Antitumor response of regional lymph node lymphocytes in human lung cancer.
We recently reported that regional lymph node lymphocytes (RLNL) from patients with primary lung cancer were in a more highly activated state than peripheral blood lymphocytes (PBL) when the activation-related molecules were studied by FACS analysis. To identify whether or not RLNL had the ability to respond to autologous tumor cells (AT), in the present study a mixed lymphocyte tumor cell reaction (MLTR) either with or without recombinant interleukin 2 (rlL-2) was performed in 41 cases with primary lung cancer. Significant proliferative responses to AT were found in RLNL from 20 of 41 cases (48.8%) without IL-2, and in 23 of 41 cases (56.1%) with IL-2. On the other hand, such responses were observed in the PBL from 8 of 30 cases (26.7%) without IL-2, and from 11 of 30 cases (36.7%) with IL-2. No significant correlation between MLTR and such clinical factors as tumor size, metastasis to lymph node, histology and stage of the disease was found. To further analyze the anti-AT response of RLNL, the cytokine production of RLNL was investigated after stimulation by AT. An increase in interferon-gamma (IFN-gamma) production was observed in RLNL with a positive reaction of MLTR, while no such increase was found in PBL. Finally, to elucidate whether the expression of MHC class II molecules was a key point in MLTR, tumor cells in primary lesions were examined for the expression of MHC class II by immunohistochemical staining, and the blocking assay of MLTR was performed with anti-MHC class II monoclonal antibody. Data suggested that there was a positive correlation between MHC class II expression of the tumor and MLTR and that MLTR were partially blocked by anti-MHC class II monoclonal antibody. These results demonstrated that RLNL were in a more highly activated state against AT than were PBL, and this finding is considered to be helpful in enhancing our understanding of the role of RLNL in lung cancer patients.


Simultaneous Determination of the Size and Shape of Single α-Synuclein Oligomers in Solution.
Soluble oligomers of amyloid-forming proteins are implicated as toxic species in the context of several neurodegenerative diseases. Since the size and shape of these oligomers influence their toxicity, their biophysical characterization is essential for a better understanding of the structure-toxicity relationship. Amyloid oligomers are difficult to characterize by conventional approaches due to their heterogeneity in size and shape, their dynamic aggregation process, and their low abundance. This work demonstrates that resistive pulse measurements using polymer-coated solid-state nanopores enable single-particle-level characterization of the size and shape of individual αSyn oligomers in solution within minutes. A comparison of the resulting size distribution with single-particle analysis by transmission electron microscopy and mass photometry reveals good agreement with superior resolution by nanopore-based characterization. Moreover, nanopore-based analysis has the capability to combine rapid size analysis with an approximation of the oligomer shape. Applying this shape approximation to putatively toxic oligomeric species that range in size from 18 ± 7 aggregated monomers (10S) to 29 ± 10 aggregated monomers (15S) and in concentration from picomolar to nanomolar revealed oligomer shapes that agree well with previous estimates by cryo-EM with the added advantage that nanopore-based analysis occurs rapidly, in solution, and has the potential to become a widely accessible technique.


CXCL8, MMP12, and MMP13 are common biomarkers of periodontitis and oral squamous cell carcinoma.
To analysis the relationship between periodontitis (PD) and oral squamous cell carcinoma (OSCC) by bioinformatic analysis. We analyzed the gene expression profiles of PD (GSE16134) from the Gene Expression Omnibus (GEO) database and OSCC samples from TCGA-HNSC (head and neck squamous cell carcinoma) and identified common differentially expressed genes (DEGs) in PD and OSCC. Then, functional annotation and signaling pathway enrichment, protein interaction network construction, and hub gene identification were performed. Subsequently, the function and signaling pathway enrichment of hub genes, miRNA interaction, and transcription factor interaction analyses were carried out. We analyzed GSE10334 and GSE30784 as validation datasets, and performed qRT-PCR experiments simultaneously for validation, and obtained 4 hub genes. Finally, immune infiltration analysis and clinical correlation analysis of 4 hub genes and related miRNAs were performed. We identified 31 DEGs (16 up-regulated and 15 down-regulated). Four hub genes were obtained by qRT-PCR and validation dataset analysis, including IL-1β, CXCL8, MMP12, and MMP13. The expression levels of them were all significantly upregulated in both diseases. The functions of these genes focus on three areas: neutrophil chemotaxis, migration, and CXCR chemokine receptor binding. Key pathways include IL-17 signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interactions pathway. Immune infiltration analysis showed that the expressions of 4 hub genes were closely related to a variety of immune cells. ROC curve analysis indicated that AUCs of 4 hub genes are all greater than 0.7, among which MMP12 and MMP13 were greater than 0.9. Kaplan-Meier survival analysis indicated that worse OS was strongly correlated with CXCL8 and MMP13 high-expression groups. MMP12 low-expression group was strongly associated with worse OS. The results of multivariate Cox regression analysis showed that age, N stage, CXCL8, MMP12, and MMP13 were independent prognostic factors for OS. We also identified 3 miRNAs, including hsa-miR-19b-3p, hsa-miR-181b-2-3p, and hsa-miR-495-3p, that were closely related to 4 hub genes. Hsa-miR-495-3p is closely related to the diagnosis and prognosis of OSCC. We identified 4 hub genes between PD and OSCC, including IL-1β, CXCL8, MMP12, and MMP13. These genes may mediate the co-morbid process of PD and OSCC through inflammation-related pathways such as the IL-17 signaling pathway. It is worth noting that CXCL8, MMP12, and MMP13 have great significance in the diagnosis and prognosis of OSCC.


Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system.
We determined the molecular basis of cystathionine beta-synthase (CBS) deficiency in three siblings with pyridoxine responsive homocystinuria using a significantly improved mutation screening method in bacteria. The phenotypic expression of the siblings differed even though their CBS genotypes were identical. The paternal allele contained a linked pair of mutations, C233G and G306C, corresponding to P78R and K102N in the polypeptide chain. Together, these inactivated the enzyme; however, expressed separately, they reduced activity by about one half. The single maternal mutation G715A (E239K) effectively abolished CBS activity. Subunits of CBS were absent from patient fibroblast extracts; however, E. coli, transformed with plasmids containing patient CBS cDNA, expressed the subunits, although in reduced amounts. The mother, an obligate heterozygote, was free from all signs of homocystinuria; nonetheless, extracts of her fibroblasts were devoid of CBS protein and activity. We conclude that fibroblast levels of CBS are only partially effective as prognosticators of disease severity and that it is important to test the in vivo response to vitamin B6 in all cases of homocystinuria, including those in which the mutations lead to the absence of the enzyme in cultured fibroblasts.


Effects of potassium citrate or potassium chloride in patients with combined glucose intolerance: A placebo-controlled pilot study.
Experimental K(+) depletion reversibly inhibits insulin secretion, while chronic metabolic acidosis decreases insulin sensitivity. We aimed to investigate the effects of potassium supplementation and alkali supplementation in non-acidotic, normokalemic humans with combined glucose intolerance. In this double-blind, placebo-controlled study in 11 subjects (7 male, 4 female, ages 47-63 years), 90meqs of oral KCl or Kcitrate per day for 2weeks each increased insulin production as measured by homeostasis model assessment Beta [KCl=86 (CI 81-91), Kcitrate=88 (82-94), placebo=78 (73-83)%, p<0.04], but only Kcitrate attenuated insulin resistance as assessed by HOMA-IR (insulin resistance, Kcitrate=2.8 (2.5-3.1), placebo=3.2 (2.9-3.5), p<0.03) and only Kcitrate increased quantitative insulin sensitivity check index (Quicki, Kcitrate=0.355 (0.305-0.405), placebo=0.320 (0.265-0.375) p<0.04). These results were confirmed by independent measurements, i.e. HOMA C-peptide and whole body insulin sensitivity index measured during oral glucose tolerance testing. Kcitrate significantly decreased systolic and diastolic 24-hour ambulatory blood pressures (-4.0 (-3 to -5) and -2.7 (-1.9 to -3.5), respectively as compared to placebo, p<0.02) while KCl was without a significant effect. K(+) supplementation in the absence of overt K(+) depletion improves beta-cell function in subjects with combined glucose intolerance. The insulin-sensitizing and hypotensive effect, however, depend on citrate as the accompanying anion.


Comparison of dosimetric parameters of volumetric modulated arc therapy and three-dimensional conformal radiotherapy in postmastectomy patients with carcinoma breast.
Our study was undertaken to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) in postmastectomy patients with left-sided carcinoma breast. This was a hospital-based cross-sectional study. Thirty plans were generated - VMAT with two partial arcs and field in field tangential 3DCRT plans. In the 3DCRT plans, planning target volume (PTV) dose coverage was 2% higher compared with the VMAT plan 98.21 ± 1.79 versus 96.30 ± 2.62 (P = 0.028). The conformity index was better for the 3DCRT plan (0.97 vs. 0.95; P = 0.022), while the homogeneity index was worse for the VMAT plans (0.16 vs. 0.23; P = 0.057). However, the organ at risk sparing was better with the VMAT plans when compared to the 3DCRT plans. This was particularly relevant for the higher doses. The V20 Gy (34.94 vs. 24.42), V30 Gy (32.32 vs. 16.19), and V40 Gy (28.23 vs. 8.03) for the lung were significantly higher for the 3DCRT plans when compared to VMAT plans (P = 0.000). Similarly, the V20 Gy (29.88 vs. 12.79), V30 Gy (27.25 vs. 4.94), and V40 Gy (24.58 vs. 1.47) for the heart was significantly higher for the 3DCRT plans when compared to the VMAT plans (P = 0.000). The V5 Gy for lung (77.86 vs. 47.38) and heart (76.18 vs. 39.36) was significantly higher for the VMAT plans when compared to the 3DCRT plans (P = 0.000). VMAT is dosimetrically superior to the field-in-field 3DCRT for left-sided breast cancer patients owing to its comparable PTV coverage and better sparing of heart and lung.


