Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion.
In order to assess the potential relationship between human growth hormone (GH) and body composition (BC) and natural immunity (NI), we measured the effects of exogenous GH on fat weight (FW), fat-free weight (FFW), and the cytotoxic activity of natural killer (NK) cells in women with impaired GH secretion. Mean peak serum concentrations of GH in response to L-dopa/arginine stimulation were 6.2 +/- 1.1 (SEM) ng/mL in 6 untreated subjects (US) and 5.4 +/- 1.5 ng/mL in 6 GH-treated subjects (TS). Moreover, the pretreatment circulating levels of IGF-I were low in both groups (US 684 +/- 121 mU/mL and TS 583 +/- 83 mU/mL), and they correlated with pretest levels of NK cell activity (r = .59, P less than .05) when both groups were combined. The TS were given 700 micrograms of human GH IM for an average of 14 days while the US were studied in parallel without GH treatment. As measured by hydrodensitometry or skinfold anthropometry, FW decreased (26.1 +/- 6.8 kg to 23.8 +/- 6.3 kg, P less than .05) and FFW increased (44.9 +/- 3.3 kg to 46.2 +/- 3.8 kg, P less than .05) in the TS. In the US, there were no significant (P less than .05) changes in either FW or FFW. Using a standard 51Cr release assay to measure the specific lytic (SL) activity of NK cells, mean SL activity increased from 24.4 +/- 7.0% to 44.1 +/- 8.9% (P less than .05) in the TS, whereas levels in the US were not altered significantly (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Letter to Editor Regarding the Article Entitled "Treatment Effects for Dysphagia in Adults with Multiple Sclerosis: A Systematic Review".
This letter is written to inform an important error in the methodology section of a systematic review article entitled "Treatment Effects for Dysphagia in Adults with Multiple Sclerosis: A Systematic Review" by Dalal Alali et al., which consequently resulted in a precise paradox probably and inadvertently affecting the search strategy, results, discussion, and/or conclusion of this systematic review.


Arylethynyltriazole acyclonucleosides inhibit hepatitis C virus replication.
Novel acyclic triazole nucleosides with various ethynyl moieties appended on the triazole nucleobase were synthesized efficiently using a convenient one-step Sonogashira reaction in aqueous solution and under microwave irradiation. One of the compounds, 1f, inhibited HCV subgenomic replication with a 50% effective concentration (EC(50)) of 22 microg/ml and did not inhibit proliferation of the host cell at a concentration of 50 microg/ml. A preliminary SAR study suggests that the appended phenyl ring as well as the rigid triple bond linker contributes importantly to the anti-HCV activity.


Phylogeography of a marsh herb Sagittaria trifolia (Alismataceae) in China inferred from cpDNA atpB-rbcL intergenic spacers.
Sagittaria trifolia L. is a perennial, erect herb that is confined to ponds, rice fields, ditches, and freshwater wetlands. Using chloroplast DNA (cpDNA) atpB-rbcL intergenic spacer sequences, we studied the phylogeographic pattern and demographic history of S. trifolia with 108 samples from 42 populations representing the entire geographic range in China. Twenty-seven haplotypes were characterized and two of them were widely distributed in the populations. In the minimum-spanning network, all tip haplotypes were unique to a particular population, while the interior nodes represented widespread haplotypes. Nested clade analysis (NCA) of cpDNA haplotypes indicated that long distance dispersal characterized the post-glacial recolonization of S. trifolia in China. No specific refugia areas were suggested because genetic differentiation was low among the sampled regions and among populations within regions although a large number of the haplotypes were unique to a single population. The present data support that the unique haplotypes in individual population most likely represent recent mutational derivatives after long distance dispersal rather than the relics in refugia. These results for S. trifolia represent the first phylogeographic analysis of a widespread marsh herb in China and support the importance of long distance dispersal events in the post-glacial migrations of plants.


Multiallelic polymorphism of the cartilage collagen gene: no association with osteoarthrosis.
To determine whether any of the type II collagen alleles are associated with generalised osteoarthrosis or osteoarthrosis of the finger joints in the genetically isolated Finnish population. Two patient cohorts with evidence for only primary osteoarthrosis and a cohort of healthy control subjects were selected from the Helsinki University Central Hospital and the Rheumatism Foundation Hospital in Finland. Forty one patients with primary generalised osteoarthrosis, 49 patients with osteoarthrosis of the finger joints, and 48 control subjects were included. Two markers of the type II collagen gene, a PvuII polymorphism and a VNTR polymorphism, were analysed from each subject. Four different alleles of the VNTR marker were observed and the relative risks associated with the different VNTR alleles varied between 0.39 and 1.24 among the patients with generalised osteoarthrosis and between 0.67 and 2.33 among the patients with osteoarthrosis of the finger joints. The PvuII polymorphism detected two different alleles and the associated relative risks were 0.82 and 1.82 for the patients with generalised osteoarthrosis, and 1.04 and 0.96 for the patients with osteoarthrosis of the finger joints. A major predisposing allele of the type II collagen gene as the causative factor for osteoarthrosis could be excluded in this population. A spectrum of mutations associated with different alleles of this gene could not be excluded, however. Further, these two forms of cartilage disease can be caused by gene defects with reduced penetrance and the effect of such an allele is easily masked under the high frequency of normal alleles.


Phencyclidine-induced activation of ventral tegmental A10 dopamine neurons is differentially affected by lesions of the nucleus accumbens and medial prefrontal cortex.
The nucleus accumbens and medial prefrontal cortex contain high concentrations of phencyclidine (PCP) binding sites as well as supply inhibitory and excitatory inputs to the ventral tegmental area (VTA). Thus these two regions could be instrumental in mediating the unique bimodal response of A10 neurons to systemically administered PCP. Therefore we evaluated electrophysiologically the effects of lesions of these two areas on this pattern of response. In sham-lesioned controls, i.v. injections of PCP elicited a typical dose-dependent bimodal effect which was characterized by an activation of A10 firing at low dose (reaching a maximum of +44% at 1 mg/kg) followed by a slowing of this response with larger doses. However, in animals with kainic acid or radiofrequency lesions of the nucleus accumbens, PCP produced only a unimodal response resulting in sustained and elevated (+88% in kainate and +55% in radiofrequency lesioned groups) firing rates. Notably, neither basal activity nor the degree of activation of the A10's at doses of PCP less than 1 mg/kg were affected by the lesions. In contrast, excitotoxic destruction of the medial prefrontal cortex had no effect on the response of A10 neurons to PCP even though basal activity was slightly elevated in this group. These results suggest that the inhibitory component of the bimodal response of VTA neurons to systemic PCP is mediated via feedback pathways from the nucleus accumbens, but that the mesocortical prefrontal cortex does not appear to modulate any portion of this bimodal response.


A Comparative Study of Endoscopic Assisted Powered Adenoidectomy Versus Conventional Adenoidectomy.
Adenoidectomy is one of the most common procedures performed in children today, either alone or in conjunction with tonsillectomy or insertion of ventilating tubes. The present study was planned to compare the endoscopic powered adenoidectomy versus conventional adenoidectomy. The present prospective observational randomized study was carried out in the Department of Otorhinolaryngology of a tertiary care teaching hospital of Rajasthan. Fifty patients with adenoid hypertrophy in the age group between 5-13 years were enrolled in the study and divided in to two groups viz. cases undergoing conventional adenoidectomy using curettage method (group A = 25) and cases undergoing endoscopic powered adenoidectomy (group B = 25). Intra operative time, primary bleeding, completeness of adenoid removal, depth of resection, and collateral damage were noted intra operatively in both the groups. Postoperative pain, recovery time, postoperative complications were also compared. Intra operative time taken in Group A was 25.6 ± 2.90 min while it was 35.04 ± 5.24 min in Group B. (p < 0.0001) Average blood loss in Group A was 18.4 ± 4.72 ml compared to an average blood loss of 29.32 ± 2.59 ml in Group B. (p < 0.0001) The postoperative recovery time in Group A was 4.93 days and it was 3.06 days in group B. (p = 0.00). The present study concluded that newer method of endoscopic powered adenoidectomy was found to be a safe and useful tool for adenoidectomy in terms of completeness of resection, better control of depth of resection and minimal collateral damage intra-operatively and less postoperative pain, complications and fast recovery period. The online version contains supplementary material available at 10.1007/s12070-023-03633-4.


An outbreak of acute rheumatic fever in a remote Aboriginal community.
We describe the public health response to an outbreak of acute rheumatic fever (ARF) in a remote Aboriginal community. In August 2021, the Northern Territory Rheumatic Heart Disease Control Program identified an outbreak of acute rheumatic fever in a remote Aboriginal community. A public health response was developed using a modified acute poststreptococcal glomerulonephritis protocol and the National Acute Rheumatic Fever Guideline for Public Health Units. 12 cases were diagnosed during the outbreak; six-times the average number of cases in the same period in the five years prior (n=1.8). Half (n=6) of the outbreak cases were classified as recurrent episodes with overdue secondary prophylaxis. Contact tracing and screening of 11 households identified 86 close contacts. This outbreak represented an increase in both first episodes and recurrences of acute rheumatic fever and highlights the critical need for strengthened delivery of acute rheumatic fever secondary prophylaxis, and for improvements to the social determinants of health in the region. Outbreaks of acute rheumatic fever are rare despite continuing high rates of acute rheumatic fever experienced by remote Aboriginal communities. Nevertheless, there can be improvements in the current national public health guidance relating to acute rheumatic fever cluster and outbreak management.


No association of endometriosis with glutathione S-transferase M1 and T1 null mutations in a Japanese population.
Endometriosis is inherited as a complex trait, which means that multiple susceptibility genes interact with each other and with environmental factors to produce the phenotype. We investigated the frequency of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) null mutations in women with endometriosis in a Japanese population. One hundred fourteen unrelated women with endometriosis were enrolled. Samples of umbilical cord blood obtained from 179 female newborn infants were used as population controls. Genomic DNA isolated from endometriosis patients and controls were subjected to multiple polymerase chain reactions to determine the GSTM1 and GSTT1 genotypes. There were no significant differences in the frequencies of the GSTM1 (P = .83, odds ratio 0.95) and GSTT1 (P = .24, odds ratio 0.75) null mutations between endometriosis patients and controls. The endometriosis group was divided into a subgroup of stage IV disease only, but no statistically significant differences were observed in the frequency of the GSTM1 null mutation (P = .88, odds ratio 0.96, 95% confidence interval 0.57-1.63) and the GSTT1 null mutation (P = .33, odds ratio 0.77, 95% confidence interval 0.45-1.30) between any of these groups and the controls. These findings suggest that the GSTM1 and GSTT1 null mutations are not likely to be associated with an increased risk of endometriosis in a Japanese population.


