Optimal electrical stimulation boosts stem cell therapy in nerve regeneration.
Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. The optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.


Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant.
Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). SLC26A4 is the second most frequently mutated gene in arHL. Despite the strong genotype-phenotype correlation, a significant part of cases remains genetically unresolved. In this study, we investigated a cohort of 28 Dutch index cases diagnosed with HL in combination with an EVA but without (M0) or with a single (M1) pathogenic variant in SLC26A4. To explore the missing heritability, we first determined the presence of the previously described EVA-associated haplotype (Caucasian EVA (CEVA)), characterized by 12 single nucleotide variants located upstream of SLC26A4. We found this haplotype and a delimited V1-CEVA haplotype to be significantly enriched in our M1 patient cohort (10/16 cases). The CEVA haplotype was also present in two M0 cases (2/12). Short- and long-read whole genome sequencing and optical genome mapping could not prioritize any of the variants present within the CEVA haplotype as the likely pathogenic defect. Short-read whole-genome sequencing of the six M1 cases without this haplotype and the two M0/CEVA cases only revealed previously overlooked or misinterpreted splice-altering SLC26A4 variants in two cases, who are now genetically explained. No deep-intronic or structural variants were identified in any of the M1 subjects. With this study, we have provided important insights that will pave the way for elucidating the missing heritability in M0 and M1 SLC26A4 cases. For pinpointing the pathogenic effect of the CEVA haplotype, additional analyses are required addressing defect(s) at the RNA, protein, or epigenetic level.


Altered protein acetylation in polyglutamine diseases.
Polyglutamine diseases are hereditary neurodegenerative disorders caused by the expansion of a CAG repeat in the disease gene. A dominant gain of function is associated with these expanded alleles. The resulting elongated polyglutamine repeats are thought to cause structural changes in the affected proteins, leading to aberrant interactions such as those that allow formation of extra- and intranuclear aggregates. However, self-association is not the only interaction the polyglutamine domain is capable of mediating. Many cellular proteins can be sequestered into inclusions or bound by more soluble forms of the mutant proteins. One group of proteins that binds to and whose activity may be altered by polyglutamines is Histone Acetyltransferases (HATs). HATs are responsible for the acetylation of histones and several other important proteins and this modification results in altered function of the target protein. HATs regulate cellular processes at levels as different as modifying transcriptional competence of chromosomes, temporal regulation of promoter activity and protein activation / inactivation. Recent studies show that the altered balance between protein acetylation and deacetylation may be a key process contributing to expanded polyglutamine-induced pathogenesis. The restoration of this balance is possible by the genetic or pharmacological reduction of the opposing enzyme group, i.e. the Histone Deacetylases (HDACs). Recent progress in HDAC research has made the development of inhibitors of specific HDAC family proteins possible and these compounds could be effective candidates for treatment of these devastating diseases.


Release of DNA from dead and dying lymphocyte and monocyte cell lines in vitro.
DNA is a nuclear macromolecule that circulates in the blood where its levels can reflect the activity of inflammatory and malignant diseases. While dead and dying cells have usually been considered the source of blood DNA, the mechanisms for its release during apoptosis and necrosis are not well defined. To elucidate DNA release, an in vitro model system was used, assessing DNA in the media of living, apoptotic or necrotic Jurkat and U937 cells. Apoptosis was induced by etoposide, camptothecin or staurosporine, while necrosis was induced by heating at 56 degrees C. DNA release was measured by fluorometry with the dye PicoGreen while the extent of death was measured by fluorescence-activated cell sorter analysis with propidium iodide and annexin. Apoptotic Jurkat cells released significantly more DNA in the media than untreated cells while necrotic cells did not show significant DNA release. U937 cells showed similar findings. Pretreatment of Jurkat cells with z-VAD-fmk, a caspase inhibitor, reduced both apoptosis and DNA release. By gel electrophoresis, extracellular DNA from apoptotic cells showed laddering with low molecular weight fragments. These studies suggest that extracellular release of DNA is a consequence of apoptosis and may account for some of the DNA in the blood.


[Changes in the liver after penetration of a stomach ulcer into it (experimental-morphologic study)].
Changes in the liver induced by gastric ulcer penetration were studied in 130 rats. The ulcers were reproduced by the Okaba's method. The penetration entails destruction of the liver capsule, with 4 zones being seen in the organ tissue: necrosis, demarcation, inflammation, necrobiosis and hepatocyte proliferation. Apart from the destructive processes the reparative processes in the parenchyma and in connective tissue develop already in early stages. Active proliferation of hepatocytes and biliary ducts results in the penetration into the granulation tissue of the ulcer fundus. Ulcer healing is followed by a complete recovery of the affected areas of the liver, but gastric commisures remain.


Optical coherence tomography for the detection of early macular edema in diabetic patients with retinopathy.
To compare the retinal thickness measurements with spectral-domain optical coherence tomography (OCT) in healthy subjects with those of type 2 diabetes patients with or without diabetic retinopathy (DR) and with no clinical evidence of diabetic macular edema (DME). The present prospective study included 29 diabetic patients (57 eyes) with no DR (group 1), 32 diabetic patients (63 eyes) with DR (group 2) and 25 healthy volunteers (39 eyes, control group). Eyes showing macular edema on slit-lamp biomicroscopy or leakage on fluorescein angiography were not included in the study. The mean retinal thickness at the central fixation point (CFP) and the 9 ETDRS macular regions were compared in subgroups of healthy volunteers by age, sex and right or left eye. These mean retinal thickness values were also compared in the control group, group 1 and group 2. Early DME was diagnosed with OCT if it exceeded the mean thickness +2.SD (standard deviation) in healthy subjects. Mean retinal thickness at the CFP and fovea in healthy eyes was 176 +/- 16.8 microm and 198.3 +/- 21.4 microm, respectively. It was significantly greater in men than in women (p < 0.05), decreased with age and showed no statistically significant difference between right and left eyes. Differences in retinal thickness were found to be significant for the CFP and all ETDRS regions (controls vs. group 1 and controls vs. group 2) and for the CFP, fovea, superior inner, temporal inner and nasal inner ETDRS regions (group 1 vs. group 2, group 2 having greater thickness). Early DME was diagnosed at retinal thickness exceeding 209.6 microm at the CFP and 241.1 microm at the fovea in 13 eyes of diabetic patients from group 2. Twelve eyes with early DME had mild non-proliferative DR and one--moderate non-proliferative DR. In the present study, mean retinal thickness was greater in diabetic patients (with and without DR) than in healthy subjects. Patients with DR had thicker retinas than patients without DR. Spectral-domain OCT seemed to be useful for the detection of early DME in patients with retinopathy and no clinical evidence of macular edema. Patients with early DME should have a closer follow-up


Metal concentrations in cosmetics commonly used in Nigeria.
Trace amounts of potentially toxic metals can be either intentionally added to cosmetics or present as impurities in the raw materials. In the present study, the levels of lead, cadmium, nickel, chromium, and mercury have been assessed in 28 body creams and lotions, 10 powders, 3 soaps, 5 eye make-ups, and 4 lipsticks widely available on Nigerian markets. The increases over suggested or mandated levels of lead in these creams and lotions ranged from 6.1 to 45.9 and from 1.2 to 9.2 mg kg⁻¹ when compared with Cosmetic Ingredients Review Expert Panel 2007 and German safe maximum permissible limit of lead in cosmetics, respectively. About 61% of the body cosmetics, the lotions, and the creams contained detectable levels of nickel ranging from 1.1 to 6.4-9.2 mg kg⁻¹. Chromium and mercury were undetected in 100% of the cosmetic product. Taken together, lead and cadmium were high in creams and lotions. Most of the imported creams and creamy white coloured cosmetics contained higher levels of metal contaminants than the other colours. Regulatory Agencies in developing nations should take appropriate action for cosmetics that contain lead and cadmium beyond the reference limits.


Technical Refinements in Gender-Affirming Top Surgery.
Chest masculinization is the most common gender-affirming operation performed. With increased access to care and improved insurance coverage, there has been a marked increase in the number of procedures performed. A video is presented with narration focused on the surgical technique of a "double-incision" mastectomy for gender-affirming chest masculinization. The Fisher grading scale used in technique selection of double-incision versus periareolar mastectomy, based on patient-specific anatomical parameters, is reviewed. Technical pearls for refinement of the double-incision top surgery technique for gender affirmation are then demonstrated.


Treatment of Femoropopliteal Artery In-stent Restenosis.
Femoropopliteal (FP) artery-in stent restenosis (ISR) is a daunting management problem that we continue to face. FP artery-ISR rates after primary stent implantation are relatively high. Although repeat FP artery-ISR and the need for additional interventions remain all too common, little consensus exists regarding the best treatment algorithm. In this article, we review the limitations of the currently used devices for the endovascular treatment of FP artery-ISR and discuss which strategies are the most effective and safe.


Effects of feed deprivation and transport on preslaughter blood metabolites, early postmortem muscle metabolites, and meat quality.
In practice, poultry have their feed with drawn several hours before being collected and put on transport to the slaughter plant. With the exhaustion of their internal energy stores, the chickens may lack energy to cope with the conditions to which they are subjected. Meat quality is affected by the energy stored in the muscle at time of slaughter and its rate of decrease postmortem. Of 320 broiler chickens, half were subjected to 5 h feed deprivation whereas the others had access to feed until transport. In both groups, half the chickens were transported for 1.5 h, and the rest were transported within 5 min to the on-site slaughter facility. Twenty chickens were equipped with an ultrafiltration-collection device for monitoring glucose and lactate profiles. After slaughter, liver pH was measured. Stimulation of muscle metabolism was minimized by avoiding plucking. Breast muscle samples were taken at 0, 1, 2, 4, and 6 h and analyzed for pH and metabolite concentrations, and meat quality was measured at 96 h. Although liver glycogen was depleted in feed-deprived chickens, feed deprivation and transport for short periods were not found to affect blood glucose or lactate levels nor glycogen levels in the muscle at slaughter. Muscle carbohydrate metabolism was found to come to a complete halt after 6 h, which was not caused by exhaustion of the glycogen store but by the muscle's ability to generate adenosine triphosphate (ATP) after 4 h. At this time, rigor mortis had set in and deboning could be done without risk of cold shortening.


Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure.
Tensile testing to failure was done on 235 cortical specimens that had been machined from forty-seven femora from human cadavera. The donors had ranged in age from twenty to 102 years at the time of death. After mechanical testing, the porosity, mineralization, and microstructure were determined. Linear regression analysis showed that the mechanical properties deteriorated markedly with age. Ultimate stress, ultimate strain, and energy absorption decreased by 5, 9, and 12 per cent per decade, respectively. The porosity of bone increased significantly with age, while the mineral content was not affected. Microstructural analysis demonstrated that the amount of haversian bone increased with age. Both bivariate and multivariate analyses demonstrated the importance of age-related changes in porosity to the decline in mechanical properties. Changes in porosity accounted for 76 per cent of the reduction in strength. Microstructural changes were highly correlated with porosity and therefore had little independent effect. Mineral content did not play a major role. Thus, the quantitative changes in aging bone tissue, rather than the qualitative changes, influence the mechanical competence of the bone.


Outcomes of COVID-19 Infection in People Previously Vaccinated Against Influenza: Population-Based Cohort Study Using Primary Health Care Electronic Records.
A possible link between influenza immunization and susceptibility to the complications of COVID-19 infection has been previously suggested owing to a boost in the immunity against SARS-CoV-2. This study aimed to investigate whether individuals with COVID-19 could have benefited from vaccination against influenza. We hypothesized that the immunity resulting from the previous influenza vaccination would boost part of the immunity against SARS-CoV-2. We performed a population-based cohort study including all patients with COVID-19 with registered entries in the primary health care (PHC) electronic records during the first wave of the COVID-19 pandemic (March 1 to June 30, 2020) in Catalonia, Spain. We compared individuals who took an influenza vaccine before being infected with COVID-19, with those who had not taken one. Data were obtained from Information System for Research in Primary Care, capturing PHC information of 5.8 million people from Catalonia. The main outcomes assessed during follow-up were a diagnosis of pneumonia, hospital admission, and mortality. We included 309,039 individuals with COVID-19 and compared them on the basis of their influenza immunization status, with 114,181 (36.9%) having been vaccinated at least once and 194,858 (63.1%) having never been vaccinated. In total, 21,721 (19%) vaccinated individuals and 11,000 (5.7%) unvaccinated individuals had at least one of their outcomes assessed. Those vaccinated against influenza at any time (odds ratio [OR] 1.14, 95% CI 1.10-1.19), recently (OR 1.13, 95% CI 1.10-1.18), or recurrently (OR 1.10, 95% CI 1.05-1.15) before being infected with COVID-19 had a higher risk of presenting at least one of the outcomes than did unvaccinated individuals. When we excluded people living in long-term care facilities, the results were similar. We could not establish a protective role of the immunity conferred by the influenza vaccine on the outcomes of COVID-19 infection, as the risk of COVID-19 complications was higher in vaccinated than in unvaccinated individuals. Our results correspond to the first wave of the COVID-19 pandemic, where more complications and mortalities due to COVID-19 had occurred. Despite that, our study adds more evidence for the analysis of a possible link between the quality of immunity and COVID-19 outcomes, particularly in the PHC setting.


The difference in seizure incidences between young and adult rats related to lipid peroxidation after intracortical injection of ferric chloride.
Clinical studies have shown that the incidence of early post-traumatic seizures is higher in children than in adults. It has been proposed that iron-induced lipid peroxidation plays an important role in the development of epileptogenic foci. This study examined some of the hypothesised reasons for the difference in the incidence of early post-traumatic seizures between children and adults. 12 young rats and 12 adult rats were randomised into four groups. Groups 1 and 2 were control groups, comprising six young rats and six adult rats, respectively, and they were administered an intracortical injection of saline. Groups 3 and 4 were injury groups, comprising six young rats and six adult rats, respectively, and they were administered an intracortical injection of FeCl3. All the rats were observed for six hours post-injection for the occurrence of seizures, and were then killed. The injected hemispheres were extirpated and tested for the malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity as indices of oxidative damage. Seizures were observed only in Group 3. Increased MDA levels and decreased SOD activity were observed in Group 3 (ANOVA, p-value is less than 0.001). Increased MDA levels and decreased SOD activity were significantly higher in rats with seizures (Group 3) than in those without seizures (independent t-test, p-value is less than 0.001). Different levels of lipid peroxidation induced by an intracortical ferric chloride injection may account for the different incidence rates of seizures between young and adult rats.


The prediction of gross motor outcome using cerebrovascular reserve measured by acetazolamide-challenged SPECT.
The purpose of this study was to evaluate the relationship between the recovery of gross motor function and cerebrovascular reserve (CVR) capacity measured by brain perfusion single-photon emission computed tomography (SPECT) in patients with first-ever supratentorial infarction. Gross motor function was assessed according to the locomotor and mobility subset of the functional independence measure. The CVR was measured as the difference in the regional cerebral blood flow (rCBF) after acetazolamide (ACZ)-challenged(99m)Tc-ECD perfusion SPECT from baseline rCBF. All 22 hemiplegic patients (mean age, 60.97 years) enrolled were admitted at a mean of 20.86 days from onset and received rehabilitation care for an average of 38.82 days. The recovery of gross motor function was significantly correlated with baseline rCBF and CVR of ACZ-SPECT in the areas of affected supratentorial hemisphere (r=0.447 and r=0.444, respectively, p < 0.05). Analysis of the linear regression model, adjusted for time to SPECT testing, revealed that the CVR in the affected supratentorial hemisphere was a significant predictor of the gross motor outcome (p< 0.05). In conclusion, the CVR of the affected supratentorial hemisphere may be employed along with other parameters to predict the gross motor recovery of patients with subacute infarction.


[Social role and paradigms of qualitative nursing research].
Bibliographic research developed among the 24 fascicles from the "Revista Brasileira de Enfermagem" presented in the SciELO database, from 2005 to 2008. The objective was to identify emergent themes on qualitative researches published on a nursing periodic; correlate theses themes with the knowledge production in nursing and reflect about the social role of these qualitative researches analyzed. After analysis, 173 qualitative studies were identified, and three categories arose: nursing training, areas of practice, nursing care basis/ principles/ conceptions, and professional issues. In the relationship among the categories, the patterns of knowledge and the social role highlight the social-political knowledge, reflecting the profession maturation regarding intrinsic social issues, part of it social body; and extrinsic, the demands from society.


The B11244 story: rovibrational calculations for C3H(+) and C3H(-) revisited.
New theoretical values for the rovibrational parameters of C3H(+) and C3H(-) in the ground vibrational states are reported for the quartic internal coordinate force fields constructed by Huang et al. [Astrophys. J., Lett. 768, L25 (2013)] and Fortenberry et al. [Astrophys. J. 772, 39 (2014)]. Effective spectroscopic parameters are derived from the rovibrational energies, calculated up to J = 20 for C3H(+) and J = 12 for C3H(-) by means of a computational strategy for numerically exact rovibrational computations. Our results help to resolve a disharmony between the experimental observations and previous theoretical predictions in the case of C3H(+): we show that the previously used perturbational approach is not sufficient to reliably predict relevant spectroscopic properties of C3H(+) and that the force field of Huang et al. in combination with the numerically exact rovibrational treatment in fact supports the experimental identification of C3H(+), in contrast to the original conclusion of Huang et al. and Fortenberry et al. that the astronomical assignment of the B11244 carrier to C3H(+) is incorrect.


Improvement of coronary flow velocity reserve with telmisartan in patients with autosomal-dominant polycystic kidney disease.
Endothelial dysfunction (ED) has been reported in patients with autosomal-dominant polycystic kidney disease (ADPKD). Coronary flow velocity reserve (CFVR) is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. The aim of this study was to investigate the effect of the angiotensin receptor blocker, telmisartan, on CFVR in patients with ADPKD. Thirteen patients with ADPKD and well-preserved renal function and 22 healthy controls were included in the study. CFVR was measured at baseline and after dipyridamole infusion by echocardiography. CFVR was calculated as the ratio of hyperemic to baseline average peak diastolic velocities. After the baseline evaluation of CFVR, patients started telmisartan at a dose of 80 mg/day and were followed for 12 months. CFVR was remeasured after 6 and 12 months of therapy. Patients with ADPKD had significantly lower CFVR compared to healthy subjects. CFVR increased significantly after 6 months and 12 months of telmisartan therapy (P = 0.001) in patients with ADPKD. One year of telmisartan therapy significantly improved CFVR in patients with ADPKD. This finding suggests that the stimulation of the renin-angiotensin-aldosterone system contributes to the ED in these patients.


ERP indexes of number attraction and word order during correct verb agreement production.
Successful subject-verb agreement production requires retrieving the verbal forms that agree with the features of the subject head noun and not of other nouns in the sentence. We investigate, for the first time, the electrophysiological indexes of number attraction and word order during agreement production. Twenty-four Basque native speakers were tested while producing auxiliary verbs during sentence completion of transitive sentence preambles involving singular subjects and singular or plural objects in canonical (SOV) and non-canonical (OSV) structures. ERP results yielded a larger production P2 (pP2) amplitude for mismatching than matching objects in SOV sentences, and larger negativity for OSV than SOV in number matching condition. We explain these results in terms of distinct contributions of number and word order during correct agreement production, with the pP2 indexing morphosyntactic retrieval difficulty of agreement-inflection, and the frontal negativity reflecting word order effects during monitoring the correctness of the selected verbal form.


