-1 gene, the protein might function in a negative manner on sericin-1 gene transcription. Alternatively, it is also possible that the sericin-1 gene might require another unidentified factor or mediator for in vivo transcription.


[In vitro synthesis of interleukin 2 (IL-2) by T lymphocytes extracted from a lymphoepithelial thymoma. Purification and biochemical characterization].
T (E+) lymphocytes purified from lymphoepithelial thymoma surgically removed from an asymptomatic 12 yrs old girl were cultured in presence of PHA-P; culture supernatant contained a T cell growth factor (IL-2) biochemically different from that purifiable from supernatants of normal T cells. Differences in molecular weight, isoelectric point and ion exchange elution pattern would allow to compare this abnormal IL-2, (named Thy-IL-2 from Thymus) to that already characterized from the HUT 102 T cell line (L-TCGF peak II). A comparison of biochemical properties of Thy-IL-2 and normal IL-2 (N-IL-2) is also presented; the biological significance of such differences are discussed.


Quantitative determination of neurotransmitters, metabolites and derivates in microdialysates by UHPLC-tandem mass spectrometry.
The main objective of the present work is to study the time-course of rat brain neurotransmitters in vivo after an oral challenge with a nutritional ingredient or an external stimulus, such as a chemical agent. An ultrahigh performance liquid chromatography-tandem mass spectrometry method for the identification and quantification of neurotransmitters, metabolites and derivates in microdialysates from rat brain was previously developed. Betaine, glutamine, glutamic acid, gamma-aminobutyric acid, phosphocholine, glycerophosphocholine, cytidine 5'-diphosphocholine, choline, acetylcholine, dopamine, norepinephrine, serotonin, tyrosine, epinephrine, tryptophan and 5-hydroxyindoleacetic acid were selected as analytes. The method involves direct injection of samples of microdialysates from rat brain onto the chromatographic equipment and quantification with a triple quadrupole mass spectrometer detector using an electrospray ionization interface in positive mode. The limits of detection ranged from 0.1 to 50 ng mL(-1) and the limits of quantification from 0.3 to 200 ng mL(-1). The inter- and intra-day variability were lower than 15%. Recovery rates ranged from 85% to 115%.


Palliative arthroscopic debridement with continuous irrigation for infected total knee arthroplasty in high mortality risk patients.
This study aimed to evaluate the infection control rate of palliative arthroscopic debridement, antibiotics, and implant retention (DAIR) for the high mortality risk or terminal cancer stage patients. From March 2018 to August 2021, 21 patients met the following inclusion criteria: old age of more than 80, diagnosed as a terminal stage of cancer, high risk of mortality and morbidity representing as Charlson comorbidity index (CCI) ≥ 5, low daily activity with disabled extremity, and re-infection after two-stage revision. Each patient underwent arthroscopic DAIR and additional continuous irrigation for 48 hours. The need for subsequent re-arthroscopic DAIR or two-stage revision was determined by the post-operative trends of C-reactive protein (CRP) levels. Infection control was defined as continuing controlled status of infection based on clinical and laboratory results by one or two times of arthroscopic DAIR within initial two months. Treatment failure was defined as more than three times arthroscopic debridement, two-stage revision surgery, or expired due to uncontrolled infection. Arthroscopic DAIR controlled the infection in 19 (90.5%) of the 21 cases. The other knee underwent a total of three times of re-arthroscopic DAIR and the other one underwent two-stage revision. Although five patients expired during the follow-up period due to worsening medical problems or terminal cancer, there were no deaths from uncontrolled infection, sepsis, or surgery-related complications. Arthroscopic debridement with continuous irrigation for the infection TKA with high mortality risk or terminal cancer patients showed a 90.5% infection control rate. For high-risk patients, arthroscopic debridement with continuous irrigation can be an alternative treatment to improve the quality of life during survival.