[Monoclonal gammopathies of undetermined significance and their progression over time. Retrospective study of 190 patients].
Monoclonal gammopathies of undetermined significance (MGUS) occur in up to 1% of persons aged 50 years or older. The risk of its progression to multiple myeloma or related disorders is also approximately 1% per year. Our study had two aims: to describe the risk of malignant progression of patients examined in our center for MGUS, and to identify predictors of this malignant progression. We retrospectively reviewed the medical records of patients with MGUS seen in our center from 1980 through 1995. Information about progression came either from the medical file or from responses to questionnaires sent to patients' general practitioners. The study included 190 patients. Median follow-up was 84 months (range: 12-240 months). MGUS remained stable for 128 patients (67.37%), whose median follow-up was 96 months. Malignant transformations occurred in 41 patients (21.58%). The median interval from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 49 months. The cumulative probability of progression was 13.05% at 5 years and 25.14% at 10 years. The initial concentration of serum monoclonal protein was a significant predictor of progression (threshold value: 15 g/L). The cumulative probability of progression in our study is higher than that observed elsewhere. Our results may well be biased by the short follow-up period and selective referrals. The initial concentration of serum monoclonal protein is a significant predictor of malignant progression of MGUS.


Minor chromosome variations and selected heteromorphisms in 200 unclassifiable mentally retarded patients and 200 normal controls.
Lymphocyte chromosome preparations from 200 mentally retarded children and 200 normal adult controls were analyzed by G-, Q-, and C-banding techniques for minor chromosome variations (G and Q) and selected heteromorphisms (G and C). Minor variations scored included inv(9), prominent or decreased short arms and/or satellites on acrocentric chromosomes, and 17 ph. C heteromorphisms analyzed included those involving 1qh, 9zh, and 16zh regions. Length variations of Yq were scored on G-banded karyo types. No significant differences in frequencies of scored minor variations or heteromorphisms were noted between the retarded and control populations.


Investigation of JAK1 and STAT3 polymorphisms and their gene-gene interactions in nonspecific digestive disorder of rabbits.
Acting in a cellular signaling pathway, Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) play critical roles in several kinds of physiological and pathological responses, including inflammatory response. In this study, we detected three coding single nucleotide polymorphisms (cSNPs) of JAK1 and four cSNPs of STAT3 in New Zealand White rabbits. We analyzed their association with genetic resistance to nonspecific digestive disorder (NSDD) based on a case-control study (253 cases and 227 controls). The rabbits were genotyped for c.1421 C>T and c.3036 G>A in JAK1 using restriction fragment length polymorphisms and for c.831 T>C and c.399 G>A of STAT3 using high-resolution melting technology. The frequencies of the alleles and genotypes differed significantly between the case and control groups (P<0.05). The case-control association analysis revealed that in JAK1, allele C increased the risk of NSDD (OR: 1.60, 95% CI 1.166-2.185, P=0.003), whereas allele A played a potentially protective role against NSDD (OR: 0.74, 95% CI 0.572-0.952, P=0.019). We used five inheritance models to evaluate the importance of the associated genotypes. Under the dominant inheritance model, the association analysis suggested that the CT/TT genotype increased the risk of NSDD (OR: 1.65, 95% CI 1.13-2.40, P=0.009). A haplotype analysis showed that allele H2 (the two cSNPs: CG; OR: 1.354, 95% CI 1.050-1.747, P=0.019) markedly increased the risk of the disorder. The association analysis revealed that in STAT3, allele G played a potentially protective role against NSDD (OR: 0.74; 95% CI 0.569-0.951; P=0.019), whereas allele C increased the risk of NSDD (OR: 1.37; 95% CI 1.059-1.760; P=0.016). Recessive inheritance was shown to be the best fitting model for c.399 and c.831. Under the recessive inheritance model, the association analysis suggested that the G/G genotype increased the risk of NSDD (OR: 1.73; 95% CI 1.07-2.80; P=0.025). A haplotype analysis showed that H1' (the two cSNPs: AC; OR: 1.365; CI 1.059-1.760; P=0.016) significantly increased the risk of the disorder. The CATMOD program (SAS 9.2) and the multifactor dimensionality reduction method were used to analyze the genetic interactions between JAK1 and STAT3. Data on the genetic interactions revealed that the JAK1 and STAT3 risk alleles described above contribute to NSDD susceptibility in combination with each other, and that model (c1421, c3036, c831) was the best model (OR: 2.7262; 95% CI: 4.7408-5.1986; P<0.0001). To our knowledge, this is the first report of the genetic polymorphisms of the JAK1 and STAT3 genes and their associations with the incidence of NSDD in rabbits.


Studies with different types of visual analog scales for measurement of pain.
We compared the sensitivity of different types of visual analog scales and of descriptive pain terms in healthy volunteers and in postoperative patients. One hundred and seven volunteers marked visual analog scales according to their perception of the descriptive pain terms--little, mild, some, moderate, severe, agonizing. Individual variation in values and preferences between the five following five different visual analog scales were analyzed: 10-cm linear horizontal and vertical scales, a curvilinear scale, and graded horizontal and curvilinear scales. Significantly more volunteers preferred the horizontal scale with gradations. Scores for the vertical linear scale had the greatest coefficient of variation and were least normally distributed. The majority of volunteers considered the phrase "agonizing pain" the best term defining the extreme limit of pain (X2(12) = 41.8, P less than 0.001). There were significant changes in the values of pain intensity measured on visual analog scales by patients using the same descriptive pain term on successive observations. However, the patients' values for pain terms in the preoperative pain-free state were not significantly different from those during postoperative pain. We conclude that graded linear horizontal scales are both more reliable and preferred by participants and that visual analog scales give a more sensitive and accurate representation of pain intensity than do descriptive pain scales.


Comparison of magnetic wire navigation with the conventional wire technique for percutaneous coronary intervention of chronic total occlusions: a randomised, controlled study.
Wire crossing of a chronic total coronary occlusion (CTO) is time consuming and limited by the amount of contrast agent and time of radiation exposure. Magnetic wire navigation (MWN) might accelerate wire crossing by maintaining a coaxial vessel orientation. This study compares MWN with the conventional approach for recanalization of CTOs. Forty symptomatic patients with CTO were randomised to MWN (n = 20) or conventional approach (n = 20) for antegrade crossing of the occlusion. In the intention-to-treat analysis, MWN showed a shorter crossing time (412 versus 1131 s; p = 0.001), and, consequently, lower usage of contrast agent (primary endpoint 42 versus 116 ml; p = 0.01), and lower radiation exposure (dose-area product: 29 versus 80 Gy*cm(2); p = 0.002) during wire crossing compared to the conventional approach. Accordingly, in the per-protocol analysis, the wire-crossing rate was, in trend, higher using the conventional approach (17 of 31) compared to MWN (9 of 28; p = 0.08). The use of MWN for revascularisation of CTOs is feasible and reduces crossing time, use of contrast agent, and radiation exposure. However, due to a broader selection of wires, the conventional approach enables wire crossing in cases failed by MWN and seems to be the more successful choice.


Assessing the performance of thermally crosslinked amorphous solid dispersions with high drug loadings.
Continuing what previous studies had also intended, the present study aims to shed light on some unanswered questions concerning a recently introduced class of high drug loading (HD) amorphous solid dispersions (ASDs), based on the in-situ thermal crosslinking of poly (acrylic acid) (PAA) and poly (vinyl alcohols) (PVA). Initially, the effect of supersaturated dissolution conditions on the kinetic solubility profiles of the crosslinked HD ASDSs having indomethacin (IND) as a model drug, was determined. Subsequently, the safety profile of these new crosslinked formulations was determined for the first time by evaluating their cytotoxic effect on human intestinal epithelia cell line (Caco-2), while their ex-vivo intestinal permeability was also studied via the non-everted gut sac method. According to the obtained findings, the in-situ thermal crosslinked IND HD ASDs present similar kinetic solubility profiles when the dissolution studies are conducted with a steady sink index value, regardless of the different dissolution medium's volume and the total dose of the API. Additionally, the results showed a concentration- and time- dependent cytotoxicity profile for all formulations, while the neat crosslinked PAA/PVA matrices did not elicit cytotoxicity during the first 24 h, even at the highest examined concentration. Finally, the newly proposed HD ASD system, resulted in a remarkably increased ex-vivo intestinal permeability of IND.


Characterization of elements, PAHs, AhR-activity and pro-inflammatory responses of road tunnel-derived particulate matter in human hepatocyte-like and bronchial epithelial cells.
The aims were to characterize the content of elements and polycyclic aromatic hydrocarbons (PAHs) in size-separated particulate matter (PM) sampled in a road tunnel, estimate the contribution of PAHs to the toxic potential, and measure the pro-inflammatory potential of PM samples and extracts with increasing polarity. Several elements/metals previously associated with cytokine responses were found. Based on PAHs levels and published PAHs potency, the calculated mutagenic and carcinogenic activities of size-separated samples were somewhat lower for coarse than fine and ultrafine PM. The AhR-activity of the corresponding PM extracts measured in an AhR-luciferase reporter model (human hepatocytes) were more similar. The highest AhR-activity was found in the neutral (parent and alkylated PAHs) and polar (oxy-PAHs) fractions, while the semi-polar fractions (mono-nitrated-PAHs) had only weak activity. The neutral and polar aromatic fractions from coarse and fine PM were also found to induce higher pro-inflammatory responses and CYP1A1 expression in human bronchial epithelial cells (HBEC3-KT) than the semi-polar fractions. Fine PM induced higher pro-inflammatory responses than coarse PM. AhR-inhibition reduced cytokine responses induced by parent PM and extracts of both size fractions. Contributors to the toxic potentials include PAHs and oxy-PAHs, but substantial contributions from other organic compounds and/or metals are likely.