[Postprandial plasma secretin and CCK release in patients with gastrectomy and pancreatoduodenectomy].
Postprandial plasma secretin and CCK release were investigated in patients with gastrectomy and pancreatoduodenectomy reconstructed by Billroth-I, Billroth-II, Roux-en-Y and Child's methods. Plasma secretin response were significantly decreased in patients with B-I and B-II reconstruction after gastrectomy, especially in total gastrectomized patients with Roux-en-Y reconstruction, which might be resulted from the reduced gastric acid secretion following gastrectomy. CCK release was not significantly changed in patients with various reconstructions after gastrectomy compared with control group. In patients with pancreatoduodenectomy reconstructed by Child's method plasma secretin and CCK release were significantly decreased as compared with normal controls.


Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4 serum levels, in patients with inflammatory bowel disease.
Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC). TIMP-1, TIMP-2 and TIMP-4 serum levels were determined in 53 patients with ulcerative colitis (UC), 52 patients with Crohn's disease (CD) and 50 HC, by means of commercially available enzyme-linked immunosorbent assays. The levels of TIMPs were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded. Mean serum TIMP-1 levels were 414.9 +/- 17.6 ng/mL in UC patients, 446.1 +/- 22.8 ng/mL in CD patients and 296.5 +/- 20.6 ng/mL in HC. UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC, (p < 0.0001 in both groups). Mean serum TIMP-1 levels were significantly higher in patients with active IBD (450.5 ng/mL) in comparison with patients with inactive disease (417.3 ng/mL, p = 0.03). Moreover, males showed significantly higher mean serum TIMP-1 levels (399.8 ng/mL), compared to females (368.5 ng/mL, p = 0.04). Mean serum TIMP-2 levels did not differ between UC and CD patients or HC (p > 0.05 in all cases). Mean serum TIMP-4 levels were 1761.2 +/- 67.7 pg/mL in UC patients, 1708.1 +/- 73.4 pg/mL in CD patients and 5573.4 +/- 1246.3 pg/mL in HC. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC (p = 0.008 and p = 0.02 respectively). Mean serum TIMP-4 levels were significantly lower in males (2772.9 pg/mL), compared to females (3299.0 pg/mL, p = 0.01). In addition, CRP levels showed a statistically significant correlation with TIMP-1 (r = 0.247, p = 0.01), and TIMP-4 levels (r = 0.217, p = 0.03). Similarly, there was a statistically significant correlation between SAA levels and both TIMP-1 (r = 0.264, p = 0.008) and TIMP-4 serum levels (r = 0.212, p = 0.03). An imbalance between TIMP-1 and TIMP-4 serum levels is present in IBD patients. TIMP-1 levels could be used not only for diagnostic purposes but also for the assessment of activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter.


A Critical Review on Application of Extraction Methods Prior to Spectrometric Determination of Trace-Metals in Oily Matrices.
The presence of heavy metals in oily matrices (edible oils or crude-oil and its derivatives) cannot be controlled or prevented as they occur naturally during oil genesis. However, the presence of these metal ions in oils has negative effects, because some metal ions can act as catalyst poisons, refinery corroders and environmental pollutants during refinery processes. Additionally, some metal ions have negative health impacts when consumed by living organisms. Therefore, evaluation of metal extraction methods prior to spectrometric determination is critical for monitoring of metal concentration levels and oil quality assurance purposes. It has to be noted that there are numerous reviews that have been published, which evaluates the use of direct (analysis without sample preparation) and indirect (dry and wet digestion) spectrometric determination of metals in oily matrices. Therefore, the current review focuses on evaluation of extraction methods followed by spectrometric determination of metals published from 2005 to 2020 (16 years). The acquired data shows that extraction induced by emulsion breaking (EIEB) has been the most preferred metal extraction method using Triton X-114 as a surfactant and atomic absorption spectrometer (AAS) as a detection technique.


Quantum effects on the free energy of ionic aqueous clusters evaluated by nonequilibrium computational methods.
Nonequilibrium simulation methods and rigid-body path-integral techniques are combined to estimate the relevance of protonic quantum effects in the free energy of ion-water clusters. The Crooks' fluctuation relation is used to quantitatively characterize the impact of quantum effects on the dissociation free energy of the paradigm I(-)(H(2)O)(5). By use of a rigorous smoothing procedure in the calculation of the work distributions, the effects are found to be about 11% and therefore non-negligible. Quantum effects on the potential of mean force of Na(+)(H(2)O)(12) were also evaluated using Jarzynski's work theorem for a reaction coordinate, and they were also found to be significant. The results suggest that quantization should play a significant role in the kinetics of ionic transport in aqueous environments.


[The PRINS technique. Aplication to the detection of X and Y chromosomes for follow-up of bone marrow allografts performed with an opposite sex donor].
The PRimed IN Situ synthesis is a method for rapid identification of chromosomes in metaphase or interphase on cytological preparations and frozen tissue sections, using oligonucleotide primers derived from chromosome specific subsets of repeated DNA families. PRINS technique is an alternative to fluorescence in situ hybridization, as sensitive as FISH but faster and more specific. This technique is potentially of great interest for pathologists involved in transplantation pathology or cytogenetic interphasic oncology.


Chitotriosidase: a marker and modulator of lung disease.
Chitotriosidase (CHIT1) is a highly conserved and regulated chitinase secreted by activated macrophages; it is a member of the 18-glycosylase family (GH18). CHIT1 is the most prominent chitinase in humans, can cleave chitin and participates in the body's immune response and is associated with inflammation, infection, tissue damage and remodelling processes. Recently, CHIT1 has been reported to be involved in the molecular pathogenesis of pulmonary fibrosis, bronchial asthma, COPD and pulmonary infections, shedding new light on the role of these proteins in lung pathophysiology. The potential roles of CHIT1 in lung diseases are reviewed in this article.


[Effect of somatostatin on kidney function].
The renal effect of cyclic somatostatin was studied on healthy subjects. The somatostatin was used at therapeutical dose in intravenous infusion. Somatostatin decreases the renal plasma flow, glomerular filtration rate, osmotic and free water clearances, sodium and potassium excretion and the tubular reabsorption of phosphorus while urinary osmolality increases. Under somatostatin infusion the urinary excretion of catecholamines, PGE2, PGF2 alfa and the plasma renin activity and the plasma concentration of glucagon and growth hormone decrease. The antidiuretic activity of somatostatin is due to a) a direct haemodinamic effect, b) an influence on the renal tubular transport as well and also c) because of change the water handling in the collecting ducts.


A patient acuity and staffing tool for stroke rehabilitation inpatients based on the FIM instrument.
We undertook to develop a tool based on the FIM instrument to predict the number of nursing hours required to care for stroke patients in an acute inpatient rehabilitation program. The initial study to evaluate the feasibility of using the FIM instrument revealed that the total FIM score had a strong inverse relation to the level of care indicated by the Patient Care Index (PCI) at days 1, 5, 7, 10, 15, and 20 of rehabilitation (rs = -.76 to -.87). The results warranted continued investigation of the FIM instrument as a guide for nurse staffing decisions. Based on data from the initial study, five categories of FIM score ranges were designated that demonstrated the most accuracy of placing patients at the correct level of care. Special care considerations unique to institutional settings were identified and incorporated into the tool's final format, as were the calculations to determine the amount of assistance needed. The study reported here was undertaken to evaluate the level of care indicated by the adapted tool, compared with that of the PCI, in a sample of 67 stroke admissions. Spearman correlations revealed a moderate relationship (rs = .49 to .54) between the amount of care determined by the Patient Acuity and Staffing tool and through the PCI at the first, second, and third team meetings. We conclude that the system is an effective, efficient guide for scheduling nurse staffing on the stroke rehabilitation unit.


Evolution in cardiovascular care for elderly patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE National Quality Improvement Initiative.
This study evaluated the impact of age on care and outcomes for non-ST-segment elevation acute coronary syndromes (NSTE ACS). Recent clinical trials have expanded treatment options for NSTE ACS, now reflected in guidelines. Elderly patients are at highest risk, yet have previously been shown to receive less care than younger patients. In 56,963 patients with NSTE ACS at 443 U.S. hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) National Quality Improvement Initiative from January 2001 to June 2003, we compared use of guidelines-recommended care across four age groups: <65, 65 to 74, 75 to 84, and > or =85 years. A multivariate model tested for age-related differences in treatments and outcomes after adjusting for patient, provider, and hospital factors. Of the study population, 35% were > or =75 years old, and 11% were > or =85 years old. Use of acute anti-platelet and anti-thrombin therapy within the first 24 h decreased with age. Elderly patients were also less likely to undergo early catheterization or revascularization. Whereas use of many discharge medications was similar in young and old patients, clopidogrel and lipid-lowering therapy remained less commonly prescribed in elderly patients. In-hospital mortality and complication rates increased with advancing age, but those receiving more recommended therapies had lower mortality even after adjustment than those who did not. Age impacts use of guidelines-recommended care for newer agents and early in-hospital care. Further improvements in outcomes for elderly patients by optimizing the safe and early use of therapies are likely.


Isolation of Zn2+ as an endogenous agonist of GPR39 from fetal bovine serum.
We attempted to determine natural agonists of GPR39 in fetal bovine serum (FBS). FBS was conditioned to extract peptides and fractionated by two types of HPLC. The activity of each fraction was monitored by intracellular calcium mobilization. Then the purified active ingredient was analyzed by inductively coupled plasma mass spectrometry. In this fashion, Zn2+ ion was identified as an agonist of GPR39, though no peptidergic molecules were found. The calcium-mobilizing activity of Zn2+ was not abolished by pertussis toxin but was by a phospholipase C (PLC) inhibitor, U73122, indicating that the activity of GPR39 is mediated through the Gqalpha -PLC pathway. In addition, Zn2+ also activated mouse and rat GPR39, showing that the function of GPR39 as a Zn2+ receptor is conserved across species. This study is the first exploration of GPR39 agonists in FBS and indicates that GPR39 functions as a Gq-coupled Zn2+-sensing receptor.


