Mortality Attributed to COVID-19 in High-Altitude Populations.
Woolcott, Orison O., and Richard N. Bergman. Mortality attributed to COVID-19 in high-altitude populations. High Alt Med Biol. 21:409-416, 2020. Background: Since partial oxygen pressure decreases as altitude increases, environmental hypoxia could worsen Coronavirus Disease 2019 (COVID-19) patient's hypoxemia. We compared COVID-19 mortality at different altitudes. Methods: Retrospective analysis of population-level data on COVID-19 deaths was conducted in the United States (1,016 counties) and Mexico (567 municipalities). Mixed-model Poisson regression analysis of the association between altitude and COVID-19 mortality was conducted using individual-level data from 40,168 Mexican subjects with COVID-19, adjusting for multiple covariates. Results: Between January 20 and April 13, 2020, mortality rates were higher in U.S. counties located at ≥2,000 m elevation versus those located <1,500 m (12.3 vs. 3.2 per 100,000; p < 0.001). In Mexico, between March 13 and May 13, 2020, mortality rates were higher in municipalities located at ≥2,000 m versus those located <1,500 m (5.3 vs. 3.9 per 100,000; p < 0.001). Among Mexican subjects younger than 65 years, the risk of death was 36% higher in those living at ≥2,000 m versus those living at <1,500 m (adjusted incidence rate ratio [IRR]: 1.36; confidence interval [95% CI], 1.05-1.78; p = 0.022). Among Mexican men, the risk of death was 31% higher at ≥2,000 m versus that at <1,500 m (adjusted IRR: 1.31; 95% CI, 1.03-1.66; p = 0.025). No association between altitude and COVID-19 mortality was found among Mexican women or among Mexican subjects 65 years of age and older. Conclusions: Altitude is associated with COVID-19 mortality in men younger than 65 years.


Structural analysis of human SEPHS2 protein, a selenocysteine machinery component, over-expressed in triple negative breast cancer.
Selenophosphate synthetase 2 (SEPHS2) synthesizes selenide and ATP into selenophosphate, the selenium donor for selenocysteine (Sec), which is cotranslationally incorporated into selenoproteins. The action and regulatory mechanisms of SEPHS2 as well as its role in carcinogenesis (especially breast cancer) remain ambiguous and need further clarification. Therefore, lacking an experimentally determined structure for SEPHS2, we first analyzed the physicochemical properties of its sequence, modeled its three-dimensional structure and studied its conformational behavior to identify the key residues (named HUB nodes) responsible for protein stability and to clarify the molecular mechanisms by which it induced its function. Bioinformatics analysis evidenced higher amplification frequencies of SEPHS2 in breast cancer than in other cancer types. Therefore, because triple negative breast cancer (TNBC) is biologically the most aggressive breast cancer subtype and its treatment represents a challenge due to the absence of well-defined molecular targets, we evaluated SEPHS2 expression in two TNBC cell lines and patient samples. We demonstrated mRNA and protein overexpression to be correlated with aggressiveness and malignant tumor grade, suggesting that this protein could potentially be considered a prognostic marker and/or therapeutic target for TNBC.


Polydatin Inhibits NLRP3 Inflammasome in Dry Eye Disease by Attenuating Oxidative Stress and Inhibiting the NF-κB Pathway.
Polydatin (also named pieceid, (E)-piceid, (E)-polydatin, trans-polydatin, or 3,5,4'-trihydroxystilbene-3-b-D-glucoside) is a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae). A previous study showed that polydatin has antioxidant and anti-inflammatory effects. However, the effect of polydatin in dry eye disease (DED) has not been elucidated. DED rat models were induced by exorbital lacrimal gland-excision. In vivo, the present study showed that the excision of lacrimal glands induced changes such as reduced tear fluid, severe corneal irregularity, damage, tear film break, and goblet cell loss as well as increased inflammation cytokine and NLRP3 expression in conjunctival tissue. However, these changes were restored by polydatin eye dropping. In vitro, polydatin inhibited hyperosmolar stress-induced inflammation through attenuation of the translocation of NF-κB to the nucleus and the mRNA expression of TNF-α, IL-6, IL-1β, and MMP9. In addition, the hyperosmolar stress-induced NLRP3 inflammasome pathway and ROS production were inhibited by polydatin. Our findings provided insight into the effect of polydatin as a candidate reagent for the treatment of DED.


The role of aspiration cytology in the management of thyroid nodules.
In the hands of an experienced cytologist aspiration cytology is a safe and hitherto the best diagnostic tool in the evaluation of nodular thyroid lesions. In histologically verified case series 50-90% of confirmed thyroid cancers can be detected by aspiration biopsy, the sensitivity being dependent on sampling errors, microscopic misinterpretation and the variation in attitude towards indeterminate diagnosis in the decision for diagnostic surgery. The number of proven benign cases that are correctly identified as such by biopsy varies accordingly and approx. 75% (specificity). In comparison with imaging procedures, including those giving information of functional activity, the combined sensitivity and specificity rates of aspiration cytology come closest to the ideal discriminatory situation. In combination with case history and careful clinical examination, fine needle aspiration cytology is the best guidance for an optimal selection of patients for therapeutic or diagnostic surgery. Future development of sensitive markers for malignant degeneration will probably increase the selective power of this diagnostic technique.


Waist circumference is the key risk factor for diabetes in Korean women with history of gestational diabetes.
This study investigated relationships between various obesity indices and an onset of type 2 diabetes mellitus (TY2DM) in Korean women with history of gestational diabetes mellitus (GDM). A total of 909 women with history of GDM were enrolled from the four major hospitals, and the first postpartum follow-up examination was made at 6 weeks, and annually thereafter. During postpartum follow-up period, mean 2.13+/-1.75 years, we conducted 2h 75 g OGTT and measured glucose, insulin, c-peptide, lipid profiles, lifestyle and dietary evaluation. For obesity parameters, we measured body weight, body mass index (BMI), waist and hip circumference, subcutaneous fat thickness, body fat percent and weight using bioelectrical impedance tests. Diabetes incidence for 6 years was 12.8% and all the obesity indices were significantly higher in subjects with diabetes or glucose intolerance than those with normal glucose tolerance (p<0.001). When obesity indices were compared between <25th versus >75th percentile, the waist circumference presented with the strongest relationship (odds ratio=5.8, 95% CI 2.8-11.8). This relationship persisted, OR=3.86 (95% CI 1.8-8.2), even after adjusting for the potential confounders. This prospective study revealed that waist circumference is one of the key risk factors for the onset of diabetes in Korean women with history of GDM.


Secondary structure and hybridization accessibility of the hepatitis C virus negative strand RNA 5'-terminus.
The positive strand RNA genome of hepatitis C virus (HCV) is transcribed exclusively from a full-length cytoplasmic replication intermediate, the negative strand RNA. Despite this essential role in hepatocellular infection, the negative strand has not yet been subjected to extensive molecular characterization, and in comparison with the HCV genome and proteome, remains relatively unexplored as a target for antiviral therapy. The highly conserved negative strand terminal sequences, complementary to the positive strand 5'- and 3'-untranslated regions, are believed to contribute structural features essential for the initiation of positive strand synthesis and the maintenance of template integrity. We investigated the solution structure of the HCV negative strand 5'-terminal region by endoribonuclease mapping and thermodynamic modelling of RNA secondary structure. The enzymatic probing data are consistent with structural models featuring a large terminal stem loop (SL), which constitutes a mirror image of the complementary 3'-X region SL I structure. Nucleotide positions within the negative strand accessible to hybridization were mapped by RNase H digestion in the presence of combinatorial oligonucleotide libraries. The hybridization data further support the existence of a terminal SL, and reveal target sites within the negative strand 5'-terminus which may be susceptible to antisense-mediated inhibition.


[Sleep disturbances among children and adolescents with learning disabilities. Comparative study between students from a mainstream school and a special school in the Valencia Community (Spain)].
Sleep disturbances affect daytime behaviour and cognitive functions in children. These disorders make the situation worse in children who already have learning difficulties. The objective of the present study was to study the prevalence of sleep disturbances among children from special schools and carry out a comparative study with children from mainstream schools. We use the Spanish version of the Paediatric Sleep Questionnaire, which was given out in three special schools of the Valencia Community. Results were compared with a previous study in children from mainstream schools. A significantly higher proportion of children in special schools had insomnia, 32.3 % against 10.5 % in main-stream school, and sleep breathing disorders, 26.8 % against 5.7 % in mainstream schools, and a lower proportion of parasomnias. Among the whole population with learning difficulties, children with cerebral palsy are the most affected. Our results clearly show that children with learning difficulties have a higher risk of sleep disturbances and these disturbances have repercussions on daily functioning. It is important to rule out sleep disturbances when we see children with learning difficulties.


Studies on peroxidation processes of model membranes and synaptosomes: role of phosphatidic acid.
Dipalmitoylphosphatidic acid (DPPA) was found to exert a strong inhibitory effect on Fe-induced peroxidation of arachidonic acid inserted into liposomal dipalmitoylphosphatidylcholine (DPPC) vesicles. This inhibition was quite effective both below and above the phase transition temperature of the liposomes. Moreover, we demonstrated the antiperoxidative activity of phosphatidic acid (PA) in synaptosomal membranes. PA enriched synaptosomes were prepared by the stimulation of the endogenous phospholipase D activity or by the incubation of the synaptosomes with Streptomyces chromofuscus phospholipase D. The possible contribution of PA to the in vivo defense mechanism against free radical-induced damage is discussed.


Mean-Field Limits for Entropic Multi-Population Dynamical Systems.
The well-posedness of a multi-population dynamical system with an entropy regularization and its convergence to a suitable mean-field approximation are proved, under a general set of assumptions. Under further assumptions on the evolution of the labels, the case of different time scales between the agents' locations and labels dynamics is considered. The limit system couples a mean-field-type evolution in the space of positions and an instantaneous optimization of the payoff functional in the space of labels.