Decomposing the urban-rural inequalities in the utilisation of maternal health care services: evidence from 27 selected countries in Sub-Saharan Africa.
There has been a substantial improvement in reducing maternal mortality in the Sub-Saharan African region. The vast rural-urban gap in maternal health outcomes, however, is obscured by this average achievement. This study attempts to measure the contribution of identified risk factors to describe the average rural-urban difference in the use of antenatal care, health facilities for delivery, and health professional assistance at delivery. To achieve this objective, we used descriptive analysis and Fairlie non-linear decomposition method to quantify covariates' contribution in explaining the urban-rural difference in maternal healthcare services utilisation. The study's finding shows much difference between urban and rural areas in the use of maternal healthcare services. Socio-economic factors such as household wealth index, exposure to media, and educational level of women and their husbands/partners contributed the most in explaining the gap between urban and rural areas in healthcare services utilisation. Interventions to bridge the gap between urban and rural areas in maternal healthcare services utilisation in Sub-Saharan Africa should be centred towards socio-economic empowerment. Government can enforce targeted awareness campaigns to encourage women in rural communities in Sub-Sharan Africa to take the opportunity and use the available maternal health care services to be at par with their counterparts in urban areas.


Evaluation of the healing potential of Nile tilapia skin collagen in traumatic oral ulcers in male rats.
To evaluate the healing potential of Nile tilapia skin collagen using a rat model with experimentally induced traumatic oral ulcers. Male Wistar rats were segregated into three experimental groups (n = 8/group/euthanasia day). Ulcers were induced using a dermatological punch on the left buccal mucosa. The rats were then euthanized on days 1, 5, 10, 15, and 20 (ntotal=120 rats). Each group received topical treatment, 2x/day, with 1 % Nile tilapia skin collagen orabase (experimental group), only orabase (negative control), or Oncilom-A® orabase (positive control). Ulcer area, closure percentage, and body mass variation were measured. Slides were prepared for histological analysis, which included Picrosirius red staining (collagen analysis), and immunohistochemistry (platelet endothelial cell adhesion molecule, alpha-smooth muscle actin, and transforming growth factor-beta). On day 15, the experimental and positive control groups displayed smaller ulcer areas, a higher percentage of closure, complete re-epithelialization, superior histological repair scores, and a reduced count of polymorphonuclear cells in comparison to the negative control group (p < 0.05). Additionally, the experimental group exhibited an increased number of blood vessels, total collagen (types I and III) and expression of platelet endothelial cell adhesion molecule, alpha-smooth muscle actin, and transforming growth factor-beta relative to the negative and positive control groups (p < 0.05). By day 20, the experimental group showed a more significant weight gain compared to the other groups (p < 0.0001). Nile tilapia skin collagen orabase optimizes the healing of traumatic ulcers by stimulating re-epithelialization, angiogenesis, and collagenesis. Transforming growth factor-beta plays a significant role in this process.


Screening for syphilis with dual algorithms: analysis of discordant and concordant serology results in a population with a low prevalence of syphilis.
Currently, many laboratories have switched the traditional screening algorithm (TSA) to reverse screening algorithm (RSA) for the efficiencies in high-volume syphilis screening. However, confusions have been arisen regarding this paradigm shift. To compare the performance of two algorithms with head-to-head mode. Sera screening for syphilis were tested in parallel with chemiluminescence immunoassay (CIA) and toluidine red unheated serum test (TRUST). CIA-reactive sera from the RSA were reflexively tested with TRUST and confirmed with Treponema pallidum particle agglutination assay (TPPA), while the TRUST-reactive serology from the TSA were afterwards tested with TPPA. A total of 110 663 serum samples were screened. The RSA identified 2259 (2.0%) CIA-reactive results, of which 377 (16.7%) showed TPPA nonreactive results, while the TSA identified 934 (0.8%) TRUST-reactive results, of which 67 (7.2%) showed TPPA-nonreactive results. Among the 2259 CIA-reactive results, 1392 (61.6%) were TRUST-nonreactive, of which 350 (25.1%) were TPPA-nonreactive. A total of 182 sera from the 350 TPPA-nonreactive sera were further tested by a second CIA (VITROS Syphilis TPA, VITROS TPA), of which 155 (85.2%) were nonreactive and 27 (14.8%) were reactive. The 27 VITROS TPA-reactive sera were further tested with a treponemal Western blot assay (Euroimmun IgG Western Blot, EuroWB), of which 11 (41%) were indeterminate, 6 (22%) were nonreactive and 10 (37%) were reactive. Among the 10 EuroWB-reactive sera, two seroconverted to TPPA 1:80+/- after 1-year follow-up. Of 867 CIA-reactive/TRUST-reactive results, 27 (3.1%) were TPPA-nonreactive. The RSA identified more patients with reactive treponemal serology. However, it also yielded an increased likely false-reactive rate compared with the TSA, especially those results with low index values and TRUST-nonreactive serology, were necessary to retest with a second treponemal test. Further testing results with TPPA, VITROS TPA and EuroWB suggested the false-reactive CIA screening results and the likely false-nonreactive TPPA results when the reactive treponemal results screened with RSA were to be identified.


Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity.
Submicrometer magnetic particles, ingested by cells and monitored via the magnetic fields they generate, provide an alternative to optical microscopy for probing movement and viscosity of living cytoplasm, and can be used for cells both in vitro and in vivo. We present methods for preparing lung macrophages tagged with magnetic particles for magnetometric study. Interpretation of the data involves fitting experimental remanent-field decay curves to nonlinear mechanistic models of intracellular particle motion. The model parameters are sensitive to mobility and apparent cytoplasmic viscosity experienced by particle-containing organelles. We present results of parameter estimation for intracellular particle behavior both within control cells and after (a) variable magnetization duration, (b) incubation with cytochalasin D, and (c) particle twisting by external fields. Magnetometric analysis showed cytoplasmic elasticity, dose-dependent motion inhibition by cytochalasin D, and a shear-thinning apparent viscosity.


Features of p53 protein distribution in the corneal epithelium and corneal tear film.
Tumor suppressor protein p53 is the key factor in the regulation of cell proliferation. Its concentration is low in the cytoplasm of most cell types. However, in corneal epithelium cells, abnormally high p53 content is detected. The aim of the present study was to characterize p53 distribution in the corneal epithelium. For this purpose, immunohistochemistry, western blot analysis and electronic microscope examinations were performed. A low level of p53 was identified in the lens, iris and retina; by contrast, a significantly high concentration of this protein was observed in the corneal epithelium. In opposite, MDM2 was identified in the lens, iris and retina while it is completely absent in the corneal epithelium. In addition, we found a significant amount of exosomes and other microvesicles containing p53 in the corneal mucin layer. We thus hypothesize that a significantly high level of p53 was caused by a combination of absents of MDM2 in parallel with p53 microvesicles storage.


The relationship between glycan structures and expression levels of an endoplasmic reticulum-resident glycoprotein, UDP-glucose: Glycoprotein glucosyltransferase 1.
In this article, we report a relationship between glycan structures and expression levels of a recombinant ER-resident glycoprotein, uridine 5'-diphosphate-glucose: glycoprotein glucosyltransferase (UGGT1). The function of glycan structures attached to a glycoprotein is actively studied; however, the glycan structures of recombinant, and not endogenous, glycoproteins have not been examined. In this study, we indicate a relationship between the glycan structure and the level of protein expression. Expression levels were controlled utilizing a series of vectors (pFN21K, pFN22K, pFN23K, and pFN24K HaloTag CMV Flexi Vectors). Qualitative and semi-quantitative confirmation of glycan structures was achieved with tandem mass spectrometry. The results of this study indicate that glycan structures are similar to endogenous glycans at low expression levels.


Metabolic syndrome in adolescence: can it be predicted from natal and parental profile? The Prediction of Metabolic Syndrome in Adolescence (PREMA) study.
There are well-established predisposing factors for the development of metabolic syndrome (MetS) in childhood or adolescence, but no specific risk profile has been identified as yet. The Prediction of Metabolic Syndrome in Adolescence (PREMA) study was conducted (1) to construct a classification score that could detect children at high risk for MetS in adolescence and (2) to test its predictive accuracy. In the derivation cohort (1270 children), data from natal and parental profile and from initial laboratory assessment at 6 to 8 years of age were used to detect independent predictors of MetS at 13 to 15 years of age according to the International Diabetes Federation definition. In the validation cohort (1091 adolescents), the discriminatory capacity of the derived prediction score was tested on an independent adolescent population. MetS was diagnosed in 105 adolescents in the derivation phase (8%), whereas birth weight <10th percentile (odds ratio, 6.02; 95% confidence interval, 2.53-10.12, P<0.001), birth head circumference <10th percentile (odds ratio, 4.15; 95% confidence interval, 2.04-7.14, P<0.001), and parental overweight or obesity (in at least 1 parent; odds ratio, 3.22; 95% confidence interval, 1.30-5.29, P<0.01) were independently associated with diagnosis of MetS in adolescence. Among adolescents in the validation cohort (86 [8%] with MetS), the presence of all these 3 predictors predicted MetS with a sensitivity of 91% and a specificity of 98%. The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing MetS in adolescence.


Infliximab chimaeric anti-tumour necrosis factor alpha monoclonal antibody treatment for patients with myelodysplastic syndromes.
Tumour necrosis factor alpha (TNF-alpha) is believed to play a major role in apoptotic death of bone marrow cells in myelodysplastic syndromes (MDS). We explored the efficacy and safety profile of infliximab chimaeric anti-TNF-alpha monoclonal antibody treatment in two MDS patients. They both had low-/intermediate-risk MDS, isolated anaemia and elevated circulating levels of TNF-alpha. Infliximab produced no adverse side-effects and resulted in sustained erythroid responses, one major and one minor. Laboratory studies indicated a remarkable decrease in the percentage of apoptotic stem cells in the bone marrow. This preliminary report indicates that infliximab may have an application as MDS therapy and warrants further investigation.