Study of the pest community of velvetleaf (Abutilon theophrasti Medic.).
Velvetleaf (Abutilon theophrasti Medicus 1787) is one of the most economically threatening weed plant in Hungary. Researching biological control against it, and identifying a possible and effective biocontrol agent is an important challenge, as chemical control is difficult and expensive, and there is an increasing claim to practice slight plant protection. Entomological studies were made in several parts of the world, for evaluating the species, occuring in velvetleaf, but none of these kind of experiments were assessed in Hungary. Our observations were made in field and plastic boxes, both under open field circumstances in 2008 and 2009 by visually assessing pests, netting and damage based identifying. Meanwhile 8 pest species were identified, including (Helix pomatia Linnaeus 1758--roman snale; Trialeurodes vaporariorum (Westwood 1856)--greenhouse whitefly; Oxycarenus lavaterae (Fabricius 1787)-- lime seed bug; Pyrrhocoris apterus (Linnaeus 1758)--fire bug; Rhopalus parumpunctatus Schilling 1829--common hyaline bug; Liorhyssus hyalinus--hyaline grass bug (Fabricius 1794); Mamestra brassicae (Linnaeus 1758)--cabbage moth; Helicoverpa armigera (Hübner 1808)--corn earworm). On the whole the literature datas were enlarged with four new velvetleaf pests (roman scale, lime seed bug, common hyaline bug, cabbage moth). Considering the earlier literature and our results, Liorhyssus hyalinus may play an important role on biological management of velvetleaf. However this pest considered as polyphagous, but discovered to occur in great numbers on velvetleaf, this points to the fact that can be its main host plant and by sucking on the plant, can cause decreased germination rate. We suggest the "hyaline velvetleaf bug" name istead of "hyaline grass bug". Of course, additional experiments are needed on this pest to may use safety and effectively in the future.


Accumulation of scandium in plasma in patients with chronic renal failure.
Scandium (Sc) is an element with many industrial applications, but relatively little is known about its physiological and/or toxicological effects, and very little data are available concerning the role of Sc in chronic renal failure (CRF). This paper examines the changes in plasma levels of Sc in predialysis patients with CRF and the relationship with blood parameters. The participants in this trial were 48 patients with CRF in predialysis and 53 healthy controls. Erythrocyte, haemoglobin, and haematocrit counts in blood were determined, and levels of creatinine, urea, uric acid, albumin, total protein and Sc were measured in plasma. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients were found to have higher plasma levels of creatinine, urea, uric acid, albumin, total protein, and Sc and a lower GFR than that the controls. Scandium in plasma was positively correlated with creatinine and plasma urea and negatively correlated with GFR, haemoglobin, and haematocrit and was associated with the risk of lower levels of erythrocytes, haemoglobin, and haematocrit. CRF was associated with increases in the circulating levels of scandium.


Correlation of in vitro activity and pharmacokinetic parameters with effect in vivo for antibiotics. Observations from experimental pneumococcus infection.
The correlation between in vitro activity, pharmacokinetic properties and effect in vivo of antibiotics has so far received relatively little attention, and the optimal dosing strategy for most antibiotics is still a matter of dispute. A review on this subject is presented based on observations from an experimental pneumococcus infection model in mice. The pneumococcus is particularly suitable as pathogen in experimental infection models for antibiotic research, since it is clinically relevant, susceptible to a range of antibiotics, and naturally virulent to most laboratory animals without the need for potentiating factors. The course of pneumococcus infection in animals is discussed in detail, including the parameters for measuring antibiotic effect in vivo. In screening models the most simple and relevant parameter is survival/death of the animal, which is usually incorporated in the determination of a 50% endpoint, e.g. the ED50 (50% effective dose). Among the variety of factors of potential influence upon the ED50, the importance of the bacterial growth kinetics in vivo is emphasized. Considering the correlation of pharmacokinetic properties with effect in vivo three parameters are considered important: The peak antibiotic concentration, the area under the drug concentration curve (AUC), and the time the antibiotic concentration remains above the minimal inhibitory concentration (time greater than MIC). For the beta-lactam antibiotics evidence is accumulating that the time greater than MIC is the most important. Comparing 14 cephalosporins in the mouse-protection test with intraperitoneal inoculation of a pneumococcus type 3, the time greater than MIC calculated from the pharmacokinetic profiles of a 5 mg/mouse dose for all the 14 cephalosporins showed a high correlation with the ED50. When studying the serum antibiotic concentrations at doses similar to the ED50's for various cephalosporins and penicillins, the time greater than MIC was the parameter that varied the least. Neither the peak drug concentrations nor the AUC's showed any correlation with effect in vivo. The role of the time greater than MIC in context with other factors such as extravascular penetration of antibiotics, serum protein binding and the post-antibiotic effect is discussed. Most other experimental studies concerning dosing strategy for the beta-lactam antibiotics, including the few clinical studies available, confirm the importance of the time factor. The clinical implication for this group of antibiotics therefore is to strive for a constant, not necessarily high, concentration above the MIC.(ABSTRACT TRUNCATED AT 400 WORDS)


Short-term warfarin reversal for elective surgery--using low-dose intravenous vitamin K: safe, reliable and convenient*.
Peri-procedural management of warfarin reflects an intricate balance between the restoration of haemostasis and appropriate thromboprophylaxis. This prospective single-arm study assessed the safety and efficacy of a convenient schedule, incorporating low-dose intravenous vitamin K (vitK(IV) ) for short-term warfarin reversal prior to elective surgery, as well as vitK-dependent factor levels (vitK-Factors) and International Normalized Ratio (INR) pre- and post-vitK(IV) . One seventy eight patients on long-term warfarin received 3mg vitK(IV) 12-18 h pre-procedure with no adverse reactions. 167/178 (94%) achieved an INR≤1·5 post-vitK(IV) on the day of surgery, while all achieved INR≤1·7. Four patients had procedure-associated major bleeding, but importantly had achieved a pre-procedure INR<1·5 and vitK-Factors >0·30iu/ml. No patient suffered a symptomatic thromboembolism during the 6-week follow-up. Median days to re-establish a therapeutic INR were 4 (range 2-11). VitK(IV) near normalized all vitK-Factors, with a uniform pattern of depletion and repletion in association with an increase and decrease in INR, respectively; and from the data, INR<1·5 correlated with vitK-Factors >0·30iu/ml. Low-dose vitK(IV) for short-term warfarin reversal was reliable and safe, and successfully lowered the INR to an acceptable level for planned surgery, with no excess of bleeding, thromboembolism, delayed discharge, or resistance to warfarin. The protocol was simple and convenient for both the patients and the healthcare institution.


Model studies of the role of oxygen in the FLASH effect.
Current radiotherapy facilities are standardized to deliver dose rates around 0.1-0.4 Gy/s in 2 Gy daily fractions, designed to deliver total accumulated doses to reach the tolerance limit of normal tissues undergoing irradiation. FLASH radiotherapy (FLASH-RT), on the other hand, relies on facilities capable of delivering ultrahigh dose rates in large doses in a single microsecond pulse, or in a few pulses given over a very short time sequence. For example, most studies to date have implemented 4-6 MeV electrons with intra-pulse dose rates in the range 106 -107 Gy/s. The proposed dependence of the FLASH effect on oxygen tension has stimulated several theoretical models based on three different hypotheses: (i) Radiation-induced transient oxygen depletion; (ii) cell-specific differences in the ability to detoxify and/or recover from injury caused by reactive oxygen species; (iii) self-annihilation of radicals by bimolecular recombination. This article focuses on the observations supporting or refuting these models in the frame of the chemical-biological bases of the impact of oxygen on the radiation response of cell free, in vitro and in vivo model systems.


Effect of garlic extract on blood glucose level and lipid profile in normal and alloxan diabetic rabbits.
Comparative hypoglycemic and hypolipidaemic activity of garlic (ethanol) extract and metformin was the aim of the study in 24 normal and diabetic rabbits. In group A of 12 rabbits, the influence of different doses (250, 300 and 350 mg/kg body weight) of garlic extract was evaluated, six of them were kept normal, while six were caused to be diabetic with alloxan (150 mg/kg body weight). In another group B of 12 rabbits, the influence of various doses of metformin (250, 375 and 500 mg/kg body weight) was also assessed in the similar grouping of six normal and six diabetic rabbits. The maximum hypoglycemic response was observed with highest doses of garlic extract (350 mg/kg body weight) in normal rabbits 4 h after garlic extract administration, while in diabetic rabbits, blood glucose level (270.3 ± 0.8 mg/dl) was significantly (p < 0.05) lowered as compared to the control level (303.8 ± 1.8 mg/dl). The levels of triglycerides (44.0 ± 0.9 mg/dl) and cholesterol (32.8 ± 0.7 mg/dl) also significantly (p < 0.05) decreased in normal rabbits after 4 h of extract administration as compared to that of 0 h samples (triglycerides 66.0 ± 1.5 mg/dl and cholesterol 47.5 ± 0.5 mg/dl). In diabetic rabbits, 0 h level of triglyceride and cholesterol was found to be 86.5 ± 1.1 mg/dl and 93.8 ± 0.9 mg/dl, respectively and levels seen in 4 h sample were 61.3 ± 1.2 mg/dl and 57.0 ± 1.8 mg/dl, respectively. In normal as well as diabetic rabbits, garlic extract produced hypoglycemia as well as hypolipidaemia like metformin, but the hypoglycemic effect was more pronounced with metformin, whereas garlic extract was more effective in causing hypolipidaemia as compared to metformin.


