Interactions between three subpopulations of Ehrlich ascites tumor and a P388 murine leukemia in mixed solid tumors in immune competent mice.
Cellular interactions between three subpopulations of Ehrlich ascites tumor and between these and the P388 murine leukemia were studied during growth of solid tumors obtained by mixtures of the cells in immune competent N/D mice. An immunogenic Ehrlich cell line (E1.15) induced an immunologically based growth inhibition of the two other Ehrlich cell lines (E1.80 and E1.95) which themselves were non-immunogenic. E1.15 was, however, unable to induce an immunological response against the P388 cell line. It is therefore suggested that when in close contact, immunologically induced cellular responses imposed by an immunogenic cell line on other cell lines require genetic and thereby close immunogenic resemblance between the cell lines. Another type of interaction was found between the E1.95 cell line and the P388 line which showed nearly identical growth characteristics as determined by tumor weight day 14, tumor growth curves, cell cycle times (per cent labelled mitoses) and cell cycle distributions (flow cytometric DNA analysis). After 2 weeks of growth of mixed P388/E1.95 tumors, flow cytometric DNA analysis on fine-needle tumor aspirates showed nearly total dominance of P388. This type of interaction required close cellular contact of viable cells, and no cellular immune response was elicited by the host animals. A third finding was that a faster growing Ehrlich cell line E1.95 dominated the tumors when inoculated in mixture with a slower growing subpopulation E1.80. This could be explained on the basis of the cell kinetic differences between these two cell lines.


Prevalence of upper airway obstruction in patients with apparently asymptomatic euthyroid multi nodular goitre.
To study the prevalence of upper airway obstruction (UAO) in "apparently asymptomatic" patients with euthyroid multinodular goitre (MNG) and find correlation between clinical features, UAO on pulmonary function test (PFT) and tracheal narrowing on computerised tomography (CT). Consecutive patients with apparently asymptomatic euthyroid MNG attending thyroid clinic in a tertiary centre underwent clinical examination to elicit features of UAO, PFT, and CT of neck and chest. Statistical analysis was done with SPSS version 11.5 using paired t-test, Chi square test, and Fisher's exact test. P value of <0.05 was considered to be significant. Fifty-six patients (52 females and four males) were studied. The prevalence of UAO (PFT) and significant tracheal narrowing (CT) was 14.3%. and 9.3%, respectively. Clinical features failed to predict UAO or significant tracheal narrowing. Tracheal narrowing (CT) did not correlate with UAO (PFT). Volume of goitre significantly correlated with degree of tracheal narrowing. Clinical features do not predict UAO on PFT or tracheal narrowing on CT in apparently asymptomatic patients with euthyroid MNG.


Anti-bacterial activity of Euphorbia fusiformis--a rare medicinal herb.
Euphorbia fusiformis Buch.-Ham. ex. D.Don (Euphorbiaceae) is a rare medicinal herb. Aqueous and organic solvent extracts of the leaves and rootstocks were investigated for anti-bacterial properties by using disc diffusion and well-in agar methods, against pathogenic strains of Gram positive (Bacillus subtilis and Staphylococcus aureus) and Gram negative bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhii A and Salmonella typhii B). The different extracts differed significantly in their anti-bacterial properties with the methanolic extract being very effective followed by acetone and chloroform extracts. Aqueous and ethanolic extract showed very least activity. The result highlights that rootstock extracts had good anti-bacterial properties than leaf extracts. The results of this study support the use of this plant in traditional medicine to treat fever, wound infections and intestinal disorders.


Ablation Index-Guided High-Power Radiofrequency Application Shortens the Procedure Time With Similar Outcomes to Conventional Power Application in Atrial Fibrillation Ablation.
Background: The impact of high-power radiofrequency (RF) application in ablation index (AI)-guided atrial fibrillation (AF) ablation has not been elucidated. Methods and Results: We investigated 1,333 patients undergoing first AF ablation (median age 68 years; interquartile range [IQR] 61-73 years). The first 301 patients underwent AI-guided conventional power RF application (CP group), whereas the following 1,032 patients underwent high-power RF application (HP group). The minimum AI target values were 400, 360, and 260 at the left atrial anterior wall, posterior wall, and esophagus, respectively. RF power in the CP group was 30-40, 20-25, and 20 W at the anterior wall, posterior wall, and esophagus, respectively, compared with 50, 40, and 25, respectively, in the HP group. Procedure time was shorter in the HP than CP group (median 153 [IQR 129-190] vs. 180 (IQR 152-229) min; P<0.0001). The percentage of first-pass pulmonary vein isolation (69% vs. 73%; P=0.07) and all procedure-related complications (2.0% vs. 3.4%; P=0.19) was similar. Kaplan-Meier analysis showed similar recurrence-free survival (RFS) for all AF types. Respective 1-year RFS in the CP and HP groups was 82% and 87% in paroxysmal AF, 78% and 82% in persistent AF, and 59% and 58% in long-standing persistent AF. Conclusions: In AI-guided AF ablation, high-power RF application shortens the procedure time without increasing complications and with similar outcomes.


Effects of Δ9-THC and Type-1 Cannabinoid Receptor Agonists in the Elevated Plus Maze Test of Anxiety: A Systematic Review and Meta-Analysis.
Δ9-THC (the main active compound from Cannabis sativa) and related cannabinoids have been used as drugs of abuse and as medications. They induce a complex set of emotional responses in humans and experimental animals, consisting of either anxiolysis or heightened anxiety. These discrepant effects pose a major challenge for data reproducibility and for developing new cannabinoid-based medicines. In this study, we review and analyze previous data on cannabinoids and anxiety-like behavior in experimental animals. Systematic review and meta-analysis on the effects of type-1 cannabinoid receptor agonists (full or partial, selective or not) in rodents exposed to the elevated plus maze, a widely used test of anxiety-like behavior. Cannabinoids tend to reduce anxiety-like behavior if administered at low doses. THC effects are moderated by the dose factor, with anxiolytic- and anxiogenic-like effects occurring at low-dose (0.075-1 mg/kg) and high-dose (1-10 mg/kg) ranges, respectively. However, some studies report no effect at all regardless of the dose tested. Finally, motor impairment represents a potential confounding factor when high doses are administered. The present analysis may contribute to elucidate the experimental factors underlying cannabinoid effects on anxiety-like behavior and facilitate data reproducibility in future studies.


Distal renal tubular acidosis in infancy: a bicarbonate wasting state.
Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion.


Saccade-related burst neurons in cat superior colliculus.
Single-unit activity was studied in the intermediate and deep layers of the superior colliculus in 4 trained cats. One class of neuron was isolated which resembles the saccade-related burst neurons (SRBNs) previously reported in monkey. These neurons produce a discrete burst of impulses preceding the onset of saccades of particular amplitudes and direction. Many of these neurons also paused during saccades in the opposite direction. Similar discharge patterns were seen when saccades were made to remember target locations as well as when a visual target was present. These findings are consistent with the idea that some neurons in the superior colliculus neurons play a role in the coding of voluntary or memory-contingent saccades as well as in the initiation of visually elicited saccades.


Systems biology reveals reprogramming of the S-nitroso-proteome in the cortical and striatal regions of mice during aging process.
Cell aging depends on the rate of cumulative oxidative and nitrosative damage to DNA and proteins. Accumulated data indicate the involvement of protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification (PTM) of cysteine thiols, in different brain disorders. However, the changes and involvement of SNO in aging including the development of the organism from juvenile to adult state is still unknown. In this study, using the state-of-the-art mass spectrometry technology to identify S-nitrosylated proteins combined with large-scale computational biology, we tested the S-nitroso-proteome in juvenile and adult mice in both cortical and striatal regions. We found reprogramming of the S-nitroso-proteome in adult mice of both cortex and striatum regions. Significant biological processes and protein-protein clusters associated with synaptic and neuronal terms were enriched in adult mice. Extensive quantitative analysis revealed a large set of potentially pathological proteins that were significantly upregulated in adult mice. Our approach, combined with large scale computational biology allowed us to perform a system-level characterization and identification of the key proteins and biological processes that can serve as drug targets for aging and brain disorders in future studies.


Roles of bradykinin in vascular permeability and angiogenesis in solid tumor.
Bradykinin (BK) is involved in tumor angiogenesis. To elucidate the mechanism underlying BK-induced angiogenesis, we evaluated the roles of BK in tumor-associated vascular permeability and angiogenesis in the different phases of tumor development in mice bearing sarcoma 180 cells. The vascular permeability was significantly enhanced in the early growth phase (which peaked at day 5), and was thereafter markedly reduced. By contrast, tumor angiogenesis increased gradually over a 20-day experimental period. Oral administration of a B2 receptor antagonist, FR173657 (30 mg/kg/day), significantly suppressed the vascular permeability, but a B1 antagonist, desArg10-Hoe140 (1 mg/kg/day) did not. An immunohistochemical study revealed the presence of immunoreactive B2 receptor in the endothelial cells in the early phase, whereas B2 receptors were also observed in the stromal fibroblasts in the late phase. We also found that VEGF was detected exclusively in the stromal fibroblasts only in the late phase. Furthermore, VEGF immunoreactivity was attenuated by the treatment with FR173657. Tumor angiogenesis was significantly reduced by treating the tumor tissues with FR173657 both in the early phase (days 1-6, 30 mg/kg/day, oral administration) and in the late phase (days 7-12, 30 mg/kg/day, oral administration), whereas it was inhibited by neutralization with anti-VEGF antibody (1 microg/site/day, local injection) only in the late phase. These results suggest that BK would promote angiogenesis by increasing vascular permeability in the early phase via B2 receptor in the endothelial cells and by promoting up-regulation of VEGF via B2 receptor in the stromal fibroblasts in the late phase.