Bilateral agenesis of the internal carotid artery: case report and approach to management.
We present the case of a 13-year-old boy who presented with two episodes of acute onset severe headache. Initial investigation with computerised tomography revealed no apparent abnormality. Magnetic resonance imaging and magnetic resonance angiography revealed that this boy had absence of both internal carotid arteries bilaterally. Absence of the internal carotid arteries is an uncommon condition, but does occur with unilateral absence being more common than bilateral absence. The condition is usually diagnosed in adulthood but may be diagnosed incidentally in childhood. When diagnosed in childhood, the main aim of management is to prevent the development of cerebrovascular accidents.


Prokaryotic K(+) channels: from crystal structures to diversity.
The deep roots and wide branches of the K(+)-channel family are evident from genome surveys and laboratory experimentation. K(+)-channel genes are widespread and found in nearly all the free-living bacteria, archaea and eukarya. The conservation of basic structures and mechanisms such as the K(+) filter, the gate, and some of the gate's regulatory domains have allowed general insights on animal K(+) channels to be gained from crystal structures of prokaryotic channels. Since microbes are the great majority of life's diversity, it is not surprising that microbial genomes reveal structural motifs beyond those found in animals. There are open-reading frames that encode K(+)-channel subunits with unconventional filter sequences, or regulatory domains of different sizes and numbers not previously known. Parasitic or symbiotic bacteria tend not to have K(+) channels, while those showing lifestyle versatility often have more than one K(+)-channel gene. It is speculated that prokaryotic K(+) channels function to allow adaptation to environmental and metabolic changes, although the actual roles of these channels in prokaryotes are not yet known. Unlike enzymes in basic metabolism, K(+) channel, though evolved early, appear to play more diverse roles than revealed by animal research. Finding and sorting out these roles will be the goal and challenge of the near future.


Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system.
The bacterial human pathogen Helicobacter pylori produces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. The cagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagIN) prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagIC with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagIC were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagIC plays a key role in cagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cagT4SS, a crucial risk factor for gastric cancer development.


Simultaneous PET/MR body imaging in rats: initial experiences with an integrated PET/MRI scanner.
We recently developed an integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) (iPET/MRI) scanner for small animals, which had relatively large field-of-view (FOV) covering up to the size of a rat body. The purpose of this study was to report results of simultaneous PET/MRI of a rat body using this scanner with some radiotracers. C-11-methionine (MET), F-18-fluorodeoxyglucose (FDG), or F-18-sodium fluoride (NaF) was injected as a radiotracer for PET portion in addition to gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid, a hepatobiliary contrast agent, for MRI portion. Simultaneous PET/MRI was performed in normal rats. PET, MRI, and co-registered fusion images were evaluated regarding image quality and feasibility for rat imaging studies. MET uptake was clearly shown in the liver and pancreas, which was confirmed with magnetic resonance (MR) and fused PET/MR images. PET/MR images depicted intense FDG uptake in the brain, Harderian glands, and myocardium. NaF uptake was observed in all bones and joints within FOV, except in ribs, which was well recognized with the help of MR and fused PET/MR images. This study demonstrated that simultaneous PET/MRI with an integrated dual-modality molecular imaging scanner was a feasible technique for imaging studies targeting on a rat body. However, further developments including attenuation correction methods are required to use this technique routinely in rat imaging studies.


Enhanced induction of LPS-induced fibroblast MCP-1 by interferon-gamma: involvement of JNK and MAPK phosphatase-1.
IFN-gamma has significant immunoregulatory activity and plays an important role in both innate and adaptive immunity. Additive effects of IFN-gamma and the Toll-like receptor ligand LPS has been investigated in macrophages, but in fibroblasts is incompletely understood. IFN-gamma and LPS synergistically induced MCP-1 and NO release in primary murine dermal fibroblasts. IFN-gamma enhanced LPS-induced JNK and p38 MAPK phosphorylation but had no effect on NF-kappaB activity. The induction of both MCP-1 and NO was attenuated by inhibition of JNK but not p38 MAPK. Serine 727 STAT1 phosphorylation by IFN-gamma was increased by LPS, and this was also attenuated by inhibition of JNK but not p38 MAPK. IFN-gamma inhibited the basal expression of MAPK phosphatase-1, a negative regulator of MAPK signaling pathway. These results suggest that enhancement of LPS-induced JNK activation by IFN-gamma associated with inhibition of MAPK phosphatase-1 may be one of the mechanisms of additive effects between IFN-gamma and LPS in fibroblasts.


LNA functionalized gold nanoparticles as probes for double stranded DNA through triplex formation.
Nanoparticle modified LNA probes have been used for colorimetric identification of double stranded DNA via parallel triplex formation, eliminating the need for prior denaturation of the target duplex.


Introducing Cysteines into Nanobodies for Site-Specific Labeling.
We have developed a generally applicable methodology for cysteine mutagenesis of nanobody (Nb) framework region serine residues. This strategy allows for subsequent labeling with thiol-reactive compounds without disrupting Nb antigen binding. We provide a protocol for production, labeling, and affinity determination of cysteine-engineered Nbs (cys-Nbs) with Alexa Fluor 488-maleimide and the mercury compound para-chloromercuribenzoic acid (PCMB). Alexa Fluor 488- and PCMB-labeled cys-Nbs can be used for immunofluorescence microscopy and experimental phasing in crystallography, respectively.


MiR-140-5p inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion through targeting TLR4.
This study was aimed to investigate the effects of miR-140-5p on the proliferation and inflammatory cytokines secretion of rheumatoid arthritis synovial fibroblasts (RASFs). Synovial tissue samples from 23 rheumatoid arthritis (RA) patients and 18 normal synovial tissue samples were collected. The RASFs were isolated and cultured. Then, miR-140-5p and TLR4 expression in both synovial tissue and RASFs were detected using the quantitative real-time PCR (qPCR) and western blot. Dual luciferase reporter gene assay was employed to evaluate the interaction between miR-140-5p and 3'UTR of TLR4. Western blotting and qPCR were used to examine TLR2 expression after upregulation or downregulation of miR-140-5p in RASFs. After RASFs co-infected with TLR4 overexpression lentivirus and lentivirus containing miR-140-5p or miR-control respectively, the cellular proliferation and secretion of IL-6 and IL-8 level were detected through the MTS assay and enzyme-linked immunosorbent assay, respectively. MiR-140-5p was significantly down-regulated, and TLR4 was significantly up-regulated in synovial tissue samples from 23 RA patients and RASFs. Dual luciferase activity assay showed that miR-140-5p could specifically bind to the 3'UTR of TLR4. Down-regulation or up-regulation of miR-140-5p not only significantly increased or decreased the expression of TLR4, but also could promote or inhibit RASF proliferation and secretion of IL-6, and IL-8 in RASFs. Furthermore, overexpression of TLR4 can reverse the inhibitory effects of miR-140-5p on proliferation and inflammatory cytokines release of RASFs. MiR-140-5p could inhibit the proliferation and secretion of IL-6 and IL-8 through regulation of TLR4 expression.


Boba sign with a twist - A variant presentation of a mature cystic teratoma complicated by torsion and rupture.
While mature cystic teratomas are relatively common ovarian neoplasms typically comprising of multiple embryologic cell types, a specific monodermal subtype involving thyroid tissue, struma ovarii, can rarely be seen. This case reviews typical imaging characteristics with MRI and ultrasound of struma ovarii and details possible complications from these masses with intraoperative and histologic correlation.


Prevalence of IgG antibodies against the severe acute respiratory syndrome coronavirus-2 among healthcare workers in Tennessee during May and June, 2020.
SARS-CoV-2 seroprevalence was low (<1%) in this large population of healthcare workers (HCWs) across the state of Tennessee (n=11,787) in May-June 2020. Among those with PCR results, 81.5% of PCR and antibody test results were concordant. SARS-CoV-2 seroprevalence was higher among HCWs working in high-community-transmission regions and among younger workers. These results may be seen as a baseline assessment of SARS-CoV-2 seroprevalence among HCWs in the American South during a period of growth, but not yet saturation, of infections among susceptible populations. In fact, this period of May-June 2020 was marked by the extension of renewed and sustained community-wide transmission after mandatory quarantine periods expired in several more populous regions of Tennessee. Where community transmission remains low, HCWs may still be able to effectively mitigate SARS-CoV-2 transmission, preserving resources for populations at high risk of severe disease, and these sorts of data help highlight such strategies.


Evaluation of propofol and medetomidine-ketamine for short-term immobilization of Gulf of Mexico sturgeon (Acipenser oxyrinchus de soti).
Parenteral anesthetic protocols for short-term immobilization were evaluated in twenty 4-yr-old Gulf of Mexico sturgeon (Acipenser oxyrinchus de soti). An initial dose-response trial determined the efficacy of either propofol (3.5-7.5 mg/kg. i.v.) or combinations of medetomidine (0.03-0.07 mg/kg, i.m.)-ketamine (3-7 mg/kg, i.m.). A subsequent study evaluated the physiologic effects of propofol (6.5 mg/kg, i.v.)-induced anesthesia and anesthesia induced with a medetomidine (0.06 mg/kg, i.m.)-ketamine (6 mg/kg i.m.) combination. The effects of medetomidine were reversed at 30 min with atipamezole (0.30 mg/kg, i.m.). Both drug protocols provided adequate short-term immobilization for minor diagnostic procedures. Sturgeon receiving propofol were in a light plane of anesthesia within 5 min after drug administration, whereas only 30% of the medetomidine-ketamine group reached a light plane of anesthesia in the same time period. Both propofol and medetomidine-ketamine resulted in mild bradycardia and apparent respiratory depression, with propofol producing more profound effects. At the dosages used in this study, both propofol and the medetomidine-ketamine combination effectively induced a light plane of anesthesia. Induction times were shorter in the propofol group.


