Spinal Cord Stimulation for Neuropathic Pain in England From 2010 to 2020: A Hospital Episode Statistics Analysis.
Spinal cord stimulation (SCS) is a recognized intervention for the management of chronic neuropathic pain. The United Kingdom National Institute of Health and Care Excellence has recommended SCS as a management option for chronic neuropathic pain since 2008. The aim of this study is to undertake an assessment of SCS uptake across the National Health Service in England up to 2020. Hospital Episode Statistics were obtained for patients with neuropathic pain potentially eligible for SCS and patients receiving an SCS-related procedure. Data were retrieved nationally and per region from the years 2010-2011 to 2019-2020. There were 50,288 adults in England attending secondary care with neuropathic pain in 2010-2011, increasing to 66,376 in 2019-2020. The number of patients with neuropathic pain with an SCS procedure increased on a year-to-year basis until 2018-2019. However, less than 1% of people with neuropathic pain received an SCS device with no evidence of an increase over time when considering the background increase in neuropathic pain prevalence. Only a small proportion of patients in England with neuropathic pain potentially eligible for SCS receives this intervention. The recommendation for routine use of SCS for management of neuropathic pain has not resulted in an uptake of SCS over the last decade.


Induction of yeast DNA ligase genes in exponential and stationary phase cultures in response to DNA damaging agents.
UV-irradiation of stationary phase cells of Saccharomyces cerevisiae and Schizosaccharomyces pombe leads to a 9-fold and 90-fold increase in transcript levels from the respective DNA ligase genes CDC9 and CDC17, whereas exponential cells show only 3-fold and 2-fold increases. Induction of CDC9 after MMS treatment and gamma-irradiation was also observed by using a CDC9-lacZ translational fusion and assaying for beta-galactosidase. Surprisingly, irradiation of S. cerevisiae induces only a 50% increase in DNA ligase itself, probably reflecting the extremely high in vivo stability of the enzyme. The UV-induction of ligase may be part of a "fail-safe" mechanism which, together with the enzyme stability, ensures adequate supplies of this essential enzyme.


Traditional Chinese Medicine Formula "Xiaofeng granules" suppressed gouty arthritis animal models and inhibited the proteoglycan degradation on chondrocytes induced by monosodium urate.
Xiaofeng Granules (XF) is a kind of granules prepared by the famous traditional Chinese medicine formula for its efficiency in treating gouty diseases. We investigated the relevance between XF that made from Modified simiaowan (MSW) as the anti-gouty arthritis drugs and protective mechanisms for cartilage matrix in order to provide the evidence for new drug application. In the present study, we evaluated the anti-gouty arthritis activity of XF in rats and rabbits models induced by MSU together with chondrocytes focusing on the link to proteoglycan degradation in vitro studies. The results demonstrated that XF significantly reduced the swelling rate and attenuated the pathological changes in joints. The XF-containing serum were used medicated serum in cellular experiments. The in vitro data were in accordance with the in vivo results, showing that the constituents in XF-containing serum had obvious inhibitory effects on the activation of pro-inflammatory mediators in chondrocytes. Moreover, XF-containing serum substantially inhibited MSU-induced expression of glycosaminoglycans(GAG) and hydroxyproline(Hyp), and up regulated proteoglycan, which might be associated with the regulation of the balance of MMP-3/TIMP-1and ADAMTS-4/TIMP-3 inchondrocytes. In conclusion, XF that made from MSW showed obvious effects on acute gouty arthritis, which also provided an effective protection on cartilage matrix degradation.


Proliferation of Schwann cells and regulation of cyclin D1 expression in an animal model of Charcot-Marie-Tooth disease type 1A.
Overexpression of PMP22 is responsible for the most common form of inherited neuropathy, Charcot-Marie-Tooth disease (CMT) type 1A. The PMP22-transgenic rat (CMT rat) is an animal model of CMT1A, and its peripheral nerves show the characteristic features of ongoing demyelination and remyelination that is also seen in CMT1A patients. Since Schwann cell proliferation is a prominent feature of peripheral nerves in inherited peripheral neuropathies, we examined proliferation and the expression of cyclin D1 in CMT rats. D-type cyclins are required for the initial steps in cell division and nuclear import is crucial for the function of cyclin D1 in promoting cell proliferation. Like normal myelinating Schwann cells in wild-type rats, remyelinating Schwann cells in CMT rats show perinuclear cyclin D1 expression. Schwann cells with nuclear cyclin D1 expression, as well as proliferating Schwann cells, were both associated with demyelinated axonal segments. Supernumerary onion bulb Schwann cells, however, do not express cyclin D1 and were not proliferating. Thus, cyclin D1 expression and its subcellular localization correlate directly with distinct physiological states of Schwann cells in this animal model of CMT1A.


Effect of changes in anthropometric measurements on the remission and progression of prediabetes: A community-based cohort study.
We assessed the impact of changes in body mass index (BMI), body fat percentage (BF%), and waist circumference (WC) on prediabetes among middle-aged and elderly Chinese adults. 2.5-year changes in BMI, BF%, and WC were calculated by subtracting baseline levels from follow-up, based on a cohort of 3,632 participants with prediabetes, and outcomes were defined as remission to normal glucose regulation (NGR), persistence in prediabetes, and progression to newly diagnosed diabetes mellitus (NDM). Among participants with prediabetes, 16.9% returned to NGR and 24.6% progressed to NDM. Changes in BMI, BF%, but not WC were associated with remission and progression of prediabetes (risk ratio per standard deviation increase of BMI: 0.86 [0.79-0.93] and 1.15 [1.08-1.23]; BF%: 0.91 [0.84-0.98] and 1.11 [1.03-1.19]). Among participants with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), only BF% change was significantly associated with remission of prediabetes. Short-term management of BMI and BF% should be emphasized to promote the remission and prevent the progression of prediabetes. Moreover, it is of particular clinical importance to monitor BF% among people with combined IFG and IGT.


Essential fatty acids and phenolic acids from extracts and leachates of southern cattail (Typha domingensis P.).
We have been able to isolate several phytotoxic compounds from aqueous extracts and leachates of cattails (Typha domingensis) using activated charcoal as an absorbant, followed by successive extraction with organic solvents, analysis by GC/MS, and structural elucidation by NMR spectroscopy when possible. The phytotoxins were identified as essential fatty acids (linoleic acid and alpha-linolenic acid) and phenolic compounds of known phytotoxic activity (caffeic acid from the aqueous extracts; caffeic, p-coumaric, and gallic acid from the leachates). Both extracts and the phytotoxins in the extracts have the potential of inhibiting the growth and chlorophyll production of several ecologically relevant species.


Dental management of patients with myasthenia gravis: a literature review.
Myasthenia gravis is a chronic neuromuscular disease characterized by muscular weakness and fatigability. Dental management of patients diagnosed with myasthenia gravis presents a challenge to the dental profession. A MEDLINE search of the English medical (limited to provision in dental care) and dental literature on myasthenia gravis and dental management published between 1975 and 2004 was conducted. In the dental literature, 12 articles were found, and only a few focused on myasthenia gravis and dental care. The purpose of this article was to review and summarize the clinical signs and symptoms associated with myasthenia gravis, highlighting the role of the dental profession in the process of the diagnosis and management of the oral and dental complications that might be associated with the disease, while avoiding myasthenic crisis.


MiR-217 regulates autophagy through OPG/RANKL/RANK in giant cell tumors.
Increasing evidence suggests that microRNAs (miRNAs) play a crucial role in cancer development and progression. Our previous study showed remarkably lower levels of miR-217 in GCT cells and tissues, and miR-217 re-expression inhibited the occurrence and development of GCT in vitro; however, the associated mechanisms remain unknown. Thus, this study aimed to explore the mechanisms underlying the proliferation inhibitory effect of miR-217 in GCT cells. The proliferative potential of the GCT cells was measured with an MTT assay and BrdU straining. Changes in GCT cell migration and invasion was assessed by a transwell assay. Finally, Western blot and RT-PCR assays were employed to evaluate OPG/RANKL/RANK signaling pathway-related protein expression. The excessive upregulation of miR-217 markedly suppressed GCT cell proliferation and tumorigenesis both in vitro and in vivo. miR-217 overexpression could inhibit the OPG/RANKL/RANK signaling pathway in vitro and in vivo. Furthermore, ALP activity was significantly decreased in GCT cells following miR-217 treatment. Importantly, miR-217 could inhibit autophagy-related protein expression and autophagosome/autolysosome formation in GCT cells and tissues. These results suggest that miR-217 upregulation could inhibit the occurrence and development of GCT by blocking autophagy. These findings offer an effective therapeutic target to improve the survival rates of patients with CGT in the future.


Insulin gene VNTR polymorphisms -2221MspI and -23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis.
A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive. We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls. For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of -23HphI on LADA. Our results support the existence of associations of INS with T1D and LADA.


Sedimentation velocity FDS studies of antibodies in pooled human serum.
The biotech industry has great interest in investigating therapeutic proteins in high concentration environments like human serum. The fluorescence detection system (Aviv-FDS) allows the performance of analytical ultracentrifuge (AUC) sedimentation velocity (SV) experiments in tracer or BOLTS protocols. Here, we compare six pooled human serum samples by AUC SV techniques and demonstrate the potential of this technology for characterizing therapeutic antibodies in serum. Control FDS SV experiments on serum alone reveal a bilirubin-HSA complex whose sedimentation is slowed by solution nonideality and exhibits a Johnston-Ogston (JO) effect due to the presence of high concentrations of IgG. Absorbance SV experiments on diluted serum samples verify the HSA-IgG composition as well as a significant IgM pentamer boundary at 19 s. Alexa-488 labeled Simponi (Golimumab) is used as a tracer to investigate the behavior of a therapeutic monoclonal antibody (mAb) in serum, and the sedimentation behavior of total IgG in serum. Serum dilution experiments allow extrapolation to zero concentration to extract so, while global direct boundary fitting with SEDANAL verifies the utility of a matrix of self- and cross-term phenomenological nonideality coefficients (ks and BM1) and the source of the JO effect. The best fits include weak reversible association (~ 4 × 103 M-1) between Simponi and total human IgG. Secondary mAbs to human IgG and IgM verify the formation of a 10.2 s 1:1 complex with human IgG and a 19 s complex with human IgM pentamers. These results demonstrate that FDS AUC allows a range of approaches for investigating therapeutic antibodies in human serum.