Clinicopathological significance of the immunologic signature (PDL1, FOXP3+ Tregs, TILs) in early stage triple-negative breast cancer treated with neoadjuvant chemotherapy.
Patients with breast cancer are appropriate candidates for neoadjuvant chemotherapy (NAC) to facilitate conservative surgery. The chemotherapeutic agents may exert their action by inducing the anti-tumor immune response. This study aimed to evaluate the tumor immune microenvironment including PD-L1, Foxp3+ Tregs, and TILs count in early stages TNBC patients (stage T1, T2) before and after neoadjuvant chemotherapy and their correlation with the clinical and pathological response. Fifty patients of TNBC patients were enrolled in this study; all of them received neoadjuvant chemotherapy. TILs count, Foxp3+ Tregs, and PD-L1 immunohistochemical expression were investigated in all cases before NAC and then evaluated in residual masses after surgery. Data on the clinical and pathological response to NAC were collected and then statistically analyzed. PDL1 expression was detected in 24% of all studied cases, all of them were node-positive (P < 0.002); while Foxp3+ Tregs expressed in 50% and high TILs in 28%. Pathological complete response (pCR) was achieved in 40% of patients and was associated with high TILs expression (P < 0.02) and absence of Foxp3+ Tregs and PDL1 (P < 0.001 for each). In conclusion, Pathologic complete response to NAC was associated with the immunological profile of TNBC. High TILs expression with concomitant decreased PD-L1 expression and low FOXP3+ Tregs is associated with favorable tumor prognosis. Combined therapeutic approaches aiming to PD-L1 block and Tregs depletion might improve treatment efficacy in TNBC.


The evolution of Australian intensive care and its related costs: A narrative review.
To conduct a narrative review on the evolution of intensive care and the cost of intensive care services in Australia. A narrative review using a search of online medical databases and grey literature with keyword verification via Delphi-technique. Using Medical Subject Headings and keywords (intensive care, critical care, mechanical ventilation, renal replacement therapy, extracorporeal membrane oxygenation, monitoring, staffing, cost, cost analysis) we searched MEDLINE, PubMed, CINAHL, Embase, Google and Google Scholar. The search yielded 30 articles from which we provide a narrative synthesis on the evolving intensive care practice in relation to key service elements and therapies. For the review of costs, we found five relevant publications and noted significant variation in methods used to cost ICU. Notwithstanding the limitations of the methods used to cost all publications reported staffing as the primary cost driver, representing up to 71% of costs. Intensive care is a highly specialised medical field, which has developed rapidly and plays an increasingly important role in the provision of hospital care. Despite the increasing importance of the specialty and the known resource intensity there is a paucity of data on the cost of providing this service. In Australia, staffing costs consistently represent the majority of costs associated with operating an ICU. This finding should be interpreted cautiously given the variation of methods used to cost ICU services and the limited number of available studies. Developing standardised methods to consistently estimate ICU costs which can be incorporated in research into the cost-effectiveness of alternate practice is an important step to ensuring cost-effective care.


The identification of mono-, di-, tri-, and tetragalactosyl-diacylglycerols and their natural estolides in oat kernels.
Oat kernels were extracted with methanol, and glycolipid-enriched fractions were prepared using silica solid phase extraction. Using direct infusion electrospray ionization (ESI) tandem mass spectrometry (MS), high performance liquid chromatography (HPLC)-ESI-MS, and HPLC-atmospheric pressure chemical ionization (APCI)-MS, we confirmed previous reports that digalactosyldiacylglycerol (DGDG) was the most abundant glycolipid in oat kernels and confirmed a previous report of the presence of a DGDG mono-estolide in oat kernels. In the current study we also identified several additional natural galactolipid estolides: two new DGDG estolides (di- and tri-estolides), two trigalactosyldiacylglycerol (TriGDG) estolides (mono- and di-estolides), and one tetragalactosyldiacylglycerol (TetraGDG) estolide (mono-estolide). The levels of total galactolipid estolides in oat kernels were estimated to be about 29% of the total glycolipid fraction. To our knowledge, this report is the first evidence of natural di- and tri-estolides of polar lipids.


Urinary bombesin-like peptide levels in infants and children with bronchopulmonary dysplasia and cystic fibrosis.
Compared to normal infants and children, there are increased numbers of neuroendocrine cells with bombesin-like peptide (BLP) immunostaining in the lungs of infants and children with bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF). However, there are no data documenting levels of urinary BLP in normal infants and children, or in children with lung disease. We therefore determined the normal developmental pattern for urinary BLP excretion in healthy infants and children, and in infants and children with BPD and CF, and correlated these findings with the subjects' clinical course. We measured urinary BLP levels in 110 subjects: 54 controls, 33 with BPD, and 23 with CF. An age-dependent decline in urinary bombesin levels was evident in the control and BPD subjects, but not in those with CF. There were no statistically significant differences in BLP levels between normal infants and those with BPD. Mean BLP levels were higher in the more immature preterm infants with BPD who required increased ventilatory support. The highest mean BLP levels were documented in BPD infants under age 3 months (882 fmol/mg creatinine), in controls between 3 and 12 months of age (625 fmol/mg creatinine), and in 12-60-month-old CF subjects (486 fmol/mg creatinine). Thus there is an age-dependent decline in BLP levels in controls and BPD, but not in CF. We speculate that the elevated urinary BLP levels in infants and children with BPD and CF may reflect increased pulmonary neuroendocrine cell activity in these conditions, due to the epithelial regenerative response to airway damage and repair.


Early hemopoietic differentiation: the action of multi-CSF is complemented by lineage specific growth factors.
Although mechanisms controlling differentiation of hemopoietic stem and early progenitor cells are still poorly understood, it is generally conceded that a pivotal role is played by hemopoietic growth factors (HGFs). However, in-vitro analysis of their action on early progenitors may be obscured by cell-cell interaction, as well as by the presence of fetal bovine serum (FBS). To overcome these limitations, we investigated the action of pure multipotent or lineage-specific HGFs on purified progenitors grown in FBS-free cultures. In the murine system, highly purified progenitors were cultured in the presence of multipotent colony-stimulating factor (multi-CSF, also termed interleukin-3), erythropoietin (Ep) and macrophagic-CSF (M-CSF). Each HGF was unable by itself to induce significant colony growth. However, combined addition of multi-CSF and either Ep or M-CSF gave rise only to pure erythroid or macrophagic colonies, respectively. Partly purified human progenitors were challenged by human granulomonocytic-CSF (GM-CSF), pluripotent CSF (PPO, also termed granulocytic-CSF, G-CSF) and Ep. Here again, each HGF was unable per se to promote colony growth, but combined addition of GM-CSF or PPO and Ep gave rise only to pure erythroid colonies. These results support a model of early hemopoietic differentiation according to which multi-lineage HGFs represent "competence" GFs, the action of which is complemented by lineage-specific "progression" HGFs.


Growth in eligibility criteria content and failure to accrue among National Cancer Institute (NCI)-affiliated clinical trials.
Cancer trial accrual is a national priority, yet up to 20% of trials fail to accrue. Trial eligibility criteria growth may be associated with accrual failure. We sought to quantify eligibility criteria growth within National Cancer Institute (NCI)-affiliated trials and determine impact on accrual. Utilizing the Aggregated Analysis of ClinicalTrials.gov, we analyzed phase II/III interventional NCI-affiliated trials initiated between 2008 and 2018. Eligibility criteria growth was assessed via number of unique content words within combined inclusion and exclusion criteria. Association between unique word count and accrual failure was evaluated with multivariable logistic regression, adjusting for known predictors of failure. Medical terms associated with accrual failure were identified via natural language processing and categorized. Of 1197 trials, 231 (19.3%) failed due to low accrual. Accrual failure rate increased with eligibility criteria growth, from 11.8% in the lowest decile (12-112 words) to 29.4% in the highest decile (445-750 words). Median eligibility criteria increased over time, from 214 (IQR [23, 282]) unique content words in 2008 to 417 (IQR [289, 514]) in 2018 (r2 = 0.73, P < 0.001). Eligibility criteria growth was independently associated with accrual failure (OR: 1.09 per decile, 95% CI [1.03-1.15], p = 0.004). Eighteen exclusion criteria categories were significantly associated with accrual failure, including renal, pulmonary, and diabetic, among others (Bonferroni-corrected p < 0.001). Eligibility criteria content growth is increasing dramatically among NCI-affiliated trials and is strongly associated with accrual failure. These findings support national initiatives to simplify eligibility criteria and suggest that further efforts are warranted to improve cancer trial accrual.


Mitochondrial toxicity of 2-bromohydroquinone in rabbit renal proximal tubules.
2-Bromohydroquinone (BHQ) is a nephrotoxic metabolite of bromobenzene and a model toxic hydroquinone. The primary goal of these studies was to determine whether BHQ produces toxicity in rabbit renal proximal tubules by inhibiting mitochondrial function. BHQ induces a specific sequence of cellular events. Initially there was decrease in tubular glutathione content followed by a decrease in nystatin-stimulated ouabain-sensitive respiration. A decrease in cell viability, as measured by a decrease in lactate dehydrogenase retention, was late event. Associated with the decrease in respiration was a decrease in intracellular ATP content. Probing of mitochondrial function in the tubule revealed that BHQ did inhibit mitochondrial function in a somewhat selective manner. State 3 respiration was inhibited prior to changes in the rate of electron flow through cytochrome c-cytochrome oxidase. It is postulated that BHQ may initially inhibit state 3 respiration by inhibiting the adenine nucleotide translocator and/or the F1-ATPase.