Impact of Anxiety on Health-Related Quality of Life and Symptoms of Burnout in Multi-Professional Residents in Brazil During the COVID-19 Pandemic.
We aimed to determine the prevalence of anxiety and to identify associated factors among multi-professional residents in Brazil during the early days of the COVID-19 pandemic. A cross-sectional study included a sample of 752 multi-professional residents selected by snowball technique. Symptoms of anxiety were measured by the Beck anxiety inventory scale (≥ 16 cut-off). We used WHOQOL-BREF to access the health-related quality of life and the Maslach Burnout Inventory to measure the burnout syndrome. PR and respective 95% confidence intervals (CI) were calculated using the Poisson regression model. The prevalence of anxiety was 41.2% (310/752). Some variables were strongly associated with anxiety: afraid of getting COVID-19; extra work demand during COVID-19 pandemic; sweating/wheezing/increased heart rate during work; feeling safe when using personal protective equipment at work, and psychological support from residence preceptors. Residents with symptoms of anxiety showed high emotional exhaustion at work (36.6 ± 9.6 vs. 24.7 ± 10.7, P = 0.001) and depersonalization (8.9 ± 6.0 vs. 5.6 ± 4.9, P = 0.001). Correlations coefficients between emotional exhaustion versus Physical WHOQOL-BREF and between emotional exhaustion versus Psychological WHOQOL-BREF were significantly lower among residents without anxiety (P = 0.027 and P = 0,03, respectively). The prevalence of anxiety was high and strongly associated with several variables, particularly with being afraid of getting COVID-19, the perception of workload, somatization (sweating, wheezing and increased heart rate during work), feeling unsafe when using personal protective equipment, and lack of psychological support from residence preceptors. Anxiety was associated with increased emotional exhaustion and depersonalization and low health-related quality of life during the COVID-19 pandemic in Brazil. Low WHOQOL-BREF environment domain, and high emotional exhaustion MBI domain increased the chances of presenting symptoms of anxiety.


The silver-silver chloride electrode: a possible generator of offset voltages and currents.
Large input currents can be generated by an asymmetry in the chloride activity seen by Ag-AgCl electrodes used at the input of intracellular amplifiers because offset compensation no longer takes place at the input of the amplifier but rather later in the circuit in many modern amplifiers. This situation occurs when chloride-free solution, such as potassium acetate, potassium citrate or various intracellular dyes are used as pipette and electrode holder filling solutions. Omitting the agar bridge at the reference electrode, or using a platinum electrode will have similar results. Values of cellular membrane potentials can be significantly contaminated under such conditions, particularly where the amplifier input resistance did not exceed 10(10) omega and where small cells were studied. Unexpected iontophoresis of Cl- can occur when the asymmetry is such as to make the recording pipette negative. These offsets can be avoided in all situations by the use of salt bridges which insure that the two Ag/AgCl junctions are in contact with Cl- of the same activity.


Comparative analysis of existence form for selenium and structural characteristics in artificial selenium-enriched and synthetic selenized green tea polysaccharides.
In recent years, selenium-enriched polysaccharides (Se-PS) have been paid more and more attention, and the activity of many Se-PSs has been studied but little on their structure. This study aimed to investigate the activity, structural characterization and present forms of selenium in two different artificial selenium-enriched tea polysaccharides (Se-TPS). The physicochemical analysis showed that both CSe-tps1 and ASe-tps1 were acidic heteropolysaccharides with different monosaccharide composition, molar ratio, and selenium content. Structural investigations including FT-IR, Raman spectra and 1D, 2D NMR analysis revealed that selenium in CSe-tps1 replaced the hydroxyl group at the C-6 position in the polysaccharide with the form of selenyl ester, while most of the selenium in ASe-tps1 replaced the hydroxyl group at the C-1 and C-6 position in the form of the SeH bond on the branch of the polysaccharide. Besides, a series of studies on the structural characteristics of the Congo red test, I2-KI reaction, FESEM, DSC, and XRD analysis showed that the two artificial Se-TPSs had a triple helix structure and more branches. However, there were significant differences in crystal morphology, apparent morphology, heat release ability, and the α-glucosidase inhibition activity. These results indicated that the difference in artificial selenization methods not only made the polysaccharide exhibit different structural characteristics and the hypoglycemic activity, but also had a significant effect on the form of selenium in polysaccharides.


Short-term intravenous fish oil and pediatric intestinal failure associated liver disease: 3-year follow-up on liver function and nutrition.
Intravenous fish oil (FO) has changed the management of intestinal failure associated liver disease (IFALD). This report describes two IFALD patients who received FO for 5 and 10 months, respectively and reports on their 3-year follow-up.


The energetic costs of tail autotomy to reproduction in the lizard Coleonyx brevis (Sauria: Gekkonidae).
Energy reserve utilization and energy budgets were compared in tailed and tailless adult female Coleonyx brevis. Carcass, fat body and caudal energy reserves were used for vitellogenesis; mass and energy content (cal/mg and/or cal/reserve) of each were significantly lower at oviposition than at the initiation of vitellogenesis. Total energy reserves accounted for 53% of the reproductive energy investment in tailed females compared to 29% in tailless females. Tailed females had over twice as many reserve calories for egg production than tailless females. Caudal energy reserves represented 60% of the total reserves of tailed females and were one-third greater than the total energy reserves of tailless females. To produce a clutch of eggs both tailed and tailless females supplemented energy reserves with net metabolizable energy that was available after metabolic costs were paid. Tailless females had a significantly greater rate of food ingestion and more net metabolizable energy available for reproduction than tailed females, yet allocated significantly fewer calories/day to reproduction than tailed females, primarily because of the loss of caudal reserves. Reproductive efforts of tailed and tailless females were equivalent. However, the loss of caudal reserves resulted in the production of eggs that were significantly lower in mass and energy content (cal/mg and cal/egg) than when caudal reserves were used. Results empirically support the hypothesis that reproduction has energetic priority over tail regeneration in short-lived, iteroparous species with a low probability of future reproductive success.


Home-based aerobic exercise in patients with lacunar stroke: Design of the HITPALS randomized controlled trial.
The effects of physical exercise in patients with lacunar stroke, seem promising in secondary prevention and only few studies have investigated the effect of high-intensity interval training in patients with lacunar stroke. This study will be investigating whether high-intensity interval training improves cardiovascular fitness as well as cognitive- and endothelial function and potentially attenuating the risk of recurrent stroke. A randomized controlled trial evaluating 12 weeks of home-based, high-intensity interval training compared with usual care. The intervention group will be exercising 15 min a day, 5 days a week, for 12 weeks. Outcomes will be evaluated at baseline, three, six and twelve months post-stroke with 'The Graded Cycling Test with Talk Test' as the primary outcome registered as power output in Watts. Additionally, an annually register-based follow-up will be performed for 5 years from date of inclusion with a composite endpoint of cardiovascular disease or death. Secondary outcomes will be: physical activity, endothelial response, mental well-being, cognition, mood, fatigue, stress, and MRI scan. This study is going to show if early initiated home-based high-intensity interval training is feasible and effective in patients with lacunar stroke. A self-chosen aerobic exercise modality allows a realistic implementation of practice, together with greater chance of long-term adherence. A limitation of the study is that recruitment bias cannot be ruled out, as there may be a preferential enrolment of patients who are self-motivated to engage in exercise.


Spatial scale analysis for the relationships between the built environment and cardiovascular disease based on multi-source data.
To examine what built environment characteristics improve the health outcomes of human beings is always a hot issue. While a growing literature has analyzed the link between the built environment and health, few studies have investigated this relationship across different spatial scales. In this study, eighteen variables were selected from multi-source data and reduced to eight built environment attributes using principal component analysis. These attributes included socioeconomic deprivation, urban density, street walkability, land-use diversity, blue-green space, transportation convenience, ageing, and street insecurity. Multiscale geographically weighted regression was then employed to clarify how these attributes relate to cardiovascular disease at different scales. The results indicated that: (1) multiscale geographically weighted regression showed a better fit of the association between the built environment and cardiovascular diseases than other models (e.g., ordinary least squares and geographically weighted regression), and is thus an effective approach for multiscale analysis of the built environment and health associations; (2) built environment variables related to cardiovascular diseases can be divided into global variables with large scales (e.g., socioeconomic deprivation, street walkability, land-use diversity, blue-green space, transportation convenience, and ageing) and local variables with small scales (e.g., urban density and street insecurity); and (3) at specific spatial scales, global variables had trivial spatial variation across the area, while local variables showed significant gradients. These findings provide greater insight into the association between the built environment and lifestyle-related diseases in densely populated cities, emphasizing the significance of hierarchical and place-specific policy formation in health interventions.


Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease.
To investigate the levels of glutathione transferase (GST), a protective enzyme against aldehydes, and especially 4-hydroxynonenal (HNE) in the brain and ventricular CSF of autopsied AD and normal control subjects. Studies have implicated increased levels of oxidative stress in the brain in the pathogenesis of AD. Decreased levels of polyunsaturated fatty acids and increased levels of markers of lipid peroxidation have been reported in the brain in AD, particularly in areas severely affected in the disease. HNE, one marker of lipid peroxidation, is neurotoxic in neuronal culture and in vivo and is elevated in AD brain and CSF. We measured levels of GST activity and protein in multiple brain regions and ventricular CSF in short-postmortem-interval AD patients and age-matched prospectively evaluated control subjects. A decrease in GST activity in all brain areas was observed in AD compared with controls with significant decreases in the amygdala, hippocampus and parahippocampal gyrus, inferior parietal lobule, and nucleus basalis of Meynert. Levels of GST protein also were depleted in most brain regions in AD. A significant decrease in GST activity and protein levels was also found in ventricular CSF in AD. Reduced levels of GST, a protective mechanism against HNE, may have a role in the pathogenesis of neuron degeneration in AD.


Effect of hippotherapy on gait symmetry in children with cerebral palsy: A pilot study.
We aimed to investigate the effect of hippotherapy on gait symmetry in children with cerebral palsy (CP). Twelve children with Gross Motor Function Classification System (GMFCS) levels II-IV received weekly hippotherapy lesson for 1 year. Gait analyses were performed during a 5-m walking test, using a portable, tri-axial accelerometer-based motion recorder. The baseline symmetry index derived from the Lissajous index (LI) figure before hippotherapy was greater than the LI in age-matched normal subjects (P < 0.01). Hippotherapy was associated with a decreased LI (-10.4 ± 4.9%, P = 0.018) and an improved GMFCS score (-0.6 ± 0.7, P = 0.02). These data suggest that hippotherapy has a beneficial effect on symmetry of the trunk movement in children with CP.