Transdermal versus subcutaneous leuprolide: a comparison of acute pharmacodynamic effect.
Transdermal administration of peptides has been limited by the barrier properties of the skin. We compared the acute luteinizing hormone (LH) response to subcutaneous and transdermal administration of an LH-releasing hormone agonist (leuprolide). Eighteen volunteers received 5 mg leuprolide added to electrically powered patches delivering a current of 0.22 microA (transdermally). One week later, they received a 5 mg subcutaneous dose. LH response was measured. The area under the curve for LH response, maximum LH response, and time to maximum LH response were similar. Time to first response was shorter (147 +/- 108 minutes [transdermally] and 73 +/- 74 minutes [subcutaneously]; p less than 0.05), and the area under the curve for the first 150 minutes was greater (3655 +/- 2246 mIU.min/ml [transdermally] and 8666 +/- 4067 mIU.min/ml [subcutaneously]; p less than 0.05) for subcutaneous delivery. No major adverse effects were seen. This electrically powered transdermal technique merits further study.


Enhanced isosteric heat of H2 adsorption by inclusion of crown ethers in a porous metal-organic framework.
Inclusion of 18-crown-6 or 15-crown-5 in a porous MOF increased the isosteric heats of H(2) adsorption significantly, which are comparable to MOFs containing open metal sites.


Effects of alcohols on the actions of VIP and secretin on acinar cells from guinea pig pancreas.
In dispersed acini prepared from guinea pig pancreas, ethanol inhibited the increase in amylase secretion caused by cholecystokinin, carbachol, secretin, or vasoactive intestinal peptide. Ethanol did not alter binding of [125I] vasoactive intestinal peptide to pancreatic acinar cells or the inhibition of binding cause by secretin or vasoactive intestinal peptide. Ethanol potentiated the increase in adenylate cyclase activity and cellular adenosine 3':5'-monophosphate caused by secretin or vasoactive intestinal peptide. This potentiating action was reversible and could also be detected with straight-chain alcohols having fewer than seven carbon atoms. At sufficiently high concentrations, straight-chain alcohols having more than two carbon atoms inhibited the action of secretin or vasoactive intestinal peptide on adenylate cyclase activity, and this and this action was irreversible.


Cultural Acceptability of a Smoking Relapse Prevention Intervention for Pregnant Women in Puerto Rico: Providers' Feedback.
Hispanic women are more likely than non-Hispanic women to quit smoking during pregnancy, indicating that relapse-prevention interventions may benefit this population. We conducted qualitative interviews with health care providers in Puerto Rico who serve pregnant women regarding the cultural acceptability of Libres Para Siempre Por Mi Bebé y Por Mi (transcreated from the English version, Forever Free for Baby and Me), a smoking relapse-prevention booklet series. Providers praised the overall quality of the content, interactive activities, vignettes, and partner booklet. Recommendations included condensing the content, and distributing the booklets during one-on-one counseling and via "charlas"(community themed presentations). Overall, these smoking relapse-prevention materials are culturally acceptable among health care providers, yet there is a need to attend to local cultural preferences for delivering the intervention.


Age, Benign Prostatic Hyperplasia, Geography of Residence, and Occupation are Predictors of Bladder Calculi in Men: A Three-Year Data Analysis.
The formation of bladder calculi is a complex multifactorial process. Our objective was to identify predictors of bladder calculi in men. This cross-sectional study was conducted at a regional public hospital. We used medical records from 2017 to 2019 for men diagnosed with urinary calculi or benign prostatic hyperplasia (BPH). The diagnosis of urinary calculi was based on urinalysis, plain x-ray, and ultrasonography (USG). The diagnosis of BPH was based on digital rectal examination (DRE), USG, and American Urological Association (AUA) Symptom Index to assess the severity of BPH. The data were analyzed using Kruskal-Wallis, Mann-Whitney U, Chi-square tests, and binary logistic regression. Of 2010 study participants, 66.0% were men with urinary calculi, 39.7% had BPH, 21.0% were aged 70 years or more, 12.5% lived in limestone mountain areas, and 24.6% had occupations that were mainly outdoors. Urinary calculi in men with BPH were found in the urethra (3.0%), bladder (27.6%), ureter (2.2%), and kidney (1.1%). Of all men with urinary calculi, the odds of having bladder calculi in men aged 70 years or more was 13.484, 95% confidence interval (95% CI): 8.336-21.811; In men with BPH was 11.182, 95% CI: 6.440-19.416; In men who lived in limestone mountain area was 1.894, 95% CI: 1.242-2.887; In men whose occupation is mainly outdoor was 3.240, 95% CI: 1.954-5.375, compared to reference groups. Age, BPH, geography of residence, and occupation were predictors of bladder calculi in men.


The Life Satisfaction Index-Form A as applied to older adults: technical note on scoring patterns.
The value of standardized scales for determining life satisfaction among older adults is being questioned, but use of the scales continues. The Life Satisfaction Index-Form A (LSIA) in its many variations continues to be among the most widely used scales for this purpose. In a comparison of two scoring methods (36-point vs. 18-point) for the LSIA, the lack of a significant difference indicated that a 36-point scale is not necessary. Caution in the use and interpretation of the variances between the two scoring methods is suggested.