The impact of video recording colonoscopy on adenoma detection rates.
The adenoma detection rate (ADR) is a quality benchmark for colonoscopy, influenced by several factors including bowel preparation, withdrawal time, and withdrawal technique. To assess the impact of video recording of all colonoscopies on the ADR. Comparison of two cohorts of patients undergoing colonoscopy before and after implementation of video recording. Academic outpatient endoscopy facility. This study involved asymptomatic, average-risk adults undergoing screening colonoscopy. Video recording of all colonoscopy procedures. Polyp findings and withdrawal times were recorded for 208 consecutive screening colonoscopies. A policy of video recording all colonoscopies was implemented and announced to the staff. Data on another 213 screening colonoscopies were subsequently collected. Adenoma detection rate, withdrawal time, advanced polyp detection rate, hyperplastic polyp detection rate. At least one adenoma was found in 38.5% of patients after video recording versus 33.7% before video recording (P = .31). There was a significant increase in the hyperplastic polyp detection rate (44.1% vs 34.6%; P = .046). Most endoscopists had a numerical increase in their ADRs, but only one was significant (57.7% vs 22.6%; P < .01). There were trends toward higher detection of adenomas of <5 mm (59.1% vs 52%; P = .23) and right-sided adenomas (40.2% vs 30.4%; P = .11) in the video recorded group. No randomization, confounding of intervention effects, and sample size limitations. Video recording of colonoscopies is associated with a nonsignificant increase in the ADR and a significant increase in the hyperplastic polyp detection rate. There may be a benefit of video recording for endoscopists with low ADRs.


Mycobacterium fortuitum granulomatous synovitis caused by a dog bite.
Mycobacterium fortuitum was isolated from the synovial tissues of the dorsum of the hand after a dog bite. Caseating granulomas with Langhans' type giant cells were demonstrated microscopically. Healing followed prolonged treatment with antituberculosis drugs. It is suggested that the organism was forced into the patient's tissues by the dog's bite.


High risk of 'failure' among emergency physicians compared with other specialists: a nationwide cohort study.
The intensive physical and psychological stress of emergency medicine has evoked concerns about whether emergency physicians could work in the emergency department for their entire careers. Results of previous studies of the attrition rates of emergency physicians are conflicting, but the study samples and designs were limited. To use National Health Insurance claims data to track the work status and work places of emergency physicians compared with other specialists. To examine the hypothesis that emergency physicians leave their specialty more frequently than other hospital-based specialists. Three types of specialists who work in hospitals were enrolled: emergency physicians, surgeons and radiologists/pathologists. Every physician was followed up until they left the hospital, did not work anymore or were censored. A Kaplan-Meier curve was plotted to show the trend. A multivariate Cox regression model was then applied to evaluate the adjusted HRs of emergency physicians compared with other specialists. A total of 16,666 physicians (1584 emergency physicians, 12,103 surgeons and 2979 radiologists/pathologists) were identified between 1997 and 2010. For emergency physicians, the Kaplan-Meier curve showed a significantly decreased survival after 10 years. The log-rank test was statistically significant (p value <0.001). In the Cox regression model, after adjusting for age and sex, the HRs of emergency physicians compared with surgeons and radiologists/pathologists were 5.84 (95% CI 2.98 to 11.47) and 21.34 (95% CI 8.00 to 56.89), respectively. Emergency physicians have a higher probability of leaving their specialties than surgeons and radiologists/pathologists, possibly owing to the high stress of emergency medicine. Further strategies should be planned to retain experienced emergency physicians in their specialties.


Anhedonia difference between major depressive disorder and bipolar disorder II.
This study aims to explore the difference in anhedonia between Major Depressive Disorder (MDD) and Bipolar Disorder II (BD-II), and attempt to distinguish the two diseases through Snaith-Hamilton Pleasure Scale (SHAPS). A total of 164 drug-free depressive patients (98 MDD patients, 66 BD-II patients) completed the investigation. 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA) and SHAPS were assessed in all participants. Our results showed that BD-II patients had higher SHAPS scores than MDD patients. The stepwise logistic regression analysis further revealed that SHAPS score, drinking habit, and extroversion as influencing factors for the identification of BD-II. The ROC curve analysis indicated that SHAPS could differentiate BD-II from MDD patients (AUC = 0.655, P = 0.001, 95% CI = 0.568 to 0.742), with the best screening cutoff at 26, and the corresponding sensitivity and specificity was 0.788 and 0.520, respectively. Our results suggest that BD-II patients had more severe anhedonia compared to MDD patients, and the difference in anhedonia may help clinicians preliminary identify BD patients from MDD patients. The preliminary findings are worthly of further exploration.


Experimental modification of cerebellar development in tissue culture: x-irradiation induces granular degeneration and unattached purkinje cell dendritic spines.
Cerebellum explants from 15--16 day fetal mice were irradiated with 500--1000 rad X-ray and were grown in tissue culture for 12--18 days. At the dose of 500 rad, a reduction of granule cell population was observed in the explant. At the dose of 1000 rad, granule cells were mostly destroyed leaving Purkinje cells disarrayed and clustered. Electron microscopy of the explants revealed the presence of unattached dendritic spines of Purkinje cell. It was noted that although numerous free spines could be seen in X-irradiated cultures, the postsynaptic specialization of these spines occurred only in ones embedded in astrocytic cytoplasm. The results indicate that (a) the formation of dendritic spines is a property of the Purkinje cell which probably is preprogrammed and (b) the postsynaptic differentiation of the unattached spines is directly related to their contacts with astrocytes.


[Comparison of the effect of chloridin on rat embryos during postimplantation periods of development in vivo and in vitro].
The effect of chloridin (2,4-diamino-5-parachlorophenyl-6-ethylpyrimidine) on the rat embryos developing in the maternal organism and on the embryos explanted 24 hrs after the treatment in the nutrient medium (homologous blood serum) was compared. The pathological processes both in vivo and in vitro were shown to be similar. The number of atypical and died embryos in vitro was, however, much higher, apparently due to the absence of some protective membranes in the cultivated embryos.


Randomized controlled trial of NSAID prior to cystoscopic ureteral stent removal in a pediatric population.
Ureteral spasm, common with ureteral stents, is partially mediated by prostaglandins and may be suppressed by cyclooxygenase inhibitors like non-steroidal anti-inflammatory (NSAIDs). Practices currently vary widely for pain management in patients with ureteral stents, sometimes including opioids. We aimed to determine if NSAID given prior to stent removal would reduce postoperative pain. We hypothesized there would be at least a 75% reduction in postoperative severe pain (pain score ≥7) in patients receiving ibuprofen compared to placebo. We performed a double-blind, placebo-controlled randomized controlled trial on pediatric urology patients with an indwelling ureteral stent undergoing removal in the operating room from 2014 to 2019. 20 patients in each arm were needed to achieve 80% power to detect a 75% reduction in the estimated 55% incidence of severe postoperative pain (α = 0.05). Patients ≥4 years old who had a unilateral stent placed after treatment of urolithiasis or ureteropelvic junction obstruction were randomized to NSAID or placebo in a 1:1 ratio at least 15 min prior to scheduled stent removal. Patients estimated pain using Faces Pain Scale-Revised (FPS-R) or visual analogue scale (VAS) prior to and 24 h after stent removal. 254 patients undergoing stent removal were assessed for eligibility, and 44 randomized patients were analyzed using intention to treat analysis. The cohorts were demographically similar and received similar anesthesia treatment. There was no significant difference in maximum post anesthesia care unit pain score (p = 0.269) or use of in-hospital opioids (p = 0.626) between the two groups. No difference was seen in the incidence of severe postoperative pain (p = 1.0), thus rejecting the hypothesis. Significant worsened postoperative pain (pain score increases of ≥2 between time points) decreased from 22.7% to 13.6% between placebo and NSAID, but this did not reach significance (p = 0.410). There was no difference in postoperative pain for patients undergoing ureteral stent removal given preoperative NSAID versus placebo. The incidence of severe pain before and after stent removal was low, ranging from 4.5 to 9.1%. Research to understand the etiology of pain after stent removal and techniques to minimize or prevent discomfort should continue in order to optimize patient outcomes.


[The physical development of infants and young children. 5. Body height--a longitudinal study].
As a result of a longitudinal study (1979-1982) distance values increments and growth velocity of the body length of 84 male and 91 female children are presented for the first three years of life. As compared to earlier longitudinal for the first three years of life. As compared to earlier longitudinal studies performed by other authors and to the G.D.R.-study of 1970/71, the investigated children are taller, in spite of a smaller body length at birth.


Sclerotic Bone Lesions as a Clue in the Diagnosis of Three Generations of Tuberous Sclerosis Complex: Case Report and Review of Literature.
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that can involve multiple organ systems. Diagnosis is based on independent clinical diagnostic criteria and genetic diagnostic criteria (pathogenic variants on TSC1 and TSC2 genes). To make a definitive diagnosis can be especially difficult in oligosymptomatic or asymptomatic patients and in those patients with genetic variants of uncertain significance (VUS). Early diagnosis and lifelong surveillance are paramount to avoid morbidity and potentially life-threatening complications. To increase diagnostic sensibility, less known manifestations of TSC can be helpful. Herein we show a case in which SBLs were used as a diagnostic clue to help diagnose three generations of oligosymptomatic TSC carrying a VUS in TSC1. SBLs are commonly detected in imaging studies of patients with TSC and have been recently included as a minor clinical diagnostic criterion. Clinicians and radiologists should be aware of their significance as they can be mistaken with osteoblastic metastases.


Effect of Fe2+ -induced lipid peroxidation upon microsomal steroidogenic enzyme activities of porcine adrenal cortex.
When porcine adrenocortical microsomes were treated with Fe2+, enhanced production of malondialdehyde was observed as a result of membrane lipid peroxidation. By treatment of the microsomes with Fe2+, the activity of delta 5-3 beta-hydroxysteroid dehydrogenase coupled with delta 5-delta 4 isomerase, concentration of cytochrome P-450 and the activity of the cytochrome-involving enzyme systems such as 17 alpha- and 21-hydroxylases were significantly reduced. 17 alpha-Hydroxylase activity was more effectively decreased by Fe2+ than that of 21-hydroxylase. On the other hand, activity of NADH- and NADPH-cytochrome c reductases remained unchanged or somewhat increased. Both the induction of lipid peroxidation and the decrease of the enzyme activities were prevented by alpha-tocopherol and N,N' -diphenyl-rho-phenylenediamine.