Prevalence and distribution of exposure to Schmallenberg virus in Irish cattle during October 2012 to November 2013.
Schmallenberg virus (SBV) was first identified in November 2011. It is a novel Orthobunyavirus (family Bunyaviridae) whose main ill effect is congenital malformation of the musculoskeletal and central nervous systems. It is borne by Culicoides spp., and has spread extensively in western Europe. The first case of SBV in Ireland was diagnosed in October 2012. It was anticipated that once the virus emerged in Ireland that there would be wide scale or nationwide spread over the course of the 2013 vector season. The objectives of this study were to determine the seroprevalence and distribution of exposure to Schmallenberg virus in Irish cattle from November 2012 to November 2013. Samples of brain for the pathology based surveillance were collected from malformed bovine and ovine foetuses submitted for post mortem examination. These samples were tested for SBV using RT-qPCR. Three serological surveys were carried out on sera submitted for the national brucellosis eradicartion programme. A spatial analysis of both sets of data was carried out. Between October 2012 and 10th May 2013, SBV was confirmed by RT-qPCR in brain tissues from malformed foetuses obtained from 49 cattle herds and 30 sheep flocks in Ireland. In national serosurveys conducted between November 2012 until November 2013 the herd-level and animal-level SBV seroprevalences in cattle were 53 and 36 % respectively for the first survey, 51 and 35 % for the second survey and 53 and 33 % for the third survey. The herd level seroprevalence in counties ranged from 0 to 100 %, with the counties in the south and southeast having the highest seroprevalence (>50 %), the midlands a moderate herd level seroprevalence (10-50 %) while northern and north western counties had a low herd level seroprevalence (0-10 %). There was close spatial agreement between the results of the two different targeted surveillance strategies. At the end of the 2012 vector season, there was widespread exposure to SBV among herds in southern and south eastern Ireland. During 2013, there was little or no evidence of further outward spread, unlike the situation in several other European countries. Given the lack of evidence for circulation of the virus since 2012, it is likely that the younger age cohort in herds previously exposed to SBV and substantial proportions of animals of all ages on the margins of affected areas are immunologically naïve to SBV, and would be susceptible to infection if the virus were to re-emerge.


[Effects of salinity on the survival and asexual reproduction of Aurelia coerulea polyps at different temperatures].
The scyphozoan genus Aurelia is one of the main contributors causing jellyfish blooms in global coastal waters. The population and reproduction of polyps are important factors to the outbreak of jellyfish. In this study, the effects of different salinity on the survival and asexual reproduction of Aurelia coerulea polyps were explored, which were cultured at the high (21 ℃) and low temperature (12 ℃), respectively. The results showed that more than 90% polyps could survive in the salinity range of 15-40 at the high temperature, with a range of salinity for budding being 20-32 and an optimum value of 28. The polyps were able to produce podocysts to tolerate low (≤15) and high (≥36) salinity conditions. At the low temperature, the survival rates of polyps were more than 90% in the salinity range of 20-40. The polyps could produce more buds in the salinity range of 20-32, with an optimum of 28. The salinity range of 20-40 was suitable for strobilation, with an optimum range of 28-32. It is concluded that the polyps of Aurelia coerulea can tolerate wide salinity variations, and that the salinity in a certain range has no significant influence on the asexual reproduction of polyps.


Direct Bragg-peak phase retrieval by a hybrid-input-output algorithm with proper intensity normalization.
A hybrid-input-output algorithm is applied to reconstruct hypothetical carbon cluster crystals in both two and three dimensions. It is shown that normalizing the Bragg peaks to those from a cluster of solid spheres or discs with uniform electron density can often lead to faithfully reconstructed objects at both atomic and low resolutions. It is shown that, even without the central peak, low-resolution structures can still be reconstructed with good fidelity. The effect of Bragg-peak noise on object reconstruction is examined throughout the paper. Successful reconstructions of 500- and 1000-atom carbon cluster crystal structures at both atomic and low resolutions are given.


Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated. In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC). Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects. Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells. TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase. Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT). TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation. In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients. Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration. The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively. The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells. Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin. In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.


Platinum and palladium nanoparticle-containing mixture, PAPLAL, does not induce palladium allergy.
Palladium (Pd) is a common metal found in jewellery and dental appliances, but it has been shown to be likely to cause metal allergy. We previously reported that platinum (nPt) and palladium (nPd) nanoparticle-containing mixture (PAPLAL) has both superoxide dismutase and catalase activities and that the topical application of PAPLAL improved skin atrophy induced by chronic oxidative damage in an ageing mouse model. However, the safety of PAPLAL for preventing Pd allergy remains unclear. In the present study, we investigated whether or not PAPLAL induces Pd allergy. We found that PAPLAL treatment caused no skin inflammation, while nPd administration caused only slight skin inflammation compared to the palladium chloride-induced severe reaction in an experimental metal allergy model. A gene expression analysis revealed that PAPLAL treatment significantly suppressed the expression of Inf-γ, Il-1β and Tnfα genes. Even in human clinical trials using patches containing metal nanoparticles, nPd and PAPLAL failed to induce significant skin inflammation. These results suggest that mixing with nPt in PAPLAL suppresses the inflammation response of nPd. PAPLAL can be expected to be applied to various skin treatments as a safe topical substance.


The isoelectric fractionation of hen's-egg ovotransferrin.
1. Hen ovotransferrin was examined by isoelectric fractionation. 2. The major component observed in starch-gel electrophoresis can be isolated from the minor component. 3. When non-saturating amounts of iron are added to ovotransferrin, isoelectric fractionation demonstrates the existence of three molecular species corresponding to the metal-free protein, the one-iron-atom-protein complex and the two-iron-atoms-protein complex. 4. Isoelectric fractionation of human serum labelled with (59)Fe suggests that the transferrin of normal human serum also exists as metal-free protein, the one-iron-atom-protein complex and the two-iron-atoms-protein complex. 5. It is concluded that the binding constants for the first and second iron atoms are similar.


Hemoglobin A2 (HbA2) has a measure of unreliability in diagnosing β-thalassemia trait (β-TT).
Detection of β-thalassemia trait or carriers (β-TT) depends significantly on an increase in Hemoglobin A2 (HbA2) levels, which is found at low levels (<3%) in normal healthy individuals and elevated levels (≥3.5%) in β-TT individuals. The study was designed to evaluate the reliability of the diagnostic parameter HbA2 in the differentiation of β-TT and non-β-TT in Saudis. The widely used high performance liquid chromatography (Variant II Bio-Rad) was used to measure HbA2 levels in blood. Sanger sequencing was used to screen the variation in globin genes (HBB, HBD, HBA1, and HBA2). All the study subjects were divided into βTT and non-βTT (wild) categories based on the presence or absence of HBB variations and further sub-divided into false positive, true positive, false negative, and true negative, based on HbA2 values. Out of 288 samples, 96 had HBB gene mutations. Of the 96 β-TT samples, sickle cell trait (SCT) samples (n = 58) were excluded, while the remaining (38 β-TT) were included in the detailed analysis: seven subjects with the HBB mutation had normal HbA2 (<3%), and three were borderline (3.1-3.9%). The remainder (n = 28) had an elevated HbA2 level (>4%). Based on HbA2 analysis alone, both these groups would be incorrectly diagnosed as normal. Similarly, of the 189 non-β-TT samples, 179 had normal HbA2, eight had borderline HbA2, and two had a HbA2 level above 4%. Based on HbA2 analysis alone, borderline and >4% HbA2 individuals, negative for β-TT, can be incorrectly diagnosed as carriers. Given the percentage of samples falling in the HbA2 "borderline" and "normal" categories, it can be concluded that HbA2 has a measure of unreliability in the diagnosis of β-thalassemia carriers.


Colonization with vancomycin-resistant Enterococcus faecium: comparison of a long-term-care unit with an acute-care hospital.
To compare the epidemiology of vancomycin-resistant Enterococcus faecium (VRE) in a long-term-care unit and an acute-care hospital. Point-prevalence surveys for VRE rectal colonization of patients were carried out over a 21-month period in patients in a long-term-care unit and an acute-care hospital (medical ward and intensive-care units). The environment and hands of healthcare workers also were sampled for VRE. Contour-clamped homogeneous electric field (CHEF) electrophoresis was used to evaluate possible transmission among roommates and the relatedness of patient strains to those in the environment and on the hands of healthcare workers. A 200-bed Veterans Affairs Medical Center with an attached 90-bed long-term-care unit. From December 1994 to January 1996, rectal VRE colonization of patients in the long-term-care unit increased significantly from 9% to 22%. In contrast, patients on the medical ward rarely were colonized after the first survey in December 1994, and only two intensive-care-unit patients were found to be colonized during the four surveys. The environment was contaminated persistently in the long-term-care unit. In the four surveys, carriage of VRE on hands of healthcare workers varied from 13% to 41%; 65% of healthcare workers with VRE found on their hands worked in the long-term-care unit. Seven different strains were identified by CHEF typing. Although the initial survey found only vanA strains, subsequent surveys showed vanB strains also were present. Residents of a long-term-care unit frequently were colonized with VRE, but infections were uncommon in this population. The environment of the long-term-care unit was contaminated with VRE, and VRE was found frequently on the hands of healthcare workers in this unit. Both vanA and vanB genotypes were found in this setting.


Host immune responses after administration of inactivated Venezuelan equine encephalomyelitis virus vaccines. I. Description and characterization of adoptive transfer by immune spleen cells.
Cellular immune responses after immunization with a number of inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccines were evaluated in mice by means of an adoptive transfer system. Formalin-inactivated, TC-83 strain VEE virus vaccine was immunogenic and highly effective in protecting recipient mice against challenge with virulent VEE virus. In contrast to immunization with live TC-83 VEE virus vaccine, however, immunization with inactivated VEE vaccine did not provide donor mice with the capacity to transfer adoptive immunity readily. Only when mice were immunized with inactivated VEE vaccine combined with specific adjuvants (particularly complete Freund's adjuvant or Bordetella pertussis) were donors capable of consistently transferring adoptive immunity. The total dose of inactivated VEE vaccine did not appear to influence the capacity to transfer adoptive immunity. On the other hand, weekly boosters of VEE vaccine and/or administration of vaccine with specific adjuvants did markedly influence donor immune responses.