Bilateral primary breast neuroendocrine carcinoma in a young woman: report of a case.
Bilateral breast carcinoma accounts for approximately 5% of all patients with breast cancer, while neuroendocrine breast carcinomas comprise less than 5% of invasive breast carcinomas. In addition, most patients with breast neuroendocrine carcinomas are older. Therefore, bilateral primary breast neuroendocrine carcinoma at a young age is extremely rare. We herein report bilateral neuroendocrine carcinoma of the breast in a 29-year-old woman who underwent bilateral lumpectomy with the initial symptom of bilateral nipple discharge. Grossly, the lesions in both breasts were masses with infinite margins. Histologically, this case was consistent with primary neuroendocrine carcinoma arising in bilateral breasts. Cells from both breast tumors were positive for chromogranin A, neuron-specific enolase, synaptophysin, cytokeratin 7, estrogen receptor, and progesterone receptor, and negative for Her2, cytokeratin 34β12, cytokeratin 5/6, smooth muscle actin, p63, S-100 protein, and p53. The Ki67 and NE proliferative indices were below 1%. To the best of our knowledge, this is the first reported case in China of bilateral primary neuroendocrine carcinoma presenting in a young woman.


Routine quantitation of white cells as low as 0.001 per microL in platelet components.
A method is described for routine quantitation of very low numbers of white cells (WBCs) in platelet components, using flow cytometry and dual nucleic acid stains. The WBC quantitation is based on the detection of nucleated cells labeled with propidium iodide and thiazole orange, with chicken red cells added as an internal counting standard. Platelet concentrates containing 0.001 to 1500 WBCs per microL (2 x 10(2)-3 x 10(8) WBCs/component) and 600 to 2800 x 10(3) platelets per microL were analyzed for the number of contaminating WBCs. The method was found to be linear throughout the 7 log10 range and to have sufficient reproducibility and sensitivity for routine analysis of WBC-reduced platelet concentrates.


Expression of c-Fos after noise-induced temporary threshold shift in the guinea pig cochlea.
c-Fos is known to be a component of a transcription factor, activator protein-1, which is induced by oxidative stress. Guinea pigs were exposed to 4 kHz band noise of 110 dB SPL for 1 or 5 h and the expression of c-Fos in the organ of Corti was determined using Western blotting analysis and immunocytochemistry. c-Fos was expressed only after the noise exposure. The c-Fos expression was mainly found in the Hensen's cells, Claudius' cells and Deiter's cells of the basal and second turns of the cochlea. Since the threshold shift was temporary, the expression of c-Fos is therefore considered to contribute to the survival or protective function of the organ of Corti.


Stress, Anxiety, and Depression in People Aged Over 60 in the COVID-19 Outbreak in a Sample Collected in Northern Spain.
This study examines the levels of stress, anxiety, and depression in people over 60 years of age at the time of the COVID-19 outbreak. The study used an exploratory-descriptive cross-sectional methodology. The resulting responses were analyzed using SPSS v.25 PARTICIPANTS: Participants (N = 290) were aged 60 years and above. The study was carried out in the Basque Country (North of Spain). Stress, anxiety, and depression were measured using the Anxiety and Stress Scale - 21 (DASS-21) RESULTS: Most of the participants did not report levels of stress, anxiety, and depression. Among participants age 66 and above and those with chronic illness, a proportion reported experiencing one, two or all three of these symptoms.


Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion.
Members of the Rho family of small GTPases have been shown to be involved in tumorigenesis and metastasis. Currently, most of the available information on the function of Rho proteins in malignant transformation is based on the use of dominant-negative mutants of these GTPases. The specificity of these dominant-negative mutants is limited however. In this study, we used small interfering RNA directed against either Rac1 or Rac3 to reduce their expression specifically. In line with observations using dominant-negative Rac1 in other cell types, we show that RNA interference-mediated depletion of Rac1 strongly inhibits lamellipodia formation, cell migration and invasion in SNB19 glioblastoma cells. Surprisingly however, Rac1 depletion has a much smaller inhibitory effect on SNB19 cell proliferation and survival. Interestingly, whereas depletion of Rac3 strongly inhibits SNB19 cell invasion, it does not affect lamellipodia formation and has only minor effects on cell migration and proliferation. Similar results were obtained in BT549 breast carcinoma cells. Thus, functional analysis of Rac1 and Rac3 using RNA interference reveals a critical role for these GTPases in the invasive behavior of glioma and breast carcinoma cells.


Calcium-stimulated sodium efflux from rabbit vascular smooth muscle.
1. The effects of the addition of Ca2+ on ouabain-resistant 22Na+ efflux from Na+-loaded strips of rabbit portal anterior mesenteric vein in Ca2+-free media have been studied. 2. Na+ efflux into Li+ media containing 5 mM-KCl is rapidly and transiently stimulated some 4- to 5-fold on the addition of Ca2+ (1.2 mM). No stimulation is observed if the Li+ medium is K+ free or if Na+ replaces Li+ ions. This Ca2+-activated Na+ efflux is not obligatorily coupled to Na+ influx. 3. The stimulation of Na+ efflux could also be triggered by the addition of 5 mM-K+ to a Ca2+-containing K+-free medium. The Ca2+-activated increase in Na+ efflux also occurred when K+ was the sole monovalent extracellular cation. Rb+ could substitute for the K+ requirement. Thus the Na+ efflux is not mediated by a system which has a specific requirement for counter-transport of Li+ or one in which Li+ but not K+ are counter-transported such as the familiar Na+-H+ exchange system. Acidification of the external medium reduced the Ca2+-stimulated Na+ efflux, in keeping with the conclusion that this efflux was not due to Na+-H+ exchange. 4. Progressive reduction of external [Ca2+] increased the time-lag to peak activation of Na+ efflux, suggesting that the effects of added Ca2+ were mediated by a rise in intracellular Ca2+. Under experimental conditions which did not result in activation of the Na+ efflux by the addition of extracellular Ca2+ alone (e.g. in Na+ media), addition of Ca2+ plus the Ca2+ ionophore, ionomycin, stimulated Na+ efflux. This further confirms that intracellular sites for Ca2+ are critical for the activation of Na+ efflux. In the absence of ionophore, in Na+ media, intracellular Ca2+ is not sufficiently increased when extracellular Ca2+ is added. A partial (40%) block of Ca2+-activated Na+ efflux by amiloride (2 X 10(-3) M) could also be overcome by the addition of ionomycin. 5. The lack of effect of a variety of inhibitors suggests that the Ca2+-stimulated Na+ efflux mechanism is not mediated via a Na+-K+-Cl- co-transport system or a Na+-H+ counter-transport system, or Na+-Ca2+ exchange. 6. The activation of Na+ efflux in smooth muscle by Ca2+ ions seems to involve Ca2+ entry partially via an extracellular Ca2+-intracellular Na+ exchange and also through other parallel pathway(s), followed by a rise in intracellular Ca2+ that activates Na+ efflux through a Ca2+-sensitive Na+ channel or other transport pathway.