Targeting Poly(ADP)ribose polymerase in BCR/ABL1-positive cells.
BCR/ABL1 causes dysregulated cell proliferation and is responsible for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). In addition to the deregulatory effects of its kinase activity on cell proliferation, BCR/ABL1 induces genomic instability by downregulating BRCA1. PARP inhibitors (PARPi) effectively induce cell death in BRCA-defective cells. Therefore, PARPi are expected to inhibit growth of CML and Ph1-ALL cells showing downregulated expression of BRCA1. Here, we show that PARPi effectively induced cell death in BCR/ABL1 positive cells and suppressed colony forming activity. Prevention of BCR/ABL1-mediated leukemogenesis by PARP inhibition was tested in two in vivo models: wild-type mice that had undergone hematopoietic cell transplantation with BCR/ABL1-transduced cells, and a genetic model constructed by crossing Parp1 knockout mice with BCR/ABL1 transgenic mice. The results showed that a PARPi, olaparib, attenuates BCR/ABL1-mediated leukemogenesis. One possible mechanism underlying PARPi-dependent inhibition of leukemogenesis is increased interferon signaling via activation of the cGAS/STING pathway. This is compatible with the use of interferon as a first-line therapy for CML. Because tyrosine kinase inhibitor (TKI) monotherapy does not completely eradicate leukemic cells in all patients, combined use of PARPi and a TKI is an attractive option that may eradicate CML stem cells.


Effect of insulin antibodies on insulin pharmacokinetics and glucose utilization in insulin-dependent diabetic patients.
To determine the impact of insulin-binding antibodies on total (TIRI) and free insulin (FIRI) as well as on insulin sensitivity, 10 insulin-dependent diabetic patients (IDDM) with poststimulatory C-peptide less than 100 pmol/L and an insulin binding capacity (IBC) between less than 1 and 294 micrograms/L serum were studied during and after a 1-h nonprimed, constant-rate insulin infusion (study 1: 0.057 U/kg body wt, study 2: 0.286 U/kg body wt). Euglycemia was maintained by variable glucose infusion. Control studies were performed in 5 healthy subjects. Basal TIRI (mU/L) was lowest in healthy subjects (16 +/- 1 [SE]) and elevated in diabetic patients (IBC less than 25 micrograms/L: 72 +/- 11, IBC greater than 25 micrograms/L: 1772 +/- 842), whereas serum concentrations of FIRI were considerably smaller but still two- to threefold greater (P less than 0.01) in the patients than in healthy subjects (13 +/- 1). After intravenous (i.v.) insulin administration, almost identical increments in serum TIRI were seen in healthy subjects and in diabetic patients with low IBC (less than 25 micrograms/L), whereas those with high IBC (greater than 25 micrograms/L) had a heterogeneous response.(ABSTRACT TRUNCATED AT 250 WORDS)


Outcomes of halo immobilization in the management of subaxial cervical facet fractures.
Spinal injury causes a significant burden on patients, families and health services. Cervical facet fractures are uncommon, and there is a paucity of functional and health-related quality-of-life data in patients who are managed non-operatively for this injury. Victorian State Trauma Registry patients managed in a halothoracic brace for cervical facet injuries from August 2006 to June 2013 were included. Health status (12-item Short-Form health survey), function (Glasgow Outcome Scale-Extended), pain and return to work outcomes were assessed at 6, 12 and 24 months post-injury. Subgroup analysis was performed for age, sex, comorbidity, compensable status, Injury Severity Score (ISS) and education. Outcome data were available for 54 patients, with road trauma being the most common mechanism (69%), followed by a fall from height (18%). Overall, good 24-month function was achieved in 35% of patients, and 51% and 77% of patients reported good physical and mental health status, respectively. Ongoing moderate-severe neck pain was present in 19% of patients. Poorer function was associated with compensable status (P = 0.05), an ISS > 12 (P = 0.001) and a lower level of education (P = 0.04). Poorer physical health status was associated with age ≥50 (P = 0.05), pre-existing comorbidities, an ISS > 12 (P = 0.04) and a lower level of education (P = 0.03). Although many patients achieved good function and health status by 24 months, neck pain remains prevalent. A number of demographic factors were associated with a poorer outcome. This understanding helps to inform prognosis when managing this injury.


[The influence of lactic acid bacteria and yeast on production of staphylococcal enterotoxins].
Research of influence of 10 lactic acid bacteria cultures on staphylococcal growth and production of staphylococcal enterotoxins SEA and SEB has shown that lactic acid bacteria slow down SEA in 5,7 fold and SEB - 1,56 fold. All investigated cultures possessed inhibition action on SEA and SEB production. Has been established, what lactic acid bacteria slow down growth of staphylococcus in 1,48 fold. It has shown that appears, that the most effective inhibitors of SEA and SEB production are strains L. casei, Lactobacillus acidophilus 317/402.


Unusual intracranial foreign bodies. Report of five cases.
Five patients surgically treated for unusual intracranial foreign bodies are presented. They include representative cases of the three most commonly encountered types of these injuries: industrial accidents, suicidal attempts and the result of criminal assault. Immediate radiological examination is mandatory because the deceptively small entrance wound is usually in no way commensurate with the large size of the foreign body the presence of which is frequently not suspected. The surgical removal of these foreign bodies requires careful pre-operative assessment to avoid hemorrhages and undue injury to the surrounding normal brain tissue.


A study of the muscarinic receptor by gel electrophoresis.
1 Muscarinic receptors from the brain of rat, guinea-pig and frog have been labelled with tritiated propylbenzilylcholine mustard ([3H]-PrBCM). 2 After solubilisation and sodium dodecyl sulphate (SDS)-polycarylamide gel electrophoresis a single radiolabelled peak was seen which was completely suppressed when labelling was carried out in the presence of 10(-6) M atropine. The results suggest the presence of a single polypeptide chain with a molecular weight of similar to or approximately 80,000. 3 In the case of intestinal smooth muscle multiple labelled peaks were found. Precautions against proteolysis led to the identification of a major peak with a molecular weight in the region of 80,000.


Open-source pipeline for automatic segmentation and microstructural analysis of murine knee subchondral bone.
μCT images are commonly analysed to assess changes in bone density and microstructure in preclinical murine models. Several platforms provide automated analysis of bone microstructural parameters from volumetric regions of interest (ROI). However, segmentation of the regions of subchondral bone to create the volumetric ROIs remains a manual and time-consuming task. This study aimed to develop an automated end-to-end pipeline, combining segmentation and microstructural analysis, to evaluate subchondral bone in the mouse proximal knee. A segmented dataset of μCT scans from 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice was used to train a U-Net type architecture to automate segmentation of the subchondral trabecular bone. These segmentations were used in tandem with the original scans as input for microstructural analysis along with thresholded trabecular bone. Manually and U-Net segmented ROIs were fed into two available pipelines for microstructural analysis: the ITKBoneMorphometry library and CTan (SKYSCAN). Outcome parameters were compared between pipelines, including: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV). There was good agreement for all bone measures comparing the manual and U-Net pipelines utilizing ITK (R = 0.88-0.98) and CTAn (R = 0.91-0.98). ITK and CTAn showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R = 0.9-0.98). However, limited agreement was seen between TbN (R = 0.73) and TbSb (R = 0.59) due to methodological differences in how spacing is evaluated. Microstructural parameters generated from manual and automatic segmentations showed high correlation across all measures. Using the CTAn pipeline yielded strong R2 values (0.83-0.96) and very strong agreement based on ICC (0.90-0.98). The ITK pipeline yielded similarly high R2 values (0.91-0.96, except for TbN (0.77)), and ICC values (0.88-0.98). The automated segmentations yield lower average values for BV, TV and BV/TV (ranging from 14 % to 6.3 %), but differences were not found to be influenced by the mean ROI values. This integrated pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone microstructure. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of microstructural analysis of trabecular bone across different research groups.


Contemporary use of coronary artery calcium for the allocation of aspirin in light of the 2022 USPSTF guideline recommendations.
Aspirin has been a cornerstone for primary prevention of cardiovascular disease for decades, however its use in primary prevention has been challenged in recent years. The 2022 USPSTF guidelines lowered the recommendation for the use of aspirin in primary prevention based on the recent trials that demonstrated a low to neutral benefit and an increased bleeding risk with the use of aspirin in primary prevention. However, these trials enrolled patients at a relatively low risk for atherosclerotic cardiovascular disease (ASCVD) and higher bleeding risk which could have contributed to the negative results of the trials. ASCVD prevention is ideal when therapies are personalized based on individual risk. Coronary artery calcium (CAC) score is a robust marker of atherosclerosis and reliably predicts the ASCVD risk in a graded fashion. Several studies have demonstrated the use of a CAC≥100 to identify patients who will benefit from the use of aspirin in primary prevention. Furthermore, a CAC=0 identifies patients in whom aspirin would lead to net harm. In the continuum of risk from primary to secondary prevention, CAC is likely to identify the level of risk that warrants aspirin use in patients with subclinical ASCVD. The ACC/AHA 2019 primary prevention guidelines recommend the use of CAC to reclassify risk and guide personalized allocation of statins and aspirin. Although the USPSTF has not endorsed the use of CAC in the past, given an extensive body of evidence for use of CAC to guide primary preventive therapies including aspirin, it seems reasonable to use CAC to identify the level of plaque burden at which the benefit of aspirin outweighs its risk in clinical practice and personalize theallocation of aspirin in primary prevention. Future studies and randomized trials assessing the role of preventive therapies should use CAC score for risk stratification.


The role of attention and study time in explicit and implicit memory for unfamiliar visual stimuli.
The effects of limited attentional resources and study time on explicit and implicit memory were studied using Schacter and Cooper's possible and impossible objects in their recognition and object decision paradigm. In one experiment, when attention at study was limited by a flanking digits procedure, object recognition was diminished but object decision priming for possible objects was unaffected; in another experiment, limiting attention plus reducing stimulus study time impaired object recognition and eliminated object priming. Recognition memory and perceptual priming for previously unfamiliar visual stimuli were both influenced by attention, although to different degrees. The intervening variable of study time determined the degree to which priming was affected by attentional resources. These results support a limited capacity attentional model for both recognition and perceptual priming of unfamiliar visual stimuli, and they highlight the need for assessing the interaction of attentional resources and study time in explicit and implicit memory tasks.


