Pigkeepers' knowledge and perceptions regarding African swine fever and the control measures in Estonia.
African swine fever (ASF) has been present in Estonia since 2014, and pigkeepers play a major role in controlling the spread of viral infection in domestic pigs. Participatory epidemiology may provide insight into livestock keepers' existing attitudes and compliance with implementing control strategies. By conducting focus group discussions and using participatory epidemiology tools, this study aimed to reveal pigkeepers' knowledge and awareness of ASF clinical signs, transmission routes, and preventive measures. Furthermore, opinions including trust in stakeholders in ASF control, acceptability of ASF eradication, and control measures by pigkeepers in Estonia were identified. The most indicative ASF signs in pigs were "increased mortality" and "fever, inappetence, lethargy". The highest risk of virus introduction into the herd was designated to "agricultural machinery, vehicles", "rodents, birds, insects", and "people". "Fencing" was the most liked ASF preventive measure, while "training of staff in biosecurity and informing the visitors" was considered the most effective measure. The least accepted ASF eradication measure was "culling of all animals on the farm". Generally, pigkeepers perceived that healthy animals should not be culled but only ASF-infected pigs. Additionally, healthy pigs could be slaughtered and used for the production of heat-treated canned meat. "Destroying the feed" of ASF-infected farms was not favoured because some pigkeepers proposed using it for other animal species. Regarding ASF territorial restrictions (zoning), "lower meat prices" and "economic losses" were regarded as consequences with the greatest impact. Pigkeepers ranked trust in "Veterinary Authority and Ministry of Rural Affairs" regarding their role in ASF prevention and control as high while perceiving themselves as the most trustworthy stakeholder within the ASF network. This study demonstrates a generally good level of awareness among the pigkeepers in Estonia concerning the clinical manifestation of ASF, the most relevant transmission routes of the virus for their farms, and preventive measures for ASF. Pigkeepers are aware of their own role in preventing ASF, and there is a high level of trust between them and government authorities. Additional efforts are needed from authorities to communicate better the purpose of some ASF control and eradication measures to the pigkeepers. Further incentives are required to support the implementation of costly biosecurity measures, assure compliance, and mitigate the consequences of these measures.


Cytogenetic and molecular cytogenetic findings in lipoblastoma.
Lipoblastoma is a rare benign tumor that arises from embryonic adipose tissue and usually occurs in young children. Here, we present a review of available cytogenetic data and the karyotypes of 10 new cases of lipoblastoma, of which 7 could be studied further by fluorescence in situ hybridization (FISH) with regard to the involvement of the PLAG1 gene. All seven tumors with clonal aberrations harbored breakpoints in 8q11 approximately q13, in agreement with literature data. Including previously published cases, 33/40 (82%) lipoblastomas had rearrangement of the 8q11 approximately q13 region. These rearrangements target the PLAG1 gene, which becomes upregulated through promoter swapping. FISH revealed that five of seven cases in our series had a rearrangement of the PLAG1 gene. Occasionally, there can be difficulties in distinguishing a lipoblastoma from a conventional lipoma or a myxoid liposarcoma. As 8q11 approximately q13 rearrangements have been reported in only 3% of conventional lipomas and never in myxoid liposarcoma, cytogenetic analysis or FISH for the PLAG1 gene can provide useful differential diagnostic information.


Managing Malperfusion Syndrome in Acute Type A Aortic Dissection With Previous Cardiac Surgery.
Patients with acute type A aortic dissection with a previous cardiac surgery (PCS) and malperfusion syndrome (MPS) are extremely difficult to manage and have poor outcomes. From 1996 to 2018, 668 patients underwent emergent open aortic repair or endovascular fenestration/stenting for MPS for an acute type A aortic dissection, including those with PCS (PCS, n = 64) and those without PCS (No-PCS, n = 604). The groups were further divided into PCS+MPS, PCS+No-MPS, No-PCS+MPS, and No-PCS+No-MPS. Compared with the No-PCS group, the PCS group had significantly more coronary artery disease, acute renal failure, and mesenteric and renal MPS. Forty-two percent of patients with PCS underwent upfront endovascular fenestration/stenting for endovascular-amendable MPS. The in-hospital mortality was significantly higher in patients with PCS+MPS (40%) compared with PCS+No-MPS (5.9%), No-PCS+MPS (30%), and No-PCS+No-MPS (6.7%). Multivariable logistic regression showed cardiogenic shock (odds ratio, 7.3) and MPS (odds ratio, 6.6) were risk factors for in-hospital mortality (P < .001). After recovering from MPS the PCS group (n = 54) had similar rates of postoperative complications, including 30-day mortality (7.4% vs 6.3%, P = .77), compared with the No-PCS group (n = 557). The 5-year survival was significantly lower in the PCS group compared with the No-PCS group (60% vs 72%, P = .004) and was lowest in those with PCS+MPS (46%). PCS was not a significant risk factor for in-hospital (odds ratio, 1.2; P = .63) or late (hazard ratio, 1.3; P = .27) mortality. Because of severe preoperative comorbidities and the complexity of open aortic repair, in acute type A aortic dissection patients with PCS and MPS, endovascular fenestration and stenting first with delayed redo sternotomy and central aortic repair was a valid approach.


Adjuvant radiation for T1-2N1 oral cavity cancer survival outcomes and utilization treatment trends: Analysis of the SEER database.
Evaluate current practice patterns in the use of adjuvant radiation for T1-2N1 OCSCC patients and investigate its efficacy in the population-based setting. This study extracted patients who were treated surgically for T1N1 and T2N1 OCSCC without adverse nodal features from the SEER database from 2004 to 2013. Patients with distant metastatic disease, unknown surgery or radiation status, or prior malignancies were excluded. Patients were divided into those who underwent surgical resection with and without adjuvant radiation. Disease-specific survival (DSS) and overall survival (OS) were the primary outcomes measured. 746 patients met inclusion criteria and 70% received adjuvant radiation therapy. Treatment with adjuvant radiation therapy was significantly associated with improved 5-year DSS (65% versus 51%; p < 0.001) and OS (54% versus 44%; p = 0.007) for T1N1 tumors. Likewise, improved 5-year DSS (58% versus 38%; p = 0.009) and OS (48% versus 28%; p = 0.004) was shown in T2N1 tumors. Patients with T2N1 tumors wer significantly more likely to receive adjuvant radiation (75% versus 63%; p < 0.001). Those with insurance and high risk primary subsites: buccal, retromolar trigone, and hard palate were more likely to receive adjuvant radiation. The percent utilization of adjuvant radiation remained constant through the study period for T2N1 tumors (72-74%) but significantly decreased for T1N1 (71-55%) (p = 0.047). Adjuvant radiation therapy is independently associated with a significant survival benefit for patients with both T1N1 and T2N1 OCSCC. However, this study demonstrates that patients with T1N1 cancer are less likely to receive adjuvant radiation and utilization is decreasing.


The effect of nutrients and inflorescence damage by insects on fruit-set by Banksia spinulosa.
We examined the role of added macronutrients (N, P, and K) and prevention of damage to inflorescences (ovule/seed predation and rachis damage) by insects in determining levels of fruit-set in Banksia spinulosa at two sites in southeastern Australia. Insecticide application eliminated damage to developing inflorescences (primarily by the lepidopteran, Arotrophora canthelias) and application of macronutrient fertilizer significantly increased nutrient concentrations in leaves at both sites. Only joint application of nutrients and insecticide increased fruit-set per infructescence significantly above that of the control, indicating that the effect of nutrients on fruit-set depends on the intensity of insect damage to inflorescences. The proportion of inflorescences that developed fruits differed between sites and higher levels of rachis damage at one site may partially explain the lower proportion of inflorescences that fruited. Neither nutrient addition or inflorescence damage influenced the position of fruit-set within an infructescence. Our results suggest that (1) macronutrient availability and inflorescence damage interact in determining levels of fruitset in B. spinulosa, and (2) other factors, such as pollen or micronutrient availability, may limit it at some sites. These results highlight site-specific variation and interaction in the factors that limit plant reproduction.


High prevalence of Mycobacterium tuberculosis mixed infection in the capital of moderate tuberculosis incidence country.
Recent studies using molecular epidemiological techniques have demonstrated mixed infection with multiple strains of Mycobacterium tuberculosis especially in countries with high tuberculosis (TB) burden. We aimed to determine the prevalence of mixed infection among patients with TB in the capital of Iran as a country with moderate incidence rate. Samples were collected randomly from January 2011 to December 2013 in Tehran, capital of Iran. A total of 75 M. tuberculosis isolates were genotyped by 24 loci mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-VNTR) for screening the mixed infection. Twenty patients (20/75) were identified with mixed infection, and the estimated rate of mixed infection was 26.6%. Thirteen out of the 24 loci were able to detect the mixed infection in our study. Mixed infections occur at high prevalence among studied Iranian TB patients. Further research is inevitable to evaluate the association of mixed infection and disease progression and treatment.


APACHE II score in massive upper gastrointestinal haemorrhage from peptic ulcer: prognostic value and potential clinical applications.
This study examined the prognostic value of the APACHE II scoring system in patients undergoing emergency operations for bleeding peptic ulcer. There were 96 operations for gastric ulcers and 58 for duodenal ulcers. The mean scores in survivors and in patients who died were 10.8 and 17.5 respectively. None of the 66 patients with an APACHE II score less than 11 died, while the mortality rate in those scored greater than 10 was 22 per cent. In patients scored greater than 10 non-resective procedures carried less risk of mortality than gastrectomy. The APACHE II score is useful when measuring the severity of the acute disease and predicting the outcome in these patients. If used in daily practice it may assist the surgeon in stratifying patients into a low-risk group (score less than 11) in which major operations are well tolerated and outcome is favourable and a high-risk group (score greater than 10) in which the risk of mortality is high and the performance of procedures of lesser magnitude is probably more likely to improve survival.