The genes coding for the muscle contractile proteins, myosin heavy chain, myosin light chain 2, and skeletal muscle actin are located on three different mouse chromosomes.
The chromosomal distribution of murine genes expressed during differentiation of skeletal muscle cells was determined by Southern blot analysis of DNA from mouse-Chinese hamster hybrid cell lines containing incomplete subsets of mouse chromosomes. All detectable myosin heavy chain genes are located on chromosome 11. The gene for the myosin light chain 2 is located on chromosome 7. The skeletal muscle alpha-actin gene and several other actin genes, or pseudogenes, are located on chromosome 3. Additional actin DNA sequences are distributed on other mouse chromosomes.


Cytosolic 5'-nucleotidase 1A autoimmunity in sporadic inclusion body myositis.
We previously identified a circulating autoantibody against a 43 kDa muscle autoantigen in sporadic inclusion body myositis (IBM) and demonstrated the feasibility of an IBM diagnostic blood test. Here, we sought to identify the molecular target of this IBM autoantibody, understand the relationship between IBM autoimmunity and muscle degeneration, and develop an IBM blood test with high diagnostic accuracy. IBM blood samples were screened using mass spectrometry and a synthetic human peptidome. Plasma and serum samples (N=200 patients) underwent immunoblotting assays, and results were correlated to clinical features. Muscle biopsy samples (n=30) were examined by immunohistochemistry and immunoblotting. Exome or whole genome sequencing was performed on DNA from 19 patients. Both mass spectrometry and screening of a 413,611 human peptide library spanning the entire human proteome identified cytosolic 5'-nucleotidase 1A (cN1A; NT5C1A) as the likely 43 kDa IBM autoantigen, which was then confirmed in dot blot and Western blot assays using recombinant cN1A protein. Moderate reactivity of anti-cN1A autoantibodies was 70% sensitive and 92% specific, and high reactivity was 34% sensitive and 98% specific for the diagnosis of IBM. One to 3 major cN1A immunodominant epitopes were identified. cN1A reactivity by immunohistochemistry accumulated in perinuclear regions and rimmed vacuoles in IBM muscle, localizing to areas of myonuclear degeneration. Autoantibodies against cN1A are common in and highly specific to IBM among muscle diseases, and may provide a link between IBM's dual processes of autoimmunity and myodegeneration. Blood diagnostic testing is feasible and should improve early and reliable diagnosis of IBM.


Selective polypeptide ligand binding to the extracellular surface of the transmembrane domains of the class B GPCRs GLP-1R and GCGR.
Crystal and cryo-EM structures of the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) bound with their peptide ligands have been obtained with full-length constructs, indicating that the extracellular domain (ECD) is indispensable for specific ligand binding. This article complements these data with studies of ligand recognition of the two receptors in solution. Paramagnetic NMR relaxation enhancement measurements using dual labeling with fluorine-19 probes on the receptor and nitroxide spin labels on the peptide ligands provided new insights. The glucagon-like peptide-1 (GLP-1) was found to interact with GLP-1R by selective binding to the extracellular surface. The ligand selectivity toward the extracellular surface of the receptor was preserved in the transmembrane domain (TMD) devoid of the ECD. The dual labeling approach further provided evidence of cross-reactivity of GLP-1R and GCGR with glucagon and GLP-1, respectively, which is of interest in the context of medical treatments using combinations of the two polypeptides.


Deviations from normative brain white and gray matter structure are associated with psychopathology in youth.
Combining imaging modalities and metrics that are sensitive to various aspects of brain structure and maturation may help identify individuals that show deviations in relation to same-aged peers, and thus benefit early-risk-assessment for mental disorders. We used one timepoint multimodal brain imaging, cognitive, and questionnaire data from 1280 eight- to twenty-one-year-olds from the Philadelphia Neurodevelopmental Cohort. We estimated age-related gray and white matter properties and estimated individual deviation scores using normative modeling. Next, we tested for associations between the estimated deviation scores, and with psychopathology domain scores and cognition. More negative deviations in DTI-based fractional anisotropy (FA) and the first principal eigenvalue of the diffusion tensor (L1) were associated with higher scores on psychosis positive and prodromal symptoms and general psychopathology. A more negative deviation in cortical thickness (CT) was associated with a higher general psychopathology score. Negative deviations in global FA, surface area, L1 and CT were also associated with poorer cognitive performance. No robust associations were found between the deviation scores based on CT and DTI. The low correlations between the different multimodal magnetic resonance imaging-based deviation scores suggest that psychopathological burden in adolescence can be mapped onto partly distinct neurobiological features.


High-affinity cannabinoid binding site: regulation by ions, ascorbic acid, and nucleotides.
The high-affinity cannabinoid site in rat brain is an integral component of brain membranes that recognizes cannabinoids with inhibitory constants (Ki) in the nanomolar range. To clarify its physiological role, we studied the regulation of [3H]5'-trimethylammonium delta 8-tetrahydrocannabinol ([3H]TMA) binding. The site is inhibited by heavy metal ions, such as La3+, at low micromolar concentrations; divalent cations, such as Ca2+ and Mg2+, inhibit [3H]TMA binding, though at somewhat higher concentrations. In contrast, [3H]TMA binding is stimulated by Fe2+, Cu2+, and Hg2+ ions. Ascorbic acid and its analogs are also stimulators of cannabinoid binding at low micromolar concentrations. Stimulation of [3H]TMA binding by ascorbate or ions is dependent upon molecular oxygen, but is not inhibited by metabolic poisons. Metabolically stable nucleoside triphosphate analogs enhance [3H]TMA binding by different mechanisms, with hydrolysis of a high-energy phosphate bond apparently requisite for these influences. These results suggest that the cannabinoid binding site is associated with a nucleotide-utilizing protein possessing multiple regulatory subsites.


The effect of drug therapy without volume restoration in experimental traumatic shock. Part II. Pethidine.
Different opinions seem to exist as to the use of analgesies in the treatment of trauma patients. For this reason we investigated experimentally the effect of pethidine in traumatic shock. Pethidine was administrated to eight of sixteen anaesthetized rabbits with lower limb injuries. The effect of pethidine was unfavourable. This was due to the effect of the drug on circulation and not on respiration.


Brief exposure to -2 Gz reduces cerebral oxygenation in response to stand test.
The aim of the present experiment was to determine whether a single 30 s of exposure to -2 Gz (foot-to-head inertial forces) as orthostatic stress results in altered brain oxygenation control in response to active standing. Cerebral oxygenation (oxy-Hb), cerebral blood volume (CBV), and mean arterial blood pressure at brain level (MAPbrain) were recorded in 12 subjects in supine and then in standing position (10 min), before and after -2 Gz centrifugation. The decrease in oxy-Hb (-5 +/- 9 vs. -9 +/- 10 microM, P < 0.001) and in CBV (-2 +/- 11 vs. -4 +/- 12 microM, P < 0.05) upon standing was more important after -2 Gz centrifugation, with unchanged MAPbrain (-6 +/- 7 vs. -6 +/- 9 mmHg). These findings suggest a downward shift in the static cerebral autoregulation curve.


Experimental comparison of photon versus particle computed tomography to predict tissue relative stopping powers.
Measurements comparing relative stopping power (RSP) accuracy of state-of-the-art systems representing single-energy and dual-energy computed tomography (SECT/DECT) with proton CT (pCT) and helium CT (HeCT) in biological tissue samples. We used 16 porcine and bovine samples of various tissue types and water, covering an RSP range from 0.90 ± 0.06 to 1.78 ± 0.05. Samples were packed and sealed into 3D-printed cylinders ( d = 2 cm, h = 5 cm) and inserted into an in-house designed cylindrical polymethyl methacrylate (PMMA) phantom ( d = 10 cm, h = 10 cm). We scanned the phantom in a commercial SECT and DECT (120 kV; 100 and 140 kV/Sn (tin-filtered)); and acquired pCT and HeCT ( E ∼ 200 MeV/u, 2 ∘ steps, ∼ 6.2 × 10 6 (p)/ ∼ 2.3 × 10 6 (He) particles/projection) with a particle imaging prototype. RSP maps were calculated from SECT/DECT using stoichiometric methods and from pCT/HeCT using the DROP-TVS algorithm. We estimated the average RSP of each tissue per modality in cylindrical volumes of interest and compared it to ground truth RSP taken from peak-detection measurements. Throughout all samples, we observe the following root-mean-squared RSP prediction errors ± combined uncertainty from reference measurement and imaging: SECT 3.10 ± 2.88%, DECT 0.75 ± 2.80%, pCT 1.19 ± 2.81%, and HeCT 0.78 ± 2.81%. The largest mean errors ± combined uncertainty per modality are SECT 8.22 ± 2.79% in cortical bone, DECT 1.74 ± 2.00% in back fat, pCT 1.80 ± 4.27% in bone marrow, and HeCT 1.37 ± 4.25% in bone marrow. Ring artifacts were observed in both pCT and HeCT reconstructions, imposing a systematic shift to predicted RSPs. Comparing state-of-the-art SECT/DECT technology and a pCT/HeCT prototype, DECT provided the most accurate RSP prediction, closely followed by particle imaging. The novel modalities pCT and HeCT have the potential to further improve on RSP accuracies with work focusing on the origin and correction of ring artifacts. Future work will study accuracy of proton treatment plans using RSP maps from investigated imaging modalities.


The strength of weak integrated information theory.
The integrated information theory of consciousness (IIT) is divisive: while some believe it provides an unprecedentedly powerful approach to address the 'hard problem', others dismiss it on grounds that it is untestable. We argue that the appeal and applicability of IIT can be greatly widened if we distinguish two flavours of the theory: strong IIT, which identifies consciousness with specific properties associated with maxima of integrated information; and weak IIT, which tests pragmatic hypotheses relating aspects of consciousness to broader measures of information dynamics. We review challenges for strong IIT, explain how existing empirical findings are well explained by weak IIT without needing to commit to the entirety of strong IIT, and discuss the outlook for both flavours of IIT.


Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: prediction of mortality by ambulatory electrocardiography.
To test the hypothesis that ventricular arrhythmias detected by ambulatory electrocardiography can stratify mortality risk in patients with ischemic and those with nonischemic dilated cardiomyopathy, clinical, hemodynamic and neurohumoral findings were evaluated in 31 patients. By Kaplan-Meier analysis, the total population had 51% survival at 12 months and 19% survival at 25 months. Subgroups based on peak complexity of ventricular arrhythmias included 9 patients with simple ventricular arrhythmias (peak Lown grades 1 to 3) and 22 patients with complex ventricular arrhythmias (peak Lown grades 4 or 5). Clinical variables and baseline catecholamine levels and renin-angiotensin system activity were similar in the simple and complex arrhythmia subgroups. Patients with simple and those with complex arrhythmias were comparable by all hemodynamic indexes except for a higher mean pulmonary capillary wedge pressure in the complex arrhythmia subgroup. Survival was strikingly related to arrhythmias: mortality was 11% (1 of 9) in the simple ventricular arrhythmia subgroup and 59% (13 of 22) in the complex ventricular arrhythmia subgroup (p less than 0.025 by log-rank test). Twelve patients died suddenly and 2 patients died in circulatory failure, and the risk of death was not affected by the etiology of cardiomyopathy. The higher mortality among the patients with complex arrhythmia could not be explained by the presence of elevated filling pressures alone. Thus, ambulatory electrocardiography can stratify mortality risk among patients with severe ischemic and nonischemic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of thermal pre-treatment on the availability of PAHs for successive chemical oxidation in contaminated soils.
This is the premier study designed to evaluate the impact of thermal pre-treatment on the availability of polycyclic aromatic hydrocarbons (PAHs) for successive removal by chemical oxidation. Experiments were conducted in two soils having different PAH distribution originating from former coking plant sites (Homécourt, H, and Neuves Maisons, NM) located in northeast of France. Soil samples were pre-heated at 60, 100, and 150 °C for 1 week under inert atmosphere (N2). Pre-heating resulted in slight removal of PAHs (<10%) and loss of extractable organic matter (EOM). Then, these pre-heated soil samples were subjected to Fenton-like oxidation (H2O2 and magnetite) at room temperature. Chemical oxidation in soil without any pre-treatment showed almost no PAH degradation underscoring the unavailability of PAHs. However, chemical oxidation in pre-heated soils showed significant PAH degradation (19, 29, and 43% in NM soil and 31, 36, and 47% in H soil pre-treated at 60, 100, and 150 °C, respectively). No preferential removal of PAHs was observed after chemical oxidation in both soils. These results indicated the significant impact of pre-heating temperature on the availability of PAHs in contaminated soils and therefore may have strong implications in the remediation of contaminated soils especially where pollutant availability is a limiting factor.


Interferon action: two (2'-5')(A)n synthetases specified by distinct mRNAs in Ehrlich ascites tumor cells treated with interferon.
(2'-5')(A)n synthetase and RNAase L (a latent endoribonuclease) are among the mediators of interferon action. The product of (2'-5')(A)n synthetase (i.e., (2'-5')(A)n) binds, and thereby activates RNAase L. Interferons induce in Ehrlich ascites tumor (EAT) cells two mRNAs (sizes 1.5 kb and 3.8 kb), which can be translated in Xenopus oocytes into (2'-5')(A)n synthetases of 20,000 to 30,000 daltons and 85,000 to 100,000 daltons, respectively. (2'-5')(A)n synthetases of corresponding sizes are induced by interferons in EAT cells. In the cell extract the bulk of the larger enzyme is in the cytoplasmic fraction, and the bulk of the smaller one in the nuclear fraction. The only known function of (2'-5')(A)n is the activation of RNAase L, and RNAase L can be selectively crosslinked to a (2'-5')(A)n derivative in a cytoplasmic extract from EAT cells. The same (2'-5')(A)n derivative can be crosslinked to several proteins in the nuclear extract of EAT cells, and some of these proteins are induced by interferon.


Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis.
Pooled data from 32 studies were reviewed to assess the timing of thrombolic complications after cardioversion of atrial fibrillation or flutter. We found that 98% of embolic episodes occurred within 10 days of cardioversion.


Longitudinal relationship between depressive symptoms and work outcomes in clinically treated patients with long-term sickness absence related to major depressive disorder.
Major depressive disorder (MDD) negatively affects a wide range of work outcomes (absenteeism, work productivity, work limitations). However, the exact longitudinal relationship between depressive symptoms and work outcomes in MDD patients with long-term sickness absence is still unclear. Therefore, the present study aimed to examine the temporal and directional relationship between depressive symptoms and various work outcomes in these patients. Patients (n = 117) were diagnosed with MDD according to DSM-IV criteria, had a median duration of MDD-related sickness absence of 4.8 months (IQR = 2.6-10.1 months) at baseline, and were referred by occupational physicians. All patients received outpatient treatment for their MDD. Depressive symptoms and work outcomes were examined during baseline, and 6-, 12- and 18-month follow-ups. Within-subject changes in the severity of depressive symptoms were significantly related to within-subject changes in all work outcomes (all scales: p < 0.001). Earlier reduction in depressive symptoms predicted subsequent improvements in all work outcomes (all scales: p < 0.05). Conversely, only earlier improvement in Time Management (p = 0.007) and Mental/Interpersonal (p < 0.001) work limitations predicted a subsequent reduction in depressive symptoms. All work outcomes were assessed through self-report. Work limitations at the start of absenteeism were retrospectively assessed. Symptom reduction remains crucial for improving adverse work outcomes in MDD patients with long-term sickness absence. In addition, a treatment focus on qualitative functioning in the workplace may accelerate depression recovery.


Structural definition of terrestrial chondroitin sulfate of various origin and repeatability of the production process.
We report results on the structure, physicochemical characteristics and purity of chondroitin sulfate (CS) samples derived from three largely available and common biological sources such as bovine and porcine trachea and chicken keel bones with the aim to define their structural signatures. Many lots of CS produced by a manufacturer at industrial scale were characterized with a view to assess the reproducibility of the process as not controlled extractive procedures may produce final products with variable structure and biological contaminants as well as not constant clinical efficacy and safety. By using standardized source animal tissues and manufacturing procedure, highly pure CS (∼92 %) products with constant structure and characteristics were obtained. Bovine CS showed a lower molecular weight (MWw of ∼21,500 Da) than porcine (MWw of ∼26,000 Da) and chicken (MWw of ∼35,900 Da) products with a CV% of ∼2.0-7.5 and a polydispersity variability of 0.7-2.7 %. The ratio between the sulfate groups main located in position 4 and 6 of N-acetyl-galactosamine (4/6 ratio) was ∼1.70 for bovine CS versus a value of 3.60 for porcine and ∼2.70 for chicken samples with a overall charge density of 0.92-0.93 and a CV% of 2.1-2.5. The final products also showed the presence of a very low and constant content of other co-purified bio(macro)molecules (hyaluronic acid, keratan sulfate, dermatan sulfate, heparan sulfate, nucleic acids and proteins), calcium and sodium, and the absence of versican. Finally, a high reproducibility of molecular weight values, disaccharide composition, specific optical rotation and particle dimension was observed. The observed parameters are structural signatures useful to specifically identify the origin of CS and obtained by a standardized and highly reproducible manufacturing process. The compositional profile determined from this study provides a measure of the norm and range of variation in CS samples of terrestrial origin produced under standardized production protocol to which future pharmaceutical/nutraceutical final products can be compared. Moreover, the physicochemical properties including molecular weight, disaccharide composition, presence of natural contaminants and particle dimension were characterized to provide the basis of CS of high quality for application as pharmaceutical/nutraceutical active agents.


Exposure to Alexandrium spp. impairs the development of Green-lipped mussel (Perna canaliculus) embryos and larvae.
The green-lipped mussel (GLM) Perna canaliculus is an economically, ecologically, and culturally important species in Aotearoa New Zealand. Since 2011, harmful algal blooms (HABs) of Alexandrium spp. have occurred annually in the Marlborough Sounds, the largest GLM aquaculture region in New Zealand. Across a similar timeframe, there has been a severe reduction in wild spat (juvenile mussel) catch. This research investigated the effects of Alexandrium pacificum (which produces paralytic shellfish toxins; PSTs) and A. minutum (a non-producer of PSTs) on the development of four GLM larval life stages (gametes, embryos, D-stage and settlement). Early life stages of GLM were exposed to environmentally relevant concentrations of Alexandrium spp. as whole cell, lysate and filtrate treatments. A 48-h exposure of embryos to whole A. pacificum cells at 500 cells mL-1 caused lysis of embryos, severe abnormalities, and reduced development through to veliger (D-stage) larvae by 85%. GLM growth was impaired at cell concentrations as low as 250 cells mL-1 during a 4-day exposure of D-stage larvae to both Alexandrium spp. Exposure of GLM to both whole and lysed treatments of Alexandrium spp. at 500 cells mL-1 resulted in halved larval growth rates (2.00 µm day-1 vs 4.48 µm day-1 in the control) and growth remained impeded during a 4-day recovery period. Both A. pacificum and A. minutum were found to negatively impact D-larvae. Both whole-cell and lysed-cell treatments of A. pacificum had similar negative effects, suggesting that Alexandrium spp. toxicity to D-larvae is independent of PSTs. Additionally, cell membrane-free treatments of A. pacificum had no negative effects on embryo development, indicating that cell surface-associated bioactive compounds may be responsible for the observed negative effects during this early life stage. Conversely, non-PST-producing A. minutum was toxic to D-stage larvae but not to embryos; larval growth was reduced following a brief 1 h exposure of sperm to cell membrane-free treatments of A. pacificum. No effects were recorded in GLM larvae exposed during settlement, highlighting the potential for differences in susceptibility of early life stages to Alexandrium spp. exposure and the influence of exposure durations. In the wild, blooms of Alexandrium spp. can persist for several months, reaching cell densities higher than those investigated in the present study, and as such may be detrimental to the vulnerable early life stages of GLM.