The Affordable Care Act and Access to Care for People Changing Coverage Sources.
We investigated how access to and continuity of care might be affected by transitions between health insurance coverage sources, including the Marketplace (also called the Exchange), Medicaid, and the Children's Health Insurance Program (CHIP). From January to February 2014 and from August to September 2014, we searched provider directories for networks of primary care physicians and selected pediatric specialists participating in Marketplace, Medicaid, and CHIP in 6 market areas of the United States and calculated the degree to which networks overlapped. Networks of physicians in Medicaid and CHIP were nearly identical, meaning transitions between those programs may not result in much physician disruption. This was not the case for Marketplace and Medicaid and CHIP networks. Transitions from the Marketplace to Medicaid or CHIP may result in different degrees of physician disruption for consumers depending on where they live and what type of Marketplace product they purchase.


Low-energy in-line electron holographic imaging of vitreous ice-embedded small biomolecules using a modified scanning electron microscope.
Cryo-electron microscopy (cryo-EM) has become the method of choice in the field of structural biology, owing to its unique ability to deduce structures of vitreous ice-embedded, hydrated biomolecules over a wide range of structural resolutions. As cryo-transmission electron microscopes (cryo-TEM) become increasingly specialised for high, near-atomic resolution studies, operational complexity and associated costs serve as significant barriers to widespread usability and adoptability. To facilitate the expansion and accessibility of the cryo-EM method, an efficient, user-friendly means of imaging vitreous ice-embedded biomolecules has been called for. In this study, we present a solution to this issue by integrating cryo-EM capabilities into a commercial scanning electron microscope (SEM). Utilising the principle of low-energy in-line electron holography, our newly developed hybrid microscope permits low-to-moderate resolution imaging of vitreous ice-embedded biomolecules without the need for any form of sample staining or chemical fixation. Operating at 20 kV, the microscope takes advantage of the ease-of-use of SEM-based imaging and phase contrast imaging of low-energy electron holography. This study represents the first reported successful application of low-energy in-line electron holographic imaging to vitreous ice-embedded small biomolecules, the effectiveness of which is demonstrated here with three morphologically distinct specimens.


Changes in plasma membrane Ca2+ -ATPase expression and ATP content in lenses of hereditary cataract UPL rats.
The UPL rat is a newly developed hereditary cataract model. We previously found that Ca2+ concentrations in UPL rat lenses increase with the development of cataract, and that the administration of disulfiram and aminoguanidine ameliorates the increase in Ca2+ and the development of cataract in UPL rats. In this study, we determined the expression and activity of plasma membrane Ca2+-ATPase (PMCA) in lenses of normal and UPL rats. We also determined the ATP content in UPL rat lenses and the effects of disulfiram and aminoguanidine administration. Expression of PMCA mRNA in UPL rat lenses, determined by a reverse transcription-PCR method, increased during the development of cataract. Ca2+-ATPase activity in UPL rat lenses also increased with the progression of lens opacification. On the other hand, ATP decreased markedly in UPL rat lenses, and the administration of disulfiram and aminoguanidine attenuate the ATP decrease. These results suggest that an ATP decrease cause cataract development and an increased Ca2+ may upregulate PMCA expression in UPL rat lenses. Disulfiram and aminoguanidine attenuate the decrease in ATP, resulting in a delay in cataract development.


Risk and Prognosis of Thyroid Cancer in Patients with Graves' Disease: An Umbrella Review.
Graves' disease (GD) is an autoimmune disease considered the most common cause of hyperthyroidism. Some studies have investigated its relationship with the risk and prognosis of developing thyroid cancer. Considering that there is no consensus on the relationship between GD and thyroid cancer risk, this umbrella review aimed to summarize the epidemiologic evidence and evaluate its strength and validity on the associations of GD with thyroid cancer risk and its prognosis. This umbrella review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed and Scopus from January 2012 to December 2022. The strength of the epidemiological evidence was graded as high, moderate, or weak by the Measurement Tool to Assess Systematic Reviews (AMSTAR-2). "Strong" evidence was found for the risk of thyroid cancer in GD patients with thyroid nodular disease (OR: 5.30; 95% CI 2.43-12) and for the risk of mortality from thyroid cancer in these patients (OR 2.93, 95% CI 1.17-7.37, p = 0.02), particularly in Europe (OR 4.89; 95% CI 1.52-16). The results of this umbrella review should be interpreted with caution; as the evidence comes mostly from retrospective studies, potential concerns are selection and recall bias, and whether the empirically observed association reflects a causal relationship remains an open question.


Risk Factors and Outcomes in Carpal Tunnel Syndrome Following Distal Radius Open Reduction Internal Fixation.
Carpal tunnel syndrome (CTS) is a common complication following the operative repair of distal radius fractures. It is unclear who is at risk of developing this complication in the postoperative period. This study sought to identify risk factors for developing CTS and to evaluate patient-reported outcomes in patients who develop postoperative CTS. A retrospective review of all distal radius fractures treated surgically at a single private academic center was performed from January 2007 to October 2019. Of the 4,487 patients, 68 were identified to have an ipsilateral carpal tunnel release within 6 months of the distal radius injury. Collected data comprised patient demographics, medical history, and functional outcome scores. Carpal tunnel syndrome was more likely to develop in older patients (62.9 years vs 57.4 years). Sex, body mass index, smoking history, and the type of insurance were not found to be significantly different between the groups. Medical history of kidney disease, psychiatric conditions, and peripheral vascular disease were found to be associated with developing CTS. Patients who developed CTS had higher average Disabilities of the Arm, Shoulder, and Hand scores than patients without CTS (28.1 vs 20.0) at the final follow-up. In a multivariable analysis, patients who developed CTS were found to be older (Odds ratio, 1.03) and less likely to be smokers (Odds ratio, 0.46). In our cohort, we observed that older patients were more likely to require carpal tunnel release following distal radius fracture. In addition, nonsmokers were more likely to require subsequent carpal tunnel release, probably as a result of confounding effects. Special care should be taken to monitor these patients for CTS in the postoperative period following a distal radius open reduction and internal fixation. Prognostic IV.


Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia.
Intrathecal injections of capsaicin (CAP) and 4 other homovanillic acid (HMV) derivatives related to the structure of CAP were carried out. Capsaicin, 1-nonenoylvanillylamide (NVA), HMV-dodecylamide (DCA) (but not HMV-cyclohexylamide (CHA) or HMV-hexadecylamide (HDC] reduced the spinal content of substance P (SP), as measured by radioimmunoassay (RIA), and increased the tail-flick latency. Similar injection of kainic acid and piperine reduced levels of SP but failed to affect the tail-flick latency. None of the agents used affected spinal levels of cholecystokinin (CCK) or vasoactive intestinal peptide (VIP) as measured by RIA. In experiments using in vivo superfusion of the rat spinal cord, CAP, DCA and NVA were found to stimulate release of SP. Capsaicin had no effect on the levels of CCK or VIP immunoreactivity in the spinal superfusate. A tachyphylaxis to the effect of CAP and DCA on spinal SP release was demonstrated. Pretreatment with either agent blocked the releasing effect of the second. Pretreatment with an inactive analogue (HDC) had no effect on the subsequent activity of CAP. Kainic acid and piperine did not induce release of SP from the spinal cord. The relative selectivity of spinally administered capsaicinoids with regard to their effects on the content and release of peptides known to be contained in primary afferents and the presence of a similar structure-activity relationship for depletion and release of SP, desensitization and antinociception suggest the presence of a specific receptor site associated with a specific population of primary afferents through which pain information may pass. Whether SP is an 'afferent pain transmitter' is not clear, but at the least, it appears to serve as a marker for a population of afferents acted upon by spinally administered capsaicinoids.


Comparison of 3 different methods used to measure the rapid shallow breathing index.
Rapid shallow breathing index (RSBI) is conveniently measured through the ventilator. If continuous positive airway pressure (CPAP) is used, it may change the RSBI value. We measured the RSBI with a handheld spirometer and through the ventilator, with and without CPAP, to assess differences. Rapid shallow breathing index was measured in 3 ways: (1) CPAP 0 cm H(2)O and fraction of inspired oxygen (Fio(2)) 0.4, (2) CPAP 5 cm H(2)O and Fio(2) 0.4, and (3) ventilator disconnected and Fio(2) 0.21. Tidal volume and respiratory frequency were recorded from ventilator monitor values in methods 1 and 2, and from a handheld spirometer and observed respiratory frequency, in method 3. A total of 170 measurements, each using all 3 methods, were obtained from 80 patients admitted to a medical intensive care unit. The mean RSBI values for methods 1, 2, and 3 were 98.1 ± 58.7, 87.6 ± 51.2, and 108.3 ± 65.3, respectively (P < .001). The RSBI decreased by 9.4% when using CPAP 0 cm H(2)O and by 19.1% when using CPAP 5 cm H(2)O. The RSBI values measured through the ventilator with CPAP 5 cm H(2)O are much lower than the values measured with a handheld spirometer. Even the RSBI values measured with CPAP 0 cm H(2)O are significantly lower. This is attributable to the base flow delivered by some ventilators. The difference must be taken into account during weaning assessment.