Detection of splice junctions from paired-end RNA-seq data by SpliceMap.
Alternative splicing is a prevalent post-transcriptional process, which is not only important to normal cellular function but is also involved in human diseases. The newly developed second generation sequencing technique provides high-throughput data (RNA-seq data) to study alternative splicing events in different types of cells. Here, we present a computational method, SpliceMap, to detect splice junctions from RNA-seq data. This method does not depend on any existing annotation of gene structures and is capable of finding novel splice junctions with high sensitivity and specificity. It can handle long reads (50-100 nt) and can exploit paired-read information to improve mapping accuracy. Several parameters are included in the output to indicate the reliability of the predicted junction and help filter out false predictions. We applied SpliceMap to analyze 23 million paired 50-nt reads from human brain tissue. The results show at this depth of sequencing, RNA-seq can support reliable detection of splice junctions except for those that are present at very low level. Compared to current methods, SpliceMap can achieve 12% higher sensitivity without sacrificing specificity.


Strong interfacial coupling through exchange interactions in soft/hard core-shell nanoparticles as a function of cationic distribution.
Exchange coupled core-shell nanoparticles present high potential to tune adequately the magnetic properties for specific applications such as nanomedicine or spintronics. Here, we report on the design of core-shell nanoparticles by performing the successive thermal decomposition of Fe and Co complexes. Depending on the thermal stability and the concentration of the Co precursor, we were able to control the formation of a hard ferrimagnetic (FiM) Co-ferrite shell or an antiferromagnetic (AFM) CoO shell at the surface of a soft FiM Fe3-δO4 core. The formation of the Co-ferrite shell was also found to occur through two different mechanisms: the diffusion of Co or the growth at the iron oxide surface. The structural properties of core-shell nanoparticles were investigated by a wide panel of techniques such as HAADF, STEM and XRD. The distribution of Fe and Co elements in the crystal structure was described accurately by XAS and XMCD. The operating conditions influenced significantly the oxidation rate of Fe2+ in the core as well as the occupancy of Oh sites by Fe2+ and Co2+ cations. The structural properties of nanoparticles were correlated with their magnetic properties which were investigated by SQUID magnetometry. Each core-shell nanoparticle displayed enhanced effective magnetic anisotropy energy (Eeff) in comparison with pristine Fe3-δO4 nanoparticles because of magnetic coupling at the core-shell interface. The Co-ferrite FiM shells resulted in better enhancement of Eeff than a CoO AFM shell. In addition, the magnetic properties were also influenced by the core size. The coercive field (HC) was increased by core reduction while the blocking temperature (TB) was increased by a larger core. Element-specific XMCD measurements showed the fine coupling of Fe and Co cations which agree with Co-ferrite in each sample, e.g. the formation of a Co-doped interfacial layer in the Fe3-δO4@CoO nanoparticles.


Fetal hepatic and neural substrate utilization as affected by induced nutritional ketosis in swine.
Systemic ketosis was induced in first-parity gilts by the isocaloric substitution of glucose with 1,3-butylene glycol to supply 20% of the total dietary energy beginning on d 23 (23 BG) or d 60 (60 BG) of gestation. Ketosis reduced (P less than .05) maternal plasma glucose, urea N and insulin concentrations. Fetal carcass dry matter and carcass glycogen contents were reduced (P less than .05) by maternal ketogenic calorie substitution, whereas fetal hepatic glycogen and lipid contents were not influenced by maternal treatment. Neural acetate oxidation was reduced (P less than .05) in the 23 BG and 60 BG fetuses, with a concurrent increase (P less than .05) in beta-hydroxybutyrate (BOHB) oxidation. Neural lipogenesis measured from acetate and BOHB substrates was nominal in the d 105 pig fetus. Fetal hepatic acetate and BOHB utilization for lipogenesis were increased (P less than .05) by maternal ketosis. Reproductive performance characteristics (litter size, number stillborn and birth weight) were not improved by maternal ketosis. The substantial improvement in lactation weight gain by litters from 23 BG and 60 BG dams (20%, P less than .05) may suggest a carryover effect of gestation dietary treatment on lactation performance.


Cost-effectiveness of switching to biphasic insulin aspart from human premix insulin in a US setting.
To evaluate the cost-effectiveness of switching to biphasic insulin aspart (BIAsp 30) from human premix insulin for type 2 diabetes patients in the United States (US) setting. The previously published and validated IMS Core Diabetes Model was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over 30 years. Patient characteristics and treatment effects were based on Canadian patients included the IMPROVE observational study (n = 311). Mean glycohaemoglobin (HbA(1c)) was 8.4%, duration of diabetes 16 years and prevalence of complications high at baseline. Simulations were conducted from the perspective of a third-party payer, with costs accounted in 2008 US dollars ($). BIAsp 30 was projected to improve life expectancy by 0.202 years and QALE by 0.301 quality-adjusted life-years (QALYs), due to a reduced incidence of most diabetes-related complications. BIAsp 30 was associated with increased lifetime direct medical costs ($76,517 vs. 67,518) and an incremental cost-effectiveness ratio of $29,870 per QALY gained. Long-term outcomes were sensitive to the impact of BIAsp 30 on hypoglycaemia and changes in HbA(1c). BIAsp 30 may represent a cost-effective treatment option in the US setting for advanced type 2 diabetes patients experiencing poor glycaemic control or hypoglycaemia on human premix insulin. The application of treatment effect data derived from a Canadian cohort to the US setting was a limitation of the cost-effectiveness analysis. The findings of this cost-effectiveness analysis are not applicable to insulin-naïve diabetes patients.


Ergot alkaloids: synthetic approaches to lysergic acid and clavine alkaloids.
Covering: 2000 to 2017Ergot alkaloids are among the most important pharmaceuticals and natural toxins. Significant progress has been achieved in recent years on the research of ergot alkaloids. In this review, we re-introduced the history of ergot alkaloids. Meanwhile, we summarized all the natural products and semi-synthetic derivatives of ergot alkaloids. We also briefly described the biosynthesis and semi-synthesis of ergot alkaloid drugs from raw materials obtained by fermentation. Moreover, we reviewed the advances that have been made in the total synthesis of ergot alkaloids since 2000.


Intracranial sewing needle - accidentally inserted from a traditional cap worn by infants.
Patients with intracranial needles have rarely been reported. Several foreign bodies penetrating the cranium such as knives, nails, pencils, and wood pieces have been described in the literature. It is rare to discover a foreign body which has been inserted through either of the fontanelles before their closure in an attempted infanticide. Here we report one such rare case of intracranial sewing needle in a 24-year-old female which was accidentally inserted through the open anterior fontanelle from the traditional skull cap she was wearing during infancy. The needle was discovered incidentally on a routine skull radiograph done for a minor head injury. It was decided against any intervention to remove the needle owing to the fact that the presence of the foreign object was not causing any symptoms.


Case report: Delayed quadriplegia from traumatic carotid cavernous fistula: a rare case with perimedullary venous drainage.
Carotid cavernous fistula (CCF) refers to the abnormal arteriovenous communication between the carotid system at the skull base and the sphenoid cavernous sinus, which is caused by trauma in almost 75% of cases. The drainage of venous blood to the spinal cord represents a distinctive mechanism, which is commonly observed in dural arteriovenous fistula (DAVF), and typically manifests clinically as progressive myelopathy. However, it is a rare occurrence in clinical practice that traumatic carotid cavernous fistula (TCCF) causes delayed quadriplegia through perimedullary venous drainage. We report the case of a 29-year-old male patient who was admitted to the hospital with a sudden onset of headache and quadriplegia. The patient had previously lost his right eye in a traffic accident 5 years ago. Cerebral angiography showed a high-flow direct CCF on the right side, accompanied by obvious drainage of cerebellar and perimedullary veins. We successfully performed coil embolization for the CCF, and the symptoms of the patient gradually improved after the operation. During follow-up at sixth-months, the patient regained the ability to walk independently. We experienced a rare case of TCCF with quadriplegia. Utilizing coil embolization, we achieved successful improvement in the patient's condition. However, the mechanism and the best treatment of CCF drainage through the perimedullary vein are still unclear. We need to further explore the pathophysiological information of CCF venous drainage.


Left main and triple vessel dissection 2 months postpartum.
Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. The majority of cases reported in the literature involve a single vessel; multivessel and left main (LM) coronary artery involvement is rare. We present a case of triple vessel and LM SCAD in a postpartum patient and review the literature regarding percutaneous coronary intervention in the setting of SCAD.


Motif Discovery in Speech: Application to Monitoring Alzheimer's Disease.
Perseveration - repetition of words, phrases or questions in speech - is commonly described in Alzheimer's disease (AD). Measuring perseveration is difficult, but may index cognitive performance, aiding diagnosis and disease monitoring. Continuous recording of speech would produce a large quantity of data requiring painstaking manual analysis, and risk violating patients' and others' privacy. A secure record and an automated approach to analysis are required. To record bone-conducted acoustic energy fluctuations from a subject's vocal apparatus using an accelerometer, to describe the recording and analysis stages in detail, and demonstrate that the approach is feasible in AD. Speech-related vibration was captured by an accelerometer, affixed above the temporomandibular joint. Healthy subjects read a script with embedded repetitions. Features were extracted from recorded signals and combined using Principal Component Analysis to obtain a one-dimensional representation of the feature vector. Motif discovery techniques were used to detect repeated segments. The equipment was tested in AD patients to determine device acceptability and recording quality. Comparison with the known location of embedded motifs suggests that, with appropriate parameter tuning, the motif discovery method can detect repetitions. The device was acceptable to patients and produced adequate signal quality in their home environments. We established that continuously recording bone-conducted speech and detecting perseverative patterns were both possible. In future studies we plan to associate the frequency of verbal repetitions with stage, progression and type of dementia. It is possible that the method could contribute to the assessment of disease-modifying treatments.