Renal interstitial guanosine cyclic 3', 5'-monophosphate mediates pressure-natriuresis via protein kinase G.
Pressure-natriuresis is the physiological protective mechanism whereby elevation of blood pressure induces a rapid increase in renal sodium (Na+) excretion. Pressure-natriuresis abnormalities are common to all forms of hypertension. We tested the hypothesis that pressure-natriuresis is mediated by renal interstitial (RI) cGMP and protein kinase G (PKG). We used anesthetized, uninephrectomized Sprague-Dawley rats and a standard pressure-natriuresis model in which bilateral adrenalectomy and renal denervation was done on rats. Renal perfusion pressure (RPP) was adjusted by manipulating clamps above and below the renal artery, and RI cGMP was quantified by microdialysis. RI cGMP increased from 3.1+/-0.5 to 5.5+/-0.4 fmol/min (P<0.05) when RPP was raised from 100 to 140 mm Hg. This increase in RI cGMP was eliminated by RI infusion of soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ). Raising RPP from 100 to 140 mm Hg increased urinary sodium excretion from 0.2+/-0.1 to 0.8+/-0.1 micromol/min, fractional sodium excretion from 0.2+/-0.1% to 0.8+/-0.1%, and fractional lithium excretion from 20.1+/-3.0% to 62.7+/-3.7% (all P<0.05). These responses were eliminated by RI infusion of nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester, ODQ, and PKG inhibitors Rp-8-pCPT-cGMP and Rp-8-Br-cGMP. Increasing RPP from 100 to 140 mm Hg decreased fractional proximal sodium reabsorption without influencing fractional distal Na+ reabsorption or glomerular filtration rate. In conclusion, pressure-natriuresis is mediated by RI cGMP and a PKG signaling pathway in target renal proximal tubule cells.


Acute Pain Management/Regional Anesthesia.
Effective and efficient acute pain management strategies have the potential to improve medical outcomes, enhance patient satisfaction, and reduce costs. Pain management records are having an increasing influence on patient choice of health care providers and will affect future financial reimbursement. Dedicated acute pain and regional anesthesia services are invaluable in improving acute pain management. In addition, nonpharmacologic and alternative therapies, as well as information technology, should be viewed as complimentary to traditional pharmacologic treatments commonly used in the management of acute pain. The use of innovative technologies to improve acute pain management may be worthwhile for health care institutions.


[Transposition of bilateral pedicled adrenal gland for the treatment of Cushing's disease].
To study the therapeutic method of Cushing's disease. 16 patients with Cushing's disease were treated by transposition of bilateral pedicled adrenal gland into the dorsal subcutaneous tissues. These patients were followed up for 4 to 48 months. No relapse was observed and 3 patients with hypoadrenocorticism were given small doses of steroid. This procedure may be a rational and satisfactory technique for the treatment of Cushing's disease.


Skin sympathetic function in complex regional pain syndrome type 1.
Cutaneous sympathetic pathophysiology in complex regional pain syndrome type 1 (CRPS-1) is not yet completely understood. To evaluate cutaneous sympathetic dysfunction in CRPS-1, we evaluated sympathetic sweat response (SSwR) and skin vasomotor reflex (SkVR) in CRPS-1 patients. We studied 10 CRPS-1 patients (age 41 ± 13 years; 5 females and 5 males; disease duration 20 ± 22 months) and 10 healthy subjects (age 44 ± 13 years; 3 females and 7 males). SkVRs and SSwRs to several sympathetic activating procedures were recorded on the palms of the CRPS-1 patients (affected side) and controls (right side). There were no significant differences in the baselines of sweat output and skin blood flow between the CRPS-1 and control groups. SSwR and SkVR amplitudes were significantly lower in the CRPS-1 group than in the control group. There was no significant correlation between disease duration and SSwR or SkVR amplitudes among the patients. The reduced SSwRs and SkVRs in the affected limb of our CRPS-1 patients may reflect underlying damage to the sympathetic postganglionic fibres.


Quantitative assessment of the in-vitro binding kinetics of antisickling aromatic aldehydes with hemoglobin A: A universal HPLC-UV/Vis method to quantitate Schiff-base adduct formation.
Aromatic aldehydes act as allosteric effectors of hemoglobin (AEH), forming Schiff-base adducts with the protein to increase its oxygen (O2) affinity; a desirable property in sickle cell disease (SCD) treatment, as the high-O2 affinity hemoglobin (Hb) does not polymerize and subsequently prevents erythrocytes sickling. This study reports the development, validation, and application of a weak cation-exchange HPLC assay - quantifying the appearance of Hb-AEH adduct - as a "universal" method, allowing for the prioritization of AEH candidates through an understanding of their Hb binding affinity and kinetics. Concentration- and time-dependent Hb binding profiles of ten AEHs were determined with HPLC, followed by the appropriate non-linear modeling to characterize their steady-state binding affinity (KDss), and binding kinetics second-order association (kon) and first-order dissociation (koff) rate constants. Vanillin-derived AEHs exhibited enhanced binding affinity to Hb, primarily due to their faster kon. Across AEH, kon and koff values are strongly correlated (r = 0.993, n = 7), suggesting that modifications of the AEH scaffold enhanced their interactions with Hb as intended, but inadvertently increased their Hb-AEH adduct dissociation. To our knowledge, the present study is the first to provide valuable insight into Hb binding kinetics of antisickling aromatic aldehydes, and the assay will be a useful platform in screening/prioritizing drug candidates for SCD treatment.


SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes.
Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1 expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known as Map2k1) and increased DNA methylation of the Shp-1 promoter. VSMCs from Shp-1-Tg mice exhibited impaired platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation with a concomitant decrease in PDGF-stimulated VSMC proliferation and migration. Similarly, HFD-fed Shp-1-Tg mice and mice treated with the SHP-1 inducer, Icariside II, were protected from the development of intimal hyperplasia following wire injury. Suppression of SHP-1 by oxidised lipids may contribute to the excessive VSMC proliferation, inflammatory cytokine production and intimal hyperplasia observed in arteries from diabetes and insulin resistance. Augmenting SHP-1 levels is a potential therapeutic strategy to maintain stent patency in patients with insulin resistance and diabetes.


The influence of HLA A, B, C, DR alleles and HLA haplotypes on cytomegalovirus-specific cell mediated immunity in seropositive Korean kidney transplant candidates.
We evaluated the effect of specific HLA alleles and haplotypes on cytomegalovirus (CMV)-specific cell mediated immunity (CMI) in kidney transplant (KT) candidates. CMV-specific ELISPOT against pp65 and IE-1 antigens (hereafter referred to as pp65 and IE-1, respectively) was performed in 229 seropositive KT candidates. We analyzed the results related to 44 selected HLA alleles (9 HLA-A, 15 HLA-B, 9 HLA-C, and 11 HLA-DR) and 13 HLA haplotypes commonly found in study participants. The pp65 and IE-1 results in 229 seropositive candidates were 227.5 (114.5-471.5) and 41.0 (8.8-185.8) (median [interquartile range]) spots/2 × 105 PBMCs, respectively. The pp65 and IE-1 results showed significant differences between candidates with different HLA alleles (A*02 vs. A*26 [p = 0.016], A*24 vs. A*30 [p = 0.031], B*07 vs. B*46 [p = 0.005], B*54 vs. B*35 [p = 0.041], B*54 vs. B*44 [p = 0.018], B*54 vs. B*51 [p = 0.025], and C*06 vs. C*14 [p = 0.034]). HLA-A*02 and B*54 were associated with increased pp65 and IE-1 results, respectively (p = 0.005 and p < 0.001, respectively). In contrast, the HLA-A*26 and B*46 alleles were associated with a decreased pp65 response, whereas the A*30 allele was associated with a decreased IE-1 response (p < 0.05). The pp65 results correlated with the HLA-A allele frequencies (R = 0.7546, p = 0.019) and the IE-1 results correlated with the HLA-C allele frequencies of the study participants (R = 0.7882, p = 0.012). Among 13 haplotypes, HLA-A*30 ~ B*13 ~ C*06 ~ DRB1*07 showed decreased CMV-CMIs compared to the other HLA haplotypes, probably due to a combination of HLA alleles associated with lower CMV-CMIs. Our results demonstrated that CMV-specific CMIs may be influenced by the HLA allele as well as the HLA haplotype. To better predict CMV reactivation, it is important to estimate risk in the context of HLA allele and haplotype information.


In situ ESWL for ureteric calculi: the optimum treatment?
In situ ESWL for ureteric calculi is associated with good stone clearance rates but is it without significant morbidity? A review of 189 patients with single ureteric calculi (150 upper ureter, 39 lower ureter calculi) revealed an 89% stone clearance for upper ureteral calculi and 80% stone clearance for lower ureteral calculi. However 11% of patients with upper ureteral calculi and 20% of patients with lower ureteral calculi required additional intervention for complications or failed treatment. In situ ESWL may not be the optimum therapy for all ureteric calculi especially those in the lower ureter.


Tacrolimus preconditioning of rat liver allografts impacts glutathione homeostasis and early reperfusion injury.
To characterize the immunosuppressant tacrolimus as a protective antioxidant in rat liver transplantation. Livers of male Lewis rats underwent 24 h of hypothermic preservation in UW solution and were rinsed with tacrolimus or placebo directly before transplantation. Markers of liver injury, such as enzymes and bile flow, were determined during a 2 h reperfusion period. Concentrations of reduced (GSH) and oxidized (GSSG) glutathione were analyzed in plasma, bile, and liver tissue for estimation of oxidant stress caused by reactive oxygen species (ROS). Administration of tacrolimus (10 ng/mL) resulted in decreased ALT plasma levels (1740 ± 1169 U/l versus 3691 ± 1144 U/l; P < 0.05) at 2 h of reperfusion. While endogenous intracellular GSH concentrations remained unchanged, GSSG, the oxidation product of GSH, was markedly decreased at 2 h of reperfusion in preconditioned livers (47.0 ± 10.4 nm/g versus 71.8 ± 30.6 nm/g; P < 0.05). Correspondingly, GSSG bile concentrations (0.19 ± 0.04 mM versus 0.13 ± 0.04 mM; P < 0.05) as well as plasma GSSG levels (2.4 ± 0.3 mM versus 1.4 ± 0.2 mM; P < 0.05) were significantly increased upon reperfusion. These findings suggest that tacrolimus impacts post-ischemic GSH metabolism when administered as a rinse solution for liver allografts through an unknown pathway. Hepatocellular injury following transplantation was significantly decreased by preconditioning with tacrolimus. One possible mechanism of action is the detoxification of ROS through the preservation of cytosolic and extracellular GSH/GSSG ratios.


An Ex-vivo Model Examining Acoustics and Aerodynamic Effects Following Medialization With and Without Arytenoid Adduction.
Quantify differences in acoustics and intraglottal flow fields between Thyroplasty Type 1 (TT1) with and without arytenoid adduction (AA) using excised canine larynx model. Basic science experiments using excised larynges. Surgical procedures were implemented in eight excised canine larynges. Acoustics and intraglottal flow measurements were taken at low and high subglottal pressures in each experimental setup. In all larynges, vocal efficiency (VE) and cepstrum peak prominence (CPP) were higher, and the mean phonatory flow rate was lower in TT1 with AA than without AA. The glottal asymmetry is reduced with AA and promotes the formation of stronger vortices in the glottal flow during the closing phase of the vibrating folds. Findings suggest a clear acoustic and aerodynamic benefit to the addition of AA when performing TT1. It shows significant improvement in CPP, translating to decreased breathiness and dysphonia and increased VE, leading to easier and more sustainable phonation. Stronger intraglottal vortices are known to be correlated with the loudness of voice produced by phonation. N/A Laryngoscope, 133:621-627, 2023.