Online analysis of chemical composition and size distribution of fresh cigarette smoke emitted from a heated tobacco product.
Online analysis of chemical composition of cigarette smoke of a heated tobacco product (HTP) was performed by using a home-made vacuum ultraviolet (VUV) lamp-based photoionization time-of-flight (TOF) mass spectrometer. A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke, without dilution and pretreatment, which can be switched from each other within minutes. A thermal desorption unit was installed to vaporize the particulate-phase into gas and its vaporization temperature was determined, based on an equilibrium between the evaporation efficiency and the thermal decomposition of organic compounds. Then these species were softly ionized by VUV photons and their ions were measured by a reflectron TOF mass analyzer. Meanwhile, the puff-by-puff resolved size distributions of the HTP smoke were probed with a commercial scanning mobility particle sizers (SMPS). The mean diameters of particles firstly increase with the puff number, mainly located in the range of 200 - 300 nm, and then approached a steady state. This method was validated to measure the physical-chemical characteristics of the HTP cigarette smoke.•A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke.•Chemical composition of the HTP smoke was measured by using a compact VUV photoionization mass spectrometer.•The particle size distribution of the HTP smoke without dilution was measured online.


Performance and scale-up of adsorptive membrane chromatography.
Separation efficiency and scalability of Pall Corporation's new Mustang stacked membrane chromatographic devices were investigated, using both the 10-ml and l(-1) models and comparing the responses of tracer pulses obtained for conventional and reverse-flow operation. Tracers included AMP, lysozyme, and thyroglobulin, which vary in relative molecular mass from less than 1000 up to 650000. Both devices showed marked insensitivity to tracer size and flow-rate and gave sharper peaks than would have been expected from conventional 15-microm bead packings. However, reverse-flow peaks were always significantly sharper than those for conventional operation, and the differences were ascribed primarily to non-uniform header residence times. Numerical simulations of the macroscopic flow confirmed that this was indeed the case. This problem was much less pronounced for the l(-1) device so scale-up is conservative.


Sleep deprivation and cardiorespiratory function. Influence of intermittent submaximal exercise.
The effects of 64 h of sleep deprivation upon cardiorespiratory function was studied in 11 young men (VO2max = 55.5 ml kg-1 min-1, STPD). Six subjects engaged in normal sedentary activities, while the others walked on a treadmill at 28% VO2max for one hour in every three; eight weeks later, sleep deprivation was repeated with a crossover of subjects. Immediate post-deprivation measurement of VO2max showed a small but statistically significant decrease (-3.8 ml min-1 kg-1, STPD), with no difference between exercise and control trials. The final decrement in aerobic power was not due to a loss of motivation, as 88% (21 of 24) of post-deprivation tests still showed a plateau of VO2max; in addition, terminal heart rates (198 vs 195 beats min-1), respiratory exchange ratios (1.14 vs 1.15) and blood lactate levels (12.1 vs 11.8 mmol l-1) were not significantly different after sleep deprivation. The decrease in VO2max was associated with a lower VEmax (127 vs 142 l min-1, BTPS) and a substantial haemodilution (13%). Physiological responses to sub-maximal exercise showed persistence of the normal diurnal rhythm in heart rate and oxygen consumption, with no added effects due to sleep deprivation. However, ratings of perceived exertion (Borg scale) increased significantly throughout sleep deprivation. The findings are consistent with a mild respiratory acidosis, secondary to reduced cortical arousal and/or a progressive depletion of tissue glycogen stores which are not altered appreciably by moderate physical activity.


Osteoarthritis year 2011 in review: biochemical markers of osteoarthritis: an overview of research and initiatives.
The "year in review" session is a key moment of the Osteoarthritis Research Society International (OARSI) Congress. This is a unique opportunity for opinion leaders to summarize and comment the recent advances in one particular field of osteoarthritis research. This review is a summary of selected studies related to soluble biomarkers published between September 1st, 2010 and August 30th, 2011 and identified by a pubmed search using the terms "biomarkers" and "osteoarthritis". In addition, I have selected some works presented during the 2011 OARSI Congress. This year was dominated by the publication of a consensus paper on the qualification of osteoarthritis (OA) biomarkers by the OARSI/Food Drug Administration (FDA) Osteoarthritis Biomarkers Working Group, and of proteomes of chondrocyte vesicles, urine and serum.


Mutation and immune profiling of metaplastic breast cancer: Correlation with survival.
The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34-0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41-0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33-23.1 and HR 8.0, 95% CI 1.53-41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01-1.16 and HR 1.05, 95% CI 1.00-1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.