Cytochrome P450-dependent arachidonic acid metabolism in human kidney.
Cytochrome P450-dependent arachidonic acid metabolism in human kidney cortex from several postmortem subjects has been characterized. Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases. This pattern of metabolism was similar to that found in rabbit and rat kidneys. The formation of these metabolites was dependent on the presence of NADPH and inhibited by IgG of NADPH-cytochrome P450 (c) reductase. Immunologic studies of renal cytochrome P450 epoxygenase demonstrated that antibodies prepared against human-purified hepatic cytochrome P450 epoxygenase recognized renal enzyme protein and inhibited the enzyme activity by 92%. In contrast, control immunoglobulin did not inhibit renal cytochrome P450 epoxygenase. Antibody inhibition of renal cytochrome P450 epoxygenase demonstrated a degree of conservation of both enzyme proteins between liver and kidney. Antibodies against lauric acid omega/omega-1 hydroxylases (P450 omega) inhibited the formation of omega/omega-1 hydroxylase products, 19- and 20-HETEs. Identical qualitative patterns of arachidonic acid metabolites were observed in all cortical microsomes studied. Interindividual variations were observed in the cytochrome P450-dependent arachidonic acid metabolism, and the activities ranged from 0.031 to 5.027 nmol arachidonic acid converted/mg protein/30 min. which is about a 150-fold difference. However, when the specific activities for total cytochrome P450-dependent arachidonic acid metabolism were calculated, two separate groups could be distinguished, high and low metabolizers of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)


The Effect of Canthotomy on Blood Perfusion During the Repair of Lower Eyelid Defects.
Canthotomy is frequently used to mobilize extra tissue when repairing larger lower eyelid defects. The aim of this study was to explore the effect of canthotomy on blood perfusion and oxygen tension. Eight pigs underwent a wedge resection of the lower eyelid and canthotomy (with cantholysis involving the lateral palpebral artery). The wedge resection was performed 8, 6, and 4 mm from the canthotomy. Perfusion and oxygen tension were monitored in the eyelid between the wedge resection and canthotomy using laser Doppler velocimetry and a Clark electrode. Verapamil was administered, and measurements were also performed 12 hours after surgery, to investigate the possible effects of vasospasm RESULTS:: The wedge resection alone did not affect perfusion. Canthotomy led to a reduction in perfusion; being 60% when the length of remaining eyelid was 8 mm, 32% when it was 6 mm, and 24% when it was 4 mm. Similar results were observed for oxygen tension. Vasospasm did not affect the results. Canthotomy in combination with a wedge resection of the lower eyelid affects blood perfusion. A smaller length of remaining eyelid tissue will have less perfusion. This may not have any implications in cases of direct closure, but may play a role when the eyelid is to provide oxygen and nutrients to avascular grafts.


Cooperative behavior of K+ channels in the tonoplast of Chara corallina.
Spontaneous cooperatively of K+ channels is studied in excised patches of Chara corallina tonoplasts. Bar histograms (dwell time versus number of open channels) are constructed from the time series of current by means of the higher-order Hinkley detector (R. Schultze and S. Draber. 1993. J. Membr. Biol. 132:41-52). A statistical test, based on these bar histograms, shows that the channels are not independent. Further analysis reveals that the channels are cooperatively changing their open probability, which leads to the idea of cooperative mode shifting.


Risk factors for female anal incontinence: new insight through the Evanston-Northwestern twin sisters study.
To evaluate risk factors for anal incontinence using an identical twin sisters study design to provide control over genetic variance. A total of 271 identical twin sister pairs (mean age 47 years) completed the validated Colorectal Anal Distress Inventory questionnaire detailing the presence and severity of anal incontinence. Data were analyzed using a stepwise logistic regression with repeated binary measures to account for correlated data within twin pairs. Three different statistical models were used to analyze nonobstetric as well as obstetric risk factors separately. Significant risk factors for anal incontinence and higher Colorectal Anal Distress Inventory anal incontinence subscale scores included age 40 years or older (fecal: odds ratio [OR] 2.82, 95% confidence interval [CI] 1.21-6.0; flatal: OR 1.90, 95% CI 1.11-3.24), menopause (fecal: OR 2.10, 95% CI 1.15-3.8; flatal: OR 2.11, 95% CI 1.43-3.13), increasing parity (parity > or = 2; fecal: OR 3.09, 95% CI 1.25-7.65; flatal: OR 2.72, 95% CI 1.65-4.51), and the presence of stress urinary incontinence (fecal: OR 2.11, 95% CI 1.12-3.98; flatal: OR 1.72, 95% CI 1.14-2.59). Obesity was associated with significantly higher Colorectal Anal Distress Inventory anal incontinence subscale scores (mean difference 5.18, P = .007). Cesarean delivery after initiation of labor was associated with a lower prevalence of anal incontinence than vaginal birth; however, this difference was not statistically significant (17% compared with 4%, P = .11). No anal incontinence was noted in women who had only elective cesarean deliveries. Age, menopause, obesity, parity, and stress urinary incontinence are the major risk factors for female anal incontinence.


Small cell (endocrine cell) carcinoma of the gallbladder with squamous and adenocarcinomatous components.
Small cell (endocrine cell) carcinoma of the gallbladder in a 62-year-old woman is reported. The palliative cholecystectomy specimen revealed a submucosally invading tumor with extensive hemorrhagic necrosis. At autopsy, performed five months after surgery, a huge tumor measuring 14 x 12 x 8 cm was located at the liver hilus. No signs or symptoms related to overproduction of hormones were recorded throughout her illness. Neither lung lesions nor gall stones were identified. Histologically, diffuse proliferation of small, spindle-shaped atypical tumor cells with numerous mitoses was evident. Intraepithelial tumor cell proliferation in the gallbladder mucosa was seen focally. The neuroendocrine nature of the tumor cells was confirmed by the histologic pattern of growth with pseudo-rosette formation, positive reaction for Grimelius' argyrophilia, neuron-specific enolase and Leu 7, and ultrastructural demonstration of neuroendocrine-type granules. Immunostaining for a variety of hormones was all negative. Characteristically, foci with squamous and adenocarcinomatous differentiation were identified in the tumor tissue. The glandular components were immunoreactive for carcinoembryonic antigen, secretory component, epithelial membrane antigen and CA19-9. The histogenesis and totipotentiality of the neoplasm were discussed.


Folate decorated magnetite nanoparticles: synthesis and targeted therapy against ovarian cancer.
Doxorubicin (DOX) loaded folate-coated magnetic Fe3 O4 nanoparticles (MNPs) were prepared by co-precipitation and emulsification cross-linking method and uniform NPs with an average particle size of 15 (bare) and 35 nm (FA-MNPs), with high encapsulation efficiencies (EE), were obtained. The release profiles of conjugated DOX showed that pH 6.0 provided suitable conditions for proper drug release. IC50 analysis of C30 and CP70 cell lines after 96 h (4 days) exposure to DOX-FA-MNPs showed that the most significant IC50 were at 5.4 ± 0.6 and 11.2 ± 2.7 mM DOX loaded onto the FA-MNPs. Thus CP70 cells are more resistant to lower concentrations of drug compared to C30 cells (P < 0.05). C30 and CP70 cells reached 91 and 81.8% apoptosis after administration of DOX-FA-MNPs (5 mg/mL) compared to 49.2 and 46.6% after administration of the free drug, respectively (P < 0.05). this study indicates that FA modified MNPs enhances the DOX-induced apoptosis in both of the human ovarian cancer cell lines with sharp decreases in the levels of bcl-2 and surviving, and increased expression of caspase-3.


Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.
The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials.


Inhibition of hIAPP amyloid-fibril formation and apoptotic cell death by a designed hIAPP amyloid- core-containing hexapeptide.
The pathogenesis of type II diabetes is associated with the aggregation of the 37-residue human islet amyloid polypeptide (hIAPP) into cytotoxic beta sheet aggregates and fibrils. We have recently shown that introduction of two N-methyl rests in the beta sheet- and amyloid-core-containing sequence hIAPP(22-27), or NFGAIL converted this amyloidogenic and cytotoxic sequence into nonamyloidogenic and noncytotoxic NF(N-Me)GA(N-Me)IL. Here, we show that NF(N-Me)GA(N-Me)IL is able to bind with high-affinity full-length hIAPP and to inhibit its fibrillogenesis. NF(N-Me)GA(N-Me)IL also inhibits hIAPP-mediated apoptotic beta cell death. By contrast, unmodified NFGAIL does not inhibit hIAPP amyloidogenesis and cytotoxicity, suggesting that N-methylation conferred on NFGAIL the properties of NF(N-Me)GA(N-Me)IL. These results support the concept that rational N-methylation of hIAPP amyloid-core sequences may be a valuable strategy to design pancreatic-amyloid diagnostics and therapeutics for type II diabetes.


Positive Fluid Balance and Association with Post-Traumatic Acute Kidney Injury.
Acute kidney injury (AKI) is common in severely injured trauma patients and is associated with poor outcomes. A positive fluid balance is associated with AKI and poor long-term renal outcomes among general ICU and cardiac surgery patients. Currently, the optimal endpoint of resuscitation of severely injured trauma patients is unknown, which may result in excess fluid administration. We hypothesized that positive fluid balance is common after severe trauma and is associated with increased AKI development. A cohort study of adult (≥16 years old) trauma patients requiring ICU admission from January 2017 to June of 2017 was conducted. Patients were excluded for early death, rhabdomyolysis, or previous history of end-stage renal disease or congestive heart failure. Acute kidney injury within 7 days of admission was defined according to Kidney Disease Improving Global Outcomes creatinine-based criteria. Univariate and multivariable analyses were performed. Of 364 patients, 74% were male. The median age was 41 years (interquartile range [IQR] 27 to 59 years), and the median Injury Severity Score (ISS) was 18 (IQR 10 to 29). Positive fluid balance (>2 L) was observed in 49% of patients. Acute kidney injury was diagnosed in 105 (29%) patients. After adjustment, there was an increased risk of AKI with a positive fluid balance >2 L (relative risk [RR] 1.98 [95% CI 1.24 to 3.17]). Additionally, the risk of AKI incrementally increased by 1.22 with each liter fluid positive above a zero balance (95% CI 1.11 to 1.34). Positive fluid balance in excess of 2 L at 48 hours occurs in half of severely injured trauma patients, and fluid positivity is independently and incrementally associated with AKI development. Fluid responsiveness should be investigated as an end point of post-traumatic resuscitation to prevent unnecessary fluid administration and subsequent AKI.


Do event-related potentials reveal the mechanism of the auditory sensory memory in the human brain?
Event-related brain potentials (ERP) to task-irrelevant tone pips presented at short intervals were recorded from the scalp of normal human subjects. Infrequent decrements in stimulus intensity elicited the mismatch negativity (MMN) which was larger in amplitude and shorter in latency the softer the deviant stimulus was. The results obtained imply memory representations which develop automatically and accurately represent the physical features of the repetitive stimulus. These memory traces appear to be those of the acoustic sensory memory, the 'echoic' memory. When an input does not match with such a trace the MMN is generated.