How Best to Manage the Spinal Epidural Abscess? A Current Systematic Review.
A spinal epidural abscess is a medical emergency. Despite urgent surgical intervention and adjuvant antibiotic therapy, neurologic prognosis remains variable and guarded. The optimal approach to managing this condition is debated with substantial variability in clinical practice, dependent on patient demographic and pretreatment neurologic status as well as radiologic appearance. A systematic search in MEDLINE and similar databases was conducted for literature published from 1990 to 2015 using the search term "spinal epidural abscess", limiting the search results to human studies published in the English language. Case series that consisted of fewer than 10 patients were excluded. The evidence strength was graded according to the Grades of Recommendation Assessment, Development, and Evaluation criteria. The search yielded 1843 patients from 34 retrospective case series. Ten studies compared surgical and medical management, with no significant difference in patients with good outcome (odds ratio, 0.65; P = 0.11) or neurologic improvement (odds ratio, 1.11; P = 0.69). However, failure rates after initial medical management requiring surgical intervention ranged from 10% to 50%. Three of 4 studies evaluating timing of surgery reported large effect sizes for neurologic outcome if early surgery was performed (P < 0.01). Other prognostic factors from a neurologic perspective included admission neurologic status, patient age, and diabetes mellitus. Surgery with adjuvant antibiotics remains the optimal treatment for the neurologically symptomatic patient with spinal epidural abscess. If antibiotic therapy alone is considered for the neurologically intact patient, we recommend interdisciplinary medical and surgical consultations with an in-depth dialogue on the potential for failure in isolated medical management and the recommendation for close neurologic monitoring.


Relation between the probability density and other properties of a stationary random process.
We consider the Pope-Ching differential equation [Phys. Fluids A 5, 1529 (1993)] connecting the probability density p(x)(x) of a stationary, homogeneous stochastic process x(t) and the conditional moments of its squared velocity and acceleration. We show that the solution of the Pope-Ching equation can be expressed as n(x)</v(x)/(-1)>, where n(x) is the mean number of crossings of the x level per unit time and </v(x)/(-1)> is the mean inverse velocity of crossing. This result shows that the probability density at x is fully determined by a one-point measurement of crossing velocities, and does not imply knowledge of the x(t) behavior outside of the infinitesimally narrow window near x.


Reference Values for Pulmonary Single-Breath Diffusing Capacity - Results of the "Study of Health in Pomerania".
The assessment of pulmonary single-breath diffusing capacity is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance examinations of pulmonary diseases.The aim of this study was to establish reference equations for pulmonary single-breath diffusing capacity parameters in a representative adult-population across a wide age range and to compare the normative values from this sample with previous ones. Diffusing capacity measurement was carried out in 3566 participants (1811 males) of a cross-sectional, population-based survey ("Study of Health in Pomerania - SHIP"). Individuals with cardiopulmonary disorders and current smoking habits were excluded, resulting in 1786 healthy individuals (923 males), aged 20 - 84 years. Prediction equations for both sexes were established by quantile regression analyses, taking into consideration the influence of age, height, weight and former smoking. The study provides a novel set of prediction equations for pulmonary single-breath diffusing capacity in an adult Caucasian population. The results are comparable to previously reported equations, underline their importance and draw attention to the need for up-to-date reference equations that adequately take into account both the subjects' origin, age, anthropometric characteristics and the equipment used.