Physiologic assessment of coronary artery stenosis without stress tests: noninvasive analysis of phasic flow characteristics by transthoracic Doppler echocardiography.
We evaluated the significance of the diastolic-to-systolic blood flow velocity ratio (DSVR) determined by transthoracic Doppler echocardiography, for a physiologic assessment of the severity of coronary stenosis without stress tests, as compared with thallium 201 single photon emission computed tomography. In 95 patients undergoing thallium 201 single photon emission computed tomography for coronary artery disease, the flow velocity in the distal left anterior descending coronary artery was obtained with transthoracic Doppler echocardiography. The mean and peak DSVR values were calculated using mean and peak coronary flow velocity. DSVR was successfully measured for 82 patients (86.3%), including 33 patients with reversible perfusion defects in the left anterior descending coronary artery territories. For predicting reversible perfusion defects in thallium 201 single photon emission computed tomography, the best cut-off points were 1.5 for mean DSVR (sensitivity 81.8%, specificity 85.7%) and 1.6 for peak DSVR (sensitivity 75.7%, specificity 83.6%). Noninvasive measurement of DSVR with transthoracic Doppler echocardiography provides physiologic estimation of the left anterior descending coronary artery stenosis severity at high success rate, without stress tests.


The effectiveness of blended versus regular Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: a study protocol of a randomized controlled trial.
Antisocial behavior during adolescence can have long-lasting negative effects and leads to high societal costs. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles aged 12-21 showing severe antisocial behavior. The intensity, content and duration of FAST can be adjusted to the needs of the juvenile and their caregiver(s), which is considered crucial for effective treatment. Next to the regular version of FAST (FASTr), a blended version (FASTb) in which face-to-face contacts are replaced by minimally 50% online contacts over the duration of intervention was developed during the Covid-19 pandemic. The current study will investigate whether FASTb is equally effective as FASTr, and through which mechanisms of change, for whom, and under which conditions FASTr and FASTb work. A randomized controlled trial (RCT) will be carried out. Participants (N = 200) will be randomly assigned to FASTb (n = 100) or FASTr (n = 100). Data collection will consist of self-report questionnaires and case file analysis, and include a pre-test at the start of the intervention, a post-test immediately after the intervention, and a six month follow-up. Mechanisms of change will be investigated using monthly questionnaires of key variables during treatment. Official recidivism data will be collected at two-year follow-up. This study aims to improve the effectiveness and quality of forensic mental health care for juveniles with antisocial behavior by studying the effectiveness of blended care, which has not been studied before in treatment of externalizing behavior. If found to be at least as effective as face-to-face treatment, blended treatment can help meet the urgent need for more flexible and efficient interventions in this field. In addition, the proposed study aims to unravel what works for whom, knowledge urgently needed in mental health care for juveniles with severe antisocial behavior. This trial was registered at ClinicalTrials.gov on 07/11/2022, registration number NCT05606978.


Laboratory snack food intake, negative mood, and impulsivity in youth with ADHD symptoms and episodes of loss of control eating. Where is the missing link?
To compare laboratory food intake, negative mood and trait impulsivity and their association with attention deficit hyperactivity disorder (ADHD) and loss of control (LOC) eating in youth (middle childhood to early adolescence). Ninety 10-14 year old youths with symptoms of ADHD, symptoms of LOC eating, and control participants took part in a laboratory snack food meal after having rated trait impulsivity. Negative mood was self-reported pre and post snack food meal, while representativeness of eating behavior and liking of the food was assessed post laboratory snack food meal. The ADHD group consumed more snack food than the other groups. Food intake was not influenced by negative mood or trait impulsivity. All groups exhibited a decrease in negative mood from pre to post food intake that was not accounted for by level of hunger or liking of the food. The greater food intake of the ADHD group compared to the other groups may contribute to the development of overweight and therefore be in accordance with the high co-morbidity reported between ADHD and obesity in youth. The influence of impulsivity and negative mood on food intake could not be shown, which corroborates a recent review on the association of negative mood and bingeing in adults but needs further assessment, particularly in the younger age groups.


National Cohort Study of Resource Utilization in Older Adults With Emergency General Surgery Conditions.
Prior studies have sought to describe Emergency General Surgery (EGS) burden, but a detailed description of resource utilization for both operative and nonoperative management of EGS conditions has not been undertaken. Patient and hospital characteristics were extracted from Medicare data, 2015-2018. Operations, nonsurgical procedures, and other resources (i.e., radiology) were defined using Current Procedural Terminology codes. One million eight hundred two thousand five hundred forty-five patients were included in the cohort. The mean age was 74.7 y and the most common diagnoses were upper gastrointestinal. The majority of hospitals were metropolitan (75.1%). Therapeutic radiology services were available in 78.4% of hospitals and operating rooms or endoscopy suites were available in 92.5% of hospitals. There was variability in resource utilization across EGS subconditions, with hepatobiliary (26.4%) and obstruction (23.9%) patients most frequently undergoing operation. Treatment of EGS diseases in older adults involves several interventional resources. Changes in EGS models, acute care surgery training, and interhospital care coordination may be beneficial to the treatment of EGS patients.


Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases.
Motilin and ghrelin are released from the upper gut during fasting, to stimulate gastric motility. Additional actions of ghrelin (e.g. changes in appetite, nausea or endocrine functions) improve the possibility of using ghrelin receptor agonists to treat complex disorders such as functional dyspepsia. However, changes in endocrine functions increase the risk of unacceptable side effects. By comparison, the more restricted prokinetic activity of motilin limits the therapeutic possibilities but improves the risk:benefit ratio. Compounds targeting both receptors are in development. Recently, additional peptides have been identified from preproghrelin (obestatin) and prepromotilin. These exert biological activity but their pathophysiological significance is unknown.


Conformational studies on parvalbumins by circular dichroism.
Structural variations of two parvalbumins, Whiting III and Pike III, in various denaturing conditions, have been studied by circular dichroism. CD signals are depressed from 4 urea. For Pike III, acidic pH, sodium dodecyl sulfate or complete removal of Ca2+ show little effect in the far ultraviolet region but rather strong effects in the near ultraviolet. For Whiting III similar results are obtained at acidic pH. Carboxymethylated Whiting III (0.15 Ca2+/mol) shows, on the contrary, decreased CD signals in the far and in the near ultraviolet spectra. Addition of Ca2+ fully restores the native CD spectra in both proteins. Ca2+ binding produces structural modifications which are found to vary according to parvalbumin and which seem in any case different from those described for troponin C.


The ubiquitination of CKIP-1 mediated by Src aggravates diabetic renal fibrosis (original article).
Renal chronic inflammation is an important hallmark of diabetic renal fibrosis. Casein kinase 2 interacting protein 1 (CKIP-1) performs a nephroprotective role in the pathogenesis of diabetic nephropathy (DN), which is dramatically decreased in diabetic kidneys. However, whether CKIP-1 regulates inflammation to ameliorate renal fibrosis remains unclear and it is interesting to clarify the degradation mechanism of CKIP-1. Here, we identified CKIP-1 expression was down-regulated in diabetic kidneys and knockout (KO) of CKIP-1 increased c-Jun expression and extra cellular matrix (ECM) in kidneys of normal mice, and knockout (KO) of CKIP-1 further exacerbated renal inflammatory fibrosis in diabetic mice. Moreover, the activated Src kinase interacted with CKIP-1 at Lys252 and increased K48 linked polyubiquitination and proteasome degradation of CKIP-1 in HG induced GMCs and diabetic kidneys. Mechanistically, Src facilitating the binding of c-Cbl with CKIP-1 by promoting the phosphorylation of c-Cbl, thereby increasing Cbl-mediated ubiquitination of CKIP-1 to down-regulate CKIP-1 protein expression. Thus, our study highlighted the anti-inflammation role of CKIP-1 and clarified the mechanism of CKIP-1 degradation in DN.


Head Start's Role in Addressing Food and Nutrition Insecurity: Focus Group Findings.
To elicit Head Start (HS) families' and employees' perspectives on family experiences with food and nutrition insecurity (FNI) and identify how HS addresses them. Four moderated virtual focus groups with 27 HS employee and family participants occurred from August 2021 to January 2022. Qualitative analysis used an iterative inductive/deductive approach. Findings were summarized in a conceptual framework and suggested that HS's current 2-generational approach is useful for families when addressing multilevel factors affecting FNI. The role of the family advocate is essential. In addition to increasing access to nutritious foods, emphasis should also be placed on skills and education to decrease generational unhealthy behaviors. Head Start intervenes in generational cycles of FNI by using the family advocate to add to skills building for 2-generational health. Other programs targeting underserved children can use a similar structure for the greatest impact on FNI.