Treatment of juvenile osteochondritis dissecans and osteochondritis dissecans of the knee.
JOCD and OCD are distinct conditions. The former has a much more favorable prognosis than the latter. Unrecognized trauma cumulating from activities of daily living and sports produces subchondral stress fractures that eventually become symptomatic and are recognized as JOCD. If JOCD does not heal by bony union prior to distal femoral epiphyseal closure, OCD results. Since JOCD is a fracture, any method used to stimulate fracture healing, except joint immobilization, should be employed. Careful monitoring of the patient's progress is essential and is most sensitively accomplished with joint scintigraphy. Historical evidence of the benign nature of JOCD is dubious and not consistent with clinical observations. The surgical precepts for treating patients in whom conservative treatment of JOCD fails and patients with OCD are traditional orthopedic concepts. Revascularization of the fragment followed by joint motion are the dictums of surgical success.


Insights into the oligomerization state-helicase activity relationship of West Nile virus NS3 NTPase/helicase.
West Nile virus (WNV) is a member of the Flaviviridae family of positive-strand RNA viruses. Its viral RNA is translated to produce a polyprotein precursor that is further processed into three structural and seven non-structural proteins. The non-structural protein 3 (NS3) possess both protease and helicase activities. The C-terminal portion of the NS3 contains the ATPase/helicase domain presumably involved in viral replication. This domain has been expressed in Escherichia coli, purified in soluble form and structurally characterized. As judged by analytical centrifugation and size exclusion chromatography, the purified enzyme behaves as a monomer in solution. It has ATPase activity that is stimulated by the presence of RNA and single-stranded DNA molecules (ssDNA). However, we were unable to detect helicase activity at protein concentrations up to 500nM. It has been reported that longer constructions of NS3 helicase domains from other flavivirus, like those which include residues of the linker region between the protease and the helicase domains, have helicase activity. Since all the conformational features of the purified WNV NS3 domain are those of a native protein, it is tempting to assume that the linker region plays a critical role in determining the protein-protein interactions that leads to the formation of the active oligomer.


Imidazole modification of aggressive behaviour in rats and mice.
Imidazole (IMID) strongly affected aggressive behaviour in rodents, the type of influence varying according to the experimental model considered. In morphine-dependent rats, during naloxone-induced abstinence syndrome, signs of irritability and mild aggressiveness were observed after treatment with IMID. Moreover, IMID enhanced aggressive posturing elicited by the dopaminergic (DA) agonist lisuride, whether rats were affected by morphine-withdrawal symptoms or not. In isolation test in mice, on the other hand, IMID inhibited aggression. Imidazoleacetic acid, one of the metabolites of histamine, comparatively investigated in the same behavioural tests, never potentiated lisuride-induced aggressiveness in rats; moreover, it was more effective than IMID in inhibiting aggression in isolated mice.


Age-related differences in sensitivity of peripheral blood monocytes to lipopolysaccharide and Staphylococcus aureus toxin B in atopic dermatitis.
As shown by atopy patch tests, atopic dermatitis (AD) is dominated in its acute phase by the development of a specific T(H)2 response after exposure of the skin to common environmental antigens. Relying on our previous data showing that Staphylococcus aureus enterotoxin B (SEB) induced the activation of monocyte-derived dendritic cells (DCs) through Toll-like receptor (TLR)2 and that SEB-pulsed DCs commit allogenic naive T cells into T(H)2, we assessed monocytes sensitivity to SEB and lipopolysaccharide (LPS) in a group of children and adult patients with AD. Monocytes from AD patients (15 adults with mostly severe disease and 15 children with mild to moderate disease) exhibited an activated and tolerant state as supported by (i) secretion of large amounts of IL-6, IL-10, and tumor necrosis factor-alpha even in the absence of stimulation; (ii) their inability to modulate neither HLA-DR and CD54 nor TLR2 and TLR4 expression after in vitro challenge with SEB; (iii) inhibition of IL-12p70 secretion in response to LPS. Interestingly, monocytes from some of the children studied responded to in vitro challenge with LPS, suggesting new hypotheses to explain disease regression. Our data support the notion that monitoring sensitivity of monocytes to bacterial toxins could prove useful to assess disease progression and prognosis in AD.


Priming and induction of eosinophil trafficking in guinea-pig cutaneous inflammation by tumour necrosis factor alpha.
Tissue eosinophilia is a hallmark of allergic and parasitic diseases. Priming mechanisms may play an important role in mediating the process of eosinophil accumulation in these conditions. We have previously shown that blockade of tumour necrosis factor alpha (TNFalpha) inhibited the capacity of lipopolysaccharide to prime skin sites for chemoattractant-induced eosinophil recruitment. The present study was carried out to investigate the capacity of TNFalpha to prime an inflammatory site for enhanced eosinophil accumulation. Initial experiments investigated the capacity of TNFalpha itself to induce eosinophil accumulation. Intradermal injection of murine TNFalpha (10-300 ng per site) in the guinea-pig induced significant accumulation of 111In-eosinophils. Kinetic studies showed the response to be delayed in onset and inhibited by cycloheximide, consistent with a dependency on protein synthesis. Trafficking of 111In-eosinophils to sites treated for 2 h with TNFalpha (10-100 ng per site) was inhibited by monoclonal antibodies (mAbs) against beta2 or alpha4 integrins. Intradermal injection of a low dose (3 ng) of TNFalpha (which by itself had no significant effect on eosinophil trafficking) prior to chemoattractants or antigen in sensitized skin sites, induced significant priming of eosinophil accumulation. Recruitment of both 111In-eosinophils and endogenous eosinophils was enhanced. Trafficking to TNFalpha-primed responses was dependent on protein synthesis and beta2 integrins. In contrast, the alpha4 integrin mAb failed to inhibit the TNFalpha primed response. Thus, TNFalpha can induce and also prime eosinophil recruitment in guinea-pig skin. Our results provide further evidence that this cytokine may be an important mediator of allergic- or parasite-induced eosinophilic inflammation.


Five-year Antibody Persistence and Safety After a Single Dose of Combined Haemophilus influenzae Type B Neisseria meningitidis Serogroup C-Tetanus Toxoid Conjugate Vaccine in Haemophilus influenzae Type B-primed Toddlers.
Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC). This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naïve toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit. The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers ≥1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations ≥0.15 μg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported. Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations ≥0.15 μg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers ≥1:8 was low (≤25%), suggesting that a MenC booster dose may be warranted before adolescence.


18F-Fluorodeoxyglucose Positron Emission Tomography Parameters can Predict Long-Term Outcome Following Trimodality Treatment for Oesophageal Cancer.
18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is routinely used for the pre-treatment staging of oesophageal or gastro-oesophageal junction cancers (EGEJC). The aim of this study was to identify objective 18FDG-PET/CT-derived parameters that can aid in predicting the patterns of recurrence and prognostication in patients with EGEJC. EGEJC patients referred for consideration of preoperative chemoradiation therapy were identified and clinicopathological data were collected. 18FDG-PET/CT imaging data were reviewed and correlated with treatment outcomes. Maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis were assessed and association with recurrence-free survival (RFS), locoregional recurrence-free survival (LR-RFS), oesophageal cancer-specific survival (ECSS) and overall survival were evaluated using receiver operating characteristic curves, as well as Cox regression and Kaplan-Meier models. In total, 191 EGEJC patients completed trimodality treatment and 164 with 18FDG-PET/CT data were included in this analysis. At the time of analysis, 15 (9.1%), 70 (42.7%) and two (1.2%) patients were noted to have locoregional, distant and both locoregional and distant metastases, respectively. The median RFS was 30 months (9.6-50.4) and the 5-year RFS was 31.1%. The 5-year overall survival and ECSS were both noted to be 34.8%. Pre-treatment MTV25 > 28.5 cm3 (P = 0.029), MTV40 > 12.4 cm3 (P = 0.018) and MTV50 > 10.2 cm3 (P = 0.005) predicted for worse LR-RFS, ECSS and overall survival for MTV definition of voxels ≥25%, 40% and 50% of SUVmax. 18FDG-PET/CT parameters MTV and total lesion glycolysis are useful prognostic tools to predict for LR-RFS, ECSS and overall survival in EGEJC. MTV had the highest accuracy in predicting clinical outcomes. The volume cut-off points we identified for different MTV thresholds predicted outcomes with significant accuracy and may potentially be used for decision making in clinical practice.


Electromyographic evaluation of trunk core muscles during Pilates exercise on different supporting bases.
To evaluate the electromyographic (EMG) activity of the rectus abdominis (RA) and internal oblique (IO) muscles during Pilates exercise on different trunk supporting bases. Sixteen female Pilates practitioners participated in the study. EMG of the RA and OI muscles was evaluated during the double leg stretch (DLS) exercise on three different supporting bases - mat, long box, and short box. Trunk stability varies according to the size and type of the base. To normalize the data, the RMS value (EMG) obtained during the DLS exercise was divided by the RMS value from the torque test - the maximal voluntary isometric contraction (MVIC) - and multiplied by 100 (%MVIC). One-way repeated-measured analysis of variance (ANOVA) and Bonferroni tests were used to compare data concerning the supporting bases and Student t-test regarding the muscles (p < 0.05). The comparison among the bases involving each muscle - RA or IO (p < 0.05) - showed significant difference (%MVIC) between the mat and the short box. No significant difference was observed between the muscles concerning the exercise on the mat (p = 0.9266), on the long box (p = 0.5113) and on the short box (p = 0.2972). The short box increased the activity of the rectus abdominis and internal oblique muscles during exercise. The DLS exercise was able to challenge the stability of the trunk and thus recruit its stabilizer and mobilizer muscles at the same intensity.


Simplifying prehospital analgesia. Why certain medications should or should not be used for pain management in the field.
Prehospital analgesia can be safely provided with only three agents: fentanyl, morphine and the mixed-gas nitrous oxide/oxygen. Of these three, fentanyl is by far the best agent for general EMS analgesic therapy by paramedics. However, to initiate prehospital analgesia earlier in the EMS response time frame, EMT's should administer nitrous oxide/oxygen. This protocol can easily be added to the EMT education program or through a continuing education session. All of the other agents discussed have absolutely no role in modern prehospital care.