Tissue-specific expression of genes encoding apolipoprotein E and apolipoprotein A-I in rabbits.
We determined the site of synthesis of apolipoprotein (apo) E and apo-A-I in rabbit by measuring in vitro translational activity of their mRNAs from the liver and from the intestine. Poly(A+) RNA isolated from liver and intestinal epithelium of rabbits fed either a chow diet or a cholesterol-rich diet was translated in vitro in the rabbit reticulocyte lysate system using [35S] methionine as the labeled precursor. Newly synthesized apolipoproteins were immunoprecipitated with specific antisera and quantitated after electrophoresed on 10% polyacrylamide slab gels in the presence of 0.2% sodium dodecyl sulfate. The levels of liver apo-E and apo-A-I mRNAs from chow-fed rabbits are 0.41 and 0.002% of total translatable mRNA, respectively. The level of liver apo-A-I mRNA in the rabbit is approximately 500-fold lower than the reported level of apo-A-I mRNA in rat and human livers. Rabbit intestinal apo-E and apo-A-I mRNAs levels are 0.0036 and 0.67%, respectively. Our results indicate that in rabbits apo-E is synthesized primarily in the liver and that apo-A-I is synthesized primarily in the intestine. When rabbits are fed a cholesterol-rich diet, liver and intestinal apo-E in mRNA levels and intestinal apo-A-I mRNA levels are not changed. In contrast, the liver apo-A-I mRNA level increases 5-fold in response to the cholesterol-rich diet. However, because the intestinal liver apo-A-I mRNA level is so low, the 5-fold induction only increases liver mRNA levels to 2.7% of the corresponding intestinal apo-A-I mRNA level.


Serum levels of soluble CD23 in patients with bullous pemphigoid.
In this study, we tested the serum levels of soluble CD23 (sCD23) in 27 bullous pemphigoid (BP) patients and compared them with the disease activity. Soluble CD23 is the cleaved portion of the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) which has an affinity for IgE and regulates IgE synthesis. Although bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgG class autoantibodies against the basement membrane of stratified squamous epithelia, several IgE-related phenomena have been reported. Recently, we have shown that Fc epsilon RII-expressing and IgE-bearing cells are detectable in the lesional skin and concluded that an IgE-Fc epsilon RII/CD23 system may be involved in the pathogenesis of this disease. The serum level of sCD23 in BP patients was significantly higher than healthy controls (p < 0.01). In 11 out of 12 patients, the alteration of serum sCD23 levels correlated well with the disease activity. Thus the serum level of sCD23 is useful as a new parameter for assessing the level of disease activity in BP. High levels of sCD23 may represent part of an IgE-mediated immune reaction which may play a role in the pathogenesis of BP.


PowerSlicing to determine fluorescence lifetimes of water-soluble organic matter derived from soils, plant biomass, and animal manures.
Time-resolved fluorescence spectroscopy was used to characterize water-soluble organic matter (WSOM) which plays an important role in soil ecosystem processes. WSOM was extracted from plant biomass, animal manures, and soils from controlled cropping systems studies with known histories of organic amendments. Lifetime constants were derived using the multi-way PowerSlicing method which provides a non-iterative, multi-exponential fitting of decay profiles. The lifetimes obtained by PowerSlicing were not significantly different from those obtained using the traditional discrete components analysis. The three components attributed to WSOM had lifetimes of 0.38 +/- 0.14, 2.11 +/- 0.72, and 7.08 +/- 1.18 ns which are in agreement with previous lifetimes reported for humic substances. This study provides further support for the new paradigm for the structure of soil organic matter where the organic matter is composed of low-molecular-weight components held together by hydrogen bonding and hydrophobic interactions.


Low-Profile Cartilage Repair With Knotless All-Suture Anchors: Surgical Technique.
Osteochondral and pure chondral lesions of the knee are common after patellar dislocations. There are multiple described techniques for the fixation of these lesions, including metallic screws, bioabsorbable screws, bioabsorbable implants, and suture devices. The purpose of this article is to describe a surgical technique for surgical fixation of a lateral condyle chondral lesion using knotless all-suture anchors, with second-look knee arthroscopy illustrating healing of the cartilage repair.


Prison health services: a utilization study.
A prospective study of health service utilization carried out in the Correctional Services of Canada (CSC), Pacific Region, is reported. Health service encounters occurring at the six Regional Institutions with on-site health care centers between May 29th and June 28th, 1984 were surveyed using a health clinic encounter form. There were 7,449 encounters during the study period. The mean rate of encounters was 5.2 per inmate. Seventy-two percent of these encounters occurred at wickets, and 28% occurred at clinics. Physician visits occurred at a mean estimated annual rate of 6.7 visits per year. This is 2.4 times higher than the mean annual physician visit rate for non-institutionalized men in Canada. The reason for visits was new illness (57%), chronic illness (31%), injuries (5%), psychosocial problems (2%), and administrative (5%). The encounter rate per 100 inmates varied from 19.7 to 1,203.6 across the institutions studied. Overall 89% of all visits were seen by health service nurses, while 11% were seen by physicians. Using ICHPPC-2 Defined, the ten most common complaints presented to the health service were headache, sore throat, stomach complaint, other respiratory complaint, tension headache, limb pain, other/not codable, medical examination, back pain and upper respiratory tract infection. These ten complaints accounted for 4896 (59%) of the total complaints recorded. The majority of visits took less than five minutes, were most often treated with medication, and did not require scheduled follow-up. The 50 most frequent visitors, those making 25 or more visits during the study period, while only 3.5% of the study population, accounted for 25% of all encounters.


Treatment recommendations of hospital-acquired pneumonia in Asian countries: first consensus report by the Asian HAP Working Group.
Many different treatment options are available for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), which are important causes of morbidity and mortality. Although guidelines for the diagnosis and treatment of HAP and VAP have been published by various American and European societies, these guidelines may not be applicable in all respects to the diagnosis and treatment of HAP and VAP in Asian countries. In addition, clinical practice may vary among Asian countries, due to such factors as availability of specific antibiotics and formulations and their relative cost. In addition, and in particular, different epidemiologic, etiologic, and resistance patterns in Asian countries may affect treatment choices compared with those in Western countries. To address these issues, the Asian-Pacific Research Foundation for Infectious Diseases, together with the Asian Network for Surveillance of Resistant Pathogens, organized the Asian HAP Working Group to discuss current clinical practices and develop consensus treatment recommendations for HAP in Asian countries. The consensus treatment recommendations, summarized herein, represent the findings of an expert panel comprising 30 representatives from 10 Asian countries.


Three-Dimensionally Planned and Printed Patient-Tailored Plates for Corrective Osteotomies of the Distal Radius and Forearm.
We evaluated the 1-year postoperative clinical and patient-reported outcomes in patients who had a 3-dimensional planned corrective osteotomy of their distal radius, radial shaft, or ulnar shaft using a printed, anatomical, patient-tailored plate to determine the feasibility and effectiveness of this methodology. Simulations in computer-assisted preoperative planning of corrective osteotomies resulted in 3-dimensionally printed surgical guides, surgical models, and anatomically customized plates for application at the distal radius and forearm. Patients with malunions of the distal radius or forearm who underwent fixation with the custom-made plates were documented in our registry. Grip strength and range of motion assessments were made before surgery (baseline), as well as at 6 weeks and 3 and 12 months. Additionally, patients rated their wrist-related pain and disability using the Patient-Rated Wrist Evaluation. Fifteen patients underwent corrective surgery, and the 1-year follow-up data of 14 patients with a median age of 56 years (interquartile range, 24-64 years) were available for analysis. The median baseline Patient-Rated Wrist Evaluation score improved from 47 to 7 after 1 year. The flexion-extension arc of motion of the wrist increased from 90° at baseline to 130° at 1 year and the pronation-supination arc of motion of the wrist increased from 135° to 160° in the same time period. Differences in radiological measurements for palmar and radial inclinations, as well as for ulnar variance between the affected and contralateral wrists, were reduced with the osteotomy. In 1 case, the plate was removed 11 months after the osteotomy. No severe adverse events were reported. Three-dimensionally planned and printed patient-tailored plates offer a reliable method for correcting even complex malunions of the distal radius and forearm. Therapeutic IV.


Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice.
Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Our goals were to establish a murine model of human equivalent GLE and to determine dose-response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Peak [BPb] were < 1, < or = 10, 24-27, and 33-42 microg/dL in control, low-, moderate- and high-dose GLE groups at PN0-10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose-response toxicant exposure should be a component of the neurotoxic risk assessment process.


Adsorption and mechanistic study of the invasive plant-derived biochar functionalized with CaAl-LDH for Eu(III) in water.
Herein, we developed the invasive plant-derived biochar (IPB) functionalized with CaAl-LDH at five mass ratios using a physical mixture method, assessed their adsorption perform for Eu(III), and explored the relative mechanisms. Results show that the IPB successfully loaded CaAl-LDH in five composites and their Eu(III) sorption affinities were strongly affected by solution pH, contact time, temperature, and the mass ratio of LDH and IPB. All the sorpiton process for Eu(III) occurred on the heterogeneous surface of five composites and the boundary layer diffusion limited the chemical sorption rate. Interestingly, the CaAl-LDH/IPB composite with high ratio of IPB had higher sorption capacity than the one with high ratio of LDH due to larger porosity of the former. Three mechanisms containing ion exchange between Al and Eu ions, surface complexation with carboxyl- and oxygen-containing functional groups, and precipitation were involved in the Eu(III) sorption, but the dominant sorption mechanism for each CaAl-LDH/IPB composite differed with different mass ratio of CaAl-LDH and IPB. In composite with more IPB (e.g., CaAl-LDH/IPB-13), both ion exchange and surface complexes dominated the sorption process and the intensity of Eu3+ was identified with the one of Eu2O3. Whereas in composites with high LDH, ion exchange dominated the sorption and the intensity of Eu3+ was obviously higher than the one of Eu2O3. This research will provide a new perspective for the application of the LDH/biochar materials.