Comparative analyses of sheep and human TRG joining regions: evolution of J genes in Bovidae is driven by sequence conservation in their promoters for germline transcription.
The availability of genomic clones representative of the T cell receptor gamma (TRG1@ and TRG2@) ovine loci enabled us to compare the germline genomic organization and nucleotide diversity of joining (J) segments and reconstruct their evolutionary history by phylogenetic analysis of cattle, sheep and human expressed sequences. Expression profiling (RT-PCR data) in fetus and adult indicated that only the ovine J genes in which two or more of the key sequence features, such as recombination signal sequences (RSS), 3' splice sites, and core sequences, are missing or severely altered fail to be transcribed. Comparative genomic examination of the two human with the six sheep germline transcription promoters located at 5' of the relevant constant (C)-distal J segments showed a strong conservation of the redundant STAT consensus motifs, indicating that TRG1@ and TRG2@ loci are under the influence of IL-7 and STAT signalling. These findings support the phylogenetic analysis of human and Bovidae (cattle and sheep) that revealed a different grouping pattern of C-distal compared to C-proximal J segments. Likewise, the phylogenetic behaviour of either C-distal and C-proximal J segments is in accordance with the Bovidae TRG clusters evolution. Comparison of sheep and human structures of recombination signal sequences (RSS) has highlighted a greater conservation in sheep 12 RSS rather than 23 RSS thus suggesting that the initial recruitment of recombination activating genes (RAG) products requires at least one relatively high-affinity RSS per recombination event.


METIS: multiple extraction techniques for informative sentences.
METIS is a web-based integrated annotation tool. From single query sequences, the PRECIS component allows users to generate structured protein family reports from sets of related Swiss-Prot entries. These reports may then be augmented with pertinent sentences extracted from online biomedical literature via support vector machine and rule-based sentence classification systems. http://umber.sbs.man.ac.uk/dbbrowser/metis/


Association of ACK1, TFRC polymorphism with diarrhoeagenic E. coli adhesion patterns and their jejunal expression profile in Indian Ghurrah pigs.
A total of 9 SNPs located in TFRC and ACK1 genes of SSC13q41 genomic region were examined for their association with the adhesion pattern of native Indian pigs using local isolate of diarrhoeagenic E. coli. Phenotypic evaluation of adhesion pattern of 150 pigs revealed 116 animals positive for adhesion, whereas 34 animals had non-adhesive phenotype. Among the adhesive animals, 6, 87 and 23 pigs were strongly adhesive, weakly adhesive and adhesive, respectively. PCR-RFLP study revealed 8 polymorphic SNPs with low to moderate PIC ranging from 7.39 to 37.25% and low to high heterozygosities (8-70%). The loci g.291 C > T, rs81218930 C > T, rs318751568 C > T of TFRC and g.93222 C > A g.94600 C > T of ACK1 showed significant departure from HWE. The genotypic frequencies of the SNPs as well as the haplotypes did not differ significantly (P > 0.05) across the adhesion patterns except one SNP (ACK1-g.107371 A > C). Among the g.107371 A > C genotypes observed, CA was associated with non-adhesive phenotype. Furthermore, TFRC mRNA expression levels were found to be significantly (P < 0.05) different among various adhesive phenotypes, whereas that of ACK1 was significantly (P < 0.05) different between non-adhesive and adhesive groups. The significant association of SNP (ACK1-g.107371 A > C), which was also previously reported to influence ETECF4 mediated diarrhoea susceptibility, implicates its wider application in genetic control of piglet diarrhoea. Furthermore, the up-regulation of TFRC gene expression in adhesive group supports its proposed role in activation of immune cells against E. coli and intracellular iron transport.


Quantitative measurement of human cytokine gene expression by polymerase chain reaction.
We have developed a method in which human cytokine gene expression can be quantitated using gene amplification technology. Total RNA was extracted from a human T cell line, reverse transcribed to cDNA, and amplified using the polymerase chain reaction (PCR). Inclusion of a radiolabeled nucleotide in the PCR reaction mixture followed by electrophoresis and quantitative imaging of the amplification product with the BetaScope imager and software enabled quantitation of the input cDNA. Linear standard curves within the exponential phase of DNA amplification using purified cytokine cDNA templates were generated over a several log concentration range of input DNA. A 10-67-fold increase in interleukin-2 (IL-2), IL-3, IL-4, IL-10, and interferon-gamma gene expression following cell activation could be identified by interpolation from the standard curve. The lower limit of linearity on the standard curve was as little as 0.01 fg of input DNA which corresponded to approximately 20 cells. This very sensitive methodology is a valuable tool in the detection and quantitation of cytokine gene expression when only small amounts of tissue or cells are available.


Dynamics of interconversion of enantiomers in chiral separation systems: a novel approach for determination of all rate constants involved in the interconversion.
When enantiomers separated by chromatography or capillary electrophoresis undergo interconversion reaction (enantiomerization) during the separation, it leads to a typical detection pattern: two individual peaks of the separated enantiomers are connected with a plateau consisting of a mixture of both separated enantiomers. We propose a separation method for determination of all individual rate constants (or inversion barriers) of the interconversion. The method enables to distinguish which part of interconversion takes place in the free (unbound) form of the analyte and which part in the complexed (bound) form. Further, we propose a complete dynamic model of capillary electrophoresis of interconverting enantiomers based on solving a complete set of continuity equations for all constituents of the separation system together with complexation and acid-base equilibria. This allows a simulation of both linear and nonlinear mode of separation and understanding all processes taking place in such enantioseparation systems. We demonstrate the applicability of the method on determination of the rate constants of interconversion of oxazepam enantiomers separated in systems with charged cyclodextrin chiral selectors.