Congenital clubfoot: pathomechanics, Radiographic analysis, and results of surgical treatment.
Twenty-one patients with resistant or relapsed clubfeet, ranged in age from four months to 7 years, and all had initially been treated with plaster by board certified orthopaedic surgeons. Surgery was recommended only after an Achilles tenotomy failed to bring the foot into dorsiflexion after approximately four months of age. Surgical correction was based upon the derotation and dorsiflexion of the talus in the ankle mortise. The criteria for a satisfactory result were: no recurrence of the equinus or varus; neutral position of the heel; dorsiflexion of the ankle to at least neutral; a fairly straight forefoot so that the center line of the foot bisected either the second or third toes or passed no further laterally than the third and fourth toes. Of the 33 feet surgically treated, 28 had satisfactory results following the first procedure, and five required additional procedures.


Alternatives to levodopa in the initial treatment of early Parkinson's disease.
Parkinson's disease (PD) is primarily a disease of elderly patients. This article reviews current knowledge and recent developments relating to drugs that can be used as alternatives to levodopa as initial treatment of PD. Synthetic orally acting dopamine agonists have found increasing favour as an option for early PD in relatively young patients. This strategy is based on evidence that this approach may delay the onset of motor fluctuations, at least during the first 5 years of treatment. Subcutaneous apomorphine infusions may attenuate motor fluctuations in late-stage disease, and transdermal rotigotine, a dopamine agonist in development, has also been shown to be efficacious. The greater proclivity for dopamine agonists to cause psychotoxicity has, however, limited their routine use in the elderly. Selective monoamine oxidase type B (MAO-B) inhibitors, used as monotherapy, delay the need for the introduction of levodopa by about 9 months. These agents appear to be less efficacious than dopamine agonists but are better tolerated. Concern has been expressed about the potential of the MAO-B inhibitor selegiline (deprenyl) to induce cardiovascular adverse effects (orthostatic hypotension), either directly or through its amphetamine catabolites. Rasagiline is a new MAO-B inhibitor that is not broken down to amphetamine derivatives and is indicated as both monotherapy in early PD and as adjunctive therapy in PD patients with motor fluctuations. Two older classes of agents have undergone a resurgence of interest in recent years. Amantadine, which enhances dopaminergic transmission and has antiglutamate activity, is occasionally used as monotherapy but has recently been widely used as an antidyskinetic agent in late-stage PD. Anticholinergic drugs, such as benztropine (benzatropine) and orphenadrine also provide control of symptoms when used as monotherapy, but their psychotoxic, cognitive and autonomic adverse events make them inappropriate for the treatment of the elderly. Effective therapy in PD should prevent disease progression and abolish motor and cognitive handicap. Currently, none of the existing drugs meets all these needs.


Neuropsychological status of subjects at high risk for a first episode of psychosis.
Thirty-six subjects aged 16 years or older judged at risk for a first episode of psychosis within a North American multi-site study of the schizophrenia prodrome [McGlashan et al., Schizophr. Res. (2003); Miller et al., Schizophr. Res. (2003)] performed at levels intermediate to population norms and data reported for schizophrenia samples on a comprehensive neuropsychological exam. In the context of normal intelligence, this intermediate status suggests that, as a group, these subjects are not fully normal in neuropsychological functioning. Conversely, the finding that they do not show the levels of impairment commonly observed in schizophrenia, including within the first episode, suggests that prodromal interventions might conceivably prevent, delay, or lessen the severity of declines associated with first psychotic episodes.


Cytotoxic effects of anthrax lethal toxin on macrophage-like cell line J774A.1.
The cytotoxic effects of anthrax lethal toxin purified from an avirulent strain were examined on mouse macrophage-like J774A.1 cells. Cell death induced by high concentration of purified lethal toxin had the characteristics of necrosis. At lower concentrations, the toxin caused no morphological change and most of the cells were viable. Interestingly, apoptotic cells were observed when the cells were preincubated with a serine/threonine phosphatase inhibitor, calyculin A, and then exposed to a toxin concentration of 0.1 microg/ml. This is the first report that lethal toxin of the anthrax bacillus can induce both necrosis and apoptosis and that protein phosphatases are implicated in the regulation of bacterial toxin-induced apoptosis.


Imaging of early-stage osteoarthritis: the needs and challenges for diagnosis and classification.
In an effort to boost the development of new management strategies for OA, there is currently a shift in focus towards the diagnosis and treatment of early-stage OA. It is important to distinguish diagnosis from classification of early-stage OA. Diagnosis takes place in clinical practice, whereas classification is a process to stratify participants with OA in clinical research. For both purposes, there is an important opportunity for imaging, especially with MRI. The needs and challenges differ for early-stage OA diagnosis versus classification. Although it fulfils the need of high sensitivity and specificity for making a correct diagnosis, implementation of MRI in clinical practice is challenged by long acquisition times and high costs. For classification in clinical research, more advanced MRI protocols can be applied, such as quantitative, contrast-enhanced, or hybrid techniques, as well as advanced image analysis methods including 3D morphometric assessments of joint tissues and artificial intelligence approaches. It is necessary to follow a step-wise and structured approach that comprises, technical validation, biological validation, clinical validation, qualification, and cost-effectiveness, before new imaging biomarkers can be implemented in clinical practice or clinical research.


Insights into the effects of Zn exposure on the fate of tylosin resistance genes and dynamics of microbial community during co-composting with tylosin fermentation dregs and swine manure.
Though heavy metals are widely reported to induce antibiotic resistance propagation, how antibiotic resistance changes in response to heavy metal abundances remains unclearly. In this study, the tylosin fermentation dregs (TFDs) and swine manure co-composting process amended with two exposure levels of heavy metal Zn were performed. Results showed that the bioavailable Zn contents decreased 2.6-fold averagely, and the removal percentage of total tylosin resistance genes was around 23.5% after the co-composting completed. Furthermore, the tylosin resistance genes and some generic bacteria may exhibited a hormetic-like dose-response with the high-dosage inhibition and low dosage stimulation induced by bioavailable Zn contents during the co-composting process, which represented a beneficial aspect of adaptive responses to harmful environmental stimuli. This study provided a comprehensive understanding and predicted risk assessment for the Zn-contaminate solid wastes deposal and suggested that low levels of Zn or other heavy metals should receive more attention for their potential to the induction of resistance bacteria and propagation of antibiotic resistance genes.


Calcium oxalate crystallizing properties of polyanions elaborated by cultured renal proximal tubular cells.
To study the influence of renal polyanions on crystallization of urinary calcium oxalate, we recovered polyanionic macromolecules from media conditioned by primary cultures of renal proximal tubular epithelial cells of rats in serum-free, hormonally defined medium. Cells cultured on microporous supports showed a higher degree of morphological and functional proximal differentiation into a polarized monolayer than those on plastic impervious substrata. Papainization of the polyanions yielded the glycosaminoglycans chondroitin/dermatan sulphate and heparan sulphate. These accounted respectively for 60% and 80% of the crystal nucleation-promoting activities of polyanions recovered from the apical and basal media conditioned by polarized cultures on microporous supports. Similar relative activities were observed among the urinary glycosaminoglycans and polyanions similarly tested. Primary cultures of polarized proximal tubular epithelial cells are useful then as an in vitro model to study the crystallizing activities of polyanionic macromolecules produced by renal cells.


Hot needles can confirm accurate lesion sampling intraoperatively using [18F]PSMA-1007 PET/CT-guided biopsy in patients with suspected prostate cancer.
Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling. In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC). In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUVmax 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm). [18F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy. NCT03187990, 15/06/2017.


Implications of an anomalous intracellular electrical response in bullfrog corneal epithelium.
The ionic dependencies of the transepithelial and intracellular electrical parameters were measured in the isolated frog cornea. In NaCl Ringer's the intracellular potential difference Vsc measured under short-circuit conditions depolarized by nearly the same amount after either increasing the stromal-side KCl concentration from 2.5 to 25 mM or exposure to 2 mM BaCl2 (K+ channel blocker). With Ba2+ the depolarization of the Vsc by 25 mM K+ was reduced to one-quarter of the control change. If the Cl-permselective apical membrane resistance Ro remained unchanged, the relative basolateral membrane resistance Ri, which includes the lateral intercellular space, increased at the most by less than twofold after Ba2+. These effects in conjunction with the depolarization of the Vsc by 62 mV after increasing the stromal-side K+ from 2.5 to 100 mM in Cl-free Ringer's as well as the increase of the apparent ratio of membrane resistances (a = Ro/Ri) from 13 to 32 are all indicative of an appreciable basolateral membrane K+ conductance. This ratio decreased significantly after exposure to either 25 mM K+ or Ba2+. The decline of Ro/Ri with 25 mM K+ appears to be anomalous since this decrease is not consistent with just an increase of basolateral membrane conductance by 25 mM K+, but rather perhaps a larger decrease of Ro than Ri. Also an increase of lateral space resistance may offset the effect of decreasing Ri with 25 mM K+. In contrast, Ro/Ri did transiently increase during voltage clamping of the apical membrane potential difference Vo and exposure to 25 mM K+ on the stromal side.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of free fatty acids on GABAA receptor ligand binding.
Phospholipase A2 (PLA2) treatment of synaptosomal membranes, which causes the release of fatty acids, particularly unsaturated fatty acids, inhibits the flux of chloride ions through the gamma-aminobutyric acid (GABA) benzodiazepine receptor ion channel in response to activation by agonists. PLA2 treatment has also been shown to affect ligand binding to the receptor. In the present study, we have investigated the effect of unsaturated free fatty acids, arachidonic acid and oleic acid and saturated free fatty acids, arachidic acid and stearic acid on various characteristics of GABAA receptor ligand binding. Only the unsaturated fatty acids showed any effect: arachidonic acid and oleic acid enhanced flunitrazepam binding and muscimol binding but inhibited tert-butylbicyclophosphorothionate (TBPS) binding in a dose-dependent manner. The effects on muscimol and TBPS binding were shown to be due to changes in receptor density by saturation analysis. Oleic acid and arachidonic acid also decreased the enhancement of flunitrazepam and muscimol binding by cartazolate and pentobarbital but did not affect GABA enhancement of flunitrazepam binding. These data indicate that unsaturated free fatty acids can mimic the effects of PLA2 treatment and underline the importance of the lipid microenvironment on ligand binding to the GABAA receptor.