Cell-nuclear accumulation of 72-kDa stress protein induced by dimethylated arsenics.
The induction and subsequent intracellular distribution of the 72-kDa heat shock (stress) protein (Hsp72) by exposure of cultured human alveolar (L-132) cells to dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, were examined. A significant induction of Hsp72 in the cells was observed by exposure to 10mM DMAA for 6 h. The induction was similar to the case by arsenite for 6 h or by heat treatment at 42 degrees C for 3h. However, the nuclear distribution of Hsp72 differed greatly between DMAA and 42 degrees C treatment or arsenite exposure, i.e., Hsp72 induced by exposure to DMAA accumulated not only in the nucleoli but also in the nucleoplasm, whereas that by 42 degrees C or arsenite exposure did not accumulate in the nucleoplasm. Furthermore, the Hsp72 accumulated in the nucleus by DMAA exposure hardly diffused with the addition of ATP, suggesting that the DMAA-induced Hsp72 strongly binds to some macromolecules in the nucleus. The fact that Hsp72 induced by DMAA exposure accumulated in the nucleus of the cells may reflect a protective response toward the nucleus-specific damaging action of dimethylarsenics.


Identification of mechano-sensitive C fibre sensitization and contribution to nerve injury-induced mechanical hyperalgesia.
C fibre hyperexcitability is fundamental to chronic pain development in humans and rodents; therefore, peripheral sensory neuronal sensitization plays a role in the development of mechanical hyperalgesia. However, the axonal properties and underlying mechanisms that are associated to these chronic pain states still require investigation. Teased fibre electrophysiology of the saphenous nerve was used to identify C fibres in naïve and nerve-injured rats. C fibres were identified using electrical stimulation which further provided conduction velocity slowing profiles. From these nerve filaments evoked responses to mechanical stimuli were recorded. Vehicle or galanin were applied directly to the saphenous nerve trunk prior to stimulation. Increased levels of mechanically evoked activity in mechano-sensitive C fibres was associated to reduced conduction failure, enhanced conduction velocity latency recovery and reduced conduction velocity slowing. Mechanical hyperalgesia developed in nerve-injured animals in which mechano-sensitive C fibres demonstrated increased mechanically evoked responses and reduced rate of adaptation. Mechano-sensitive C fibres in nerve-injured animals had reduced levels of conduction velocity slowing, enhanced rate of conduction velocity recovery and reduced firing frequency failure versus naïve animals; all hallmarks of enhanced sensory neuronal excitability. Directly applying the antinociceptive agent galanin to the saphenous nerve trunk in naive animals led to increased conduction failure, reduced latency recovery rate and increased levels of conduction velocity slowing. Nerve injury-induced enhanced neural responses to mechanical stimulation are associated to defined parameters setout by conduction velocity slowing, mediated via axonal processing. Application of galanin inhibits axonal excitability.


[Establishment of the prediction model for ischemic cardiovascular disease of elderly male population under current health care program].
To establish and verify the prediction model for ischemic cardiovascular disease (ICVD) among the elderly population who were under the current health care programs. Statistical analysis on data from physical examination, hospitalization of the past years, from questionnaire and telephone interview was carried out in May, 2003. Data was from a hospital which implementing a health care program. Baseline population with a proportion of 4:1 was randomly selected to generate both module group and verification group. Baseline data was induced to make the verification group into regression model of module group and to generate the predictive value. Distinguished ability with area under ROC curve and the predictive veracity were verified through comparing the predictive incidence rate and actual incidence rate of every deciles group by Hosmer-Lemeshow test. Predictive veracity of the prediction model at population level was verified through comparing the predictive 6-year incidence rates of ICVD with actual 6-year accumulative incidence rates of ICVD with error rate calculated. The samples included 2271 males over the age of 65 with 1817 people for modeling population and 454 for verified population. All of the samples were stratified into two layers to establish hierarchical Cox proportional hazard regression model, including one advanced age group (greater than or equal to 75 years old), and another elderly group (less than 75 years old). Data from the statically analysis showed that the risk factors in aged group were age, systolic blood pressure, serum creatinine level, fasting blood glucose level, while protective factor was high density lipoprotein;in advanced age group, the risk factors were body weight index, systolic blood pressure, serum total cholesterol level, serum creatinine level, fasting blood glucose level, while protective factor was HDL-C. The area under the ROC curve (AUC) and 95%CI were 0.723 and 0.687 - 0.759 respectively. Discriminating power was good. All individual predictive ICVD cumulative incidence and actual incidence were analyzed using Hosmer-Lemeshow test, χ(2) = 1.43, P = 0.786, showing that the predictive veracity was good. The stratified Cox Hazards Regression model was used to establish prediction model of the aged male population under a certain health care program. The common prediction factor of the two age groups were: systolic blood pressure, serum creatinine level, fasting blood glucose level and HDL-C. The area under the ROC curve of the verification group was 0.723, showing that the distinguished ability was good and the predict ability at the individual level and at the group level were also satisfactory. It was feasible to using Cox Proportional Hazards Regression Model for predicting the population groups.


Serum cholesterol levels in neutropenic patients with fever.
Hypocholesterolemia, which often accompanies infectious diseases has been suggested to serve as a prognostic marker in hospitalized patients. Even though patients with chemotherapy-induced leukopenia are at high risk of infection and mortality, only limited information is available on serum cholesterol levels in these patients. We therefore measured serum cholesterol levels in 17 patients with hematological malignancies during chemotherapy-induced neutropenia and correlated it with clinical outcome. Patients with fever (>38.5 degrees C) showed a significant decrease in serum cholesterol levels within 24 hours. Eight days after onset of the fever non-survivors had significantly lower serum cholesterol levels (median 2.09 mmol/l, range 0.49-2.79, n=6) compared to survivors (median 3.23 mmol/l, range 1.68-4.86, n=11). Cholesterol levels in survivors returned to baseline levels at the time of discharge from the hospital. At the onset of fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients, but only TNF and TNF receptor p75 levels were significantly different in survivors and non-survivors. Our data suggest that a decrease in serum cholesterol levels is a prognostic marker in neutropenic patients with fever. Release of inflammatory cytokines may in part be responsible for hypocholesterolemia in these patients.


Vascular endothelial growth factor increases the ultrafiltration coefficient in isolated intact Wistar rat glomeruli.
Vascular endothelial growth factor (VEGF) is expressed by the podocytes of renal glomeruli, and has profound influences on systemic microvascular permeability and haemodynamics. We describe an extensive refinement of a model that permits evaluation of the ultrafiltration coefficient (LpA) of isolated mammalian glomeruli, in the absence of circulating and haemodynamic influences, and tested the hypothesis that VEGF influences glomerular LpA via an effect on endothelial cells. Glomeruli were isolated by sieving Wistar rat renal cortical tissue, and individually loaded onto a suction micropipette. Flowing perifusate containing 1% bovine serum albumin (BSA) was rapidly switched to an oncopressive perifusate containing 8% BSA, eliciting transglomerular fluid efflux. The rate of the resultant reduction in glomerular volume was used to calculate glomerular LpA (1.07 +/- 0.53 nl min(-1) mmHg(-1) (mean +/-s.d.), n= 51), which compares favourably with those reported in the same rat strain using different techniques. A significant relationship between LpA and initial glomerular volume (Vi) (r= 0.72, n= 41, P < 0.0001) necessitated correction of LpA for Vi. The initial rate of change of glomerular volume, normalized for Vi, showed a strong positive correlation with applied oncotic gradient (Pearson r= 0.59, n= 28, P < 0.001), as predicted by Starling's law of filtration. A 60 min exposure of glomeruli to 1 nm VEGF increased glomerular LpA/Vi (1.19 +/- 0.19 (n= 10) to 2.23 +/- 0.33 (n= 9) min(-1) mmHg(-1) (mean +/-s.e.m.); P < 0.02). Time- and concentration-dependent relations between VEGF and LpA/Vi were observed. The VEGF-induced elevation of LpA/Vi was blocked by the selective VEGF-R2 inhibitor ZM323881. We suggest that glomerular VEGF contributes to the high physiological permeability of mammalian glomeruli to water through an action on endothelial cells.


COVID-19: UK frontline intensivists' emerging learning.
The Intensive Care Society held a webinar on 3 April 2020 at which representatives from 11 of the most COVID-19 experienced hospital trusts in England and Wales shared learning around five specific topic areas in an open forum. This paper summarises the emerging learning and practice shared by those frontline clinicians.


How well do network models predict observations? On the importance of predictability in network models.
Network models are an increasingly popular way to abstract complex psychological phenomena. While studying the structure of network models has led to many important insights, little attention has been paid to how well they predict observations. This is despite the fact that predictability is crucial for judging the practical relevance of edges: for instance in clinical practice, predictability of a symptom indicates whether an intervention on that symptom through the symptom network is promising. We close this methodological gap by introducing nodewise predictability, which quantifies how well a given node can be predicted by all other nodes it is connected to in the network. In addition, we provide fully reproducible code examples of how to compute and visualize nodewise predictability both for cross-sectional and time series data.


Ultrastructural, cytochemical, and biochemical characterization of alpha-amylase produced by human gastric cancer cells in vitro.
Ectopic production of salivary-type amylase was demonstrated in a human gastric carcinoma cell line (KMK-2) maintained in vitro for more than 3 years. Electron-dense granules, which appeared as zymogens, were observed in the tumor tissue, in cancer cells in the peritoneal fluid (from which the present cell line had been derived), and in cultured cells in early passages. These granules, however, decreased and gradually disappeared during cultivation. Although such a morphologic alteration was recognized, the property of amylase synthesis has been maintained. The presence of alpha-amylase in the cultured cells was demonstrated cytochemically by the immunoperoxidase method. The enzyme secreted and accumulated in the culture medium was partially purified and characterized. Alpha-amylase of KMK-2 cells closely resembled salivary-type amylase in gel filtration profile and disk gel electrophoresis. Immunologic cross-reaction was observed between these enzymes. Secretion into the medium was constant, and the enzyme concentration in the cytoplasm was relatively high when the cells had reached confluence. Prednisolone increased the amylase production two-fold in the cells.