Zinc induces caspase-dependent mitochondrial pathway of the programmed cell death in haemocytes of Drosophila melanogaster.
Zinc is an essential trace element in cells. However, its high level in cytoplasm promotes activation of stress signaling pathways and may lead to cell death. In the present study we used Drosophila melanogaster blood cells (haemocytes), obtained from the third instar larvae, to study the effects of high concentrations of Zn(2+) on programmed cell death (PCD). We analyzed the activity of caspases, the level of caspase inhibitor protein DIAP1 and metallothioneins, as well as calcium concentrations and activity of mitochondria in haemocytes exposed to 0.35 and 1.7 mM concentrations of Zn. The obtained results showed that rapid increase of [Zn(2+)]( i ) in the cytoplasm up-regulates metallothionein MtnB but not MtnA gene expression in cells treated with Zn(2+) in both concentrations. Excess of Zn(2+) also induced activation of the initiator caspase Dronc, associated with the mitochondrial pathway of PCD, and the effector caspase DrICE. In turn, the activity of receptor-regulated Dredd caspase was not changed. The level of DIAP1 decreased significantly in haemocytes in the presence of high Zn(2+) concentration in comparison to untreated cells. Moreover, mitochondrial membrane potential was significantly decreased after exposure to Zn ions. These results indicate that high concentration of Zn(2+) in the cytoplasm of haemocytes induces PCD via a mitochondrial pathway and that caspases play a pivotal role in this process.


Effect of acylation on the interaction of the N-Terminal segment of pulmonary surfactant protein SP-C with phospholipid membranes.
SP-C, the smallest pulmonary surfactant protein, is required for the formation and stability of surface-active films at the air-liquid interface in the lung. The protein consists of a hydrophobic transmembrane alpha-helix and a cationic N-terminal segment containing palmitoylated cysteines. Recent evidence suggests that the N-terminal segment is of critical importance for SP-C function. In the present work, the role of palmitoylation in modulating the lipid-protein interactions of the N-terminal segment of SP-C has been studied by analyzing the effect of palmitoylated and non-palmitoylated synthetic peptides designed to mimic the N-terminal segment on the dynamic properties of phospholipid bilayers, recorded by spin-label electron spin resonance (ESR) spectroscopy. Both palmitoylated and non-palmitoylated peptides decrease the mobility of phosphatidylcholine (5-PCSL) and phosphatidylglycerol (5-PGSL) spin probes in dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG) bilayers. In zwitterionic DPPC membranes, both peptides have a greater effect at temperatures below than above the main gel-to-liquid-crystalline phase transition, the palmitoylated peptide inducing greater immobilisation of the lipid than does the non-palmitoylated form. In anionic DPPG membranes, both palmitoylated and non-palmitoylated peptides have similar immobilizing effects, probably dominated by electrostatic interactions. Both palmitoylated and non-palmitoylated peptides have effects comparable to whole native SP-C, as regards improving the gel phase solubility of phospholipid spin probes and increasing the polarity of the bilayer surface monitored by pK shifts of fatty acid spin probes. This indicates that a significant part of the perturbing properties of SP-C in phospholipid bilayers is mediated by interactions of the N-terminal segment. The effect of SP-C N-terminal peptides on the chain flexibility gradient of DPPC and DPPG bilayers is consistent with the existence of a peptide-promoted interdigitated phase at temperatures below the main gel-to-liquid-crystalline phase transition. The palmitoylated peptide, but not the non-palmitoylated version, is able to stably segregate interdigitated and non-interdigitated populations of phospholipids in DPPC bilayers. This feature suggests that the palmitoylated N-terminal segment stabilizes ordered domains such as those containing interdigitated lipids. We propose that palmitoylation may be important to promote and facilitate association of SP-C and SP-C-containing membranes with ordered lipid structures such as those potentially existing in highly compressed states of the interfacial surfactant film.


An angiographic study of brain swelling in cerebral infarction.
In order to assess the characteristics of brain swelling due to infarction, 322 angiograms in patients with cerebral infarction have been reviewed. The rate of incidence of swelling related to time from onset, sequential angiographic changes, and factors contributing to the phenomenon are presented. Some clinical and differential diagnostic aspects are discussed.


Histopathological changes in leiomyomata treated with leuprolide acetate.
Several studies have shown a decrease in uterine and/or leiomyoma volume when treated with leuprolide acetate (LA), a widely used gonadotropin-releasing hormone agonist. The mechanism by which these changes occur is unknown. In this study, the histopathological slides of 31 women of reproductive age who underwent hysterectomy or myomectomy were blindly reviewed by a pathologist. Seventeen women underwent myomectomy. Among those, 10 were treated with LA. The tumors in all of these patients were reduced in size after therapy. Histopathologically, the LA treatment correlated with a significant reduction in cellularity. No significant change in fibrosis, edema, or mitotic activity was seen.


How 'hidden' reading frames are expressed.
Secondary reading frames, 'hidden' under other reading frames, are used for coordinated expression of proteins in several eukaryotic viruses. In some genes, ribosomal frameshifting and initiation or reinitiation of protein synthesis on internal AUG codons are translational mechanisms allowing access to such 'hidden' reading frames. In others, secondary reading frames are translated from alternatively spliced or edited mRNAs.


Bilateral anterior opercular syndrome: localizing value of SPECT and MRI.
Bilateral anterior opercular syndrome is clinically characterized by facio-pharyngo-glossomasticatory diplegia due to bilateral opercular lesions. Reported cases of the syndrome have been relatively rare probably because of difficulty in determining opercular damage on clinical symptoms alone. We report a case of this syndrome in whom bilateral opercular damage could be detected not by CT, but suggested by SPECT, and confirmed by MR imaging.