Prevention of the hypercontractile response to thrombin by proteinase-activated receptor-1 antagonist in subarachnoid hemorrhage.
Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). Its pathogenesis still remains elusive, and effective therapeutic strategies are yet to be established. We investigated the role of proteinase-activated receptor-1 (PAR1) in the hypercontractile state in SAH. Rabbit double hemorrhage model was used as a model of SAH. The contractile response to thrombin and the PAR1 expression were evaluated in the isolated rings of basilar artery. Thrombin exhibited only a minor contractile effect in the control, whereas it induced augmented contractions in SAH. The expression of PAR1 was upregulated in SAH. Intracisternal injection of PAR1 antagonist E5555 prevented the enhancement of the contractile responses to thrombin in SAH. The maximal prevention was obtained with 2 microg/kg weight/injection. The contractile responses to K(+) depolarization or endothelin-1 remained unaffected. The upregulation of PAR1 was also prevented by E5555 (2 microg/kg weight/injection) to a level similar to that seen in the control. Ex vivo treatment with E5555 (1 micromol/L) inhibited the contraction induced by thrombin, whereas it had little effect on the contraction induced by K(+) depolarization or endothelin-1, in the basilar artery of SAH. E5555 also inhibited the [Ca(2+)](i) elevation induced by thrombin, but not trypsin, in cultured smooth muscle cells. PAR1 plays a critical role in upregulating PAR1 itself, thereby enhancing the contractile response to thrombin in SAH. PAR1 could thus be a therapeutic target. However, the usefulness of PAR1 antagonist remains to be investigated in vivo.


Effects of Orientation on the Stability and Affinity of Antibody-GNP Conjugation.
In medicine, gold nanoparticles are widely used because of its unique properties. They are usually attached to a monoclonal antibody in treatment and diagnosis. Computational and laboratory work has demonstrated that the structure of the protein can change after interaction with gold nanoparticle and the effect of nanoparticle on the protein is dependent on the type of bond between them. Thus, finding out how nanoparticles affect the protein structure can help us to design the optimal complex of gold nanoparticle-antibody. In the present study, docking and molecular dynamic simulation were performed to obtain an insight at the molecular level in the binding of immunoglobulin G to the Gold nanoparticles, the structure change in immunoglobulin G, and binding energies of Fab and Fc domains of Immunoglobulin G to the GNP. We found the Fab region was more stable than the Fc region when bound to the GNP surface and it also had less structural changes. In neutral pH, Van der Waals interactions contribute more to the Fab-GNP interaction compared to electrostatic interactions; However, in Fc-GNP interaction, the main contributor is the electrostatic energy.


Metabolomics in Exercise and Sports: A Systematic Review.
Metabolomics is a field of omics science that involves the comprehensive measurement of small metabolites in biological samples. It is increasingly being used to study exercise physiology and exercise-associated metabolism. However, the field of exercise metabolomics has not been extensively reviewed or assessed. This review on exercise metabolomics has three aims: (1) to provide an introduction to the general workflow and the different metabolomics technologies used to conduct exercise metabolomics studies; (2) to provide a systematic overview of published exercise metabolomics studies and their findings; and (3) to discuss future perspectives in the field of exercise metabolomics. We searched electronic databases including Google Scholar, Science Direct, PubMed, Scopus, Web of Science, and the SpringerLink academic journal database between January 1st 2000 and September 30th 2020. Based on our detailed analysis of the field, exercise metabolomics studies fall into five major categories: (1) exercise nutrition metabolism; (2) exercise metabolism; (3) sport metabolism; (4) clinical exercise metabolism; and (5) metabolome comparisons. Exercise metabolism is the most popular category. The most common biological samples used in exercise metabolomics studies are blood and urine. Only a small minority of exercise metabolomics studies employ targeted or quantitative techniques, while most studies used untargeted metabolomics techniques. In addition, mass spectrometry was the most commonly used platform in exercise metabolomics studies, identified in approximately 54% of all published studies. Our data indicate that biomarkers or biomarker panels were identified in 34% of published exercise metabolomics studies. Overall, there is an increasing trend towards better designed, more clinical, mass spectrometry-based metabolomics studies involving larger numbers of participants/patients and larger numbers of metabolites being identified.


Motor performance and functional connectivity between the posterior cingulate cortex and supplementary motor cortex in bipolar and unipolar depression.
Although implicated in unsuccessful treatment, psychomotor deficits and their neurobiological underpinnings in bipolar (BD) and unipolar (UD) depression remain poorly investigated. Here, we hypothesized that motor performance deficits in depressed patients would relate to basal functional coupling of the hand primary motor cortex (M1) and the posterior cingulate cortex (PCC) with the supplementary motor area (SMA). We performed a longitudinal, naturalistic study in BD, UD and matched healthy controls comprising of two resting-state functional MRI measurements five weeks apart and accompanying assessments of motor performance using a finger tapping task (FTT). A subject-specific seed-based analysis describing functional connectivity between PCC-SMA as well as M1-SMA was conducted. The basal relationships with motor performance were investigated using linear regression models and all measures were compared across groups. Performance in FTT was impaired in BD in comparison to HC in both sessions. Behavioral performance across groups correlated significantly with resting state functional coupling of PCC-SMA, but not of M1-SMA regions. This relationship was partially reflected in a reduced PCC-SMA connectivity in BD vs HC in the second session. Exploratory evaluation of large-scale networks coupling (SMN-DMN) exhibited no correlation to motor performance. Our results shed new light on the association between the degree of disruption in the SMA-PCC anticorrelation and the level of motor impairment in BD.


The peroxidase activity of ADM-Fe(3+) cooperates with lipid peroxidation: The participation of hydroperoxide and hydroxyl radicals in the damage to proteins and DNA.
To investigate the mechanisms of cardiotoxicity induced by adriamycin (ADM), the enzymatic activities of ADM-Fe(3+), including the peroxidase and lipoxygenase (LOX) activity, and participation of active oxygen species in the damage to biological components were examined. ADM-Fe(3+), but not ADM, steadily oxidized tetramethyl-p-phenylenediamine in the presence of peroxides, indicating that ADM-Fe(3+) acts as a peroxidase. However, the activity of ADM-Fe(3+) as peroxidase was very low compared with that of heme peroxidase, but was similar to that of LOX, which has a known peroxidase activity. Conversely, the activity of ADM-Fe(3+) as a LOX was also very low compared with that of LOX itself. However, the lipid hydroperoxides (LOOH) produced by ADM-Fe(3+) were the substrate for ADM-Fe(3+) as a peroxidase. These findings indicate that lipid peroxidation cooperates with the peroxidase activity of ADM-Fe(3+). Hydroxyl radicals (HO) were generated when ADM-Fe(3+) was incubated with H2O2, but not with LOOH. Alcohol dehydrogenase was inactivated by LOOH. Conversely, DNA was mainly damaged by ADM-Fe(3+) with H2O2. A small amount of DNA remained at the starting point on agarose gels during incubation with ADM-Fe(3+) with LOOH and ADM-Fe(3+) with H2O2. It seems that HO and compound I-like species participate in the strand breaks and the aggregation of DNA, respectively.


Gynecological influencing factors on the rectovaginal septum's morphology.
The objective was to determine the mean morphometric characteristics of the rectovaginal septum (RVS) and its variations in correlation with the number of pregnancies, method of delivery, parity, and estrogenic exposure. An observational, cross-sectional, retrospective, descriptive, and comparative study was carried out. Pelvic MRI of Hispanic women (≥15 years of age) from the northeast of Mexico were obtained. Age and obstetric and gynecological history were registered and the sample women were categorized by their variables. Length and thickness measurements were standardized. A total of 102 MRI studies were included, with a mean age of 41; 24.5% were nulligravida, the rest primi- or multigravida. Vaginal delivery was the most common type (49.35%), 16.88% had a cesarean section, and 31.17% had mixed delivery. 74.5% of the women were premenopausal. The mean RVS length was 73.2 ± 15.3 mm, with a thickness of 2.8 ± 1.7, 2.2 ± 1.2, and 2.5 ± 1.3 mm for the upper, middle, and lower thirds respectively. There were tendencies to increase the length of the RVS, and the thickness of the upper and middle thirds in the non-pregnancy and the at-least-one-pregnancy groups; to increase the length and middle-third thickness in those with mixed delivery, and increased upper- and lower-third thickness in those with only a cesarean section. Multiparous women with vaginal delivery had significantly longer and thicker RVS than primiparous. Premenopausal women had significantly longer RVS with a tendency to lose thickness toward postmenopause. The morphology of RVS can be modified by different factors such as age, number of pregnancies, number of births, and estrogenic exposure. This structure should be evaluated and taken into account in preoperative management and surgical technique planning.


Comparison of the biomechanical properties of internal fixation materials for zygomaticomaxillary complex fractures, A finite element analysis.
Regarding the three distinct types of zygomaticomaxillary complex (ZMC) fractures, this study developed finite element models (FEMs) of absorbable material and titanium material for repair and fixation, respectively. By applying a force of 120 N to the model to simulate the masseter muscle strength, the maximum stress and displacement of the repair materials and the fracture ends were measured. In discussing various models, the maximum stress values of absorbable and titanium materials are less than their yield strength, and the maximum displacement values of the titanium material and fracture end were less than 0.1 mm and 0.2 mm. The maximum displacement values of absorbable material and fracture end in incomplete zygomatic fracture and dislocation were less than 0.1 mm and 0.2 mm. While in the zygomatic complex complete fractures and dislocation, the maximum displacement values of the absorbable material and the fracture end exceeded 0.1 mm and 0.2 mm. Consequently, the distinction between the maximum displacement values of the two materials was 0.08 mm, and the distinction between the maximum displacement values of the fracture ends was 0.22 mm, despite the fact that the absorbable material can withstand the fracture end's strength, it is not as stable as the titanium material.


Computer optimization of a minimal biped model discovers walking and running.
Although people's legs are capable of a broad range of muscle-use and gait patterns, they generally prefer just two. They walk, swinging their body over a relatively straight leg with each step, or run, bouncing up off a bent leg between aerial phases. Walking feels easiest when going slowly, and running feels easiest when going faster. More unusual gaits seem more tiring. Perhaps this is because walking and running use the least energy. Addressing this classic conjecture with experiments requires comparing walking and running with many other strange and unpractised gaits. As an alternative, a basic understanding of gait choice might be obtained by calculating energy cost by using mechanics-based models. Here we use a minimal model that can describe walking and running as well as an infinite variety of other gaits. We use computer optimization to find which gaits are indeed energetically optimal for this model. At low speeds the optimization discovers the classic inverted-pendulum walk, at high speeds it discovers a bouncing run, even without springs, and at intermediate speeds it finds a new pendular-running gait that includes walking and running as extreme cases.