Chronic unilateral groin pain in a young patient who injects drugs: a case report of needle fragment retentions.
Subcutaneously retained needle fragments in people who inject drugs (PWIDs) are a possible cause of local symptoms, most commonly pain and infections. It remains unknown how common retained needle fragments are among PWIDs. A young PWID consulted a primary care physician due to chronic left-sided groin pain. The patient suspected retention of a broken needle as the cause. She had used a re-used needle 3 months earlier. A plain pelvic radiograph confirmed a needle fragment in the patient's left groin, and a computed tomography scan located it adjacent to the femoral artery and vein. Another asymptomatic needle fragment was found in the right groin. Needle fragments are possible causes of local symptoms among PWIDs. The clinical examination presents a potential risk of needlestick injury to the examiner, especially because patients may not be aware of all needle fragments as some are asymptomatic.


On the symmetry and asymmetry of the bifurcation of the common carotid artery: a study of bilateral carotid angiograms in 100 adults.
Bilateral carotid angiograms of the neck in 100 consecutive adult patients show the bifurcation of the left common carotid artery to be located cranial to the right in 50% of the cases, while the right bifurcation was higher in 22%. The origin of the internal carotid artery was at the dorsal or dorsolateral aspect of the common carotid artery in 82% on the right side and in 94% on the left, while a dorsomedial or medial origin was found in 18% on the right side and in 6% on the left.


rhFGF-21 accelerates corneal epithelial wound healing through the attenuation of oxidative stress and inflammatory mediators in diabetic mice.
Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1β, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.


Interaural level difference-dependent gain control and synaptic scaling underlying binaural computation.
Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a "push-pull"-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation of contralaterally evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes.


[Incorporation of the gender perspective in community health. SESPAS Report 2018].
The concepts of community health and gender perspective are often misunderstood or interpreted differently between different sectors and disciplines. For this reason, this article starts with the definition of both concepts and continues with a proposal for the incorporation of a gender perspective in community health. The gender norms determine different pathways and opportunities for people according to their sex, which are associated with gender inequalities in health and therefore must be incorporated in community health interventions. The gender perspective requires considering gender inequalities in power, in the access to and control over resources, the sexual division of labour and gender socialization in all phases of community health strategy implementation. Incorporating a gender perspective in community health is not only a matter of ethics and justice but also of the effectiveness of interventions.


Are psychology's tribes ready to form a nation?
Collaboration between social psychologists and cognitive neuroscientists is giving rise to a new approach that its practitioners call 'social cognitive neuroscience'. Scientists from each discipline are using the theories and techniques of the other to generate new answers to fundamental questions about attitudes, beliefs, the self, moral judgment, and other issues. Is this interdisciplinary endeavor an exercise in wishful thinking and good intentions, or is it a preview of psychology's future?


Stimulatory effects of protein synthesis inhibitors on the spreading rate of 3T3 cells.
Three protein synthesis inhibitors, puromycin, cycloheximide and anisomycin were found to increase the rate of spreading of Swiss-3T3 cells after 1 h incubation in the presence of low concentrations of serum. Data from experiments with anisomycin suggest that this effect is roughly proportional to the extent of inhibition of protein synthesis.


American College of Surgeons National Surgical Quality Improvement Program assessment of risk factors for 30-day unplanned readmission in patients undergoing head and neck surgery requiring free tissue reconstruction.
Unplanned readmissions have become a metric for measuring quality of care. We analyzed the factors associated with 30-day unplanned readmission (30dUR) following head and neck cancer resections that included free tissue reconstruction (FTR). The 2012-2014 ACS-National Surgical Quality Improvement Program (NSQIP) data set was queried. Univariate and multivariate logistic regression analyses were performed. Out of 1114 cases, 121 had a 30dUR. The most common reasons were wound complications, including incisional infections, hematoma, and hemorrhage. A significant independent risk factor for 30dUR included a clean/contaminated wound class (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.20-4.76). Patients receiving an osseous FTR had lower readmission rates (OR, 0.51; CI, 0.27-0.91). Discharge destination had no statistical significance. Based on the NSQIP data set, 10.9% of patients receiving an FTR for head and neck malignancy had a 30dUR. Although large, population-based data sets have limitations, these results elucidate that these patients are at an increased risk for unplanned readmissions, which can guide patient expectations and discharge planning.


Differential mechanisms of hepatic vascular dysregulation with mild vs. moderate ischemia-reperfusion.
Endotoxemia produces hepatic vascular dysregulation resulting from inhibition of endothelin (ET)-stimulated NO production. Mechanisms include overexpression of caveolin-1 (Cav-1) and altered phosphorylation of endothelial nitric oxide (NO) synthase (NOS; eNOS) in sinusoidal endothelial cells. Since ischemia-reperfusion (I/R) also causes vascular dysregulation, we tested whether the mechanisms are the same. Rats were exposed to either mild (30 min) or moderate (60 min) hepatic ischemia in vivo followed by reperfusion (6 h). Livers were harvested and prepared into precision-cut liver slices for in vitro analysis of NOS activity and regulation. Both I/R injuries significantly abrogated both the ET-1 (1 microM) and the ET(B) receptor agonist (IRL-1620, 0.5 microM)-mediated stimulation of NOS activity. 30 min I/R resulted in overexpression of Cav-1 and loss of ET-stimulated phosphorylation of Ser1177 on eNOS, consistent with an inflammatory response. Sixty-minute I/R also resulted in loss of ET-stimulated Ser1177 phosphorylation, but Cav-1 expression was not altered. Moreover, expression of ET(B) receptors was significantly decreased. This suggests that the failure of ET to activate eNOS following 60-min I/R is associated with decreased protein expression consistent with ischemic injury. Thus hepatic vascular dysregulation following I/R is mediated by inflammatory mechanisms with mild I/R whereas ischemic mechanisms dominate following more severe I/R stress.


The LFU ratio R π in the Standard Model and beyond.
We discuss the possibility of performing precise tests of μ / e universality in B → π ℓ + ℓ - decays. We show that in wide regions of the dilepton invariant mass spectrum the ratio between muonic and electronic decay widths can be predicted with high accuracy, both within and beyond the Standard Model. We present numerical expressions which can be used to extract precise information on short-distance dynamics if a deviation from universality is observed in the data.


Separation of non-proliferating from proliferating thymic lymphocytes based on light scatter analysis.
Two populations of thymic lymphocytes from eight-week-old mice were separated based on the light scatter intensity they generated while passing through a flow cell analyser. The two populations were subsequently studied morphologically and analysed for the relative amount of DNA present in each cell. Cells having a low light scatter intensity had a high nuclear:cytoplasmic ratio, a heterochromatic nucleus, and a proliferative index (S + G2 + M) of only 23%. Cells with a high light scatter intensity had a low nuclear:cytoplasmic ratio, dispersed chromatin, frequently a uropod with budding microvilli and a proliferative index of 71%. The low light scatter cells resemble small cortical thymocytes or lymphocytes from the thoracic duct described by others. The highest light scatter cells resemble medium lymphocytes shown by others to be proliferative.


Increase in amino acids in the pons after sleep deprivation: a pilot study using proton magnetic resonance spectroscopy.
Total sleep deprivation (TSD) is an efficient method to relieve depression. An involvement of GABAergic and glutamatergic neurotransmission in the pathophysiology of depression and the mechanism of action of TSD has been suggested. To directly assess the content of GABA, glutamate (Glu) and glutamine (Gln) before and after TSD, we estimated their concentrations in four brain regions in six healthy subjects using proton magnetic resonance spectroscopy. The unresolved estimate of GABA, Glu and Gln, as well as GABA and Gln were increased in the pons after 24 h of TSD, the effect being prominent in three subjects. There were no significant changes in the hypothalamus, thalamus or parietooccipital cortex. These preliminary data support earlier animal data and indirect findings in humans suggesting that GABA and Gln, especially in the pontine structures, may play a key role in the mechanism of TSD.


Filmless medical imaging: experiences of the Massachusetts General Hospital.
As the concept of picture archival communication systems (PACS) gathers momentum, the vision of a filmless digital department and digital image management has become a reality. This report will discuss the experiences of a major health-care institution with implementation of a large-scale PACS. Specifically, we discuss success with a modular, nonproprietary, multivendor solution that offers flexibility and state of the art functionality at our institution.


Machinery of protein folding and unfolding.
During the past two years, a large amount of biochemical, biophysical and low- to high-resolution structural data have provided mechanistic insights into the machinery of protein folding and unfolding. It has emerged that dual functionality in terms of folding and unfolding might exist for some systems. The majority of folding/unfolding machines adopt oligomeric ring structures in a cooperative fashion and utilise the conformational changes induced by ATP binding/hydrolysis for their specific functions.


Perceived need for care and stigma experiences among individuals with methamphetamine-related admissions to inpatient mental health wards.
There are gaps in our understanding of treatment needs among people who use methamphetamine. We examined the demographics, perceived treatment needs, barriers to accessing care, and stigma experienced by an inpatient sample of people who use methamphetamine. This study surveyed a convenience sample of patients admitted to psychiatry wards with a history of methamphetamine use in Winnipeg, Canada, between May 1 and July 31, 2019. The Perceived Need for Care Questionnaire (PNCQ-9) was used to assess treatment needs and barriers to care, and the Substance Use Stigma Mechanisms Scale (SU-SMS) was used to assess enacted, anticipated, and internalized stigma. Prevalence rates of perceived need, stigma, and demographic variables were determined. A total of 103 potential participants were identified, with 34 completing the survey. The most common age group was 21-30 years of age (41.2%); an approximate equal number of men and women; and almost all were single and never married (91.1%). Rates of perceived need for care were very high across all treatment types, including 91% identifying a need for medication treatment for their mental health or substance use. Despite the majority receiving care across the seven types of care described in the PNCQ-9, most felt they did not receive enough care. Unmet need for care was therefore high in many categories, including rates of 87% for counselling and skills training. The most common barriers to having needs met were a desire to self-manage substance use, and not receiving care after asking for help. Almost all participants reported experiencing stigma (94%). Stigma from family was endorsed significantly more than stigma from health care providers (p = 0.005). The average hospitalized person who uses methamphetamine in this sample is young, single, and has not completed any post-secondary education. High rates of perceived treatment need suggest an awareness of problems with methamphetamine, yet most interventions are perceived as inadequate. People who used methamphetamine felt highly stigmatized, particularly by their family members. Trial registration Registered with the Health Research Ethics Board at the University of Manitoba (Number HS22605 (H2019:072), renewed February 14, 2022).