Characteristics of sagittal spinopelvic alignment in patients with Parkinson's disease.
The aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD). The study included patients with idiopathic PD (aged <80 years and with abnormal posture). All patients underwent whole-spine lateral and coronal radiography. Sagittal spinopelvic alignment was evaluated using nine parameters. Motor symptoms were evaluated using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score-with bradykinesia and axial motor sub-scores. Multivariate analysis was used to analyze associations between motor symptoms and sagittal spinopelvic alignment in PD patients according to sex. The study subjects were 79 PD patients (39 men, 40 women; median age, 70 years). Clear sex-related differences were noted. In male patients, the MDS-UPDRS part III score correlated significantly with cervical sagittal vertical axis (SVA), and bradykinesia and axial motor scores correlated significantly with SVA, cervical SVA, and T1 slope. In female patients, the MDS-UPDRS part III score correlated significantly with thoracic kyphosis, bradykinesia score correlated significantly with cervical SVA and thoracic kyphosis, and the axial motor score correlated significantly with SVA, cervical SVA, T1 slope, sacral slope, and pelvic tilt. Our results showed clear correlations among various motor symptoms and sagittal global alignment in PD patients and that these correlations are different in female PD patients and their male counterparts.


Idiopathic cysts of the anterior uvea.
Idiopathic cysts of the anterior uveal tract most frequently involve the epithelial layers of the ciliary body and iris. Idiopathic cysts occur less frequently in the iris stroma. Characteristically asymptomatic, most of the cases reported in the literature have been discovered during routine eye examination by slitlamp biomicroscopy as an iris elevation. Cysts of the epithelial layers rarely enlarge to cause ocular complications. Stromal cysts, although extremely rare, appear to have a greater propensity to enlarge. The visual prognosis for patients with idiopathic anterior uveal cysts is quite good. A review of the literature and examples of these disorders are presented to emphasize the clinical characteristics and management of patients with a diagnosis of idiopathic anterior uveal cyst.


The Relationship Between Study Engagement and Critical Thinking Among Higher Vocational College Students in China: A Longitudinal Study.
Numerous cross-sectional studies have explored the correlation between study engagement and critical thinking, but the relationship between the development of these two key variables over time is unclear and the causal relationship between them remains controversial. In this study, we examined the developmental trajectories of and the interplay between study engagement and critical thinking. We used a questionnaire method to follow 654 first-year students in Chinese higher vocational college over a period of one year and three times, of which 231 (35.321%) were male and 423 (64.679%) were female, with an average age of 18.11 years. Descriptive statistics were used to present general characteristics of the study participants, and latent growth model was used to explore the developmental trajectories of study engagement and critical thinking, and to explore the interplay between study engagement and critical thinking from a developmental perspective. Based on this, a cross-lagged model was used to verify the causal relationship between study engagement and critical thinking. During the first year of higher vocational college in China, students' levels of study engagement and critical thinking declined continuously. The initial level and development of study engagement can positively influence the initial level and development of critical thinking, respectively, while the initial level and development of critical thinking can in turn positively influence the initial level and development of study engagement, respectively. Study engagement and critical thinking can predict each other. The above results help researchers and educators to develop study engagement and critical thinking in higher vocational college students from a developmental perspective. The development of either aspect of study engagement and critical thinking can contribute to the joint improvement of both.


The girl who would not sit--case report.
A 21 year old girl presented with severe fear of contamination leading to 11 hours of cleaning per day and refusal to sit down anywhere except at home or in mother's car. She also had a moderate depressive episode secondary to social stressors and further isolation due to her lack of time to socialize as cleaning was her priority. She was supported according to the biopsychosocial model of care i.e. An antidepressant (Sertraline), 1:1 psychology and alternative housing away from precipitating and perpetuating stressors. She improved significantly over 6 months, but the cultural issues and stigma continued to hinder the longer-term care plans. The importance of understanding the beliefs and customs of the Travellers' community is highlighted with this case report.


PillarX: A Microfluidic Device to Profile Circulating Tumor Cell Clusters Based on Geometry, Deformability, and Epithelial State.
Circulating tumor cell (CTC) clusters are associated with increased metastatic potential and worse patient prognosis, but are rare, difficult to count, and poorly characterized biophysically. The PillarX device described here is a bimodular microfluidic device (Pillar-device and an X-magnetic device) to profile single CTCs and clusters from whole blood based on their size, deformability, and epithelial marker expression. Larger, less deformable clusters and large single cells are captured in the Pillar-device and sorted according to pillar gap sizes. Smaller, deformable clusters and single cells are subsequently captured in the X-device and separated based on epithelial marker expression using functionalized magnetic nanoparticles. Clusters of established and primary breast cancer cells with variable degrees of cohesion driven by different cell-cell adhesion protein expression are profiled in the device. Cohesive clusters exhibit a lower deformability as they travel through the pillar array, relative to less cohesive clusters, and have greater collective invasive behavior. The ability of the PillarX device to capture clusters is validated in mouse models and patients of metastatic breast cancer. Thus, this device effectively enumerates and profiles CTC clusters based on their unique geometrical, physical, and biochemical properties, and could form the basis of a novel prognostic clinical tool.


Knowledge and attitude of radiation safety and the use of protective measures among healthcare workers in a tertiary center.
World Health Organization (WHO) reports that medical applications used in different fields account for the majority of the artificial source of radiation. Due to the high exposure to ionizing radiation, healthcare workers (HCWs) and patients are considered at high risk of suffering its harmful effects. A questionnaire survey was used to conduct a cross-sectional study that aimed to estimate the radiation safety, knowledge, attitude and the use of protective measures among HCWs in a tertiary hospital. A total of 174 participants were included in our study, the majority of them were physicians (100, 57.1%), nurses staff were 67 (38.3%), and the technicians were 8 (4.6%). Across the entire spectrum, the low level of attitude toward radiation safety was 96 (54.8%), majority of them were physicians 69 (71.9%). On the other hand, the high level of attitude toward radiation safety was 79 (45.2%), majority were nurses staff 42 (53.2%). Regarding the knowledge of radiation safety, out of all low-level attitudes, 53 (55.2%) had knowledge about the optimal thickness of the lead shield, 80 (83.3%) had knowledge about leukemia and lymphoma, 56 (58.3%) had knowledge regarding cataract, and 70 (72.9%) had knowledge regarding birth defect. Our study found that the majority of our physicians had a low attitude regarding radiation safety, although the majority of them were found to have knowledge about it. A recommendation for solid curricular application of radiation safety should be implemented in medical schools, postgraduate with continuous training, and practical courses which may help to improve the level of attitude and knowledge among HCWs regarding radiation safety.


[Cardiac performance during insulin clamp: its evaluation by bioimpedance measurement].
Ten patients with dilated cardiomyopathy, 7 ischemic heart disease and 3 idiopathic (7 males and 3 females, mean age 54.8 +/- 11 years), were studied. An insulin euglycemic clamp was performed to evaluate the influence of insulin infusion on cardiac performance. All the subjects were in NYHA functional class II-III and had an ejection fraction < 60% at a previous echocardiographic examination. They were submitted to a noninvasive continuous cardiac output monitoring by variations of thoracic impedance at three stops: a basal evaluation (T0); 1.2 mU/kg/min insulin infusion (T1); 5 mU/kg/min insulin infusion (T2). Moreover at the same times Na+, K+, hematocrit (Hct) and catecholamines were measured in the plasma. The total time required for the study was about 4 hours. Cardiac performance improved as shown by a significant increase in T1 and T2 with respect to the basal condition (T0), of ejection fraction: 57.87 +/- 11.3% (T1) vs 52.25 +/- 14.1% (T0; p < 0.01); 59.5 +/- 10.7% (T2) vs 52.25 +/- 14.1% (T0; p < 0.005); stroke volume: 2.61 +/- 0.5 l/min/m2 (T1) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001); 3.35 +/- 0.66 l/min/m2 (T2) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001) and cardiac output: 41.14 +/- 9.1 ml/m2 (T1) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.01); 46.45 +/- 8.56 ml/m2 (T2) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.001). This improvement in cardiac function was not due to an increase in preload because end diastolic volume, Hct, Na+ did not differ through the study. Similarly, afterload measured as mean blood pressure did not decrease. Cardiac function improvement was obtained in the presence of increased catecholamines. In conclusion, exogenous insulin infusion was able, in the presence of euglycemic condition, to improve cardiac performance. This improvement could be due to a direct inotropic effect of insulin perhaps mediated by its metabolic properties on cardiac muscular cells and/or by increasing the cellular intake of Ca+2.


Characterization of a reo-like virus and its isolation from and pathogenicity for parrots.
Necropsy of an African Grey parrot (Psittacus erithacus) revealed subcutaneous hemorrhages, multiple foci and microfoci of necrosis in the liver, spleen, bone marrow, and intestinal lamina propria, mild air sacculitis, and epicarditis. A virus, isolated from the liver, was non-enveloped, was polyhedral with a diameter of 84.9 +/- 3.4 nm, possessed a double-stranded RNA genome, and was stable at pH 3.0 for 30 minutes and at 56 C for up to 120 minutes. The virus was propagated in cell culture, purified by limiting dilution, and inoculated into two African Grey parrots. The experimental infections were fatal on the 8th and 9th days postinoculation in the orally and intramuscularly inoculated birds, respectively, and produced hemorrhages and necrotic lesions that recapitulated those of the index case.