Prevalence and determinants of sarcopenia in community-dwelling older adults in Ireland.
Data on the prevalence of sarcopenia among older adults in Ireland are lacking. To assess the prevalence and determinants of sarcopenia among community-dwelling older adults in Ireland. This cross-sectional analysis involved n = 308 community-dwelling adults aged ≥ 65 y living in Ireland. Participants were recruited via recreational clubs and primary healthcare services. Sarcopenia was defined according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Skeletal muscle mass was estimated using bioelectrical impedance analysis, strength was measured via handgrip dynamometry, and physical performance was assessed using the Short Physical Performance Battery. Detailed information was collected on demographics, health, and lifestyle. Dietary macronutrient intake was measured via a single 24 h recall. Binary logistic regression was used to examine potential demographic, health, lifestyle, and dietary determinants of sarcopenia (where both probable and confirmed sarcopenia were combined). The prevalence of EWGSOP2-defined probable sarcopenia was 20.8% and confirmed sarcopenia was 8.1% (5.8% had severe sarcopenia). Polypharmacy (OR 2.60, 95% confidence interval [CI] 1.3, 5.23), height (OR 0.95, 95% CI 0.91, 0.98), and Instrumental Activities Of Daily Living (IADL) score (OR 0.71, 95% CI 0.59, 0.86) were independently associated with sarcopenia (probable and confirmed combined). There were no independent associations between energy-adjusted macronutrient intakes, as determined by 24 h recall, and sarcopenia. Sarcopenia prevalence within this sample of community-dwelling older adults in Ireland is broadly similar to other European cohorts. Polypharmacy, lower height, and lower IADL score were independently associated with EWGSOP2-defined sarcopenia.


β-Tricalcium phosphate induces apoptosis on dental follicle cells.
Dental stem cells represent a good treatment option in regenerative dentistry. Regeneration of large bone defects can be achieved by a cell-based therapy consisting of osteogenic progenitor cells, such as dental follicle precursor cells (DFCs), in combination with bone substitute material used as a scaffold. A previous trial had shown that β-tricalcium phosphate (TCP) improves the osteogenic differentiation of DFCs. In the present trial, we investigated the attachment, survival, and proliferation of DFCs on TCP in more detail. A high initial cell number was required for the adhesion, attachment, and sufficient proliferation of DFCs on a TCP scaffold. The TCP scaffold released fine soluble particles enriched in TCP eluates that induced cell death and showed typical characteristics of programmed cell death (apoptosis) in DFCs. During cultivation on the TCP scaffold, DFCs showed a highly upregulated expression of antiapoptotic genes but a downregulated expression of proapoptotic markers. In conclusion, TCP supports osteogenic differentiation in DFCs but also induces programmed cell death. Our data suggest that surviving DFCs avoid programmed cell death by inducing antiapoptotic genes.


High-performance liquid chromatographic column-switching method for two cyclosporine metabolites in blood.
Cyclosporine (CSA) is biotransformed to many metabolites which may contribute to its immunosuppressive and nephrotoxic activity. We report a rapid and sensitive, automated column-switching high-performance liquid chromatographic (HPLC) method for measuring CSA-M17 in whole blood; the method also separates CSA-M1. CSA metabolite standards were isolated by a preparative-scale HPLC method. Samples were prepared by protein precipitation with acetonitrile followed by dilution with water. CSA-M17 was initially separated on a C8 column; final separation was on a C18 column. The inter-day relative standard deviation at 50 ng/ml was 8% (n = 3). Limit of detection was 20 ng/ml.


Complete σ* intramolecular aromatic hydroxylation mechanism through O2 activation by a Schiff base macrocyclic dicopper(I) complex.
In this work we analyze the whole molecular mechanism for intramolecular aromatic hydroxylation through O2 activation by a Schiff hexaazamacrocyclic dicopper(I) complex, [Cu(I) 2(bsH2m)](2+). Assisted by DFT calculations, we unravel the reaction pathway for the overall intramolecular aromatic hydroxylation, i.e., from the initial O2 reaction with the dicopper(I) species to first form a Cu(I)Cu(II)-superoxo species, the subsequent reaction with the second Cu(I) center to form a μ-η(2):η(2)-peroxo-Cu(II) 2 intermediate, the concerted peroxide O-O bond cleavage and C-O bond formation, followed finally by a proton transfer to an alpha aromatic carbon that immediately yields the product [Cu(II) 2(bsH2m-O)(μ-OH)](2+).


CTLA-4 polymorphism in the pathogenesis of chronic spontaneous autoreactive urticaria.
Autoimmune mechanisms are considered to play a significant role in chronic urticaria pathophysiology. Additionally, clinical experience emphasises the coexistence of chronic urticaria manifestation with thyroid autoimmunity. As the role of CTLA-4 polymorphism in autoimmune thyroid diseases is well proven we speculated on the possible role of this polymorphism in the background of chronic urticaria. We included 128 chronic spontaneous autoreactive urticaria patients (87 females and 41 males) and 101 healthy volunteers (71 females and 30 males). In all examined subjects CTLA-4 A49G polymorphism was analysed. Disease severity with Urticaria Activity Score as well as age of disease onset was also studied. No statistically significant differences in the allele or genotype distribution between urticaria patients and controls were observed. Furthermore, we found no association between CTLA4 polymorphism and urticaria severity as well as the age of disease onset. Our data suggest that there is no contribution of CTLA-4 A49G polymorphism to chronic spontaneous autoreactive urticaria susceptibility. We recommend further research on other polymorphisms in chronic urticaria patients to explore in detail the potent role of the genetic background in the pathogenesis of this disorder.


Design of hybrid β-hairpin peptides with enhanced cell specificity and potent anti-inflammatory activity.
Antimicrobial peptides (AMPs) have attracted considerable attention for their broad-spectrum antimicrobial activity and reduced tendency to cause bacterial resistance. Emerging concerns over the host cytotoxicity of AMPs, however, may ultimately compromise their development as pharmaceuticals. In order to optimize AMPs with potent cell specificity and anti-inflammatory activity, we designed β-hairpin hybrid peptides based upon progetrin-1, bovine lactoferricin and cecropin A. The synthetic hybrid peptides LB-PG and CA-PG demonstrated high selectivity over a wide range of microbes from Gram-positive and Gram-negative bacteria in porcine red blood cells. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) show that these peptides kill microbial cells by penetrating the cell membrane and damaging the membrane envelope. Gel retardation demonstrates that the peptides have a high affinity for DNA, indicating an additional possible intracellular bactericidal mechanism. Moreover, the hybrid peptides inhibit the expression of LPS-induced proinflammatory cytokines and chemokines, such as tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), macrophage inflammatory protein-1α (MIP-1α) and monocyte chemoattractant protein 1(MCP-1), following LPS stimulation in RAW264.7 cells. Our results indicate that these hybrid peptides have considerable potential for future development as antimicrobial and anti-inflammatory agents.


Features of pigmented vulval lesions on dermoscopy.
The dermoscopic criteria for benign and malignant lesions on the vulva are not well established due to the lack of large series of such lesions. Melanoma should always be included in the differential diagnosis of pigmented lesions on the vulva especially when they are wide, or of recent onset. Elsewhere on the skin dermoscopy plays an important role in the selection of suspicious pigmented lesions, as well as in the selection of the best site to perform the biopsy. To analyse the dermoscopic patterns observed in pigmented lesions of the vulva. We analysed a nonselected consecutive series of 68 histopathologically proven cases comprising five melanomas, 16 naevi, 20 lentigos, 12 benign vulval melanoses, 11 cases of postinflammatory pigmentation, three pigmented cases of usual vulval intraepithelial neoplasia (VIN) and one seborrhoeic keratosis seen at our institution. The dermoscope was covered by translucent disposable food wrap and/or antibacterial gel to prevent possible transmission of infections. Descriptive statistics were performed using multiple correspondence analysis. The parallel (37%), ring-like (9%), homogeneous (22%), globular-like (13%) and reticular-like (6%) patterns were observed on benign lesions (naevi, lentigo, vulval melanosis and postinflammatory pigmentation). The cerebriform pattern (6%) was observed only on VIN and seborrhoeic keratosis. The multicomponent pattern (6%) was associated with melanoma (60%). In cases of melanoma we also occasionally observed an irregular pattern, a whitish or blue-whitish veil, irregularly distributed dots and globules and atypical vascular pattern. Using multiple correspondence analysis, we designed a new algorithm for the early detection of vulval melanomas. Dermoscopy can play a role in the noninvasive classification of vulval melanosis. However, further studies of larger collaborative series are needed to validate our vulval melanoma diagnostic algorithm. VIN and seborrhoeic keratosis share the same dermoscopic features and biopsy should be considered for seborrhoeic-like keratosis. In case of doubt pathological examination of a biopsy remains mandatory.


[Relationship between dietary behavior and malnutrition of children aged 3-5 years in five cities of China].
To explore the status of malnutrition and dietary behavior characteristics of children aged 3-5 in Tonghua, Nanchang, Changsha, Kunming and Weinan, and to analyze the relationship between them. Data was from National Nutrition and Health Systematic Survey for 0-18 Years Old Children in China. A total of 1741 children were randomly selected from five cities by multi-stage stratified cluster sampling, and their physical fitness was measured and investigated by questionnaire. Chi-square test and multivariate binomial Logistic regression analysis were used to assess the relationship between nutritional deficiency and diet and feeding behavior. Among the investigated children, the underweight rate, stunting rate and wasting rate were 0.52%, 1.09% and 1.03%, respectively. Dietary behavior restriction was the risk factor for stunting(OR=4.72, 95% CI 1.41-15.84), poor eating habits were the risk factor for wasting(OR=3.64, 95% CI 1.01-13.34). No statistical association was found between underweight and diet and feeding behavior. The incidence of malnutrition among children aged 3-5 years in five urban areas of China is low. There is a correlation between malnutrition and poor diet and feeding behavior. Measures should be taken to correct the poor eating habits of children and the feeding behavior of caregivers, so as to improve the nutritional status of children.