Resource-Efficient Chemistry on Quantum Computers with the Variational Quantum Eigensolver and the Double Unitary Coupled-Cluster Approach.
Applications of quantum simulation algorithms to obtain electronic energies of molecules on noisy intermediate-scale quantum (NISQ) devices require careful consideration of resources describing the complex electron correlation effects. In modeling second-quantized problems, the biggest challenge confronted is that the number of qubits scales linearly with the size of the molecular basis. This poses a significant limitation on the size of the basis sets and the number of correlated electrons included in quantum simulations of chemical processes. To address this issue and enable more realistic simulations on NISQ computers, we employ the double unitary coupled-cluster (DUCC) method to effectively downfold correlation effects into the reduced-size orbital space, commonly referred to as the active space. Using downfolding techniques, we demonstrate that properly constructed effective Hamiltonians can capture the effect of the whole orbital space in small-size active spaces. Combining the downfolding preprocessing technique with the variational quantum eigensolver, we solve for the ground-state energy of H2, Li2, and BeH2 in the cc-pVTZ basis using the DUCC-reduced active spaces. We compare these results to full configuration-interaction and high-level coupled-cluster reference calculations.


A Dilution Model for Embryonic Scaling.
A recent study in Nature Cell Biology (Almuedo-Castillo et al., 2018) describes a mechanism for tissue scaling in zebrafish embryos. The authors show that a fixed relative amount of the diffusible Nodal inhibitor Lefty produces an extended gradient in larger embryos, ensuring proportionally scaled germ layers, irrespective of embryo size.


Erratum: Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells: Erratum.
[This corrects the article DOI: 10.7150/jca.50512.].


Natural History and Disease Progression of Early Cardiac Amyloidosis Evaluated by Echocardiography.
Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Preamyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain [AL] or amyloid transthyretin [ATTR]). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 [interquartile range {IQR} 1.0, 1.5] cm) ≥3 years before the diagnosis of CA and relative wall thickness was increased (0.47 [IQR 0.41, 0.50]) ≥7 years prediagnosis. One to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction ≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased relative wall thickness (0.74 [IQR 0.62, 0.92] versus 0.62 [IQR 0.54, 0.76], p = 0.004) and LV mass index (144 [IQR 129, 191] versus 115 [IQR 105, 146] g/m2, p = 0.020) and reduced LV ejection fraction (50 [IQR 44, 58] versus (60 [IQR 53, 60]%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography.


Spatio-temporal patterns in the gene expression of the calanoid copepod Temora longicornis in the Belgian part of the North Sea.
Marine zooplankton are increasingly being affected by recent environmental changes, such as climate change, and respond with profound spatial relocations and shifts in phenology and physiology. In order to predict whether populations are able to persist or adapt to such new conditions, it is essential to understand the molecular basis of such adaptations, which ultimately get translated into these physiological responses. To explore variation in population gene expression across time and space, we investigated transcriptome-level profiles of the calanoid copepod Temora longicornis, that were collected at four different locations in the Belgian Part of the North Sea (BPNS) on three different time points (April, June, October) in 2018. RNA-seq analysis of field collected adults identified large seasonal differences in gene expression, mainly between spring-summer and autumn samples. The largest log-fold changes occurred in a set of genes encoding for ribosomal and myosin (heavy chain) transcripts. Enrichment analysis revealed a strong seasonal pattern in vitellogenin, cuticle and glycolytic gene expression as well. We also found a positive correlation between vitellogenin expression and densities of T. longicornis. No clear spatial variation in expression patterns was found in the BPNS. This study underlines the potential of field gene expression studies for biomonitoring purposes and the significance of considering seasonal variation in future studies.


Hemothorax Management After Endovascular Treatment For Thoracic Aortic Rupture.
The aim was to describe and analyze the management of hemothorax (HTX) and the occurrence of respiratory complications after endovascular repair of thoracic aortic rupture (TEVAR). This was a multicenter study with retrospective analysis. Between November 2000 and December 2012, all patients with confirmed HTX due to rupture of the descending thoracic aorta treated with TEVAR were included. Respiratory function (acid base status, Pao2, Paco2, lactate, and respiratory index) was monitored throughout hospitalization. Primary endpoints were survival and post-operative respiratory complications. Fifty-six patients were treated. The mean age was 62 ± 21 years (range 18-92 years). Etiology included traumatic rupture (n = 23, 41%), atherosclerotic aneurysm (n = 20, 36%), Debakey type IIIa dissection (n = 8, 14%), and penetrating aortic ulcer (n = 5, 9%). The primary technical success of TEVAR was 100%. The in hospital mortality rate was 12.5% (n = 7). Hemothorax was drained in 21 (37.5%) cases. In hospital respiratory complications occurred in 23 (41%) patients who required a longer intensive care unit stay (days 2.3 ± 0.7 vs. 1.9 ± 0.8, p = .017), and hospitalization (26 ± 17 vs. 19 ± 17, p = .021). Those who developed post-operative respiratory complications had lower pre-operative PO2 values (mmHg, 80 ± 24 vs. 91 ± 21, p = .012). Respiratory complications and in hospital mortality did not differ among aortic pathologies (p = .269 and p = 1.0, respectively), nor did in hospital mortality differ between patients with and without respiratory complications (13% vs. 12%; p = .990). Thoracic aortic rupture still has a high mortality rate. Respiratory complications have not been eliminated by endovascular repair. HTX evacuation may have had a positive influence on the survival in these patients. Although traumatic and degenerative ruptures are two significantly different scenarios, survival and respiratory outcomes were similar and were not affected by the underlying aortic disease.


[Prevalence of coagulase-negative staphylococci in blood cultures at the Ibn-Rochd University Hospital in Casablanca].
Blood cultures are the best diagnostic tool for the detection of bacteremia. However, false positive results may lead to confusion about antibiotic regimens, putting the lives of patients at risk. The main purpose of this study was to assess the prevalence of coagulase negative Staphylococci (CoNS) as well as of Corynebacterium spp and Bacillus spp in the bags of blood culture analyzed in the microbiology laboratory at the Ibn-Rochd University Hospital in Casablanca. This prevalence was evaluated according to various Hospital Departments over the year 2016. We conducted a descriptive, retrospective study by analysing the computerized database of the Laboratory of bacteriology and virology at the Ibn-Rochd University Hospital in Casablanca over a 12-month period from 1st January to 31st December 2016. Our study focused on bacteria forming part of the commensal flora (coagulase negative Staphylococcus, Corynebacteria spp and Bacillus spp). The blood culture bags were incubated in the automated blood culture system (Bactec FX). The identification of the germs from a positive culture was performed according to the standard techniques of bacteriology and susceptibility testing was performed according to EUCAST 2015. We conducted an analysis of the computerized database of KALISIL system (Netika) version (2.2.10.) of the Microbiology Laboratory at the Ibn-Rochd University Hospital in Casablanca. Out of 7959 requests for blood cultures obtained from 5801 patients addressed to the laboratory of bacteriology, 2491 were positive, of which 848, reflecting a rate of 34% of positive bags or 10.6% of the whole of bags received over the year 2016, were positive for coagulase negative Staphylococcus, 56 bags of blood cultures, reflecting a rate of 2.2%, were positive for Corrynébacteruim SP, followed by 60 bags of blood cultures, reflecting a rate of 2.4%, which were positive for Bacillus sp. The frequency of isolation of coagulase negative Staphylococcus compared to other bacteria according to Clinical Departments showed a higher frequency in the Paediatric Department (47.2%) followed by the Medicine Department (44.1%). This study shows that coagulase negative Staphylococci are the organisms most frequently isolated from blood cultures. They are a non-negligible cause of nosocomial infections, but they are also the most common blood culture contaminants.


Biochemical and biophysical studies of isolated horizontal cells from the teleost retina.
Neurons in the vertebrate retina are interconnected by a complex network of chemical and electrical synapses which make it difficult to study the intrinsic biochemical and biophysical properties of individual cells. During the past decade, enzymatic methods have been developed for dissociating adult retinas into viable and readily identifiable single cells. Using this preparation, we and other investigators have studied the physiological and biochemical properties of several classes of isolated retinal cells. In particular, we have shown that a type of retinal interneuron, the GABA-ergic horizontal cell of teleost retinas, may be an excellent model system for examining the intrinsic membrane properties as well as the cellular mechanisms regulating GABA uptake, synthesis and release from an identified CNS neuron.


Respiratory system mechanics, gas exchange, and outcomes in mechanically ventilated patients with COVID-19-related acute respiratory distress syndrome: a systematic review and meta-analysis.
The association of respiratory mechanics, particularly respiratory system static compliance (CRS), with severity of hypoxaemia in patients with COVID-19-related acute respiratory distress syndrome (ARDS) has been widely debated, with some studies reporting distinct ARDS phenotypes based on CRS. Ascertaining whether such phenotypes exist is important, because they might indicate the need for ventilation strategies that differ from those used in patients with ARDS due to other causes. In a systematic review and meta-analysis of studies published between Dec 1, 2019, and March 14, 2022, we evaluated respiratory system mechanics, ventilator parameters, gas exchange parameters, and clinical outcomes in patients with COVID-19-related ARDS. Among 11 356 patients in 37 studies, mean reported CRS, measured close to the time of endotracheal intubation, was 35·8 mL/cm H2O (95% CI 33·9-37·8; I2=96·9%, τ2=32·6). Pooled mean CRS was normally distributed. Increasing ARDS severity (assessed by PaO2/FiO2 ratio as mild, moderate, or severe) was associated with decreasing CRS. We found no evidence for distinct CRS-based clinical phenotypes in patients with COVID-19-related ARDS, and we therefore conclude that no change in conventional lung-protective ventilation strategies is warranted. Future studies should explore the personalisation of mechanical ventilation strategies according to factors including respiratory system mechanics and haemodynamic status in patients with ARDS.