The lid subdomain of DnaK is required for the stabilization of the substrate-binding site.
We examined the effect of deletion of different segments in the helical subdomain (the so-called "lid") of the DnaK peptide-binding domain on peptide binding and protein stability. At 25 degrees C, wt DnaK and the deletion mutant proteins are able to stably bind peptides with similar affinity. However, at physiological (37 degrees C) and stress (42 degrees C) temperatures, removal of the N-terminal half of alphaB and the rest of the lid drastically decreases the ability of the protein to bind substrates. Differential scanning calorimetry and infrared spectroscopy show that this behavior is accompanied by destabilization of the peptide-binding domain. Our data suggest that the reversible interaction between the lid and beta-sandwich subdomains of DnaK peptide-binding domain is required for the stabilization of the loops that form the peptide-binding site, which in turn modulates the protein affinity for peptide substrates. This interaction might have functional implications because it could prevent rebinding of the peptide substrate, which would be forced to fold.


[Computer-assisted screening system for individualized treatment of type 2 diabetes mellitus].
To establish a computer-assisted screening system for individualized treatment of type 2 diabetes mellitus. The clinical data of the diabetic patients were retrospectively analyzed, and the regression equation for the affecting factors and therapeutic effect was established. With computer-aided programming, a computer-assisted screening system was established. A computer-assisted screening system for individualized treatment type 2 diabetes was established, which showed a concordance rate was 98% in clinical verification. Using epidemiological methods and assistance by computer technique, a computer-assisted screening system for individualized prescription can be established for selecting therapeutic regimen for type 2 diabetes.


Influence of alcohol on antimicrobial immunity.
Prolonged consumption of excessive amounts of alcohol by itself, as well as possibly leading to a state of alcoholism, has been a long-standing biological/social problem. As a major public health concern, there is an estimated expenditure of about 20% of total health care costs for medical/hospital care related to alcohol-induced illness. In addition, a significant proportion of both men and women who are hospitalized can be classified as alcoholics. This review focuses primarily on one of the many biomedical problems attributed to alcohol abuse--its adverse effects on our immune-defense system. A considerable body of evidence has mounted, over the past several decades, indicating that those who abuse alcohol are more susceptible to certain infectious disorders and are more prone to bacteremia. Such infections tend to be continuous and are often associated with a high rate of mortality. Also, along these lines, various and suitable animal models have been developed to further elucidate what the causes are for the greater frequency and severity of infectious illnesses, and this review deals primarily with those studies linking alcohol abuse to disruption in the normal functioning of the host's immune surveillance system. Based on the results from both clinical and experimental studies, it would seem that exposure to high levels of alcohol causes decreased humoral and cellular immune responses, thereby seriously limiting our ability to be protected from certain infectious agents.


Characterization of lignite deposits of Barmer Basin, Rajasthan: insights from mineralogical and elemental analysis.
The geochemistry of fly ash produced from the combustion of coal at thermal power plants presents a significant challenge for disposal and environmental impact due to its complex mineralogical and elemental composition. The objective of this study was to investigate the mineralogical and elemental distribution of thirty lignite samples from the Barmer Basin using advanced techniques such as X-ray diffraction (XRD), X-ray fluorescence spectrometry (XRF) and inductively coupled plasma mass spectrometry (ICP-MS). XRD analysis revealed the presence of minerals such as haematite (Fe2O3), nepheline, anhydrite, magnesite, andalusite, spinel and anatase. Other minor minerals included albite, siderite, periclase, calcite, mayenite, hauyne, pyrite, cristobalite, quartz, nosean and kaolinite. XRF analysis demonstrated that the most abundant elements in the Barmer Basin lignite ash were iron oxide (Fe2O3), sulphur oxide (SO3), calcium oxide (CaO), and quartz (SiO2) followed by minor traces of toxic oxides (SrO, V2O5, NiO, Cr2O3, Co2O3, CuO) that are known to have adverse effects on human health and the environment. The rare earth element (REE) composition showed higher concentrations of Tb, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc at the Giral and lower concentrations at Sonari mine. The Barmer lignites recorded higher concentration of trace elements such as V, Cr, Co, Ni, Cu and Sr while lower concentration of Rb, Cs, Ba, Pb, As, Th and U were observed within optimal range. The study findings revealed the predominant mineral concentration, elemental makeup, trace elements and rare earth elements associated with lignite reserves in the Barmer Basin.


Concentration-activity profile of the modulation of cyclooxygenase product formation by reduced glutathione in microsomal fractions from the goat lung.
Age-related changes in pulmonary formation of arachidonic acid (AA) metabolites are thought to play an important role in regulating cardiopulmonary function. This study addresses the potential role of reduced glutathione (GSH) in modulating cyclooxygenase product formation in the developing lung. Prostaglandin H2 (PGH2) metabolism was studied in microsomal fractions isolated from the lungs of unventilated fetal, neonatal and adult goats. GSH-dependent PGH2 to PGE2 isomerase activity in microsomal fractions from the perinatal (fetal and neonatal) goat lung was not saturable with respect to GSH and can respond to changes in GSH concentration over the range of 0.01 to 30 mM, which encompasses the full range the intracellular GSH levels reported in the literature. However, in fractions from the adult, a lower rate of PGE2 formation is observed at higher GSH concentrations. In addition, the tissue levels of GSH exhibited developmental stage-related differences with fetal being higher than neonatal or adult. The present observations may have physiologic relevance, in that decreases in pulmonary GSH levels after birth may contribute to decreases in plasma PGE2 levels by decreasing pulmonary PGE2 synthesis, thereby contributing to closure of the ductus arteriosus; conversely, increased GSH levels associated with hyperoxia may contribute to persistence of ductal patency. Formation of 6-keto-PGF1 alpha and of TXB2 (the stable metabolites of prostacyclin and TXA2) was decreased when PGE2 formation was increased by GSH activation of PGE2 isomerase in fractions isolated from all three developmental stages. A similar pattern of product formation was observed when AA was employed as substrate. These data suggest the possibility that changes in GSH concentration may modulate eicosanoid formation in cells that contain GSH-dependent PGE2 isomerase, as well as either or both prostacyclin or thromboxane synthase(s).


The Trouble with MEAM2: Implications of Pseudogenes on Species Delimitation in the Globally Invasive Bemisia tabaci (Hemiptera: Aleyrodidae) Cryptic Species Complex.
Molecular species identification using suboptimal PCR primers can over-estimate species diversity due to coamplification of nuclear mitochondrial (NUMT) DNA/pseudogenes. For the agriculturally important whitefly Bemisia tabaci cryptic pest species complex, species identification depends primarily on characterization of the mitochondrial DNA cytochrome oxidase I (mtDNA COI) gene. The lack of robust PCR primers for the mtDNA COI gene can undermine correct species identification which in turn compromises management strategies. This problem is identified in the B. tabaci Africa/Middle East/Asia Minor clade which comprises the globally invasive Mediterranean (MED) and Middle East Asia Minor I (MEAM1) species, Middle East Asia Minor 2 (MEAM2), and the Indian Ocean (IO) species. Initially identified from the Indian Ocean island of Réunion, MEAM2 has since been reported from Japan, Peru, Turkey and Iraq. We identified MEAM2 individuals from a Peruvian population via Sanger sequencing of the mtDNA COI gene. In attempting to characterize the MEAM2 mitogenome, we instead characterized mitogenomes of MEAM1. We also report on the mitogenomes of MED, AUS, and IO thereby increasing genomic resources for members of this complex. Gene synteny (i.e., same gene composition and orientation) was observed with published B. tabaci cryptic species mitogenomes. Pseudogene fragments matching MEAM2 partial mtDNA COI gene exhibited low frequency single nucleotide polymorphisms that matched low copy number DNA fragments (<3%) of MEAM1 genomes, whereas presence of internal stop codons, loss of expected stop codons and poor primer annealing sites, all suggested MEAM2 as a pseudogene artifact and so not a real species.


Understanding barriers to and facilitators of diabetes control and prevention in the New York City Bangladeshi community: a mixed-methods approach.
We have reported results from the formative stage of a community health worker intervention designed to improve diabetes management among Bangladeshi patients in New York City. Trained community health workers conducted focus groups (n = 47) and surveys (n = 169) with Bangladeshi individuals recruited from community locations. Results indicated that participants faced numerous barriers to care, had high rates of limited English proficiency, and had low levels of knowledge about diabetes. Most participants expressed interest in participating in a community health worker intervention.


Reductive activation of 5-fluorodeoxyuridine prodrug possessing azide methyl group by hypoxic X-irradiation.
We prepared a 5-fluorodeoxyuridine (5-FdUrd) derivative possessing azide methyl group (N(3)-FdUrd) as a novel radiation-activated prodrug. The parent antitumor agent, 5-FdUrd, was released efficiently from N(3)-FdUrd by hypoxic X-irradiation. On the other hand, the activation of N(3)-FdUrd was suppressed upon X-irradiation under aerobic conditions. A biological assay using A549 cells revealed that the cytotoxicity of N(3)-FdUrd was significantly enhanced by hypoxic X-irradiation.


Virtual screening and in vitro validation of natural compound inhibitors against SARS-CoV-2 spike protein.
The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a major public health burden and has resulted in millions of deaths worldwide. As effective treatments are limited, there is a significant requirement for high-throughput, low resource methods for the discovery of novel antivirals. The SARS-CoV-2 spike protein plays a key role in viral entry and has been identified as a therapeutic target. Using the available spike crystal structure, we performed a virtual screen with a library of 527 209 natural compounds against the receptor binding domain of this protein. Top hits from this screen were subjected to a second, more comprehensive molecular docking experiment and filtered for favourable ADMET properties. The in vitro activity of 10 highly ranked compounds was assessed using a virus neutralisation assay designed to facilitate viral entry in a physiologically relevant manner via the plasma membrane route. Subsequently, four compounds ZINC02111387, ZINC02122196, SN00074072 and ZINC04090608 were identified to possess antiviral activity in the µM range. These findings validate the virtual screening method as a tool for identifying novel antivirals and provide a basis for future drug development against SARS-CoV-2.


A model of the olivo-cerebellar system as a temporal pattern generator.
The olivo-cerebellar system has been implicated in temporal coordination of task components. Here, we propose a novel model that enables the olivo-cerebellar system to function as a generator of temporal patterns. These patterns could be used for timing of motor, sensory and cognitive tasks. The proposed mechanism for the generation of these patterns is based on subthreshold oscillations in a network of inferior olivary neurons and their control by the cerebellar cortex and nuclei. Our model, which integrates a large body of anatomical and physiological observations, lends itself to simple, testable predictions and provides a new conceptual framework for olivo-cerebellar research.