Support practices by an interdisciplinary team in a palliative-care unit for relatives of patients in agonal phase.
In the absence of extant recommendations, the aim of this study was to formalise support practices used by an interdisciplinary team in a palliative-care unit (PCU) for the relatives of patients in the agonal phase preceding death. The secondary objective was to understand the expectations of relatives during this phase in terms of the support provided by professionals and volunteers. Thirty-two people took part in this study; all were interviewed through focus groups (FGs). Each FG comprised one category of individuals working in the PCU: nurses, care- assistants, doctors, psychologists, other professionals, palliative-care volunteers, and relatives. Groups were surveyed using an interview guide, and the interviews were recorded and transcribed to enable identification and characterization of all practices. Care practices were classified into four categories: current consensual practices (i.e. performed by all team members), occasional consensual practices, non-consensual practices (performed by one or a few participants), and practices to be developed. In total, 215 practices were mentioned by professionals and palliative-care volunteers: 150 current consensual practices, 48 occasional consensual practices, 1 non-consensual practice, 16 practices yet to be developed, and 29 practices for relatives. Many practices were mentioned by different categories of participants; thus, after cross-checking, the number of practices decreased from 215 to 52. A list of practices deemed desirable by all was drawn up and then validated by the entire interprofessional team. These practices were organised around four themes: providing care and ensuring comfort; communicating, informing, and explaining; interacting; and mobilising interdisciplinary skills. These results underline the importance of the quality of care provided to patients, the attention given to the relatives themselves, and they highlight the importance of the helping relationship. Following this study, which established a list of varied practices aimed at supporting the relatives of patients in agonal phase, it will be important to set up a broader study seeking to establish a consensus on these practices with an interprofessional group of experts from other PCUs using broad surveys and an adapted methodology. Such studies will make it possible to develop training modules for teams working with relatives.


The molecular biology of polycystic kidney disease.
In recent years there have been a number of developments in polycystic kidney disease (PKD) research. The genes associated with the predominant forms of autosomal dominant PKD have been cloned, and the gene associated with a mouse model for autosomal recessive PKD has been identified and characterized. Other studies have yielded new information regarding the role of the epidermal growth factor receptor gene in promoting renal cyst formation. In this review article we summarize recent published data on the molecular genetics of autosomal dominant and autosomal recessive PKD and provide a working model of how multiple genes participate in the PKD disease pathway.


Platinum-alginate-chitosan nanobioconjugate decorated carbon backbone layered biosensor for highly sensitive and selective detection of BACE-1.
Chitosan (CS) and sodium alginates (SA) have been revealed for the design of layer-by-layer (LbL) assembly to develop pharmaceutical dosage forms owing to their versatile characteristics. Recently, the preference for unique LbL assemblies in biosensor development has offered the modified performance for detection interest analyte. Beta (β)-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) is a pivotal biomarker of Alzheimer's disease (AD) and demands high sensitivity and selective identification for the early-stage diagnosis. In this work, CS-SA‑platinum nanoparticles (Pt-NPs) LbL-based nanobioconjugate decorated carbon backbone-layered affinity surface plasmon resonance (Anti-BACE-1-LbL@Pt-NPs-GO-SPR) biosensor was designed for extremely sensitive and selective sensing of BACE-1. Primarily, LbL nanobioconjugate was synthesized by integrating cationic 'CS' and anionic 'SA' on the face of green-made Pt-NPs. Here, the amines of 'CS' offers a softer surface for anti-BACE-1 immobilization that leads to maintaining the bio-functionality of bioreceptors, provides the specific orientation for bioreceptors, etc. As well, the synthesized graphene oxide (GO, 2D carbon backbone) was preferred as non-plasmonic nanomaterials due to their plenty of merits in biosensors. Here, the designed biosensor provides a low detection limit (LOD) of 5.63 fg/mL and a wide linear range from 5 fg/mL to 150 ng/mL. Moreover, selectivity and real-time analyses in spiked samples exhibited their practical usefulness in complex specimens for BACE-1 detection. Hence, the decorating of antibody-immobilized CS-SA coated Pt-NPs nanobioconjugate on the face of GO has various benefits mainly extremely sensitive and superb specificity. Overall, CS and SA coated Pt-NPs bioconjugate decorated GO layered SPR biosensors can provide highly sensitive, selectivity, rapid, label-free, etc. detection of BACE-1 in clinical samples.


Assessment of left ventricle myocardial deformation in a hemorrhagic shock swine model by two-dimensional speckle tracking echocardiography.
Trauma-induced secondary cardiac injury has been associated with significant adverse cardiovascular events. Speckle tracking echocardiography is a novel technology that allows an accurate and reproducible cardiac structure and function assessment. We evaluated the left ventricle (LV) myocardial deformation by speckle tracking echocardiography in a hemorrhagic shock (HS) swine model. Seven healthy male Landrace pigs were included in this study. Severe HS was reached through three sequentially blood withdraws of 20% of estimated blood volume, and it was maintained for 60 minutes. Volume resuscitation was performed using all precollected blood volume. A 1.8- to 4.2-MHz phased-array transducer was used to acquire the two-dimensional echocardiography images. Strain measurements were obtained semiautomatically by wall motion tracking software. Results are presented as medians and interquartile ranges and compared using Wilcoxon rank-sum test. A p value of <0.05 was considered statistically significant. The median weight was 32 (26.1-33) kg, and the median total blood volume withdrawn was 1,100 (1,080-1,190) mL. During the severe HS period, the median arterial systemic pressure was 39 (36-46) mm Hg, and the cardiac index was 1.7 (1.6-2.0) L/min/m 2 . There was statistically significant absolute decrease in the global longitudinal strain 2 hours postresuscitation comparing with the basal measurements (-9.6% [-10.7 to -8.0%] vs. -7.9% [-8.1 to -7.4%], p = 0.03). There were no statistically significant differences between the basal and 2 hours postresuscitation assessments in the invasive/noninvasive hemodynamic, other two-dimensional echocardiogram (LV ejection fraction, 49.2% [44-54.3%] vs. 53.2% [51.5-55%]; p = 0.09), and circumferential strain (-10.6% [-14.4 to -9.0%] vs. -8.5% [-8.6 to -5.2%], p = 0.06) parameters. In this experimental swine model of controlled HS, LV global longitudinal strain analysis accurately characterizes the timing and magnitude of subclinical cardiac dysfunction associated with trauma-induced secondary cardiac injury.


Effects of minimally invasive percutaneous and trans-spatium intermuscular short-segment pedicle instrumentation on thoracolumbar mono-segmental vertebral fractures without neurological compromise.
To compare the outcomes of minimally invasive percutaneous short-segment pedicle instrumentation (SSPI) with that of trans-spatium intermuscular SSPI on thoracolumbar mono-segmental vertebral fracture without neurological compromise. A total of 39 patients with thoracolumbar mono-segmental vertebral fracture without neurological deficit receiving treatment between January 2009 and July 2011 were enrolled. Percutaneous SSPI was performed for 18 patients (the percutaneous group), and trans-spatium intermuscular SSPI was performed for 21 patients (the trans-spatium intermuscular group). Peroperative indices, intraoperative radiation exposure time, postoperative and follow-up lumbodorsal pain, function scores, and radiological data were compared. The percutaneous group had significantly less intraoperative blood loss and less severe postoperative pains, but suffered significantly longer fluoroscopy time and higher hospitalization costs compared with the trans-spatium intermuscular group. No significant difference was observed in operating time. All patients were followed up for 17.3 ± 9.2 months (ranging from 5 to 35 months). No significant differences were observed between the two groups in terms of postoperative relative vertebral height (RVH) and regional kyphotic angle (RKA), as well as last follow-up RVH, RKA, lumbodorsal pain, and Oswestry disability index. Percutaneous SSPI has the virtues of less intraoperative blood loss and less severe pains in the treatment of thoracolumbar mono-segmental vertebral fracture without neurological deficit. When compared with trans-spatium intermuscular SSPI, it results in longer intraoperative radiation exposure time and a higher surgery cost. To us, percutaneous SSPI has no advantage over trans-spatium intermuscular SSPI in therapeutic outcomes. Level IV. Retrospective study.


Redox status of serum apolipoprotein E and its impact on HDL cholesterol levels.
Apolipoprotein E (apoE) is closely involved in the pathogenesis of apoE-related diseases, such as Alzheimer's disease and cardiovascular disease. The redox modulation of cysteine-thiols in a protein is involved in various pathophysiological regulations; however, that of apoE has not been studied in detail. Herein, we devised an analytical method to determine the redox status of serum apoE and assessed its relation to serum cholesterol levels and apoE phenotype. The present method was based on a band shift assay, using a photocleavable maleimide-conjugated polyethylene glycol. The basic characteristics of the present method were found to be satisfactory to determine the redox status of serum apoE quantitatively. Serum apoE was separated into its reduced-form (r-), non-reduced-form (nr-), apoE-AII complex, and homodimer using this method. R-apoE could be detected as a 40-kDa band, whereas nr-apoE remained as monomeric apoE. R-apoE displayed a preference for VLDL; however, the levels showed the correlation with HDL-cholesterol levels (p<0.005). Redox status of serum apoE was significantly different among apoE phenotypes. The quantitative ratios of nr-apoE to total apoE in serum from subjects with apoE4/E3 were higher than in serum from subjects with apoE3/E3 (p<0.0001) and apoE3/E2 (p<0.001). The redox status of serum apoE might be related to the synthesis of HDL. The information concerning the redox status of serum apoE provided by the present method may be a potent indicator to evaluate various apoE-related diseases.