Current Practices for Esthetic Facial Bone Contouring Surgery in Asians.
In this article, authors mainly introduce new digital technology in facial bone contouring surgery. In our experience, these new technologies are crucial in ensuring the satisfaction of surgical accuracy. Our previous studies have shown surgeons can use precise pre-operative design to reduce operative time, reduce bleeding during surgery. Additionally, augmented reality can enhance the perspective perception of surgeons combining virtuality and reality. What's more, robot-assisted surgical technology also has a strong application prospect in facial contouring surgery. In the future, the combination of soft tissue contouring surgery will make the facial bone contouring surgery safer and more effective.


Altered metabolism of chloroplastic NAD kinase-overexpressing Arabidopsis in response to magnesium sulfate supplementation.
Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADPH) is essential for numerous redox reactions and serve as co-factors in multiple metabolic processes in all organisms. NAD kinase (NADK) is an enzyme involved in the synthesis of NADP+ from NAD+ and ATP. Arabidopsis NADK2 (AtNADK2) is a chloroplast-localizing enzyme that provides recipients of reducing power in photosynthetic electron transfer. When Arabidopsis plants were grown on MS medium supplemented with 5 mM MgSO4, an AtNADK2-overexpressing line exhibited higher glutathione and total sulfur accumulation than control plants. Metabolomic analysis of major amino acids and organic acids using capillary electrophoresis-mass spectrometry demonstrated that overexpression of AtNADK2 affected a range of metabolic processes in response to MgSO4 supplementation.


Use of high concentrations of dimethyl sulfoxide for cryopreservation of HepG2 cells adhered to glass and polydimethylsiloxane matrices.
Animal cells are generally cryopreserved in cryovials in a cell suspension state containing 5%-10% v/v dimethyl sulfoxide (DMSO) used as a cryoprotective agent. However, cryopreservation of cells in an attached state has not been intensively studied, and the effective freezing solution remains unknown. Here we determined the suitable DMSO concentration for the cryopreservation of human hepatoma HepG2 cells attached to glass and polydimethylsiloxane (PDMS) matrices coated with poly-l-lysine. With the use of the glass matrix, the rate of cell adhesion increased with the DMSO concentration up to 30% v/v in the freezing solution. In contrast, the cell-adhesion rate remained constant in the case of the PDMS matrix irrespective of the DMSO concentration between 10% v/v and 30% v/v. The viability of post-thawed cells attached to glass or PDMS matrix was also investigated. The viability was highest at the DMSO concentration of 20% v/v in the freezing solution. The DMSO concentration of 30% v/v, however, had a cytotoxic effect on the cell viability. Thus, the 20% v/v DMSO concentration was found to be most suitable for the cryopreservation of HepG2 cells in the attached state. This dose is high compared to the DMSO concentration used for the cryopreservation of cells in the suspended state.


Therapeutic results of primary aldosteronism with special reference to renal or renovascular lesions.
A study was made of 9 patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 8 subjects with idiopathic adrenal hyperplasia (IHA) to clarify the pathogenesis of sustained hypertension after surgical or non-surgical treatment. Following each treatment, a complete improvement of hypertension was obtained in 12 patients (6 APA, 6 IHA), while 5 (3 APA, 2 IHA) showed still hypertensive status. Renal or renovascular lesions were prominent only in the hypertension-unchanged group. Under regular sodium diet, the ratio of urinary excretion of sodium to creatinine of this hypertensive group was significantly lower than that of the hypertension-improved group. However, the results of other renal function tests were similar in both groups. After respective treatments, suppressed plasma renin activity and elevated plasma aldosterone concentration were improved in all patients. In addition, patients of both groups showed normal response of the renin-aldosterone system following diuretic and dietary induced sodium and volume depletion. Based on these findings, renal or renovascular lesions appear to play an important role in the pathogenesis of maintenance of hypertension in this disorder after respective treatments.


Compassion satisfaction, resilience and passion for work among nurses and physicians working in intensive care units: A mixed method systematic review.
To identify, appraise, and synthesise current evidence on prevalence, correlates, and interventions to enhance compassion satisfaction, resilience, and passion for work among nurses and physicians working in intensive care units. A mixed methods systematic review was conducted. The comprehensive search used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seven databases (MEDLINE, EMBASE, CINAHL, JBI, ProQuest, PsycINFO, and Cochrane Library) were searched for literature published between January 2011 and June 2021. The Mixed Methods Appraisal Tool was used to assess methodological quality. Data from included studies were analysed using a convergent mixed methods design. The protocol was prospectively registered (PROSPERO 2021 CRD42021252051). A total of 37 studies met the inclusion criteria. Most studies reported moderate levels of compassion satisfaction among intensive care health professionals, whereas levels of resilience varied. Compassion satisfaction and resilience were positively correlated, but relationships between compassion satisfaction and resilience and other correlates (personal factors, psychological factors, and work-related factors) were inconsistently reported. Only four interventions aimed to improve compassion satisfaction or resilience among intensive care health professionals. None of the included studies investigated passion for work. Compassion satisfaction, resilience, and passion for work among staff in the intensive care unit are important in the current global COVID-19 pandemic. Health professionals report a moderate level of compassion satisfaction but findings in relation to resilience are mixed. No studies examined passion for work. Further research to determine ongoing psychological wellbeing and professional quality of life and evaluate tailored interventions to support intensive care staff well-being is recommended.