Avoidable maternal mortality in Enugu, Nigeria.
The aim of this study was to identify avoidable factors in maternal mortality in Enugu, Nigeria. A hospital-based descriptive study. The case records of maternal deaths in the Obstetric Unit of the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria, between January 2003 and December 2005, were studied to identify maternal characteristics and avoidable factors for maternal mortality. Booked women were those who received formal prenatal care in a medical facility. Abortion-related deaths were not included in the study. There were 49 maternal deaths, 2131 deliveries and 2044 live births during the study period, giving a maternal mortality ratio of 2397.3 maternal deaths per 100,000 live births. The average age of the women was 29.8 years. Twelve women (25.5%) booked in the UNTH, 23 (48.9%) booked elsewhere and 12 (25.5%) were unbooked. Ten women (21.3%) were nulliparous, 15 (31.9%) were Para 1-2, 17 (36.2%) were Para 3-4 and five (10.6%) were Para 5 or above. Twenty-one women (44.7%) first sought medical attention at a private medical clinic, six (12.8%) at the general/mission hospital, five (10.6%) at maternity/health centres, one (2.1%) from a traditional birth attendant and 14 (29.8%) at the UNTH. Fourteen women (39.8%) died within 24h of admission, 12 (25.5%) between 24 and 48h, seven (14.9%) between 48 and 96h and 14 (29.8%) after 96h. Two women (4.3%) delivered at home, eight (17.0%) in private medical clinics, 23 (48.9%) in the UNTH and 14 (29.8%) died undelivered. Major avoidable factors were substandard care (27.7%), delay in seeking care (19.1%), financial constraints (8.4%), delay in recognizing a problem (6.4%), lack of blood (4.3%), lack of drugs (2.1%) and industrial strike action by health workers (2.1%). No major avoidable factor was identified in 14 women (29.8%). Avoidable factors are still prevalent in maternal deaths in Nigeria.


Pan proximal migration of ureteral stent: case report.
The upward migration of double J stent is rare. We recently had the opportunity to study one case with complete proximal migration of "double coil" JJ stent, a situation not previously described to our knowledge.


Use of insecticide treated nets by pregnant women and associated factors in a pre-dominantly rural population in northern Ethiopia.
To describe the use of insecticide treated nets (ITNs) among pregnant women and examine factors associated with its access and use. Community-based cross-sectional study of 815 pregnant women in eight malarious kebeles in northern Ethiopia based on two-stage cluster design from May to June 2006. Knowledge on malaria, its cause and preventive measures; treatment seeking behaviour; possession and use of ITNs by pregnant women and under-five children were ascertained through interview and observation. Logistic regression was used to determine factors associated with ITNs use. Knowledge about the cause, transmission and preventive measures of malaria was relatively good; 90.2% of women associated malaria with mosquito bites and 94.2% with living near water ponds. Ten per cent reported malaria illness within the 14 days before the survey, and sought treatment mainly from public health facilities (56.5%) and community health workers (37.6%). Of 815 households surveyed, 59% owned at least one non-long lasting or long-lasting ITN (59.5% rural vs. 54.5% urban; P = 0.401). Lack of access to ITNs (68.3%) and the perception that nets could not prevent malaria (27%) were the main reasons for non-ownership of nets. A total of 58.4% of 481 pregnant women from households owning at least one ITN had slept under it during the previous night. Fewer rural (56.7%) than urban women (76.2%) used ITNs (P = 0.001). In 57.6% of households with at least one ITN, under-five children had used it the night before. Higher educational attainment was an important predictor of ITNs use (OR = 3.1, 95% CI = 2.1, 4.6). Household ownership of ITNs and their use by pregnant women is promising with the current efforts to scale-up ITNs implementation, but the gap between ownership and use remains high. Consistent and proper use of nets by pregnant women should be ensured through information campaigns. Rapid expansion of access to long lasting ITNs requires that government and NGOs supply them in adequate numbers.


trans-Carbonyl-chlorido-bis-(tri-ethyl-phosphane-κP)platinum(II) tetra-fluorido-borate.
The chemical formulation of the title compound was established as trans-[PtCl{P(C2H5)3(CO)}BF4 by single-crystal X-ray analysis, in contrast to the five-coordinate tetra-fluoro-ethyl-ene complex that had been anti-cipated. The compound had been prepared by reaction of trans-PtHCl(P(C2H5)3)2 with C2F4 in the absence of air, and the presence of the carbonyl group was not suspected. The square-planar cations and BF4 - anions are linked by C-H⋯F and C-H⋯O inter-actions into thick wavy (010) sheets. The present crystal-structure refinement is based on the original intensity data recorded in 1967.


Safety of intravitreal metoprolol in eyes with central serous chorioretinopathy.
To investigate ocular safety of intravitreal metoprolol in eyes with central serous chorioretinopathy. Five eyes of five patients diagnosed with chronic central serous chorioretinopathy (cCSC) previously treated unsuccessfully with oral spironolactone, micropulse laser and intravitreal anti-vascular endothelial growth factor agents were enrolled and received off-label intravitreal metoprolol (50 µg/0.05 ml). Baseline and follow-up examinations included measurement of best-corrected visual acuity (BCVA), intraocular pressure, anterior chamber cellular/flare scores, vitritis classification, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography and electroretinography (ERG), recorded by means of DTL electrodes and following the standard suggested by the International Society for Clinical Electrophysiology of Vision (ISCEV). The total follow-up period was 4 weeks. There were no significant differences between baseline and follow-up ERG parameters: scotopic or photopic, a- and b-wave amplitude and implicit time, nor oscillatory potentials amplitude, or whatsoever. No intraocular inflammation sign was observed. In addition, BCVA showed small improvement in 4 or kept baseline values in 1 patient. The subretinal and/or intraretinal fluid volume reduced in all patients at 1 month after treatment. Patients with refractory cCSC treated with intravitreal 50 µg/0.05 ml metoprolol showed no signs of acute ocular toxicity, along with intraretinal fluid reduction and slight BCVA improvement 1 month after injection. This data suggest that intravitreal metoprolol may be a safe alternative for cCSC.


Osmotic stress, plasma renin activity, and spermatogenesis in Vipera aspis.
Circulating electrolytes (Na+, K+), plasma renin-like activity, testosterone, and testis morphology were investigated in early summer during the spermatogenic progressive phase in Vipera aspis subjected to sodium loading and sodium depletion. After sodium loading, plasma sodium and plasma testosterone levels were significantly elevated compared with those of controls, while plasma renin-like activity was depressed, spermiogenesis was increased, the epithelium lining the epididymis was very thick, and the Leydig cells were hypertrophied. After sodium depletion, plasma sodium and plasma testosterone levels were significantly depressed and plasma renin-like activity was significantly elevated. Spermiogenesis seemed to be slightly regressed: the epithelium lining the epididymis was very thin, and the lumen was devoid of spermatozoa. The Leydig cells were hardly visible. All the data strongly suggest that osmotic stress affects gonadal activity in the snake. V. aspis.


The mechanism of E. coli RNA polymerase regulation by ppGpp is suggested by the structure of their complex.
Guanosine tetraphosphate (ppGpp) is an alarmone that enables bacteria to adapt to their environment. It has been known for years that ppGpp acts directly on RNA polymerase (RNAP) to alter the rate of transcription, but its exact target site is still under debate. Here we report a crystal structure of Escherichia coli RNAP holoenzyme in complex with ppGpp at 4.5 Å resolution. The structure reveals that ppGpp binds at an interface between the shelf and core modules on the outer surface of RNAP, away from the catalytic center and the nucleic acid binding path. Bound ppGpp connects these two pivotal modules that may restrain the opening of the RNAP cleft. A detailed mechanism of action of ppGpp is proposed in which ppGpp prevents the closure of the active center that is induced by the binding of NTP, which could slow down nucleotide addition cycles and destabilize the initial transcription complexes.


Bacillus megaterium spore germination is influenced by inoculum size.
The effect of spore density on the germination (time-to-germination, percent germination) of Bacillus megaterium spores on tryptic soy agar was determined using direct microscopic observation. Inoculum size varied from approximately 10(3) to 10(8) cfu ml(-1) in a medium where pH=7 and the sodium chloride concentration was 0.5% w/v. Inoculum size was measured by global inoculum size (the concentration of spores on a microscope slide) and local inoculum size (the number of spores observed in a given microscope field of observation). Both global and local inoculum sizes had a significant effect on time-to-germination (TTG), but only the global inoculum size influenced the percentage germination of the observed spores. These results show that higher concentrations of Bacillus megaterium spores encourage more rapid germination and more spores to germinate, indicating that low spore populations do not behave similarly to high spore populations. A likely explanation for the inoculum size-dependency of germination would be chemical signalling or quorum sensing between Bacillus spores.


Assessment of potential health risk of major contaminants of groundwater in a densely populated agricultural area.
As a key part of Bohai New Area development, Haixing County has been undergoing rapid development. In order to estimate potential risks of chemical parameters to human health of local residents, carcinogenic and non-carcinogenic risks via direct ingestion of drinking water were calculated using human health risk assessment (HHRS) based on triangular fuzzy number. The levels of pH, total dissolved solids, total harness, SO4 2-, Na+, Cl-, SO4 2-, F-, Fe (total iron), NO3 -, and NO2 - were more or less higher than the permissible limits except parameters As and Mn. The analysis results show that risk level for different crowds in the study area demonstrated an obvious variation, generally in the order of infants > children > adult males > adult females for non-carcinogenic risk values (R n), while the sequence of the carcinogenic risk values (R c) are adult males > adult females > children > infants. When the confidence level was 0.8, the non-carcinogenic risk values (R n) through drinking water intake were higher than 1, and this implied that potential health impacts on human health for local residents. However, the risks of carcinogenic risk values (R c) were lower than 1.0E-4, demonstrating minimal and acceptable health risk. Furthermore, according to the middle values (α = 1) of R n, the total non-carcinogenic risks for local residents were obtained in the following order: GW (Gaowan Town) > XJ (Xinji-Xiangfang County) > ZM (Zhaomaotao County) > HX (Haixing-Suji Town) > ZH (Zhanghuiting County) > XS (Xiaoshan County), and ZM > XJ > GW > HX > XS > ZH for R c. It was also found that the spatial distribution of fluoride level in drinking water is urgently needed to be identified. In conclusion, the potential health risks to residents should cause enough attention both from society and the academic community.