Malignant melanomas contain only the vimentin type of intermediate filaments.
Six malignant melanomas have been examined for the type of intermediate filament they contain. All six cases showed positive staining of intermediate filaments with antibodies to vimentin, with cells containing large numbers of melanosomes being stained less strongly in general. The tumor cells did not react with antibodies to keratin, desmin, neurofilaments or glial fibrillary acidic protein. Thus typing of intermediate filaments can distinguish melanoma from undifferentiated carcinoma, but not from lymphoma or sarcoma. Since melanocytes are known to be vimentin positive, and since most of the samples we studied were from metastases, these results are a further indication that the intermediate filament type typical of the parental cell is retained in the metastases, as well as in the primaries of solid tumours. The implications of vimentin positivity for the histiogenesis of the melanocyte are also discussed.


Synthesis and Application of MOF-808 Decorated with Folic Acid-Conjugated Chitosan as a Strong Nanocarrier for the Targeted Drug Delivery of Quercetin.
Herein, MOF-808 (MOF = metal-organic framework) based on zirconium tricarboxylate was synthesized to investigate the influence of decorating groups of folic acid-conjugated chitosan (CS-FA) on drug-delivery efficiency. Quercetin (QU) was loaded on nondecorated MOF-808 and then decorated with a folic acid-chitosan conjugate. The properties and activities of modified MOF-808 were compared with unmodified MOF-808. QU@MOF-808@CS-FA exhibited favorable drug-release properties, high drug-loading capacity, efficient targeting capability, and pH-dependent release behavior, highlighting the critical role of organic modification. A variety of characterization techniques were used to characterize MOF nanoparticles, including Fourier transform infrared, powder X-ray diffraction, field-emission scanning electron microscopy, energy-dispersive X-ray, transmission electron microscopy, Brunauer-Emmett-Teller, ζ potential, and 1H NMR. Additionally, Monte Carlo simulation calculations were carried out to examine the interactions between the structures of MOF-808 and QU. An in vitro cytotoxicity test was conducted, and the results identified that QU@MOF-808@CS-FA demonstrated more superior therapeutics than QU@MOF-808 on FR-positive MCF7 cancerous cells. On the basis of the results, QU@MOF-808@CS-FA is a promising drug carrier by selective targeting and sustained release.


Effect of peptide YY on insulin release stimulated by 2-deoxyglucose and neuropeptides in dogs.
Peptide YY (PYY) is a hormone released from gut after a meal. The objective of this study was to determine the effect of PYY on insulin release stimulated by either 2-deoxyglucose (2-DG) or neuropeptides in conscious dogs with gastric and duodenal fistulas. In control experiments dogs received either 2-DG (75 mg/kg i.v. bolus) or atropine (25 micrograms/kg bolus followed by 20 micrograms/kg/h i.v.) plus 2-DG (75 mg/kg i.v.) or bethanechol (80 micrograms/kg/h i.v.) or vasoactive intestinal peptide (VIP, 4 micrograms/kg i.v. bolus) or gastrin-releasing peptide (GRP, 400 pmol/kg/h i.v.) or tetragastrin (G4, 100 micrograms/dog, i.v. bolus). On separate days, PYY was also infused intravenously in combination with one of the above stimulants. Given intravenously, PYY (200, 400 pmol/kg/h) significantly inhibited 2-DG stimulated-insulin secretion in a dose-dependent fashion. This inhibitory effect also existed in the presence of atropine. Peptide YY (400 pmol/kg/h) depressed the insulin levels in response to GRP or G4 but failed to inhibit bethanechol- and VIP-stimulated insulin release. After administration of the above stimulants, PYY did not modify the blood sugar concentrations. These results demonstrated that PYY might inhibit the cephalic phase of insulin release from dogs triggered by 2-DG and by the neuropeptides GRP and G4. Thus, PYY may play a negative feedback regulatory role on insulin release.


Autoimmunity in myocardial infarction.
Myocardial infarction is associated with an immune response. Physiological inflammation response causes self-repair and protection, while pathological autoimmune response leads to ventricular remodeling and heart failure. Laying emphasis on regulating the immune function may become a new target for the prevention of heart failure after myocardial infarction. This review focuses on the mechanism of immune-mediated ventricular remodeling and the immune therapy after myocardial infarction.


How interruptions in students' medical education affect their clinical performance evaluations.
The enrollment records of 380 medical students from the graduating class of 1983-1988 at a four-year medical school were compared with the students' performances on two measures, third-year clinical rotation grades and National Board of Medical Examiners Part II examination (NBME-II) scores. Thirty-seven students (9.7%) interrupted their progress through medical school for negative (school-initiated, academic) reasons or neutral (student-initiated, nonacademic, or personal) reasons. On both performance measures, the students in the neutral group performed similarly to regular-progress students and significantly better than students who interrupted their attendance in medical school for negative reasons.


The absence of acute tolerance during remifentanil infusion in volunteers.
The development of acute opioid tolerance in humans remains controversial. We tested the hypothesis that continuous remifentanil infusion leads to rapid development of opioid tolerance. Twenty healthy male volunteers were enrolled onto a randomized, placebo-controlled, double-blinded, cross-over design study to receive a 3 h continuous infusion of remifentanil (0.08 microg x kg(-1) x min(-1)) or saline. Test procedures included determination of pain perception thresholds and pain tolerance thresholds to heat and cold and neuroselective sine wave constant current at 5 Hz and 250 Hz. Test procedures were performed at baseline and then repeated at 25, 55, 85, 115, and 160 min (heat/cold) and at 35, 65, 95, 125, and 170 min (electrical current) during infusion. No significant decrease of the pain threshold devolutions between 55 and 180 min after the start of infusion of remifentanil could be detected. In conclusion, no development of acute opioid tolerance was observed during constant remifentanil infusion of 3 h in volunteers. The opioid remifentanil was applied to 20 volunteers at a constant concentration for 3 h while pain thresholds to temperature and current were repeatedly assessed. Our aim was to study whether thresholds decrease over time because of the rapid development of opioid tolerance. No development of rapid opioid tolerance was observed.


Single and combined effect of tetracycline and polyethylene microplastics on two drought contrasting cultivars of Oryza sativa L. (Rice) under drought stress.
Co-exposure of tetracycline (TC) and polyethylene microplastic (MP-PE) pollution might result in more intricate effects on rice growth and grain quality. In present study, two different rice cultivars of contrasting drought tolerance, Hanyou73 (H73, drought-resistant) and Quanyou280 (Q280, drought-sensitive) were grown on MP-PE and TC-contaminated soils under drought. It was found that drought stress had different influence on TC accumulation in the two rice cultivars. H73 accumulated more TC in leaves and grains without drought stress while Q280 accumulated more TC under drought stress. Furthermore, metabolomics results demonstrated that under drought stress, about 80 % of metabolites in H73 and 95 % in Q280 were down-regulated as compared to non-drought treatments. These findings provide insights into the effects of TC and MP-PE with and without drought stress on potential risks to rice growth and grain quality, which has implications on rice production and cultivar election under multiple-stress conditions.


Sulfated N-linked oligosaccharides affect secretion but are not essential for the transport, proteolytic processing, and sorting of lysosomal enzymes in Dictyostelium discoideum.
Although previous studies have indicated that N-linked oligosaccharides on lysosomal enzymes in Dictyostelium discoideum are extensively phosphorylated and sulfated, the role of these modifications in the sorting and function of these enzymes remains to be determined. We have used radiolabel pulse-chase, subcellular fractionation, and immunofluorescence microscopy to analyze the transport, processing, secretion, and sorting of two lysosomal enzymes in a mutant, HL244, which is almost completely defective in sulfation. [3H]Mannose-labeled N-linked oligosaccharides were released from immunoprecipitated alpha-mannosidase and beta-glucosidase of HL244 by digestion with peptide: N-glycosidase. The size, Man9-10GlcNAc2, and processing of the neutral species were similar to that found in the wild type, but the anionic oligosaccharides were less charged than those from the wild-type enzymes. All of the negative charges on the oligosaccharides for HL244 were due to the presence of 1, 2, or 3 phosphodiesters and not to sulfate esters. The rate of proteolytic processing of precursor forms of alpha-mannosidase and beta-glucosidase to mature forms in HL244 was identical to wild type. The precursor polypeptides in the mutant and the wild type were membrane associated until being processed to mature forms; therefore, sulfated sugars are not essential for this association. Furthermore, the rate of transport of alpha-mannosidase and beta-glucosidase from the endoplasmic reticulum to the Golgi complex was normal in the mutant as determined by the rate at which the newly synthesized proteins became resistant to the enzyme, endo-beta-N-acetylglucosaminidase H. There was no increase in the percentage of newly synthesized mutant precursors which escaped sorting and were secreted, and the intracellularly retained lysosomal enzymes were properly localized to lysosomes as determined by fractionation of cell organelles on Percoll gradients and immunofluorescence microscopy. However, the mutant secreted lysosomally localized mature forms of the enzymes at 2-fold lower rates than wild-type cells during both growth and during starvation conditions that stimulate secretion. Furthermore, the mutant was more resistant to the effects of chloroquine treatment which results in the missorting and oversecretion of lysosomal enzymes. Together, these results suggest that sulfation of N-linked oligosaccharides is not essential for the transport, processing, or sorting of lysosomal enzymes in D. discoideum, but these modified oligosaccharides may function in the secretion of mature forms of the enzymes from lysosomes.


Quantitative proteomics using uniform (15)N-labeling, MASCOT, and the trans-proteomic pipeline.
Stable isotope labeling combined with MS is a powerful method for measuring relative protein abundances, for instance, by differential metabolic labeling of some or all amino acids with (14)N and (15)N in cell culture or hydroponic media. These and most other types of quantitative proteomics experiments using high-throughput technologies, such as LC-MS/MS, generate large amounts of raw MS data. This data needs to be processed efficiently and automatically, from the mass spectrometer to statistically evaluated protein identifications and abundance ratios. This paper describes in detail an approach to the automated analysis of uniformly (14)N/(15)N-labeled proteins using MASCOT peptide identification in conjunction with the trans-proteomic pipeline (TPP) and a few scripts to integrate the analysis workflow. Two large proteomic datasets from uniformly labeled Arabidopsis thaliana were used to illustrate the analysis pipeline. The pipeline can be fully automated and uses only common or freely available software.