Iron utilization and liver mineral concentrations in rats fed safflower oil, flaxseed oil, olive oil, or beef tallow in combination with different concentrations of dietary iron.
Diets with a higher proportion of polyunsaturated fatty acids (i.e., linoleic acid) have decreased iron absorption and utilization compared with diets containing a higher proportion of the saturated fatty acid stearic acid (e.g., beef tallow). However, less is known regarding the influence of other polyunsaturated or monounsaturated fatty acids, along with higher dietary iron, on iron absorption and utilization. The present study was conducted to compare the effects of dietary fat sources known to vary in (n-3), (n-6), and (n-9) fatty acids on iron utilization and liver mineral concentrations. Male weanling rats were fed a diet containing 10, 35, or 100 microg/g iron in combination with safflower oil, flaxseed oil, olive oil, or beef tallow for 8 wk. Indicators of iron status, iron utilization, and liver iron concentrations were unaffected by an interaction between the fat source and iron concentration. Plasma copper was the only variable affected by an interaction between the fat source and dietary iron. Findings of this study demonstrate that flaxseed oil and olive oil may alter tissue minerals and affect iron utilization. Further studies should be conducted to establish the effect of varying (n-3), (n-6), and (n-9) fatty acids on trace mineral status and iron utilization.


Smaller, weaker, and less stiff bones evolve from changes in subsistence strategy.
We propose a computational model with which to examine the evolution of bone. Our results indicate that changes in subsistence strategy have influenced the evolution of bone growth and mechanoregulation, and predict that bone size, stiffness, and structural strength may decrease in future generations, bringing increased risk of fracture and prevalence of osteoporosis. Archeological data suggest that bone size and strength have decreased over evolution. We hypothesize that changing evolutionary pressures and levels of physical activity, both arising from changes in subsistence strategy, have affected the evolution of bone. We propose a computational model with which to examine the evolution of bone growth and mechanoregulation due to the transitions from hunter-gatherer to agricultural to modern lifestyles. The evolution of genes governing growth and mechanoregulation in a population of bones is simulated, where each individual is represented by a 2-D bone cross-section. Genetic variability is assumed to modulate growth through mechanoregulatory factors that direct periosteal expansion, endosteal expansion/infilling, and ash content accretion in response to strains incurred during walking. The model predicts decreases in cortical area and section modulus (a measure of structural strength) and increases in maximum compressive strain over the course of the simulation, meaning evolution of smaller, less strong, and less stiff bones is predicted for the population average. The model predicts small but continued decreases in size, strength, and stiffness in modern populations, despite the absence of a strong evolutionary advantage to efficient bones during this phase. In conclusion, our results show that changing loading regimes and evolutionary pressures may have influenced the evolution of bone growth and mechanoregulation, and predict that bone size and strength may continue to decrease in future generations, bringing increased risk of fracture and prevalence of osteoporosis.


Mef2 promotes spine elimination in absence of δ-catenin.
δ-Catenin is a component of the cadherin-catenin cell adhesion complex and its loss has been implicated in the mental retardation associated with the Cri du chat syndrome. We have previously demonstrated that loss of δ-catenin in a murine model during development results in excessive spine and synaptic density and function. In order to examine the role of potential molecules that might cooperate with δ-catenin to regulate spine density, we focused on Mef2. Our data demonstrate that while loss of δ-catenin does not alter the expression levels of endogenous Mef2, expression of Mef2 in neurons that are knocked down for δ-catenin promotes spine elimination. These results establish a molecular mechanism by which excessive spines in the absence of δ-catenin may be eliminated and may point toward pharmacological therapy for the Cri du chat syndrome.


Erratum: Clinical significance of shared T cell epitope analysis in early de novo donor-specific anti-HLA antibody production after kidney transplantation and comparison with shared B cell epitope analysis.
[This corrects the article DOI: 10.3389/fimmu.2021.621138.].


Top-Down Extraction of Silk Protein Nanofibers by Natural Deep Eutectic Solvents and Application in Dispersion of Multiwalled Carbon Nanotubes for Wearable Sensing.
With typical nanofibrous structure, silks spun by silkworms and spiders are the representative fibrous proteins that embody excellent mechanical properties and biological functions. However, it is still a challenge to directly extract silk nanofibers (SNFs) from natural silk fibers, to retain their nanostructures and properties, by a human- and environment-friendly approach for practical applications. Here, an all-natural strategy for simple, green, and scalable extraction of silkworm and spider silk protein nanofibers in natural deep eutectic solvents has been developed. The liquid-exfoliated SNFs have adjustable diameters from 20 nm (at the single SNF scale) to 100 nm and could be dispersed in water and organic solvents, enabling the production of useful macroscopic biomaterials. The free-standing SNF membranes made from silkworm silk nanofibers (SSNFs) exhibited cytocompatibility, flexibility, and excellent mechanical performance, providing the ability to fabricate sustainable materials for tissue engineering and green electronics. Moreover, the SSNF could be used as a green and efficient dispersant of multiwalled carbon nanotubes (MWCNTs), and the SSNFs/MWCNTs nanocomposite membranes could be used in wearable devices to monitor human activities.


Massive perivillous fibrin deposition of the placenta and pregnancy outcome: A retrospective observational study.
Massive perivillous fibrin deposition (MPVFD) in the placenta is associated with pregnancy complications and maternal disease. The aim of the current study was to contribute with increased knowledge regarding MPVFD by comparing maternal characteristics, obstetric and perinatal outcome and recurrence rate according to the degree of MPVFD. This retrospective observational study included 141 cases of MPVFD collected between January 2003 to December 2018 in the Stockholm region, Sweden. The extent of fibrin deposition was assessed as low (20-32%), moderate (33-50%) or severe (>50%) according to macroscopic examination. The study covered 48 placentas with low MPVFD, 41 with moderate and 52 with severe MPVFD. Severe MPVFD was associated with more prematurity than moderate and low MPVFDs (56.3% vs 34.2% and 34.0% respectively, p = 0.05 and p = 0.04). In cases with severe MPVFD, 72.3% of the liveborn infants were growth-restricted compared to 34.2% in the moderate group (p = 0.001) and 52.2% in the low group (p = 0.06). The incidence of intrauterine fetal death was 31.3% in the severe MPVFD group, which was significantly higher than in the low MPVFD group (8.5%, p = 0.01) and twice as much as in cases with moderate MPVFD (15.8%, p = 0.07). 105 subsequent pregnancies after an index pregnancy with MPVFD were identified. The outcome was favourable with a liveborn rate of 91-100%. The extent of fibrin in the placenta plays a role in pregnancy outcome. Cases with severe MPVFD in the placenta was associated with more prematurity, fetal growth restriction and intrauterine fetal death.


Terminals of subthalamonigral fibres are enriched with glutamate-like immunoreactivity: an electron microscopic, immunogold analysis in the cat.
Wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) histochemistry was combined with post-embedding immunogold cytochemistry in order to establish whether the subthalamic nucleus (STN) gives origin to glutamate (Glu)-enriched nerve terminals in substantia nigra, pars reticulata (SNr). Two adult cats served as normal controls and in two other animals crystalline WGA-HRP had been implanted bilaterally in STN. In all four animals ultrathin sections from SN were subjected to an immunogold procedure using antiserum raised against either Glu or gamma-aminobutyric acid (GABA). In some experiments the sections were subjected to consecutive incubations with both GABA and Glu antisera. These two antisera label two morphologically distinct types of boutons in SNr. The GABA antiserum labels boutons with pleomorphic vesicles, and they establish symmetrical synaptic contacts, mainly with dendritic shafts and spines, and occasionally with cell bodies. The Glu antiserum labels boutons with vesicles which are smaller and more uniform with regard to size and shape than those seen in the GABA-labelled boutons. The Glu-labelled boutons are engaged in asymmetrical synaptic contacts mainly with dendritic shafts and more rarely with cell bodies. The number of GABA-labelled boutons in SNr greatly exceeds the number of Glu-labelled ones. In the experimental material a considerable number of boutons in SNr are labelled with WGA-HRP reaction product. Several of these boutons are enriched in Glu-like immunoreactivity (Glu-LI), but not in GABA-LI. It is concluded that the subthalamonigral projection in the cat is likely to use Glu as a transmitter. The findings are briefly discussed with respect to the role played by STN in movement disorders and the involvement of excitatory amino acids in SN for the propagation of epileptic seizures and development of neurotoxicity.


Fe-loaded alginate hydrogel beads activating peroxymonosulfate for enhancing anaerobic fermentation of waste activated sludge: Performance and potential mechanism.
The recovery of volatile fatty acids (VFAs) through anaerobic fermentation (AF) is usually restricted by the poor biodegradability of waste activated sludge (WAS). This study proposed a novel strategy, i.e. peroxymonosulfate (PMS) activated by Fe-loaded sodium alginate hydrogel beads (Fe-SA), to enhance AF performance. Experimental results demonstrated that the as-synthesized Fe-SA and PMS co-pretreatment synergistically enhanced WAS solubilization and VFAs production. The maximal VFAs yield of 2013 mg COD/L was achieved at the Fe-SA dosage of 4.0 mM/g TSS, which was 93.7% higher than that with sole PMS addition and 8.82 times higher than that of the control. Mechanistic studies elucidated that the generation of reactive radicals such as SO4•- and •OH from PMS was greatly induced by Fe-SA, which contributed to WAS disintegration and degradation of refractory compounds. Additionally, analysis of the key enzyme activities indicated that the Fe-SA could strengthen biological hydrolysis and acidogenesis of sludge during AF. Microbial analysis illustrated that Fe-SA evidently improved the abundances of fermentative microorganisms as well as functional gene expression via creating a favorable environment for microbial growth. This study demonstrated the applicable potential of Fe-SA hydrogel beads activating PMS for VFAs production and provides an important reference for developing advanced oxidation processes-based application in AF.


Anesthesia for the obstetric patient with multiple sclerosis.
Data on all obstetric patients delivering at the Brigham and Women's Hospital during the years 1982 through 1987 were collected. The anesthetic techniques used, the type and amount of anesthetic agents administered, and the postpartum relapse rate of multiple sclerosis patients were compared. Women who received epidural anesthesia for vaginal delivery did not have a significantly higher incidence of relapse than those who received local infiltration. However, all of the women who experienced postpartum relapses had received concentrations of bupivacaine greater than 0.25%. This finding may suggest that a higher concentration of drug over a longer period of time may adversely influence the relapse rate.