Simplified bladder botulinum-toxin delivery technique using flexible cystoscope and 10 sites of injection.
Recently, the use of botulinum toxin A has been extended to patients with non-neurogenic urologic disorders such as refractory idiopathic overactive bladder. We describe a modification of our original injection technique that allows one to deliver botulinum toxin into the bladder quickly and efficiently in an office setting with reliable results and no local or systemic side effects.


Preconditioning calves for the feedlot.
Preconditioning is a theoretically sound concept; however, it has not gained wide acceptance by cow-calf producers or feeders owing to logistics and expense. Many of the claims of preconditioning are not substantiated by controlled research data. Many of the positive claims made for preconditioning may be a result of the calves moving more rapidly through the marketing channels. Although preconditioning is profitable to some producers, on the average, preconditioning is difficult to justify economically. Modifications of the preconditioning concept have the potential to make it more feasible to the majority of cow-calf producers. Any producer or feeder considering a preconditioning program or feeding preconditioned calves should first calculate an economic projection.


Fostering healthcare innovation in public hospitals: the Queensland experience.
Faced with scarce resources and a demand for health care that exceeds supply, health policy makers at all levels of government need to adopt some form of rationing when deciding which health services should be funded in the public health system. With a relatively small investment, programs such as Queensland Health's New Technology Funding Evaluation Program (NTFEP) fosters innovation by providing funding and pilot studies for new and innovative healthcare technologies. The NTFEP assists policy makers to make informed decisions regarding investments in new safe and effective technologies based on available evidence gathered from real-world settings relevant to Queensland patients and clinicians. In addition, the NTFEP allows appropriate patient access, especially in rural and remote locations, to potentially beneficial technologies and acts a gatekeeper, protecting them from technologies that may be detrimental or harmful.


Induction of sister chromatid exchanges by 5-fluorodeoxycytidine: correlation with DNA methylation.
Chinese hamster ovary cells grown in medium containing 10 microM 5-fluorodeoxycytidine for forty-eight hours were found to have up to 5% of the deoxycytidine residues of the DNA substituted by this analog. Cytological studies of these cells showed that the incorporated 5-FdC caused a two-fold increase of sister chromatid exchanges (SCE) over the control level. However, 5-FdC was capable of inducing SCE only after it had been present in the cell for at least two cycles of DNA synthesis. This is in contrast to several other chemicals that we have tested which induced SCE immediately after the first DNA synthesis. We consider the possibility that the delayed effect may be related to hypomethylation of cytosine in the newly replicated DNA.


Adapted bikes: what children and young people with cerebral palsy told us about their participation in adapted dynamic cycling.
Children and young people with Cerebral Palsy have limited opportunities for participation and there has been limited research to explore this concept. Adapted dynamic cycling (ADC) is one activity that can enable them to participate in the community. The aim of this paper is to report the views and experiences of children and young people with CP and their families regarding their participation in ADC. This was part of a mixed methods study of which the qualitative findings are reported here. Iterative creative methods were developed which involved semi-structured interviews and diaries about the ADC experience. The themes that emerged were the staff and the environment at the cycling hire project, the facilitators and barriers to ADC, the technical set up of the bike and the impact on the child and family in terms of developments over time, future aspirations, learning cycling skills, social participation and health benefits. The data showed that children's experiences of ADC were fun and enjoyable. This fun exercise should be incorporated into a physiotherapy programme as part of the child or young person with CP's rehabilitation. Policy makers and parents may find the information useful to increase the child's participation.


Active nematics.
Active matter extracts energy from its surroundings at the single particle level and transforms it into mechanical work. Examples include cytoskeleton biopolymers and bacterial suspensions. Here, we review experimental, theoretical and numerical studies of active nematics - a type of active system that is characterised by self-driven units with elongated shape. We focus primarily on microtubule-kinesin mixtures and the hydrodynamic theories that describe their properties. An important theme is active turbulence and the associated motile topological defects. We discuss ways in which active turbulence may be controlled, a pre-requisite to harvesting energy from active materials, and we consider the appearance, and possible implications, of active nematics and topological defects to cellular systems and biological processes.


Diversity and physiology of culturable bacteria associated with a coastal Antarctic ice core.
Microbiological studies of polar ice at different depths may provide important comparisons, as they preserve records of microbial cells and past climate. In this study, we examined bacterial abundance, diversity and glaciochemical composition from three depths of an ice core from coastal Dronning Maud Land, East Antarctica. Higher bacterial abundance corresponded with high in situ sea-salt Na(+) and dust concentration, suggesting that bacteria might have been transported and deposited into ice along with dust particles and marine aerosols. Fourteen bacterial isolates belonging to the genera Methylobacterium, Brevundimonas, Paenibacillus, Bacillus and Micrococcus were retrieved. Frequent isolation of similar bacterial genera from different cold environments suggests that they possess features that enable survival and metabolism for extended periods of time at sub-zero temperatures. The highest number and diversity of recoverable bacteria was obtained from 49 m depth corresponding to 1926 AD and consisted of bacteria from 4 different genera whereas at 11 m (1989 AD) and 33 m (1953 AD) samples only species belonging to the genera Bacillus was recovered. Among the Bacillus species, Bacillus aryabhattai which has been reported only from the upper stratosphere, was isolated and is the first record from the Earth's surface. Methylobacterium was the most dominant genera at 49 m depth and its prevalence is attributable to a combination of high in situ methanesulfonate concentration, specialized metabolism and environmental hardiness of Methylobacterium. Some of the isolated bacteria were found to respire and grow using methanesulfonate, suggesting that they may utilize this substrate to sustain growth in ice. In addition, NO(3)(-) (2.93-3.69 μM), NH(4)(+) (1.45-3.90 μM) and PO(4)(3-) (0.01-0.75 μM) present in the ice could be potential sources fueling bacterial metabolism in this environment. It could be deduced from the study that variation in bacterial abundance and diversity was probably associated with the prevailing in situ conditions in ice.


Subtle ocular movements in a patient with brain death.
Introduction and Case Presentation: Brain death can be associated with limb movements that are attributed to spinal reflexes. Although head/face movements have been rarely reported, no case of overt eye movements in brain death has been documented. We report a case of a patient with subtle eye movements whose exam was otherwise consistent with brain death. The presence of eye movements delayed pronouncing the patient as brain dead and delayed organ donation. We agree with American Academy of Neurology Position statement from 2019 that brain death does not mean demise of every neuron. Discussion: This case raises important questions about the types of movements that should be "allowed" during the determination of brain death to avoid delays in diagnosis.


Considering race in the administration of fertility preservation. A commentary on: "Equal opportunity for all? An analysis of race and ethnicity in fertility preservation in a major American city".
Studies that focus on disparities in care should aim to discern differences both within their communities and also among larger populations to improve the applicability of important findings. Such work should attempt to discern what factors may be influential in creating or contributing to racial inequities.


Enhanced p53 gene transfer to human ovarian cancer cells using the cationic nonviral vector, DDC.
Previously we have formulated a new cationic liposome, DDC, composed of dioleoyltrimethylamino propane (DOTAP), 1,2-dioeoyl-3-phosphophatidylethanolamine (DOPE), and cholesterol (Chol), and it efficiently delivered plasmid DNA into ovarian cancer cells. Mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities to be described in ovarian cancer. However, there has been so far no report of nonviral vector-mediated p53 gene deliveries in ovarian cancer. In this study, wild-type p53 DNA was transfected into the ovarian cancer cells, using the DDC as a nonviral vector and the expression and activity of p53 gene were evaluated both in vitro and in vivo. DDC liposomes were prepared by mixing DOTAP:DOPE:Chol in a 1:0.7:0.3 molar ratio using the extrusion method. Plasmid DNA (pp53-EGFP) and DDC complexes were transfected into ovarian carcinoma cells (OVCAR-3 cells) and gene expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis. The cellular growth inhibition and apoptosis of DDC-mediated p53 transfection were assessed by trypan blue exclusion assay and annexin-V staining, respectively. The OVCAR-3 cells treated with DDC/pp53-EGFP complexes were inoculated into female balb/c nude mice and tumor growth was observed. The transfection of liposome-complexed p53 gene resulted in a high level of wild-type p53 mRNA and protein expressions in OVCAR-3 cells. In vitro cell growth assay showed growth inhibition of cancer cells transfected with DDC/pp53-EGFP complexes compared with the control cells. The reestablishment of wild-type p53 function in ovarian cancer cells restored the apoptotic pathway. Following the inoculation of DDC/pp53-EGFP complexes, the volumes of tumors in nude mice were significantly reduced more than 60% compared to the control group. The DDC-mediated p53 DNA delivery may have the potential for clinical application as nonviral vector-mediated ovarian cancer therapy due to its effective induction of apoptosis and tumor growth inhibition.


High-density three-dimensional localization microscopy across large volumes.
Extending three-dimensional (3D) single-molecule localization microscopy away from the coverslip and into thicker specimens will greatly broaden its biological utility. However, because of the limitations of both conventional imaging modalities and conventional labeling techniques, it is a challenge to localize molecules in three dimensions with high precision in such samples while simultaneously achieving the labeling densities required for high resolution of densely crowded structures. Here we combined lattice light-sheet microscopy with newly developed, freely diffusing, cell-permeable chemical probes with targeted affinity for DNA, intracellular membranes or the plasma membrane. We used this combination to perform high-localization precision, ultrahigh-labeling density, multicolor localization microscopy in samples up to 20 μm thick, including dividing cells and the neuromast organ of a zebrafish embryo. We also demonstrate super-resolution correlative imaging with protein-specific photoactivable fluorophores, providing a mutually compatible, single-platform alternative to correlative light-electron microscopy over large volumes.