Neurotoxicity evoked by organophosphates and available countermeasures.
Organophosphorus compounds (OP) are a constant problem, both in the military and in the civilian field, not only in the form of acute poisoning but also for their long-lasting consequences. No antidote has been found that satisfactorily protects against the toxic effects of organophosphates. Likewise, there is no universal cure to avert damage after poisoning. The key mechanism of organophosphate toxicity is the inhibition of acetylcholinesterase. The overstimulation of nicotinic or muscarinic receptors by accumulated acetylcholine on a synaptic cleft leads to activation of the glutamatergic system and the development of seizures. Further consequences include generation of reactive oxygen species (ROS), neuroinflammation, and the formation of various other neuropathologists. In this review, we present neuroprotection strategies which can slow down the secondary nerve cell damage and alleviate neurological and neuropsychiatric disturbance. In our opinion, there is no unequivocal approach to ensure neuroprotection, however, sooner the neurotoxicity pathway is targeted, the better the results which can be expected. It seems crucial to target the key propagation pathways, i.e., to block cholinergic and, foremostly, glutamatergic cascades. Currently, the privileged approach oriented to stimulating GABAAR by benzodiazepines is of limited efficacy, so that antagonizing the hyperactivity of the glutamatergic system could provide an even more efficacious approach for terminating OP-induced seizures and protecting the brain from permanent damage. Encouraging results have been reported for tezampanel, an antagonist of GluK1 kainate and AMPA receptors, especially in combination with caramiphen, an anticholinergic and anti-glutamatergic agent. On the other hand, targeting ROS by antioxidants cannot or already developed neuroinflammation does not seem to be very productive as other processes are also involved.


Foods and respiratory allergy.
Foods may induce respiratory symptoms by both reaginic and nonreaginic mechanisms. Asthma is one of the most common respiratory manifestations in children, and it is well known that many factors may provoke an attack. When considering the relationship between foods and asthma, we must keep in mind that food allergy may coexist with an inhalant allergy and that other nonallergens, such as pollutants, smoke, or additives, may modulate or modify bronchial reactivity and thus favor the food allergen action. In a study using clinical history, prick test, radioallergosorbent test, and double-blind food challenge, we demonstrated respiratory symptoms related to food allergy in 13 of 140 (9.2%) children with asthma. Asthma, in particular, was demonstrated in 8 of 140 (5.7%) patients. Food allergy respiratory symptoms are, in our experience, almost always associated with other clinical manifestations (e.g., cutaneous, gastrointestinal). The recognition of food-dependent IgE-mediated respiratory symptoms is essentially limited to those cases characterized by food allergy with asthmatic expression. It is possible, however, that in many cases foods may have a nonspecific role in the determination of asthma or in the preparation of bronchi for the possible consequent stimulus.


Experimental Study of Antidepressant Properties of Afobazole.
We studied the effects of oral administration of Afobazole in a dose of 10 mg/kg for 5 days on depressive-like behavior of male C57BL/6 mice in the tail suspension test in comparison with amitriptyline (10 mg/kg) or fluoxetine (20 mg/kg) treatment. Afobazole produced an antidepressant effect similar to amitriptyline, but inferior to fluoxetine. The σ1 receptor antagonist BD-1047 in a dose of 5 mg/kg blocked the antidepressant effect of Afobazole, which indicates the involvement of σ1 receptors in the antidepressant effect of the drug.


Investigating natural attenuation of pharmaceuticals through unsaturated column tests.
The growing consumption of pharmaceuticals together with their incomplete removal in wastewater treatment plants (WWTPs) implies the occurrence of these compounds in natural water resources. To investigate the natural attenuation of selected pharmaceuticals (caffeine, acetaminophen, sulfamethoxazole, naproxen and carbamazepine) during vadose zone infiltration, unsaturated column (L 26.67 cm, Ø 7.62 cm) experiments, filled with a sandy-loamy soil, were performed using two input concentrations (100 and 1000 μg L-1). The software Hydrus 1D was used to simulate experimental data. Caffeine and acetaminophen were never detected at the column outlet indicating a low environmental concern. On the other hand, attenuation of the detected pharmaceuticals could be reproduced by a combination of retardation and removal approaches. Carbamazepine is among the selected contaminants the most persistent. A dependence of removal rates on input concentrations was detected for sulfamethoxazole (μw from 2.78 d-1 to 1.16 d-1) and naproxen (μw from 1.16 d-1 to 0.63 d-1) attributed mainly to decreased metabolism of microorganisms when a higher input concentration is applied. Two transformation products (TPs) (N4-Acetylsulfamethoxazole and epoxycarbamazepine) derived from sulfamethoxazole and carbamazepine transformation, respectively, were detected during the experiment with the highest input concentration.


The clinical significance of cardiac troponins in medical practice.
Troponins are regulatory proteins that form the cornerstone of muscle contraction. The amino acid sequences of cardiac troponins differentiate them from that of skeletal muscles, allowing for the development of monoclonal antibody-based assay of troponin I (TnI) and troponin T (TnT). Along with the patient history, physical examination and electrocardiography, the measurement of highly sensitive and specific cardiac troponin has supplanted the former gold standard biomarker (creatine kinase-MB) to detect myocardial damage and estimate the prognosis of patients with ischemic heart disease. The current guidelines for the diagnosis of non-ST segment elevation myocardial infarction are largely based on an elevated troponin level. The implementation of these new guidelines in clinical practice has led to a substantial increase in the frequency of myocardial infarction diagnosis. Automated assays using cardiac-specific monoclonal antibodies to cardiac TnI and TnT are commercially available. They play a major role in the evaluation of myocardial injury and prediction of cardiovascular outcome in cardiac and non-cardiac causes. In this review we discuss the clinical applications of cardiac troponins and the interpretation of elevated levels in the context of various clinical settings.


Studies on the plasma membrane of normal and psoriatic keratinocytes. 2. Cyclic AMP and its response to hormonal stimulation.
Cyclic AMP levels have been determined for the first time in isolated keratinocytes. Values were more reproducible than those reported using epidermal slices. Evidence is presented to show that damage to hormone receptors is minimal. Other observations include the following: (1) Keratinocytes from psoriatic lesions showed reduced 'resting' levels of cyclic AMP as well as a diminished response to adrenaline. (2) Cyclic AMP levels were maximal in the basal cells, falling dramatically in fully differentiated keratinocytes. (3) The topical application of a corticosteroid (fluocinolone acetonide) did not modulate the response of adenyl cyclase to hormonal stimulation.


Impact of 18F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis.
To evaluate the influence of 18F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT. Management changes after PET/CT were classified as major and minor changes. A subgroup of 107 patients (stage I, N = 5; stage II, N = 3; stage III, N = 42; stage IV, N = 57) was planned for complete metastasectomy initially, based on conventional imaging. Management changes and outcome were evaluated by linkage with the information obtained from patients' medical records. In 28 of 107 patients (26%), the surgical treatment plan remained unchanged after PET/CT. In 24 patients (22%), minor changes were performed, such as enlargement or reduction of the surgical field. In 55 patients (51%, 95% CI 42%-61%) major changes of the intended treatment plan occurred; of those, 20 patients (19%) were classified to be tumor-free with PET/CT, 32 patients (30%) were found to have multiple previously unrecognized metastases and had to be treated by systemic therapy, three patients (3%) had to be changed to palliative radiotherapy or isolated extremity perfusion. The 1-year and 2-year overall survival (OS) in patients with complete metastasectomy (N = 52) was 90% and 79%, respectively. Systemically treated patients (N = 32) resulted in 1-year OS of 72% and 2-year OS of 61%. Eleven of 32 patients (34%) with systemic therapy experienced a complete response. Until December 2016, all 20 patients classified as tumor-free by PET/CT were alive. The study confirms the high impact of PET/CT on clinical management in patients with advanced melanoma planned for radical metastasectomy. PET/CT resulted in frequent management changes, preventing futile surgery in half of the patients.


Climate change and water resources in arid mountains: an example from the Bolivian Andes.
Climate change is projected to have a strongly negative effect on water supplies in the arid mountains of South America, significantly impacting millions of people. As one of the poorest countries in the region, Bolivia is particularly vulnerable to such changes due to its limited capacity to adapt. Water security is threatened further by glacial recession with Bolivian glaciers losing nearly half their ice mass over the past 50 years raising serious water management concerns. This review examines current trends in water availability and glacier melt in the Bolivian Andes, assesses the driving factors of reduced water availability and identifies key gaps in our knowledge of the Andean cryosphere. The lack of research regarding permafrost water sources in the Bolivian Andes is addressed, with focus on the potential contribution to mountain water supplies provided by rock glaciers.


Mechanisms Underlying Induction of Tolerance to Foods.
Oral tolerance refers to a systemic immune nonresponsiveness to antigens first encountered by the oral route, and a failure in development of this homeostatic process can result in food allergy. Clinical tolerance induced by allergen immunotherapy is associated with alterations in immune mechanisms relevant to the allergic response, including reduction of basophil reactivity, induction of IgG4, loss of effector Th2 cells, and induction of Tregs. The relative contribution of these immune changes to clinical tolerance to foods, and the duration of these immune changes after termination of immunotherapy, remains to be identified.


Environmental unpredictability, economic inequality, and dynamic nature of life history before, during, and after the Industrial Revolution.
It is emphasized that environmental predictability is another important condition that plays roles in slow strategies that are related to innovation; that economic inequality, except as measured by Gross Domestic Product (GDP) per capita, influences innovation; and that switching global life history from a slow to a fast strategy is a response adopted in response to new challenges during the post-Industrial Revolution period.


Endovascular management of an aortic rupture following transcatheter aortic valve replacement.
We report a case of aortic rupture during transcatheter aortic valve replacement (TAVR) managed successfully by urgent stent-graft implantation.


Salbutamol dry powder inhaler: efficacy, tolerability, and acceptability study.
Dry powder inhaler (DPI) devices are frequently used in children over 5 years of age in order to avoid coordination difficulties often seen with the use of pressurized metered dose inhalers (pMDI). This study assessed the efficacy, tolerability, and acceptability of salbutamol delivered via two delivery systems, in a population of pediatric patients. The primary aim of the study was to investigate the bronchodilator efficacy of a single dose (100 microg) of salbutamol administered via a dry powder inhaler (Clickhaler) compared to a similar dose administered by a pressurized metered dose inhaler via a large-valved holding chamber (VHC) to children with asthma. The study comprised two phases: the first comparator phase, followed by an open 4-week treatment period. Sixty-one children with a mean (SD) age of 11.3 years (2.9) (range, 6-17) and mild or moderate asthma completed the study. The primary efficacy endpoint, forced expiratory volume in 1 sec (FEV1), indicated that there was no clinically or statistically significant difference between the bronchodilator effects of salbutamol delivered via either device, with a maximum posttreatment percentage change in FEV1 (SD) of 12.4% (10.0) and 14.15 (9.3) for Clickhaler and pMDI plus VHC, respectively. Most patients rated the Clickhaler as easy to use (97%) and liked the device (84%). Both treatments were well--tolerated. These results support the suitability of salbutamol Clickhaler as an acceptable, well-tolerated, and effective alternative to a pMDI plus VHC in mild to moderate asthmatic children over age 6 years.


Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer's disease.
Obstructive sleep apnoea (OSA) has a high prevalence in patients with Alzheimer's disease (AD). Both conditions have been shown to be associated with lipid dysregulation. However, the relationship between OSA severity and alterations in lipid metabolism in the brains of patients with AD has yet to be fully elucidated. In this context, we examined the cerebrospinal fluid (CSF) lipidome of patients with suspected OSA to identify potential diagnostic biomarkers and to provide insights into the pathophysiological mechanisms underlying the effect of OSA on AD. The study included 91 consecutive AD patients who underwent overnight polysomnography (PSG) to diagnose severe OSA (apnoea-hypopnea index ≥ 30/h). The next morning, CSF samples were collected and analysed by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform. The CSF levels of 11 lipid species were significantly different between AD patients with (N = 38) and without (N = 58) severe OSA. Five lipids (including oxidized triglyceride OxTG(57:2) and four unknown lipids) were significantly correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Our analyses revealed a 4-lipid signature (including oxidized ceramide OxCer(40:6) and three unknown lipids) that provided an accuracy of 0.80 (95% CI: 0.71-0.89) in the detection of severe OSA. These lipids increased the discriminative power of the STOP-Bang questionnaire in terms of the area under the curve (AUC) from 0.61 (0.50-0.74) to 0.85 (0.71-0.93). Our results reveal a CSF lipidomic fingerprint that allows the identification of AD patients with severe OSA. Our findings suggest that an increase in central nervous system lipoxidation may be the principal mechanism underlying the association between OSA and AD.


On-chip Extraction of Intracellular Molecules in White Blood Cells from Whole Blood.
The extraction of virological markers in white blood cells (WBCs) from whole blood--without reagents, electricity, or instruments--is the most important first step for diagnostic testing of infectious diseases in resource-limited settings. Here we develop an integrated microfluidic chip that continuously separates WBCs from whole blood and mechanically ruptures them to extract intracellular proteins and nucleic acids for diagnostic purposes. The integrated chip is assembled with a device that separates WBCs by using differences in blood cell size and a mechanical cell lysis chip with ultra-sharp nanoblade arrays. We demonstrate the performance of the integrated device by quantitatively analyzing the levels of extracted intracellular proteins and genomic DNAs. Our results show that compared with a conventional method, the device yields 120% higher level of total protein amount and similar levels of gDNA (90.3%). To demonstrate its clinical application to human immunodeficiency virus (HIV) diagnostics, the developed chip was used to process blood samples containing HIV-infected cells. Based on PCR results, we demonstrate that the chip can extract HIV proviral DNAs from infected cells with a population as low as 10(2)/μl. These findings suggest that the developed device has potential application in point-of-care testing for infectious diseases in developing countries.


Novel gel formulations with catanionic aggregates enable prolonged drug release and reduced skin permeation.
The aim of this study was to investigate skin permeation rates of a drug substance when applied in novel gel formulations with catanionic aggregates. Reference gel without catanionic aggregates was compared with formulations with catanionic aggregates composed of tetracaine and either sodium dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare the effect of different gel types to elucidate if physically cross-linked, 'self-destructing' systems had benefits compared with classical, covalently cross-linked, gels. The rheological investigation showed that the interactions between the SoftCAT polymer and tetracaine/SDS aggregates were stronger than when the tetracaine/capric acid aggregates were used. The skin permeation was measured ex vivo in horizontal Ussing chambers and the permeation of tetracaine was significantly lower when formulations with tetracaine/SDS aggregates were applied (P < 0.001), but not statistically different from the reference when capric acid was used. No morphological differences could be distinguished between the skin samples exposed to the different formulations or the reference. Skin permeation was compared with silicone sheet permeation and the results indicated that silicone sheets could be used as a model of skin when using these formulations.


The Effect of Resection Margin on Local Recurrence and Survival in High Grade Soft Tissue Sarcoma of the Extremities: How Far Is Far Enough?
The significance of surgical margins after resection of soft tissue sarcomas in respect to local-recurrence-free survival and overall survival is evaluated. A total of 305 patients with deep-seated, G2/3 soft tissue sarcomas (STS) of the extremity, the trunk wall, or the pelvis were reviewed. The margin was defined according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification system (R0-2), the Union Internationale Contre le Cancer (UICC) classification (R + 1 mm) for which a margin <1 mm is included into the R1 group, and in groups of <1 mm, 1-5 mm, >5 mm, or >10 mm. Of these patients, 31 (10.2%) had a contaminated margin, 64 (21%) a margin of <1 mm, 123 (40.3%) a margin of 1-5 mm, 47 (15.4%) a margin of >5 mm, and 40 (13.1%) a margin of >10 mm. The 5-year local recurrence-free survival (LRFS) was 81.6%. Overall survival (OS) at 5 years was 65.9%. Positive margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. This finding supports use of the UICC classification. A margin of more than 10 mm did not improve LRFS or OS.


Predicting the auto-ignition temperatures of organic compounds from molecular structure using support vector machine.
A quantitative structure-property relationship (QSPR) study is suggested for the prediction of auto-ignition temperatures (AIT) of organic compounds. Various kinds of molecular descriptors were calculated to represent the molecular structures of compounds, such as topological, charge, and geometric descriptors. The variable selection method of genetic algorithm (GA) was employed to select optimal subset of descriptors that have significant contribution to the overall AIT property from the large pool of calculated descriptors. The novel modeling method of support vector machine (SVM) was then employed to model the possible quantitative relationship existed between these selected descriptors and AIT property. The resulted model showed high prediction ability with the average absolute error being 28.88 degrees C, and the root mean square error being 36.86 for the prediction set, which are within the range of the experimental error of AIT measurements. The proposed method can be successfully used to predict the auto-ignition temperatures of organic compounds with only nine pre-selected theoretical descriptors which can be calculated directly from molecular structure alone.


Assessing permanent damage to primitive hematopoietic stem cells after chemotherapy using the competitive repopulation assay.
The competitive repopulation assay was used to document the effects of six chemotherapeutic agents on primitive hematopoietic stem cells. The assay measures the relative abilities of donor cells to produce circulating erythrocytes and lymphocytes in lethally irradiated congeneic mice over a period of 6 months. Long-lasting marrow reconstitutive deficits in cells of donor origin occurred after exposure to 5-fluorouracil (5FU), bis-chloronitrosourea (BCNU), cyclophosphamide (CTX), vincristine (VCR), and actinomycin D (ACT) but not after exposure to cytosine arabinoside (ARA). Repopulating abilities were reduced after as little as a single dose of CTX or BCNU. A second dose of BCNU caused even more severe effects. A single dose of 5FU had no effect on repopulating abilities despite a temporary 10-fold reduction in marrow cell number, but multiple doses reduced the marrow stem-cell replicative ability to less than half of the normal control levels. These effects were not reliably predicted or detected by colony-forming assays or by reductions in marrow cell number. Thus, long-lasting proliferative defects in the primitive hematopoietic stem-cell (PHSC) population can result from the use of chemotherapeutic agents. Such findings may have clinical implications, especially in individuals receiving repeated or prolonged administration of these agents or in instances of marrow transplantation.


Metallothionein 1+2 protect the CNS during neuroglial degeneration induced by 6-aminonicotinamide.
6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes. Metallothionein 1+2 (MT-1+2) are neuroprotective factors in the central nervous system (CNS), and to determine the roles for MT after 6-AN, we have examined transgenic mice overexpressing MT-1 (TgMTI* mice) after an i.p. injection with 6-AN. In control mice injected with 6-AN, astrocytes in specific gray matter areas of the brainstem showed degeneration. Reactive astrocytes surrounded the degenerated areas, which were heavily infiltrated by macrophages and T lymphocytes. MT-1+2 expression was significantly decreased in the damaged brainstem areas, but it increased in reactive astrocytes surrounding these areas and also in infiltrating macrophages. The levels of oxidative stress, as determined by immunoreactivity for inducible nitric-oxide synthase (iNOS), malondialdehyde (MDA), and nitrotyrosine (NITT), and the number of terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridine triphosphate [dUTP]-digoxigenin nick end labeling-positive (TUNEL+), caspase-3+ apoptotic cells were significantly increased in the brainstem of normal mice after 6-AN. In the TgMTI* mice, the 6-AN-induced tissue damage was decreased in comparison to control mice, and they showed significantly reduced numbers of recruited macrophages and T lymphocytes, and a drastic reduction of oxidative stress and apoptotic cell death. In addition, the accompanying reactive astrogliosis was increased in the transgenic mice. To further study the potential protective role of MT, we administered intraperitoneally Zn-MT-2 to 6-AN-injected normal mice and found essentially the same results as those obtained in TgMTI* mice. Thus, we hereby report that endogenous MT-1 overexpression and exogenous MT-2 treatment have significant neuroprotective roles during CNS pathological conditions.


Transportation in the Interstitial Space of the Brain Can Be Regulated by Neuronal Excitation.
The transportation of substances in the interstitial space (ISS) is crucial for the maintenance of brain homeostasis, however its link to neuronal activity remains unclear. Here, we report a marked reduction in substance transportation in the ISS after neuronal excitation. Using a tracer-based method, water molecules in the interstitial fluid (ISF) could be specifically visualized in magnetic resonance (MR) imaging. We first observed the flow of ISF in the thalamus and caudate nucleus of a rat. The ISF flow was then modulated using a painful stimulation model. We demonstrated that the flow of ISF slowed significantly following neuronal activity in the thalamus. This reduction in ISF flow continued for hours and was not accompanied by slow diffusion into the ISS. This observation suggests that the transportation of substances into the ISS can be regulated with a selective external stimulation.