Tris(pentafluoroethyl)difluorophosphorane: A Versatile Fluoride Acceptor for Transition Metal Chemistry.
Fluoride abstraction from different types of transition metal fluoride complexes [Ln MF] (M=Ti, Ni, Cu) by the Lewis acid tris(pentafluoroethyl)difluorophosphorane (C2 F5 )3 PF2 to yield cationic transition metal complexes with the tris(pentafluoroethyl)trifluorophosphate counterion (FAP anion, [(C2 F5 )3 PF3 ]- ) is reported. (C2 F5 )3 PF2 reacted with trans-[Ni(iPr2 Im)2 (ArF )F] (iPr2 Im=1,3-diisopropylimidazolin-2-ylidene; ArF =C6 F5 , 1 a; 4-CF3 -C6 F4 , 1 b; 4-C6 F5 -C6 F4 , 1 c) through fluoride transfer to form the complex salts trans-[Ni(iPr2 Im)2 (solv)(ArF )]FAP (2 a-c[solv]; solv=Et2 O, CH2 Cl2 , THF) depending on the reaction medium. In the presence of stronger Lewis bases such as carbenes or PPh3 , solvent coordination was suppressed and the complexes trans-[Ni(iPr2 Im)2 (PPh3 )(C6 F5 )]FAP (trans-2 a[PPh3 ]) and cis-[Ni(iPr2 Im)2 (Dipp2 Im)(C6 F5 )]FAP (cis-2 a[Dipp2 Im]) (Dipp2 Im=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) were isolated. Fluoride abstraction from [(Dipp2 Im)CuF] (3) in CH2 Cl2 or 1,2-difluorobenzene led to the isolation of [{(Dipp2 Im)Cu}2 ]2+ 2 FAP- (4). Subsequent reaction of 4 with PPh3 and different carbenes resulted in the complexes [(Dipp2 Im)Cu(LB)]FAP (5 a-e, LB=Lewis base). In the presence of C6 Me6 , fluoride transfer afforded [(Dipp2 Im)Cu(C6 Me6 )]FAP (5 f), which serves as a source of [(Dipp2 Im)Cu)]+ . Fluoride abstraction of [Cp2 TiF2 ] (7) resulted in the formation of dinuclear [FCp2 Ti(μ-F)TiCp2 F]FAP (8) (Cp=η5 -C5 H5 ) with one terminal fluoride ligand at each titanium atom and an additional bridging fluoride ligand.


Tempo and mode of early gene loss in endosymbiotic bacteria from insects.
Understanding evolutionary processes that drive genome reduction requires determining the tempo (rate) and the mode (size and types of deletions) of gene losses. In this study, we analysed five endosymbiotic genome sequences of the gamma-proteobacteria (three different Buchnera aphidicola strains, Wigglesworthia glossinidia, Blochmannia floridanus) to test if gene loss could be driven by the selective importance of genes. We used a parsimony method to reconstruct a minimal ancestral genome of insect endosymbionts and quantified gene loss along the branches of the phylogenetic tree. To evaluate the selective or functional importance of genes, we used a parameter that measures the level of adaptive codon bias in E. coli (i.e. codon adaptive index, or CAI), and also estimates of evolutionary rates (Ka) between pairs of orthologs either in free-living bacteria or in pairs of symbionts. Our results demonstrate that genes lost in the early stages of symbiosis were on average less selectively constrained than genes conserved in any of the extant symbiotic strains studied. These results also extend to more recent events of gene losses (i.e. among Buchnera strains) that still tend to concentrate on genes with low adaptive bias in E. coli and high evolutionary rates both in free-living and in symbiotic lineages. In addition, we analyzed the physical organization of gene losses for early steps of symbiosis acquisition under the hypothesis of a common origin of different symbioses. In contrast with previous findings we show that gene losses mostly occurred through loss of rather small blocks and mostly in syntenic regions between at least one of the symbionts and present-day E. coli. At both ancient and recent stages of symbiosis evolution, gene loss was at least partially influenced by selection, highly conserved genes being retained more readily than lowly conserved genes: although losses might result from drift due to the bottlenecking of endosymbiontic populations, we demonstrated that purifying selection also acted by retaining genes of greater selective importance.


Exercise testing in patients with chest pain to sumatriptan.
In order to assess whether chest pain attributed to sumatriptan is associated with abnormalities on cardiac exercise testing, we performed a case-control study. Cases were selected as consumers of sumatriptan who reported sumatriptan associated chest pain. A reference group was selected randomly from consumers of sumatriptan with the same GP as the case, who reported no chest pain after use of sumatriptan. If possible, controls were matched for age (within 5-year groups) and gender. In a total of 74 cases and 55 controls symptom-limited exercise tests were performed. Besides a small difference in age, there were no differences in basic characteristics between cases and controls. Three cases had ST-depression on ECG during exercise. However, none of the variables measured during exercise testing differed significantly between cases and controls. The prevalence of abnormal exercise tests in patients with sumatriptan-induced chest pain is low, and not statistically different from patients without chest pain after intake of sumatriptan. Routine performance of exercise testing in patients with sumatriptan-associated chest pain is not recommended.


Activity Recognition on Streaming Sensor Data.
Many real-world applications that focus on addressing needs of a human, require information about the activities being performed by the human in real-time. While advances in pervasive computing have lead to the development of wireless and non-intrusive sensors that can capture the necessary activity information, current activity recognition approaches have so far experimented on either a scripted or pre-segmented sequence of sensor events related to activities. In this paper we propose and evaluate a sliding window based approach to perform activity recognition in an on line or streaming fashion; recognizing activities as and when new sensor events are recorded. To account for the fact that different activities can be best characterized by different window lengths of sensor events, we incorporate the time decay and mutual information based weighting of sensor events within a window. Additional contextual information in the form of the previous activity and the activity of the previous window is also appended to the feature describing a sensor window. The experiments conducted to evaluate these techniques on real-world smart home datasets suggests that combining mutual information based weighting of sensor events and adding past contextual information into the feature leads to best performance for streaming activity recognition.


[Hepatic resection with removal of tumor thrombi for hepatocellular carcinoma with tumor thrombi in portal vein and curative analysis].
To study the therapeutic effects of surgical treatment for hepatocellular carcinoma (HCC) with tumor thrombi in the main trunk or the first branch of the portal vein (PVTT) and factors affecting prognosis. 111 HCC patients with PVTT underwent hepatic resection with removal of tumor thrombi in the first left or the right branch of the portal vein or removal of tumor thrombi by direct opening of the main trunk of the portal vein. Hepatic artery infusion and/or portal vein infusion were performed after hepatic resection with removal of tumor thrombi for HCC with PVTT in 22 of the patients. Among 111 patients, 32 received postoperative transhepatic arterial chemoembolization and/or portal vein chemotherapy. Conservative treatment and surgical exploration or hepatic artery ligation (HAL) and infusion (HAI) and/or portal vein infusion (PVI) were performed in other 14 and 20 HCC patients with PVTT, respectively. The 1-, 2-, 3-, 4- and 5- year survival rates were 61.7%, 36.2%, 32.3%, 24.4% and 22.4% in the resected group, respectively, whereas 14 HCC patients with PVTT treated conservatively died in three months and the 1-, 2- year survival rates were 6.0% and 0 in the 20 patients with surgical exploration or HAL and HAI and/or PVI respectively. Hepatic resection with removal of tumor thrombi for HCC with PVTT should be encouraged for the prolongation of life span and quality of life.


Parent--child obesity and cardiovascular risk factors.
Blood pressure, cholesterol, high density lipoprotein cholesterol, and triglycerides were studied in obese children and obese parents selected to participate in a weight treatment program. The relationships between parent and child risk levels, as well as the relationship between child and parent weight and risk factors, were established. Results showed that children's cholesterol and triglycerides were related to parental lipid levels, independent of weight. Children's blood pressure readings were strongly related to their weight, but not to parental blood pressure. High density lipoprotein cholesterol levels were negatively related to weight in both child and parent female populations, and weakly positively related to weight for male children. Implications of these risk factor patterns for intervention are discussed.


Characterizing carotenoids in cyanobacterial cultures - Opportunities and implications for paleolimnological studies.
Cyanobacterial blooms are increasing in frequency and intensity globally, impacting lake ecosystem health and posing a risk to human and animal health due to the toxins they can produce. Cyanobacterial pigments preserved in lake sediments provide a useful means of understanding the changes that have led to cyanobacterial blooms in lakes. However, there is some uncertainty as to whether specific carotenoids are unique to certain genera or types of cyanobacteria. To fill this knowledge gap, we analyzed pigments in 34 cyanobacteria cultures and applied the findings to sediments from three New Zealand lakes. The cyanobacterial carotenoids canthaxanthin, echinenone and zeaxanthin were detected in all cultures, whereas myxoxanthophyll was only detected in ten cultures (Microcoleus, Planktothrix and the picocyanobacteria cultures; Synechococcaceae). The sum of the individual carotenoid concentrations provided the strongest relationship with cyanobacterial biomass (R2 = 0.58) and could be used in paleolimnology studies to evaluate general cyanobacterial abundance. Ratios of canthaxanthin, zeaxanthin and myxoxanthophyll relative to echinenone indicated that carotenoid ratios could be used to differentiate picocyanobacteria and bloom-forming cyanobacteria, to some degree. High zeaxanthin/echinenone ratios were measured in picocyanobacteria and low zeaxanthin/echinenone ratios were measured in bloom-forming cyanobacteria. The zeaxanthin/echinenone ratio was applied to sediment core samples where the cyanobacterial community was also evaluated by 16S rRNA gene metabarcoding, with the zeaxanthin/echinenone ratios showing similar patterns to those observed in the cultures. The preliminary assessment described here suggests that zeaxanthin/echinenone ratios could provide a valuable paleoecological proxy for evaluating historical shifts in cyanobacterial communities and warrants further exploration.