Development of cortical connections as measured by EEG coherence and phase delays.
The purpose of this study was to explore human development of EEG coherence and phase differences over the period from infancy to 16 years of age. The electroencephalogram (EEG) was recorded from 19 scalp locations from 458 subjects ranging in age from 2 months to 16.67 years. EEG coherence and EEG phase differences were computed for the left and right hemispheres in the posterior-to-anterior direction (O1/2-P3/4, O1/2-C3/4, O1/2-F3/4, and O1/2-Fp1/2) and the anterior-to- posterior direction (Fp1/2-F3/4, Fp1/2-C3/4, Fp1/2-P3/4, and Fp1/2-O1/2) in the beta frequency band (13-25 Hz). Sliding averages of EEG coherence and phase were computed using 1 year averages and 9 month overlapping that produced 64 means from 0.44 years of age to 16.22 years of age. Rhythmic oscillations in coherence and phase were noted in all electrode combinations. Different developmental trajectories were present for coherence and phase differences and for anterior-to-posterior and posterior-to-anterior directions and inter-electrode distance. Large changes in EEG coherence and phase were present from approximately 6 months to 4 years of age followed by a significant linear trend to higher coherence in short distance inter-electrode distances and longer phase delays in long inter-electrode distances. The results are consistent with a genetic model of rhythmic long term connection formation that occurs in cycles along a curvilinear trajectory toward adulthood. Competition for dendritic space, development of complexity, and nonlinear dynamic oscillations are discussed.


Automated landmarking and labeling of fully and partially scanned spinal columns in CT images.
The spinal column is one of the most distinguishable structures in CT scans of the superior part of the human body. It is not necessary to segment the spinal column in order to use it as a frame of reference. It is sufficient to place landmarks and the appropriate anatomical labels at intervertebral disks and vertebrae. In this paper, we present an automated system for landmarking and labeling spinal columns in 3D CT datasets. We designed this framework with two goals in mind. First, we relaxed input data requirements found in the literature, and we label both full and partial spine scans. Secondly, we intended to fulfill the performance requirement for daily clinical use and developed a high throughput system capable of processing thousands of slices in just a few minutes. To accomplish the aforementioned goals, we encoded structural knowledge from training data in probabilistic boosting trees and used it to detect efficiently the spinal canal, intervertebral disks, and three reference regions responsible for initializing the landmarking and labeling. Final landmarks and labels are selected by Markov Random Field-based matches of newly introduced 3-disk models. The framework has been tested on 36 CT images having at least one of the regions around the thoracic first ribs, the thoracic twelfth ribs, or the sacrum. In an average time of 2 min, we achieved a correct labeling in 35 cases with precision of 99.0% and recall of 97.2%. Additionally, we present results assuming none of the three reference regions could be detected.


CpG-ODN-based immunotherapy is effective in controlling the growth of metastasized tumor cells.
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG-ODN) act as potent immune stimulators by activating innate immunity through toll-like receptor 9. These immunomodulatory effects of CpG-ODN have been reported to be associated with anti-tumor immunity. In this study, we used a murine B16F10 melanoma model and a CT26 colon cancer model to assess whether CpG-ODN-based immunotherapy was effective in inhibiting tumor cells that have already metastasized to distant organs. Systemic administration of CpG-ODN after melanoma cell injection resulted in a significant inhibition of pulmonary colonization. When CpG-ODN was administered after tumor cell injection, it also inhibited pulmonary metastasis of the tumor cells, albeit to a lesser degree in the latter case. Systemic administration of CpG-ODN after subcutaneous inoculation of CT26 colon cancer cells diminished pulmonary metastasis from the primary tumor sites. Additionally, CpG-ODN also inhibited the growth of pulmonary colonization of the colon tumor cells when CpG-ODN was administered after the primary tumors had been surgically removed. These data indicate that CpG-ODN was effective in inhibiting pulmonary metastasis of the B16F10 melanoma and CT26 colon cancer cells, as well as the growth of metastasized tumor cells. Our results suggest that CpG-ODN-based immunotherapy may be beneficial in controlling micrometastasis after surgery in clinical settings.


[Reye's syndrome].
Reye's syndrome, characterized by acute encephalopathy and fatty degeneration of the viscera with hepatic failure, is a life-threatening illness that affects children of all ages. Although Reye's syndrome has been investigated extensively, its etiology and pathogenesis remain obscure. Metabolic pathophysiology appears to include a process affecting liver mitochondria. Recently disturbances in fatty acid oxidation have been described with a similar clinical picture. The cause of these events is presumably related to triggering viral illnesses, in ways that are unclear. Since prompt treatment might provide a better chance for recovery, early diagnosis is important.


The significance of the pars plana exudate in pars planitis.
We divided 61 patients (111 eyes) with pars planitis into three groups based on clinical appearance. Patients in Group I had bilateral vitreous cells and bilateral pars plana exudates (36 patients, 72 eyes); patients in Group II had bilateral vitreous cells but a pars plana exudate in one eye only (14 patients, 28 eyes); and patients in Group III had vitreous cells and exudate formation in the single eye involved (11 patients, 11 eyes). The presence of a pars plana exudate was associated with more severe vitreous disease and increased incidence of cystoid macular edema.


[HIV and dentistry. Part 5. Practice hygiene].
When complying a good standard hygiene protocol in the dental office the risk of cross-infection of whatever type of microorganism, including the hepatitis-B-virus and HIV, is almost eliminated.


Dimerization is essential for HAb18G/CD147 promoting tumor invasion via MAPK pathway.
HAb18G/CD147 is a transmembrane glycoprotein of the immunoglobulin superfamily (IgSF) and is reported to be correlated with invasion and metastasis of many cancers. The crystal structure of HAb18G/CD147 ectodomain has shown that it can form homodimers in crystal. However, the functional significance of HAb18G/CD147 dimerization remains unclear. In the present study, guided by the crystal structure, we performed extensive mutational and functional studies to identify residues critical for dimerization and molecular function of HAb18G/CD147. Fourteen mutants were purified and evaluated for their ability to form dimers in solution and in living cells. Subsequent functional validation revealed that K63E and S193A mutants, which disrupted CD147 dimerization both in solution and in living cells, showed clearly dominant-negative effects on MAPK activation, MMP2 induction and invasiveness in tumor cells. Taken together, the present study provides mutational and functional evidences demonstrating for the first time the functional importance of CD147 dimerization and its direct correlation with invasion and metastasis of tumor cells.


Internal Carotid Artery and its Relationship with Structures in Sellar Region: Anatomic Study and Clinical Applications.
Complications of the internal carotid artery (ICA) in surgery are rare but severe. This study aimed to locate the ICA with 5 stationary bony structures in the sellar region: the anterior clinoid process, the tuberculum sellae, the bottom of the hypophyseal fossa, the posterior edge of the hypophyseal fossa, and the postclinoid process and to do measurements to determine their anatomic relationship with the ICA. After multiple planar reconstructions on computer tomographic angiography images of 120 ICA in 60 individuals, we defined the 5 bony structures as 5 origins in the horizontal, sagittal, and vertical planes with the 3D coordinate system and got the cross-sections of bilateral ICA on the coronal plane passing through each origin. We measured the distances between the cross-sections and the origins and angles between the horizontal plane and the line passing through the origin and the cross-sections on each coronal plane. We also measured the distances between the bilateral ICA on the 5 coronal planes. Besides, we measured the coordinate of the anterior edge of bilateral ICA, taking the anterior clinoid process as the origin. With the 3-dimensional coordinate system, we located the ICA to the bony structures in skull base. The distance between the bilateral ICA on coronal planes were 18.8 ± 2.9 mm, 23.6 ± 3.7 mm, 19.9 ± 3.4 mm, 24.7 ± 4.3 mm, and 23.5 ± 3.5 mm, from anterior to posterior, respectively. The 3D coordinate system used in this study is of value in preoperational assessment, and data we obtained indicate the safety ranges avoiding damage to the ICA in surgery.


Temperature change affected groundwater quality in a confined marine aquifer during long-term heating and cooling.
Global warming and urbanization together with development of subsurface infrastructures (e.g. subways, shopping complexes, sewage systems, and Ground Source Heat Pump (GSHP) systems) will likely cause a rapid increase in the temperature of relatively shallow groundwater reservoirs (subsurface thermal pollution). However, potential effects of a subsurface temperature change on groundwater quality due to changed physical, chemical, and microbial processes have received little attention. We therefore investigated changes in 34 groundwater quality parameters during a 13-month enhanced-heating period, followed by 14 months of natural or enhanced cooling in a confined marine aquifer at around 17 m depth on the Saitama University campus, Japan. A full-scale GSHP test facility consisting of a 50 m deep U-tube for circulating the heat-carrying fluid and four monitoring wells at 1, 2, 5, and 10 m from the U-tube were installed, and groundwater quality was monitored every 1-2 weeks. Rapid changes in the groundwater level in the area, especially during the summer, prevented accurate analyses of temperature effects using a single-well time series. Instead, Dual-Well Analysis (DWA) was applied, comparing variations in subsurface temperature and groundwater chemical concentrations between the thermally-disturbed well and a non-affected reference well. Using the 1 m distant well (temperature increase up to 7 °C) and the 10 m distant well (non-temperature-affected), the DWA showed an approximately linear relationships for eight components (B, Si, Li, dissolved organic carbon (DOC), Mg(2+), NH4(+), Na(+), and K(+)) during the combined 27 months of heating and cooling, suggesting changes in concentration between 4% and 31% for a temperature change of 7 °C.