Distortion of endothelial repair. The effect of hypercholesterolaemia on regeneration of aortic endothelium following injury by endotoxin. A scanning electron microscope study.
Five young male New Zealand White rabbits were fed a semi-synthetic diet containing 0.2% cholesterol for 2 weeks and a control group of 5 animals was fed a normal stock diet. All animals were then injected intravenously with a single dose of endotoxin from Serratia marcescens (200 microgram/kg body weight) and continued on their respective diets for a further 4 weeks. The aortas were then stained with silver nitrate and fixed under pressure for Scanning Electron Microscopy (SEM). Argyrophilic endothelial cells were present in both groups of animals 4 weeks after endotoxin injections. In the cholesterol-fed animals, however, these cells were often covered with pits and craters. These findings suggest that the hypercholesterolaemia may affect the regeneration of arterial endothelial cells.


Commentary: What happens when a combined entity is lesser than the sum of its parts?
Elsewhere in this issue, Kastor examines the failed merger of the Mount Sinai and New York University (NYU) medical schools and hospitals. The failure of the merger is even more remarkable today than it was when the hospitals began disassociating in 2001. Today, both Mount Sinai and NYU hospitals and medical schools are stronger than they were when merger discussions began, and they are certainly far stronger than when the merger began to unwind. This fact calls into question the validity of the assumptions that initiated the desire to merge, as well as the execution of the merger. The author of this commentary offers his perspective as a leader with more than 40 years of experience at Mount Sinai. He examines the reasons behind dissolving the merger and the factors that have led to Mount Sinai's success since then.


Correction: Imamichi et al. Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy. Biology 2022, 11, 420.
In the original publication [...].


Mercury exposure assessment in indigenous communities from Tarapaca village, Cotuhe and Putumayo Rivers, Colombian Amazon.
Mercury (Hg) is a complex and multifaceted global pollutant. Artisanal and small-scale gold mining activities are largely responsible for Hg contamination in developing countries, in many cases impacting areas of high biodiversity such as the Amazon. The aim of the study was to establish Hg exposure in indigenous citizens from the Tarapaca village, Cotuhe and Putumayo Rivers, at the Colombian Amazon. Total Hg (T-Hg) concentrations were measured employing a DMA-80 Hg analyzer. For that purpose, 190 hair samples were taken from volunteers living in different communities of Tarapaca. The overall mean T-Hg level for all samples was 10.6 ± 0.4 μg/g, with values ranging from 0.61 to 31.1 μg/g. The mean T-Hg level decreased in the order Puerto Huila > Puerto Ticuna > Ventura > Nueva Union > Buenos Aires > Santa Lucia > Puerto Nuevo > Caña Brava > Pupuña. Based on recommendations from the United States Environmental Protection Agency (US EPA), 99.5% of the samples exceeded the maximum level of 1.0 μg/g. Hg content in human hair was significantly associated with fish consumption (ρ = 0.253; p < 0.001). According to the health survey, at least 24.7% of the volunteers manifested some signs and symptoms of Hg poisoning. In short, these data support the extensive Hg exposure in the environment of the Colombian Amazon, a process that could be impacting the quality of life of its vulnerable indigenous groups. Immediate actions must be taken by competent authorities to protect these communities from Hg poisoning.


Validation of two PROMIS item banks for measuring social participation in the Dutch general population.
The Patient-Reported Outcomes Measurement Information System (PROMIS) item banks 'Ability to Participate in Social Roles and Activities' (35 items) and 'Satisfaction with Social Roles and Activities' (44 items) were developed to measure (satisfaction with) participation more efficiently and precisely than current instruments, by using Computerized Adaptive Testing (CAT). We validated these item banks in a Dutch general population. Participants in an internet panel completed both item banks. Unidimensionality, local dependence, monotonicity, Graded Response Model item fit, Differential Item Functioning (DIF) for age, gender, education, region, ethnicity, and language (Dutch compared to US Social Supplement), and reliability were assessed. A representative Dutch sample of 1002 people participated. We found for the Ability to Participate and Satisfaction with Participation item banks, respectively, sufficient unidimensionality (CFI: 0.971, 0.960; TLI: 0.970, 0.958; RMSEA: 0.108, 0.108), no local dependence, sufficient monotonicity (H: 0.75, 0.73), good item fit (2 out of 35 items, 1 out of 44 items with S-X2p-value < 0.001). No DIF was found. We found a reliability of at least 0.90 with simulated CATs in 86% and 94% of the participants with on average 4.7 (range 2-12) and 4.3 (range 3-12) items, respectively. The PROMIS participation item banks showed sufficient psychometric properties in a general Dutch population and can be used as CAT. PROMIS CATs allow reliable and valid measurement of participation in an efficient and user-friendly way with limited administration time.


Independent pragmatic replication of the Dove Confident Me body image program in an Australian Girls Independent Secondary School.
Following calls for the independent replication of universal body image programs under diverse conditions, this research aimed to investigate whether the universal co-educational prevention program developed for audiences in the United Kingdom (Dove Confident Me, DCM), was an acceptable and effective intervention when delivered by teachers to adolescent girls attending a single-sex Australian school. Comprising two studies, Study 1, evaluated DCM among Grade 8 students (N = 198) at a single-sex private school, and compared the results with students (N = 208) s from a matched comparison group. No improvements were observed on outcome measures between the comparison and intervention girls over the three time points. Study 2 involved minor modifications to the aesthetics and content of the program, as well as the logistics of delivery. Delivered by teachers to Grade 8 students (N = 242 intervention and N = 354 comparison), there were significant improvements in acceptability of the modified DCM program, yet no interaction effects observed on outcome measures. While the program did no harm, it is possible that there are adjustments to the methods utilized and content of programs that are trialed in efforts to prevent body image concerns and eating disorders in the school setting.


Large pseudocyst of the umbilical cord detected in the second trimester.
We present a case of a large umbilical cord cyst detected at 21 weeks of gestation. Serial ultrasonographic examination revealed a single umbilical artery and progression of the cystic mass. A 2,842-g male infant was delivered at 37 weeks of gestation, and we confirmed that the umbilical cord cyst was a pseudocyst in our pathological examination. This case demonstrated an uneventful course of pregnancy despite the large umbilical cord pseudocyst.


Cervical lymph node metastasis of bladder cancer: a case report and review of literature.
To report an extremely rare case of bladder cancer patient with cervical lymph nodes, abdominal lymph nodes, and bone metastases at the same time. The case was investigated by follow-up and immunohistochemistry was used in the pathological part. The patient was diagnosed with bladder cancer (high-grade urothelial metastatic epithelial cell carcinoma) by pathology and immunohistochemistry after transurethral resection of bladder tumor (TURBT) and metastatic bladder cancer by pathology and immunohistochemistry after cervical lymph node aspiration due to neck lymph node enlargement 1 year later, and a CT of the chest and abdomen suggested that the patient also had abdominal lymph node and bone metastases.At the 2.5-year regular chemotherapy follow-up, the patient showed that the abdominal lymph node metastasis disappeared, the cervical lymph node fusion shrank, and the bone metastasis still existed. 1. Regular postoperative review is particularly important; 2.For patients with UCB who undergo TURBT, a effective regular perfusion program should be performed throughout the postoperative period; 3. For patients with postoperative metastatic symptoms of UCB, Complex treatment has a positive effect on patient prognosis; 4.The presence of enlarged head and neck lymph nodes in patients with bladder cancer should also be considered as metastatic of UCB.


Cervical conization and preterm delivery/low birth weight. A systematic review of the literature.
Evaluate the effect of cervical conization on preterm birth/low birth weight (LBW). A systematic review of the literature using external or internal controls. The typical odds ratio for preterm delivery in women with prior cervical conization using external controls was 3.23 (95% confidence interval 2.29-4.55). Using internal controls the typical odds ratio for LBW was 2.97 (95% confidence interval 1.09-8.05). Using external controls the typical odds ratio for LBW was 2.31 (95% confidence interval 1.33-3.99). Women with cervical conization are at higher risk for preterm birth than external controls, and the surgical intervention as such is a major determining factor.


Polyunsaturated fatty acids cause physiological and behavioral changes in Vibrio alginolyticus and Vibrio fischeri.
Vibrio alginolyticus and Vibrio (Aliivibrio) fischeri are Gram-negative bacteria found globally in marine environments. During the past decade, studies have shown that certain Gram-negative bacteria, including Vibrio species (cholerae, parahaemolyticus, and vulnificus) are capable of using exogenous polyunsaturated fatty acids (PUFAs) to modify the phospholipids of their membrane. Moreover, exposure to exogenous PUFAs has been shown to affect certain phenotypes that are important factors of virulence. The purpose of this study was to investigate whether V. alginolyticus and V. fischeri are capable of responding to exogenous PUFAs by remodeling their membrane phospholipids and/or altering behaviors associated with virulence. Thin-layer chromatography (TLC) analyses and ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC/ESI-MS) confirmed incorporation of all PUFAs into membrane phosphatidylglycerol and phosphatidylethanolamine. Several growth phenotypes were identified when individual fatty acids were supplied in minimal media and as sole carbon sources. Interestingly, several PUFAs acids inhibited growth of V. fischeri. Significant alterations to membrane permeability were observed depending on fatty acid supplemented. Strikingly, arachidonic acid (20:4) reduced membrane permeability by approximately 35% in both V. alginolyticus and V. fischeri. Biofilm assays indicated that fatty acid influence was dependent on media composition and temperature. All fatty acids caused decreased swimming motility in V. alginolyticus, while only linoleic acid (18:2) significantly increased swimming motility in V. fischeri. In summary, exogenous fatty acids cause a variety of changes in V. alginolyticus and V. fischeri, thus adding these bacteria to a growing list of Gram-negatives that exhibit versatility in fatty acid utilization and highlighting the potential for environmental PUFAs to influence phenotypes associated with planktonic, beneficial, and pathogenic associations.