Ultrafine MnO2 nanowires grown on RGO-coated carbon cloth as a binder-free and flexible supercapacitor electrode with high performance.
Reduced graphene oxide coated carbon cloth has been used as a substrate for the growth of ultrafine MnO2 nanowires (CC/RGO/MnO2), forming binder-free and flexible supercapacitor electrode materials. The experimental results indicate that a maximum area-specific capacitance of 506.8 mF cm-2 was gained from the CC/RGO/MnO2 electrode at the current density of 0.128 mA cm-2. Furthermore, the electrode exhibits excellent cycling stability (98.6% specific capacitance was still retained after 10 000 galvanostatic charge-discharge (GCD) tests when the current density was 1.28 mA cm-2). What's more, the area-specific capacitance of the CC/RGO/MnO2 electrode was hardly changed, when the electrode was operated under bending mechanical conditions. In addition, the charge storage performance and mechanism of the MnO2 nanostructures was discussed.


Effect of season and sunlight on viral kinetics during hepatitis C virus therapy.
Rapid viral response (RVR) during antiviral treatment for hepatitis C virus (HCV) predicts sustained viral response (SVR). Recently, vitamin D levels have been associated with SVR. As sunlight is the most important source of vitamin D and shows seasonal variation, we evaluated the effect of season on viral kinetics during peginterferon/ribavirin-based therapy for HCV. Consecutive HCV patients treated with peginterferon/ribavirin and boceprevir/ telaprevir (June 2011-July 2014) were included. Patients were grouped according to season when therapy was initiated (Season A: May-October and Season B: November-April) depending on hours of daily sunlight. Multiple logistic regression analysis included factors known to influence SVR to treatment. The dependent variables were undetectable viral load (VL) or VL ≤15 UI/mL (VL ≤15) at weeks 4, 8 and 12, end of treatment and SVR. The study included 930 patients (66.8% men; median 54 years) treated with telaprevir (n=537) or boceprevir, without (n=481) or with lead-in therapy of peginterferon/ribavirin. Baseline characteristics of patients in Season A (45.3%, n=421) and Season B groups were similar. Overall, a higher rate of RVR (23.5% vs 16.1%, p=0.005) and VL ≤15 (51.0% vs 38.6%, p≤0.001) was observed in patients starting treatment during Season A versus Season B. By logistic regression analysis, initiating treatment in Season A proved to be an independent predictor of RVR and VL ≤15. In our setting, seasonality affects viral kinetics in HCV genotype 1 patients treated with peginterferon/ribavirin-based therapy. Our findings support the hypothesis that vitamin D influences viral response to peginterferon/ribavirin-based therapy.


Discovery of new potential hits of Plasmodium falciparum enoyl-ACP reductase through ligand- and structure-based drug design approaches.
We here report the discovery of novel Plasmodium falciparum enoyl-ACP reductase (PfENR) inhibitors as new antimalarial hits through ligand- and structure-based drug design approaches. We performed 2D and 3D QSAR studies on a set of rhodanine analogues using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Statistical and satisfactory results were obtained for the best HQSAR (r(2) of 0.968 and qLOO(2) of 0.751), CoMFA (r(2) of 0.955 and qLOO(2) of 0.806) and CoMSIA (r(2) of 0.965 and qLOO(2) of 0.659) models. The information gathered from the QSAR models guided us to design new PfENR inhibitors. Three new hits were predicted with potency in the submicromolar range and presented drug-like properties.