Functional inhibition or genetic deletion of acid sphingomyelinase bacteriostatically inhibits Anaplasma phagocytophilum infection in vivo.
Anaplasma phagocytophilum infects neutrophils to cause granulocytic anaplasmosis. It poorly infects mice deficient in acid sphingomyelinase (ASM), a lysosomal enzyme critical for cholesterol efflux, and wild-type mice treated with desipramine that functionally inhibits ASM. Whether inhibition or genetic deletion of ASM is bacteriostatic or bactericidal for A. phagocytophilum and desipramine's ability to lower pathogen burden requires a competent immune system were unknown. Anaplasma phagocytophilum-infected severe combined immunodeficiency disorder (SCID) mice were administered desipramine or PBS, followed by the transfer of blood to naïve wild-type mice. Next, infected wild-type mice were given desipramine or PBS followed by transfer of blood to naïve SCID mice. Finally, wild-type or ASM-deficient mice were infected and blood transferred to naïve SCID mice. The percentage of infected neutrophils was significantly reduced in all desipramine-treated or ASM-deficient mice and in all recipients of blood from these mice. Infection was markedly lower in ASM-deficient and desipramine-treated wild-type mice versus desipramine-treated SCID mice. Yet, infection was never ablated. Thus, ASM activity contributes to optimal A. phagocytophilum infection in vivo, pharmacologic inhibition or genetic deletion of ASM impairs infection in a bacteriostatic and reversible manner and A. phagocytophilum is capable of co-opting ASM-independent lipid sources.


New cytotoxic analogues of annonaceous acetogenins.
A series of new acetogenin analogues incorporating a central catechol moiety instead of the tetrahydrofuran ring(s) have been prepared and tested against L1210 leukemia cells. Although less potent than bullatacinone, which has the same terminal lactone, these compounds display interesting cell cycle effects.


STAT1 and CXCL10 involve in M1 macrophage polarization that may affect osteolysis and bone remodeling in extrapulmonary tuberculosis.
This study was aimed to reveal the molecular mechanism of bone destruction due to macrophage polarization leading to during extrapulmonary tuberculosis (EPTB) infection. The dataset GSE83456 was downloaded from the GEO database, and the xCell tool was used to obtain the 64 types of immune cells. The flow cytometry was performed to identified the differences between M1 and M2 macrophages between EPTB and the healthy controls (HCs). The enrichment analyses were performed on the differentially expressed genes (DEGs) and their functionally related modules. The hub genes were screened out, and their relationships with EPTB and the immune cell subtypes were further analyzed. The flow cytometric analysis validated this hypothesis of M1-macrophage polarization correlated with the pathogenesis of EPTB. Of the obtained 103 DEGs, 97 genes were upregulated, and 6 genes were downregulated. The GO and KEGG pathway analyses showed that the DEGs were particularly involved in the immune-related processes. The hub genes (STAT1 and CXCL10) might be involved in M1-macrophage polarization and correlated with the pathogenesis of EPTB. STAT1 and CXCL10 could also behave as biomarkers for EPTB. STAT1 and CXCL10 were involved in the M1-macrophage polarization and correlated with the pathogenesis of EPTB. Besides, both of them could also behave as biomarkers for EPTB diagnosis and provide the required clues for targeted therapy in the future.


Detection thresholds of potassium salts are related to the molar conductivity of the anion.
In a previous study, we found that human taste detection thresholds for Na+ salts were linearly correlated with molar conductivity values at infinite dilution of their anions. In the present study, detection threshold concentrations for potassium salts were also found to be linearly correlated (r = -0.92) with the molar conductivity of the anion of the salt. Detection thresholds were determined here for nine potassium salts with the same anions as the sodium salts previously tested. The mean detection thresholds for these potassium salts were found to be: K Acetate (0.00311 M), K Carbonate (0.00286 M), K Chloride (0.00242 M), K Citrate (0.000300 M), K Phosphate (0.00196 M), K Sulfate (0.00090 M), K Tartrate (0.00164 M), K Glutamate (0.00153 M), and K Ascorbate (0.00375 M). The rank order correlation between the detection threshold values for sodium and potassium salts was 0.88. This finding suggests that detection thresholds for both Na+ and K+ salts are determined by the charge mobility of the anion.


[Perception of adolescent medicine among French pediatric residents].
The perception of adolescent medicine (AM) among future pediatricians in France has scarcely been explored although adolescent health care is an integral part of the pediatrician's job. Moreover, pediatric residents seem to have a lack of enthusiasm for this field. The aim of this study was to assess the beliefs and perceptions of fourth-year French pediatric residents regarding adolescents and AM. We conducted a national electronic survey among French pediatric residents in their last year of residency. An original 51-item, open-ended declarative questionnaire was sent out including questions on demographics, career expectations, AM block rotation experiences, and perceptions and beliefs regarding adolescents and AM. Difficulties and barriers experienced in this field were investigated. Queries about residents' specific AM courses and about their educational needs were also explored. The survey was conducted online between January and March 2015. There were 121 respondents, achieving a 43% response rate. The majority of respondents perceived teens as interesting (75%), vulnerable (83%), and time-consuming (84%). Up to four fifths of respondents (81%) considered AM to be a skill that all pediatricians should acquire. A subgroup analysis showed that the residents who had not experienced an AM block rotation did not seem to be convinced of the need for training in this field (P=0.09). The following issues were reported as major difficulties by residents: providing care for teens reluctant to seek health care (65%), managing violent behavior among adolescents in the emergency ward (98%), and managing adolescents who attempt suicide (80%). Less than half (45%) of the residents reported their residency program had a specific AM course. Among them, 73% attended the lectures and 57% found them useful. One third (32%) of the respondents had experienced a 2-month block rotation in the field of AM during their residency. This is the first nationwide study in France in this field. Although the response rate is below 50%, it exceeded our expectations. Our results are in line with previous studies showing that pediatric residents report a high interest in working with adolescents and yet their educational needs in AM are unmet. The limitations of this study include the self-selection bias and implicit limitations carried by the phrasing of the survey questions. There is a need to devise a better educational approach combining a broader proposal of AM block rotations together with a specific competency framework in adolescent health, since we know it improves the quality of health care delivered to adolescents. Moreover, training pediatricians in AM is a public health priority so as to comply with medical schools' principles of social accountability and address the priority health needs for an efficient, equitable, and sustainable health system. At a time when postgraduate reform is being made, the inclusion of an AM curriculum in the general pediatrician course is necessary.


Superselective arterial embolization for the control of postsurgical bleeding.
Superselective catheterization and Gelfoam embolization of a muscular branch of the deep femoral artery was successfully performed; a profuse postsurgical bleeding requiring repeated transfusion of blood was stopped. The time of persistence, advantages and disadvantages of commonly used embolic materials are discussed. It is concluded that embolization is an effective method to stop bleeding in selected patients.


Subjective and objective nasal obstruction assessment in children with chronic rhinitis.
The present study was undertaken, to test the hypothesis that schoolchildren on long-term treatment for chronic rhinitis under-report their nasal congestion. Ninety-seven children aged 8.3-15.5 years (median 12.7) with non-purulent perennial rhinitis, for 1.4-8.5 years (median 2.8) self-graded their nasal blockage as "severe" (group-A), "moderate" (group-B), "mild" (group-C) or "absent" (group-D). An additional 48 normal children served as controls (group-E). Subsequently active anterior rhinomanometry for total nasal airway resistance (TNAR) measurement and decongestion test (>20% TNAR fall) were employed as objective means of nasal congestion. Mean pre-decongestion TNAR values did not show any significant difference between the group-A, -B and -C; significant differences were observed between group-A and -D (p=0.04) and between all groups as compared to -E. Positive decongestion test was detected in 57.1%, 53.8%, 48.3%, 32.3% and 10.4% of children in group-A, -B, -C, -D and -E, respectively (group-A, -B, -C versus -E p<0.001, group-D versus -E p=0.03). Schoolchildren on long-term treatment for perennial rhinitis frequently under-report their symptom of nasal stuffiness.


Multiscale analysis of reaction networks.
In most natural sciences there is currently the insight that it is necessary to bridge gaps between different processes which can be observed on different scales. This is especially true in the field of chemical reactions where the different abilities to form bonds between different types of atoms and molecules create much of the properties we experience in our everyday life, especially in all biological activity. There are essentially two types of processes related to biochemical reaction networks, the interactions among molecules and interactions involving their conformational changes, so in a sense, their internal state. The first type of processes can be conveniently approximated by the so-called mass-action kinetics, but this is not necessarily so for the second kind: here molecular states do not define any kind of density or concentration. In this paper, we demonstrate the necessity to study reaction networks in a stochastic formulation for which we can construct a coherent approximation in terms of specific space-time scales and the number of particles. The continuum limit procedure naturally creates equations of Fokker-Planck type where the evolution of the concentration occurs on a slower time scale when compared to the evolution of the conformational changes, for example triggered by binding or unbinding events with other (typically smaller) molecules. We apply the asymptotic theory to derive the effective, i.e. macroscopic dynamics of a general biochemical reaction system. The theory can also be applied to other processes where entities can be described by finitely many internal states, with changes of states occurring by arrival of other entities described by a birth-death process.


Towards connecting carbon emissions with asymmetric changes in economic growth: evidence from linear and nonlinear ARDL approaches.
The well-established emissions-growth debate relies on the symmetric nexus between CO2 emissions and economic growth, thereby ignoring a fundamental component of macro economy in the form of asymmetric relation. This paper considers how CO2 emissions respond asymmetrically to changes in economic growth. While utilizing both linear and nonlinear time series approaches for an environmentally exposed country, Pakistan over the period 1971-2018, we find convincing evidence that CO2 emissions rise more rapidly during negative shocks to economic growth than increase during economic expansions. Thus, contrary to what has previously been reported, the effect is strong as holds both at short run and long run. This is partly due to the increase in informal sector as GDP declines. Our estimated results show that accounting for the shadow economy results a higher magnitude of CO2 emissions due to decrease in economic growth, thus question the traditional symmetric decoupling of economic growth and CO2 emissions. The estimated results are robust to alternative estimators such as fully modified least squares (FMOLS) and dynamic OLS (DOLS). Thus, the findings of this study call for a re-thinking on climate policy design that rarely pays attention to the aforementioned outcomes due to fall in economic growth.