Exploring the associations between resilience, dispositional hope, preventive behaviours, subjective well-being, and psychological health among adults during early stage of COVID-19.
During the pandemic, people may experience various mental health problems. Psychological strengths may help them to cope with emerging challenges and foster mental health and well-being. This study examined the associations between resilience, dispositional hope, preventive behaviours, subjective well-being, and psychological health among adults during early stage of COVID-19. A total of 220 participants from general public participated this study completing a battery of measures (134 men [M age = 42.36 years, SD = 8.99, range = 18 to 60] and 86 women [M age = 36.73 years, SD = 7.44, range = 18 to 51]). This cross-section study indicated that resilience mediated the relationship between hope and psychological health and subjective well-being. Results also showed that hope, and resilience had significant direct effects on psychological health, and subjective well-being while preventive behaviours did not manifest a significant effect on these two variables except on resilience. Preventive behaviours mediated the relationship between hope and resilience. The results suggest that we should more pay attention to hope and resilience for the development and improvement of well-being and psychological health during the times of crisis.


Identification and characterization of a novel antigenic epitope in the hemagglutinin of the escape mutants of H9N2 avian influenza viruses.
H9N2 avian influenza virus (AIV) evolves rapidly in both genovariation and antigenicity. It is essential to monitor the change of antigenicity, in particular in the hemagglutinin (HA) protein. Here we reported the selection of antigenic variants from A/Chicken/Shanghai/F/98 (H9N2) and A/chicken/Taixing/10/2010 (H9N2) viruses using HA-specific monoclonal antibodies (MAbs). Based on the reactivity of these variant and wild-type strains with the MAbs, we identified 6 critical amino acid positions (92, 145, 166, 167, 168, and 197) in the H9 antigenic sites, including the position 92 that has never been reported. Among AIVs originated from chicken in mainland China, the rates of Gly and Arg at position 92 within BJ/94-like (A/chicken/Beijing/1/1994) lineage viruses were 62.2% (28/45) and 37.8% (17/45), respectively; whereas the rates of Gly and Arg at position 92 within Y280-like (A/duck/Hong Kong/Y280/97) lineage viruses were 0.3% (2/670) and 99.1% (673/679), respectively. Our study suggests that G92R mutation together with other identified antigenic sites may serve as molecular markers for H9N2 virus evolution, and may aid improving AIV vaccine effectiveness.


Intracranial hemorrhage from undetected aneurysmal rupture complicating transphenoidal pituitary adenoma resection.
We report a case of a 39-year-old man who presented with a nonfunctioning pituitary macroadenoma which extended into the suprasellar region. He underwent a transcranial resection of the tumor followed eight months later by transsphenoidal surgery for the residual tumor. Postoperatively he developed massive subarachnoid and intraventricular hemorrhage. A cerebral angiogram revealed a leaking anterior communicating artery aneurysm which was not seen on the computed tomography angiography and magnetic resonance angiography before the surgery. Complications of transsphenoidal surgery, particularly vascular hemorrhagic complications, and risk of rupture of undetected aneurysms are discussed.


Indicators of Hypoxia Tolerance as Determined by Cellular Elements of Rat Blood.
Although hypoxia tolerance is mainly determined genetically, it is important to study individual variability of animal organisms in order to identify the factors that underlie their tolerance to hypoxic exposure. We investigated blood cell counts and coagulograms in Wistar rats as predictors allowing the animal population to be split into hypoxia-tolerant and hypoxia-intolerant individuals. The validity of the specific predictors' choice was proved by a coincidence between the population split in accordance with the detected individual parameters and the results of testing animals in a decompression chamber at a rarefaction corresponding to the "rise to an altitude" of 11500 m above sea level. Circulating blood cells were quantitatively assessed by eighteen indicators before and after hypoxic exposure. The differences between animals low-tolerant (LT), high-tolerant (HT), and medium-tolerant (MT) to hypoxia were determined by five indicators: white blood cell count (WBC), granulocyte count (Gran#), red blood cell count (RBC), reticulocyte count/percent (RTC), and mean corpuscular hemoglobin (MCH). The RBC, RTC, and MCH values in HT rats were significantly higher than in LT animals (by 1.4, 1.9, and 1.1 times, respectively). The WBC and Gran# values in HT rats were lower than in LT individuals. The hypoxia tolerance indices (HTI) were calculated using the original formula. It was established that in LT rats, the HTI ≤ 0.203, in HT rats ≥ 0.335, and in MT rats < 0.335 but > 0.203. After testing in a decompression chamber, the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) decreased, but the fibrinogen level increased. LT rats were characterized by the lowest APTT, TT, and PT values and the highest values of the fibrinogen level. Our results indicate that one of the most important mechanisms underlying a high hypoxia tolerance in rats consists in sustaining reciprocal relationships between the complex of RBC indicators, which tend to increase under hypoxia, and Gran# indicators, which tend to decrease after hypoxic exposure.


Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor I, acid-labile subunit, and growth hormone-binding protein levels.
It is not exactly known when patients with acromegaly should be evaluated for cure after transsphenoidal adenomectomy (TA). The objective of this study was to define the optimal time point of postoperative evaluation by serial measurements of glucose-suppressed GH levels [oral glucose tolerance test (OGTT)] and the GH-dependent parameters IGF-I, free IGF-I, acid labile subunit (ALS), and GH-binding protein (GHBP). We describe a prospective study with 1-yr follow-up. The study was conducted at a university hospital. Seventeen patients with acromegaly were included in the study. The main outcome measures were OGTT results at 1, 2, 3, 8, and 12 wk after TA; weekly measured GH, (free) IGF-I, ALS, and GHBP levels up to 12 wk; and total IGF-I levels measured at 52 wk. Postoperatively, nine patients were in remission with an OGTT GH nadir of less than 0.5 microg/liter and normalized IGF-I levels, whereas eight patients had persistent acromegaly. In both cured and noncured patients, OGTT results at 1 wk after TA were highly reproducible over time. In contrast, early postoperative IGF-I levels fluctuated and only stabilized at 12 wk. In all cured patients, free IGF-I levels rapidly normalized within 2 wk after TA (specificity, 100%). Preoperative ALS levels were elevated in all patients and normalized only in the cured patients after TA (specificity, 89%). Preoperative GHBP levels were low and increased from 2 wk after surgery. We show that in the postoperative evaluation of patients with acromegaly, already 1 wk after surgery, an OGTT using 0.5 microg as the GH nadir cutoff value has a high predictive value for cure, whereas early IGF-I levels show varying patterns toward stabilization. Therefore, IGF-I should be measured as a predictive parameter not within 3 months after surgery. Free IGF-I and ALS levels may have an additional value in the postoperative assessment of disease activity.


[Anthropometric indexes of obesity as an instrument of screening for high coronary risk in adults in the city of Salvador--Bahia].
To compare some anthropometric indexes of obesity and identify among them which one best discriminates the high coronary risk (HCR). A cross-section study, with sample consisting of 968 adults, between 30 and 74 years old, being 391 (40.4%) men. Many Receiver Operating Characteristic (ROC) curves were obtained and compared to areas under them among the conicity index (C index), body mass index (BMI), waist-hip circumference ratio (WHCR), waist circumference (WC) and HCR. The sensitivity and specificity to identify and compare the best cut-off point among the many indexes of obesity to discriminate the HCR were also identified. A confidence interval of 95% was used. The largest area under ROC curve was found between the C index and the HCR, in individuals of male sex, 0.80 (0.74-0.85), significantly differing from the other indexes of obesity. In women, the largest area found under the ROC curve was 0.76 (0.71-0.81), being equal between C, WHCR and HCR indexes. Those results show that C and WHCR indexes are the best indexes of obesity to discriminate HCR. WC has intermediate discriminatory power and the BMI was the least suitable anthropometric index of obesity to discriminate HCR. Those data suggest that the indexes of abdominal obesity are better to discriminate HCR than the indexes of general obesity.


Comparison of the osseointegration of implants placed in areas grafted with HA/TCP and native bone.
This study evaluated the osseointegration of implants in areas grafted with biphasic ceramic based on hydroxyapatite/β-tricalcium phosphate (HA/TCP) and in native bone (NB). Twenty-eight rats were randomly assigned into two groups of 14 animals each: HA/TCP group: implants installed in areas grafted with HA/TCP and NB group: implants installed in areas of native bone. Bone defects were made in both tibiae of the rats belonging to the HA/TCP group and then filled with this bone substitute. After 60 days, the rats were submitted to surgical procedures for implant placement in grafted areas in both tibiae in the HA/TCP group while the implants were installed directly in native bone in the NB group. The animals were euthanized 15 and 45 days, respectively, after the implant placement. Biomechanical (removal torque), microtomographic (volume of mineralized tissues around the implants), and histomorphometric (Bone-Implant contact-%BIC and bone area between the implant threads-%BBT) analyzes were conducted to assess the osseointegration process. The HA/TCP group showed lower values of removal torque, volume of mineralized tissue around the implants, lower %BIC, and %BBT compared to the NB group in both experimental periods. Osseointegration of implants placed in grafted areas with HA/TCP was lower compared to the osseointegration observed in native bone areas. RESEARCH HIGHLIGHTS: The areas grated with HA/TCP presented poor biological conditions. The reduced biological properties for bone formation impaired the osseointegration in HA/TCP grafted areas.


Mechanisms of MHC class I-restricted antigen processing and cross-presentation.
In this review, we discuss recent data from our laboratory that address two aspects of major histocompatibility complex (MHC) class I-restricted antigen processing. First, we consider the nature of the peptide-loading complex, which is the assembly of proteins in the endoplasmic reticulum (ER) into which newly synthesized MHC class I-beta(2) microglobulin (beta(2)m) heterodimers are incorporated, and the mechanisms involved in MHC class I assembly and peptide loading that are facilitated by the peptide-loading complex. Second, we discuss mechanisms of cross-presentation, the phenomenon whereby extracellular and luminal protein antigens can be processed by antigen-presenting cells, particularly dendritic cells, and presented by MHC class I molecules to CD8(+) T cells. The focus of the discussion is mainly on the human MHC class I system.