The effects of vasoactive intestinal peptide (VIP) antagonists, and VIP and peptide histidine isoleucine antisera on non-adrenergic, non-cholinergic relaxations of tracheal smooth muscle.
1. The effects of several drugs, including antagonists of vasoactive intestinal peptide (VIP), and antisera to VIP or peptide histidine isoleucine (PHI), on relaxation responses of guinea-pig isolated trachea to electrical field stimulation (EFS) have been examined. 2. beta-Adrenoceptor blockade with propranolol only partially blocked the inhibitory response to EFS, but had no effect in tissues from animals pretreated with 6-hydroxydopamine or reserpine. 3. Neither adenosine deaminase, in the presence of dipyridamole, nor the potent adenosine antagonist NPC205 (1,3-n-dipropyl-8-(4-hydroxyphenyl)-xanthine) had any effect on the inhibitory response to EFS. 4. The VIP antagonists, [Ac-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP had no effect on the inhibitory response to EFS. Moreover, they were without effect on responses to exogenous VIP or PHI. 5. Overnight incubation with VIP antisera markedly reduced the inhibitory response to EFS. PHI antisera had a similar, but smaller effect. 6. In the presence of a concentration of VIP that is maximal for its relaxant effect, inhibitory responses to electrical stimulation were greatly inhibited. 7. Naloxone and reactive blue 2 each had no effect on inhibitory responses indicating that endogenous opioids and adenosine 5'-triphosphate (ATP) respectively are not involved. 8. The results suggest that VIP and PHI, but not adenosine, contribute to non-adrenergic, noncholinergic inhibitory nerve responses of guinea-pig trachea. Moreover, the surprising lack of effect of both VIP antagonists on these responses, and in particular, on responses to exogenous VIP, suggests that the receptors mediating VIP-induced tracheal relaxation are different from those that mediate pancreatic secretion.


Contributions of Gut Bacteria and Diet to Drug Pharmacokinetics in the Treatment of Parkinson's Disease.
Parkinson's disease is the second-most common neurodegenerative disorder worldwide. Besides deciphering the mechanisms that underlie the etiology of the disease, it is important to elucidate the factors that influence the efficacy of the treatment therapeutics. Levodopa, which remains the golden treatment of the disease, is absorbed in the proximal small intestine. A reduction in levodopa absorption, leads to reduction in striatal dopamine levels and, in turn, an "off"-episode. In fact, motor fluctuations represent a major problem during the progression of the disease and alteration between "on" (mobility often with dyskinesia) and "off" (immobility, akinesia) episodes contribute to a decreased quality of life. Dietary amino acids can interfere with the absorption of levodopa from the gut lumen and its transport through the blood brain barrier. In addition, higher abundance of specific gut bacteria that restrict levodopa absorption plays a significant role in motor fluctuations in a subset of Parkinson's disease patients. Here, we review the impact of factors potentially interfering with levodopa absorption, focusing on levodopa transport, diet, and gut bacterial interference with the bioavailability of levodopa.


Activity Theory: Quest for the Unattainable and Hope for the Future (Reply to Commentaries).
In reference to commentaries on the paper (Mammen and Mironenko, Integrative Psychological and Behavioral Science 49(4):681-713, 2015) some clarifications are introduced concerning the general landmarks and objectives in the development of psychological science, in respect to which activity theories (AT) can be assessed and evaluated. Contemporary psychological science is developing along the path of integration, as part of the emerging global world. AT has some special value and importance in this respect. It can contribute to the development of the emerging multi-paradigmatic system of the global psychological science because it combines two aspirations, which are rarely combined in psychological theories: a) consistent focus on scientific method, objectivity and conclusiveness; b) the pursuit of a holistic and complete, not simplified and not one-sided comprehension of the subject. The former provides good bases for dialogue with "objective" psychological approaches, close to natural sciences. The latter is suggesting dialogue with teleological humanitarian psychologies. Therefore, AT can engage in networking with a wide range of theories, facilitating the integration of psychological knowledge. It can contribute to resolve the much discussed collision of reductionist "scientific" theoretical models and loose "comprehensive" descriptions in contemporary psychological science. Developing dialogue and cooperation with other schools is of special importance for the RAT, which should return to the international science, where it was rooted, overcoming the language and conceptual barriers. Some new considerations are suggested regarding the theory of the two types of categories of Jens Mammen.


Potential clinical applications of derivative and wavelength-modulation spectrometry.
Absorption spectrophotometers are now becoming available that can record the first and second derivatives of absorbance with respect to wavelength. The advantages of this technique and its potential application to clinical analysis are discussed.