Molecular cloning of a cDNA encoding the "61-kDa" calmodulin-stimulated cyclic nucleotide phosphodiesterase. Tissue-specific expression of structurally related isoforms.
We have isolated a 2287-bp cDNA encoding the 61-kDa calmodulin-stimulated cyclic nucleotide phosphodiesterase (CaM PDE) from a bovine brain library. A large open reading frame within the cDNA encodes a 530-residue polypeptide which is identical to the sequence of the purified protein previously determined by direct amino acid sequencing. Moreover, COS cells transfected with the cDNA express a cAMP and cGMP hydrolytic activity that is stimulated by calcium and calmodulin, confirming that the cDNA represents a mRNA species encoding a CaM PDE isozyme. RNase protection analyses indicate that either 61-kDa CaM PDE mRNA or structurally related transcripts encoding different CaM PDE isoforms are expressed in a tissue-specific manner. Total RNA isolated from brain (cerebral cortex, basal ganglia, hippocampus, cerebellum, and medulla/spinal cord), heart, aorta, liver, kidney outer medulla, kidney papilla, trachea, and lung completely protected a 410-base antisense riboprobe corresponding to sequence encoding a portion of the catalytic domain. Little or no protection was detected using adrenal cortex, adrenal medulla, liver, kidney cortex, spleen, or T-lymphocyte total RNA. Only brain RNA completely protected a 240-base antisense riboprobe corresponding to the 61-kDa CaM PDE amino terminus encompassing a putative calmodulin-binding domain. However, heart, aorta, liver, kidney, trachea, and lung RNA protected 150 bases of this riboprobe suggesting that these tissues express an isoform structurally related to the 61-kDa CaM PDE. Northern analysis of mRNA isolated from brain, heart, aorta, liver, kidney, lung, and trachea revealed that the cDNA hybridizes with a 3.8- and a 4.4-kb (kilobase) mRNA species. Interestingly, Northern blots of bovine cerebral cortex and heart mRNA probed under stringent conditions with antisense transcripts corresponding to either the 5'- or 3'-untranslated sequence of the 61-kDa CaM PDE cDNA hybridized with only the 4.4-kb mRNA from both tissues. Since different, yet structurally similar CaM PDE isoforms are expressed in brain and in heart, this result, in addition to the RNase protection data, is consistent with the idea that the mRNAs encoding these two CaM PDE isoforms are products of an alternately spliced gene.


In vivo cytogenetic effects of cooked food mutagens.
Using a variety of in vivo cytogenetic endpoints, we have investigated the effects of several compounds formed during the cooking of meat. C57Bl/6 mice were used to test for an increase in the frequency of sister-chromatid exchanges (SCEs), chromosomal aberrations, and micronucleated erythrocytes by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). MeIQx and DiMeIQx did not induce SCEs in mouse bone marrow cells. PhIP induced sister-chromatid exchanges, but not chromosomal aberrations in bone marrow. In peripheral blood lymphocytes, PhIP did induce aberrations at 100 mg/kg, the highest dose tested. PhIP induced a low but significantly increased frequency of micronuclei in normochromatic but not polychromatic erythrocytes in bone marrow and peripheral blood. However, dose responses were not observed. With the exception of the SCEs induced by PhIP, these results contrast with observations made in vitro, where these compounds were found to have significant genotoxicity in mammalian cells and a very high mutation frequency in prokaryotic systems.


Measuring contact area, force, and pressure for bioengineering applications: using Fuji Film and TekScan systems.
The goal of this study was to compare the TekScan I-Scan Pressure Measurement System with two methods of analysis involving the Fuji Film Prescale Pressure Measuring System in estimating area, force and pressure. Fuji Film and TekScan sensors were alternately placed between a cylindrical peg and a finely ground steel base plate, and compressed with known forces. All Fuji stains were digitally scanned and analyzed. The Erase method of Fuji Film analysis consisted of manually removing portions of the image judged by the user to be outside the perimeter of the stain. The second method of Fuji Film analysis, termed the Threshold method, used the threshold tool to analyze only those pixels that were stained from loading. The TekScan system utilized special matrix-based sensors interfaced with a Windows compatible desktop computer that was equipped with specialized data acquisition hardware and analysis software. The data from this study did not support the hypothesis that all three methods would have accuracies within +/-5% of a known value, when estimating area, force and pressure. Specifically, the TekScan system was found to be more accurate than either of the Fuji Film methods when estimating area and pressure.


NT Pro-BNP can be used as a risk predictor of clinical atrial fibrillation with or without left atrial enlargement.
NT Pro-BNP is a blood marker secreted by cardiomyocytes. Myocardial stretch is the main factor to stimulate NT Pro-BNP secretion in cardiomyocytes. NT Pro-BNP is an important risk factor for cardiac dysfunction, stroke, and pulmonary embolism. So does atrial myocyte stretching occur when patients have atrial fibrillation (AF)? Whether atrial muscle stretch induced by AF leads to increased NT Pro-BNP remains unclear. The purpose of this study is to investigate the relationship between NT Pro-BNP and AF. AF can cause changes in myocardial tension. Changes in myocardial tension may lead to increased secretion of NT Pro-BNP. We hypothesize that NT Pro-BNP may increase in AF with or without LAD enlargement. This clinical study is an observational study and has been approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University. Ethical approval documents is attached. The study retrospectively reviewed 1345 patients with and without AF. After excluding 102 patients who were not eligible, the final total sample size was 1243 cases: AF group 679 patients (378, 55.7% males) and non-AF group 564 patients (287, 50.8% males). NT Pro-BNP was observed in AF group and non-AF group with or without LAD. After adjusting for age, gender, BMI, left atrial diameter, hypertension, diabetes, coronary heart disease, and cerebral infarction, NT Pro-BNP remains statistically significant with AF. NT Pro-BNP can be used as a risk predictor of AF with or without left atrial enlargement.


WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner.
N6-methyladenosine (m6A) regulators are involved in the progression of various cancers via regulating m6A modification. However, the potential role and mechanism of the m6A modification in osteosarcoma remains obscure. In this study, WTAP was found to be highly expressed in osteosarcoma tissue and it was an independent prognostic factor for overall survival in osteosarcoma. Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of osteosarcoma in vitro and vivo. Mechanistically, M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 was identified as the target gene of WTAP, which regulated HMBOX1 stability depending on m6A modification at the 3'UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in osteosarcoma and was an independent prognostic factor for overall survival in osteosarcoma patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on osteosarcoma growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway. In conclusion, this study demonstrated the critical role of the WTAP-mediated m6A modification in the progression of osteosarcoma, which could provide novel insights into osteosarcoma treatment.


Identification of Functional HLA-A*01:01-Restricted Epstein-Barr Latent Membrane Protein 2-Specific T-Cell Receptors.
Adoptive transfer of genetically engineered T cells expressing antigen-specific T-cell receptors (TCRs) is an appealing therapeutic approach for Epstein-Barr virus (EBV)-associated malignancies of latency type II/III that express EBV antigens (LMP1/2). Patients who are HLA-A*01:01 positive could benefit from such products, since no T cells recognizing any EBV-derived peptide in this common HLA allele have been found thus far. HLA-A*01:01-restricted EBV-LMP2-specific T cells were isolated using peptide major histocompatibility complex (pMHC) tetramers. Functionality was assessed by production of interferon gamma (IFN-γ) and cytotoxicity when stimulated with EBV-LMP2-expressing cell lines. Functionality of primary T cells transduced with HLA-A*01:01-restricted EBV-LMP2-specific TCRs was optimized by knocking out the endogenous TCRs of primary T cells (∆TCR) using CRISPR-Cas9 technology. EBV-LMP2-specific T cells were successfully isolated and their TCRs were characterized. TCR gene transfer in primary T cells resulted in specific pMHC tetramer binding and reactivity against EBV-LMP2-expressing cell lines. The mean fluorescence intensity of pMHC-tetramer binding was increased 1.5-2 fold when the endogenous TCRs of CD8+ T cells was knocked out. CD8+/∆TCR T cells modified to express EBV-LMP2-specific TCRs showed IFN-γ secretion and cytotoxicity toward EBV-LMP2-expressing malignant cell lines. We isolated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can potentially be used in future TCR gene therapy to treat EBV-associated latency type II/III malignancies.


Redistribution of the flux-control coefficients in mitochondrial oxidative phosphorylations in the course of brain edema.
This work describes the control exerted by dicarboxylate carrier and succinate dehydrogenase activities on the oxidative phosphorylations in rabbit brain mitochondria as an edema develops. Vasogenic edema leads to an uncompetitive inhibition of succinate dehydrogenase activity and to a large decrease of oxidative phosphorylations linked to succinate utilisation. Naftidrofuryl treatment in vivo restores both a high succinate dehydrogenase activity and a normal respiratory rate. In order to quantify the control of oxidative phosphorylations by the succinate dehydrogenase step, we applied the control analysis (Kacser, H. and Burns, J.A. (1973) in Rate Control of Biological Processes (Davies, D.D., ed.), pp. 65-104, Cambridge University Press, London; Heinrich, R. and Rapoport, T.A. (1974) Eur. J. Biochem. 42, 89-95). By using two inhibitors, one (phenylsuccinate) acting only on the dicarboxylate carrier and another (malonate) acting on both the dicarboxylate carrier and the succinate dehydrogenase, a method was developed to calculate the control coefficients of these two steps. The main result is that in mitochondria isolated from normal tissue succinate dehydrogenase exerted no control, but in the course of edema this enzymatic step became a controlling one: a transition from zero to a high control coefficient (0.5) was observed from the onset of intracellular edema for the threshold value of water/dry-weight tissue of 4.6.


Detection of Streptococcus pneumoniae and Moraxella catarrhalis in patients with paranasal chronic sinusitis by polymerase chain reaction method.
Sinusitis is a complex involvement of the upper respiratory system by bacteria, viruses, fungi, or other allergens. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the dominant bacterial microorganisms involved in acute sinusitis, whereas in chronic sinusitis, Staphylococcus aureus and some anaerobic bacteria are the prevailing pathogens. Appropriate antibiotic treatment requires sinusitis bacteriology assessment. The aim of this study was to isolate bacteria in clinical samples from patients with chronic sinusitis. A total of 55 samples were collected from patients with chronic sinusitis undergoing surgery at Imam Khomeini Hospital in Ahvaz, Iran. Samples were cultured in conventional medium, and for each culture, Gram staining, catalase, coagulase, oxidase, and DNAse tests were performed and isolates were stored for polymerase chain reaction analysis. Twenty-three isolates were obtained from five patients, including S. aureus (23.6%), Rhizomucor (1.8%), and Escherichia (1.8%) by the culture method and M. catarrhalis (3.6%) and S. Pneumoniae (7.2%) by the polymerase chain reaction method. Compared with acute sinusitis, the microbiology of chronic sinusitis remains controversial. Results are affected by many factors, including diversity of molecular and culture methods, sterilization of sampling area, sample transfer to laboratory, use of antibiotics prior to surgery, and nasal polyps. In Iran, the causative agents of chronic sinusitis are similar to those in other countries. Compared with other bacteria, S. aureus was observed more often in asthmatic patients with sinusitis.