Survey for internal parasites in cattle in Kentucky (1993).
Fecal samples were examined between 17 September and 1 November 1993 from 1765 cattle (one bull, 533 cows, 474 heifers, 22 steers, and 735 calves) on pasture on 15 farms in 11 counties in Kentucky for eggs or larvae of internal parasites. All of the cattle were beef-type except for 22 which were dairy-type. In fecal samples from the bull, cows, heifers, steers, and calves, the types of helminth eggs present were trichostrongyles (excluding Nematodirus) in 0%, 25%, 31%, 86%, and 93%, Nematodirus in 0%, 0%, < 1%, 0%, and 34%, Strongyloides in 0%, 0%, < 1%, 0%, and 7%, Trichuris in 0%, 0%, 0%, 0%, and 2%, Capillaria in 0%, 0%, 0%, 0%, and < 1%, and Moniezia in 0%, 1%, 8%, 5%, and 21%, respectively. Dictyocaulus viviparus larvae were present in feces of calves (7%) on one farm and heifers (< 1%) on another farm.


Seizure-induced damage in the substantia nigra pars reticulata: lesions in the frontal cortex prior to the seizure period mitigate the damage.
Flurothyl-induced status epilepticus in the rat causes a hypermetabolic necrosis in the substantia nigra pars reticulata (SNPR). We studied if cortically generated excitatory input into the SNPR was causative of the structural damage. Rats were subjected to a unilateral frontal cortex lesion prior to induction of 40 min status epilepticus. A distinct mitigation in the size of the necrotic region in the ipsilateral SMPR was noted when compared to the contralateral side of the same animals (N = 10). No side difference was noted in animals where a lesion of similar size was placed in the parietal cortex region (N = 2) or in unlesioned animals subjected to seizures (N = 4). Neither analyses of energy metabolites in the cerebral cortex nor EEG revealed any side differences during seizures in the animals with lesions in the frontal cortex. This suggests that difference in seizure intensity was not the explanation for the mitigation of SNPR damage. It is suggested that the excitatory input from the frontal cortex was necessary for development of neuronal necrosis in the SNPR due to seizures.


Tachycardia detection in implantable antitachycardia devices.
We have developed a microcomputer algorithm for tachycardia identification suitable for use in an implanted antitachycardia pacemaker. The algorithm distinguishes atrial, ventricular, and AV reentrant tachycardia, while ignoring high rates due to sinus tachycardia. A new method whereby the pacemaker delivers an atrial extrastimulus has been developed for distinguishing paroxysmal 1:1 tachycardia from sinus tachycardia, and has undergone preliminary testing in the electrophysiology laboratory. Preliminary results indicate sinus tachycardia can be reliably distinguished from paroxysmal 1:1 tachycardia by a properly timed extrastimulus delivered to the right atrium.


Enhancement stabilization of heavy metals (Zn, Pb, Cr and Cu) during vermifiltration of liquid-state sludge.
This paper illustrated the potential effect of earthworms on heavy metal stabilization after vermifiltration of liquid-state sludge. Significant enhancement of organics degradation in sludge caused an increase of heavy metal concentrations in VF effluent sludge. However, the analysis of heavy metal chemical speciation indicated earthworms made unstable fractions of heavy metals transformed into stable fractions. Further investigation using principal component analysis revealed that transformations of heavy metal fractions were mainly due to the changes in sludge physico-chemical properties of pH, soluble chemical oxygen demand and available phosphorus. The bioassay of earthworms indicated that only zinc was accumulated by earthworms because the unstable fraction was its main chemical speciation. Furthermore, risk analysis demonstrated that earthworm activities weakened heavy metal risk due to the formation of stable fractions although their total concentrations increased. These results indicated that earthworms in vermifilter had a positive role in stabilizing heavy metals in sewage sludge.


Neurosyphilis.
In the future it seems probable that cases of neurosyphilis will be seen sporadically by physicians and neurologists. As a result of the almost universal ingestion of antibiotics for trivial conditions, many cases of syphilis will be modified or arrested and some patients will be cured of the disease without ever knowing that they have acquired it. In others, developing neurosyphilis may be attenuated by inadequate chance treatment and the clinical and laboratory manifestations may become more subtle and difficult to recognize, leading to errors in diagnosis. Clinical experience of the varied manifestations of neurosyphilis has become less widespread among physicians and consequently greater care should be taken to ensure that the diagnosis is not missed.


Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction--a meta-analysis.
The effect of angiotensin converting enzyme (ACE) inhibitors on symptoms in patients with left ventricular systolic dysfunction (LVSD) is controversial. To perform a meta-analysis of studies evaluating effect of ACE inhibitors on New York Heart Association (NYHA) class in patients with LVSD. Individual data from 10389 patients in NYHA classes I-IV from four large long-term studies (2-4-year follow-up) and summary data from 2302 patients in NYHA classes II-IV from 16 short-term studies (3 months follow-up) were meta-analysed to assess changes in NYHA class. The large long-term studies showed a significant improvement in the worst NYHA classes (classes II-IV compared to class I) in the ACE inhibitor arm versus placebo, odds ratio (OR) = 0.875 (0.811-0.943) p = 0.0005. This effect was only present in studies which included patients with chronic heart failure and was particularly pronounced on deterioration to the worst NYHA class IV, OR = 0.66 (0.52-0.84) p = 0.001. There was no effect in the studies which included patients after myocardial infarction. The short-term chronic heart failure studies showed a significant improvement in NYHA class; OR for improvement of at least one NYHA class was 2.11 (1.48-2.98, 95% CI) p < 0.0001. ACE inhibition significantly improves symptomatic status measured as NYHA classification in patients with chronic heart failure.


An assessment of the current and future options for domestic waste management in Kaunas, Lithuania.
The main purpose of this study was to carry out a retrospective analysis of solid waste generation in Kaunas city from 1994 to 2003 and to calculate the theoretical waste generation in the future. This paper also presents measurements of the annual variations of waste amounts and calculations on a theoretical waste incineration facility. Two waste treatment scenarios were considered. Scenario A: waste deposit at the landfill with 'implementation of domestic waste separation and recycling'. Scenario B: waste removal to a landfill with 'multi-treatment: household separation, recycling and energetic recovery'. Three levels of waste treatment were proposed. The first level was implementation of the recycling system, which included household waste separation. The next step involved mechanical-biological treatment. The third level was the construction and operation of a new waste incineration plant in Kaunas. Two sites in Kaunas city were proposed; however, more detailed analysis, including the economic factors, will need to be done.


Determination of iodide in seawater samples by ion chromatography with chemically-bonded poly(ethylene glycol) stationary phase.
An ion chromatographic method for the rapid and direct determination of iodide in seawater is reported. Poly(ethylene glycol) (PEG) groups were chemically bonded onto silica gel or C30-bonded silica gel via diol groups. PEG-bonded C30 binary phases allowed determination of iodide in seawater samples without any interference. Effects of eluent composition on retention behavior of inorganic anions have been investigated. Both cation and anion of the eluent affected the retention of analyte anions. The retention time of anions increased with increasing eluent concentration. The detection limit for iodide obtained by injecting 0.2 microl of sample was 13 microg l(-1) (S/N=3) while the limit of quantitation was 43 microg l(-1) (S/N=10). The present method was successfully applied to the rapid and direct determination of iodide in seawater with long-term durability.


What is the role of surgical simulation on operative opportunity for the trainee ENT surgeon?
This study sought to assess the impact of simulation training in influencing trainees' initial surgical participation as perceived by experienced surgeon trainers. Twenty ENT surgeons assessed how much of a given procedure they would expect to allow a trainee to perform for their first time. Responses were provided for trainees who had undergone a relevant simulation course and those who had not, and scored according to the eLogbook levels of involvement in surgery. This was completed for simulated procedures with validated models, across four grades of junior doctors. A total of 1120 judgements on the trainees' intended level of involvement were made. The median involvement score was higher in the simulation group versus the non-simulation group (Mann-Whitney U, p = 0.0001), corresponding to a translation in surgical opportunity from a primarily assisting role to an active role. Trainer perception of a relevant ENT simulation course appears to positively impact on the initial surgical opportunities afforded to the trainee.


Response to partial selection on clean fleece weight in south Australian strong-wool Merino sheep. III. Genetic distance between flocks.
Divergence over time in flocks selected for clean fleece weight and for fecundity is measured by gene frequency changes at the R-r-i blood group, haemoglobin, and transferrin loci. No unequivocal effect of selection is demonstrable. Problems of interpretation even in flocks of known history are discussed.


Creating a positive feedback loop in leadership to accelerate cultural change.
Leadership skills are highly valued in institutional environments, but in the context of persons excluded because of ethnicity or race (PEERs) in science, support for developing those skills often is lacking. To increase leadership diversity, institutions and programs should practice and teach diverse leadership strategies.


Comparison of hospital delivery costs between cesarean section and natural delivery and analysis of influencing factors.
The increasing costs of hospital delivery have increased the economic burden of pregnant women, and the mode of delivery is the main factor affecting the costs of hospital delivery. This study aims to explore the difference in costs between cesarean section and natural delivery, and to provide reference for controlling the increase of hospital delivery costs. The data of inpatient delivery in the Hunan Maternal and Child Health Care Hospital from January 2016 to December 2020 were selected to compare the total inpatient costs and average daily costs of cesarean section and natural delivery. The linear trend model was used to analyze the trend change of inpatient delivery costs and the generalized linear model was used to analyze the influential factors for inpatient delivery costs. The average hospitalization costs of cesarean section (10 447.25 yuan) were higher than that of natural delivery (5 567.95 yuan), and the average daily costs of cesarean section (1 902.57 yuan) were higher than those of natural delivery (1 666.40 yuan). There was no significant increase or decrease in trend for cesarean section, while the average annual growth rate of the costs of natural delivery was 11.79%. The main factors affecting the hospitalization costs of cesarean section and natural delivery included age, occupation, medical insurance, route of admission, length of stay, premature delivery and complications (all P<0.05). The total hospitalization costs and average daily costs of cesarean section are higher than those of natural delivery, but the costs of natural delivery show a faster growth trend, and the hospitalization costs of cesarean section and natural delivery should be controlled by targeted measures.