Measuring the shape and size of microcracks in bone.
Microcracks in bone are normally measured from two-dimensional, transverse sections but this provides incomplete information about their three-dimensional shape and size. The methods of stereology can usefully be applied in such a case. This problem has been addressed using a theoretical model and a numerical simulation. Results show that the data are consistent with a crack shape which is elliptical, with axis ratio approximately 4.5:1 and with size variation (expressed as the ratio of standard deviation to mean length) of at least 0.1. Measured lengths will, on average, be smaller and have more scatter than true lengths. Errors caused by omitting small cracks are relatively unimportant. Knowledge of the true crack dimensions, and their variability, is important for the analysis of damage, stress fracture, remodelling and adaptation.


Modification of brain mitochondrial enzymes by the oxygen analogue of ronnel at various stages of development and aging.
This paper describes the effect of the organophosphorus compound, the oxygen analogue of ronnel (OAR), on the activity of some membrane-bound enzyme systems in the brain mitochondria of developing, young-adult, and old rats. Age-related changes were noted in the cholesterol-to-protein ratio, whereas the phospholipid content in mitochondria showed little change during development as well as aging. The results obtained suggest that development of brain succinate dehydrogenase may consist in a decrease of Km and increase of Vmax values. In aged rats an altered, perhaps inhibited form of the enzyme is produced. The oxygen analogue of ronnel caused a mixed-type inhibition of the succinate dehydrogenase derived from brains of 4-day-old, 16-day-old and 2-month-old animals. In the case of enzyme from the brain of 18-month-old rats, a typical competitive-type inhibition was observed. Mechanisms responsible for inhibition of the succinate: cytochrome c reductase from brains of developing animals are similar to those for succinate dehydrogenase. In aged rats (18 months old), however, a noncompetitive mechanism of inhibition of succinate: cytochrome c reductase was revealed. The experiments reported here provide evidence that lipid-soluble molecules of OAR may interact with membrane phospholipids and lead to modification of membrane architecture and also of enzyme kinetic behaviour. It may be also concluded, that the sensitivity of the enzyme systems studied to inhibition by OAR is an age-dependent phenomenon. Modification of membrane by development or aging alters the kinetics as well as the sensitivity of enzymes to inhibitors.


Mechanisms for enhanced biodegradation of petroleum hydrocarbons by a microbe-colonized gas-liquid foam.
A microbe-colonized gas-liquid foam formulation has been previously shown to provide enhanced biodegradation capabilities in soil microcosms. The present study considers the reservoir properties of this foam and how this affects hydrocarbon degradation rates. Oxygen solubility in protein hydrolysate solutions draining from aerated and oxygenated foams was measured. The suitability of oxygenated foam to enhance the degradation of n-hexadecane in soil microcosms was assessed. Sorption of bacterial isolates at the gas-liquid interface was also investigated using a range of microscopy techniques. Oxygenated bioactive foam enhanced biodegradation rates by improving oxygen availability and transfer. Biodegradation of n-hexadecane was also stimulated by the protein hydrolysate used and by the inclusion of known bacterial hydrocarbon-degrading bacteria. The interaction of bacteria with the gas-liquid interface was shown to be a significant factor governing the drainage of the bacteria from the bioactive foam. Protein hydrolysate-based bioactive foam may be a suitable treatment technology to enhance the biodegradation of petroleum hydrocarbons in soil.


Evaluation of calcium, phosphorus, and selected trace mineral status in commercially available dry foods formulated for dogs.
To evaluate concentrations of calcium, phosphorus, zinc, iron, copper, manganese, and selenium in several commercially available dry dog foods and compare these with current Association of American Feed Control Officials (AAFCO) recommendations for maintenance of healthy dogs. Descriptive study. 45 over-the-counter dry foods formulated for maintenance of healthy dogs (ie, maintenance foods) and 5 therapeutic dry foods formulated for dogs with hepatic or renal disease. Mineral concentrations were measured via inductively coupled plasma mass spectrometry or inductively coupled plasma atomic emission spectroscopy and compared with AAFCO-recommended minimum and maximum values. Most (39/45) maintenance foods were in compliance with AAFCO recommendations for all mineral concentrations evaluated. Calcium concentration was > 7. 1 g/1,000 kcal of metabolizable energy (ME) in 4 of 45 maintenance foods, and phosphorus concentration was > 4.6 g/1,000 kcal ME in 3 of these; 2 maintenance foods contained < 34 mg of zinc/1,000 kcal ME. These values were not within AAFCO-recommended ranges. Calcium-to-phosphorus ratio in foods formulated for dogs with renal disease was above, and copper concentration in foods formulated for dogs with hepatic disease was below, recommended ranges for healthy dogs. Calcium concentrations exceeded recommended limits in some maintenance foods labeled for all life stages, underscoring the need to feed diets appropriately formulated for specific life stages, particularly for large- and giant-breed puppies. Studies investigating the bioavailability of minerals are necessary before firm recommendations can be made.


Flow-distributed oscillations: stationary chemical waves in a reacting flow.
A recent prediction of stationary waves in open, reacting flows is experimentally verified. We show that stationary waves are generated by a mechanism whereby the flow carries a time-oscillating subelement, behaving like a batch reactor, through space while a fixed boundary condition at the inflow locks the phase of the oscillation. This mechanism can generate stationary patterns when all diffusion coefficients are equal. The experimental system is the ferroin-catalyzed Belousov-Zhabotinsky reaction in a tubular reactor, fed by the outflow of a continuous flow stirred tank reactor (CSTR). Parameter conditions are such that the concentrations are constant in the CSTR while they oscillate in the flow tube.


Impacts of COVID-19 lockdown on private domestic groundwater sample numbers, E. coli presence and E. coli concentration across Ontario, January 2020-March 2021: An interrupted time-series analysis.
Approximately 1.5 million individuals in Ontario are supplied by private water wells (private groundwater supplies). Unlike municipal supplies, private well water quality remains unregulated, with owners responsible for testing, treating, and maintaining their own water supplies. The COVID-19 global pandemic and associated non-pharmaceutical interventions (NPIs) have impacted many environmental (e.g., surface water and air quality) and human (e.g., healthcare, transportation) systems over the past 15-months (January 2020 to March 2021). To date, the impact of these interventions on private groundwater systems remains largely unknown. Accordingly, the current study aimed to investigate the impact of a province-wide COVID-19 lockdown (late-March 2020) on health behaviours (i.e., private domestic groundwater sampling) and groundwater quality (via Escherichia coli (E. coli) detection and concentration) in private well water in Ontario, using time-series analyses (seasonal decomposition, interrupted time-series) of a large-spatio-temporal dataset (January 2016 to March 2021; N = 743,200 samples). Findings indicate that lockdown concurred with an immediate (p = 0.015) and sustained (p < 0.001) decrease in sampling rates, equating to approximately 2200 fewer samples received per week post-interruption. Likewise, a slightly decreased E. coli detection rate was observed approximately one month after lockdowns began (p = 0.003), while the proportion of "highly contaminated" samples (i.e., E. coli > 10 CFU/100 mL) was shown to increase within one month (p = 0.02), followed by a sustained decrease for the remainder of the year (May 2020-December 2020). Analyses strongly suggest that COVID-19 interventions resulted in discernible impacts on both well user behaviours and hydrogeological mechanisms. Findings may be used as an evidence-base for assisting policy makers, public health practitioners and private well owners in developing recommendations and mitigation strategies to manage public health risks during extreme and/or unprecedented future events.


Dexamethasone versus diclofenac sodium eyedrops to treat inflammation after cataract surgery.
We compared the postoperative anti-inflammatory effect of diclofenac sodium 0.1% and dexamethasone phosphate 0.1% in a prospective, randomized, double-masked pilot study. Anterior chamber inflammation was evaluated by measuring aqueous flare and cells with a laser flare-cell meter at one, three, 12, 30, and 60 days after cataract surgery. Flare values in the two groups did not significantly differ at any time, nor did aqueous cell counts at one, three, 12, and 60 days after surgery. At 30 days, however, cell count was significantly lower in the diclofenac group. Diclofenac sodium seems to be as potent as dexamethasone phosphate, as good as anti-inflammatory agent, and may replace corticosteroid therapy after cataract surgery.


Neuroimaging research in human MDMA users: a review.
Determining whether, under what circumstances, and to what extent 3,4-methylenedioxymethamphetamine (MDMA) exposure produces chronic changes in human brain function is a critical public health issue. MDMA is a widely used recreational drug commonly sold as "Ecstasy". Because findings from the animal literature have indicated that specific dosage regimens of MDMA can produce long-lasting alterations in serotonergic function, existing studies of MDMA effects in humans have examined brain serotonin (5-HT) transporters (5-HTT) and receptors or have examined brain structures or functions potentially affected by MDMA. The objectives of this review are to provide a background for interpreting human MDMA neuroimaging research, to examine existing neuroimaging data regarding the rationale for and limitations to human MDMA research, and to provide suggestions for improving the design and interpretation of future neuroimaging approaches. Of the existing neuroimaging studies in human MDMA users, few experimental designs have been replicated across different research groups. Only investigations employing nuclear imaging methods to assay brain 5-HTT levels have been replicated across methods and research laboratories. These studies have found reduced levels of the 5-HTT in recently abstinent MDMA users with some evidence for normalization of 5-HTT levels with prolonged abstinence. However, the sensitivity of these methods is unknown. The current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure. Future study designs might benefit from improved sample homogeneity, increased length of MDMA abstinence, longitudinal study design, test-retest measures, serotonergic specificity, and multimodal approaches.


Review of benzodiazepine use in children and adolescents.
Clinically, benzodiazepines are used in adult populations much more frequently than in children and adolescents. There may be a number of reasons for this disparity including a dearth of well controlled clinical studies and the issue of dependence associated with long term use. However, over a ten year span there has been nearly a three fold increase in the use patterns for these agents in the child population. In open studies much of the literature has indicated potentially useful results, but these findings have not been replicated when more refined methodological studies have been conducted. The lack of encouraging results in these later studies may be attributable to a number of factors such as modest sample sizes and less than optimal patient selection. Nonetheless, with increasing prescriptions being written for these agents it is not clear what is compelling clinicians to use them. In this paper we will review the available literature on benzodiazepine use in the child and adolescent population, focusing primarily on psychiatric applications.