Adiposity and the menopausal transition.
This review summarizes the published literature on the potentially circular relationship between adiposity and the menopause. Although data are limited, current information suggests there are substantial effects of obesity and adiposity on the magnitude of hormone changes experienced during the transition, as well as on the risks of chronic disease resulting from the menopause transition. However, evidence regarding the reverse, namely, effects of the menopause transition and its associated hormone changes on weight gain and redistribution of body fat, are inconclusive.


Are both necessity and opportunity the mothers of innovations?
Baumard's perspective asserts that "opportunity is the mother of innovation," in contrast to the adage ascribing this role to necessity. Drawing on behavioral ecology and cognition, we propose that both extremes - affluence and scarcity - can drive innovation. We suggest that the types of innovations at these two extremes differ and that both rely on mechanisms operating on different time scales.


Percussion pacing in a three-year-old girl with complete heart block during cardiac catheterization.
Complete heart block frequently requires emergency pacing to restore systemic perfusion. We report the case of a 3-yr-old girl undergoing interventional atrial septal defect closure who suffered from transient complete heart block with circulatory arrest. Transthoracic mechanical pacing for more than 3 min provided temporary support, sustaining an adequate cardiac output until sinus rhythm resumed.


Development of prototype bandage lapper for constant tension bandaging required for effective medical-clinical treatments.
Application of the bandaging materials is a skilled task and required considerable practice to perform it correctly. The variation in bandaging pressure is introduced due to different tensions applied by different persons during lapping. So, a handy mechanical bandage lapper is developed. This helps in keeping lapping tension uniform and adjustable irrespective of the bandager. Its proficiency is checked by bandaging two persons with different fore-arm circumferential measures. Bandaging is done at three different limb positions with and without the use of bandage lapper up to three layers by the same bandager. Three different lapping tensions viz; 0.40 kgf, 0.45 kgf and 0.50 kgf are set up for bandage lapper to study their impact on bandage pressure. Pneumatic bandage pressure mapper is developed for the measurement of bandage pressure. Seven trials separated by different time intervals are conducted for each variable. This has prevented record of consistency of bandage pressure measure by chance. Crepe bandage, normally employed for the management of Oedema in clinical treatment is used throughout the study. Higher coefficient of variations up to 15% in pressure values are found when bandaging done without the lapper. However, identical pressure, coefficient of variation less than 0.3% for all except 0.8% for bandaging done at 0.45 kgf for second person at position 1, is mapped when bandaging done with the lapper by the same bandager.


Learning top-down gain control of feature selectivity in a recurrent network model of a visual cortical area.
We propose that the effects of attentional top-down modulations observed in the visual cortex reflect the simple strategy of strengthening currently relevant pathways in a task-dependent manner. To exemplify this idea, we set up a network model of a visual area and simulate the learning of a context-dependent 'go/no-go'-task. The model learns top-down gain-modulations of sensory representations based on reinforcements received from the environment. We also discuss how this idea relates to alternative interpretations like optimal coding hypotheses.


Efficacy and cost-effectiveness analysis of pretreatment percutaneous endoscopic gastrostomy in unresectable locally advanced esophageal cancer patients treated with concurrent chemoradiotherapy (GASTO 1059).
We launched a single-arm phase II study to determine the efficacy and cost-effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco-regional objective response rate (ORR), loco-regional progression-free survival (LRFS), overall survival (OS), and toxicities. A 3-state Markov model was applied for cost-effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). Sixty-three eligible patients received pretreatment PEG-based CCRT. The mean change of weight during CCRT was -1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco-regional ORR and 1-year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco-regional ORR (p = 0.036) and longer 1-year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost-effectiveness ratio of $3457.65 per quality-adjusted life-years (QALY) compared with the ONS group with a probability of cost-effectiveness of 77.7% at the $10,000 per QALY willingness-to-pay threshold. Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost-effective because of its significant clinical benefits.


Exploring the mechanism of the PTP1B inhibitors by molecular dynamics and experimental study.
Protein tyrosine phosphatase 1B (PTP1B) has proven to be an attractive target for the treatment of cancer, diabetes and other diseases. Although many PTP1B inhibitors with various scaffolds have been developed, there is still a lack of PTP1B inhibitor with high specificity and acceptable pharmacological properties. Therefore, it is urgent to develop more methods to explore complex action mode of PTP1B and ligands for designing ideal PTP1B modulators. In this work, we developed a potential molecular dynamics (MD) analytic mode to analyze the mechanism of active compounds 6a and 6e against PTP1B from different perspectives, including the stable ability, interactions and binding site of ligand and protein, the binding energy, relative movement between residues and changes in protein internal interactions. The simulated results demonstrated that compound 6a bound more stably to the active pocket of PTP1B than 6e due to its smaller molecular volume (326 Å3), matched electronegativity, and enhanced the positive correlation motion of residues, especially for WPD loop and P loop. Lastly, compound 6a as a competitive inhibitor for PTP1B was verified by enzyme kinetic assay. This work successfully studied the mechanism of compound 6a against PTP1B from various aspects, enriched the analysis of interaction mode between PTP1B and inhibitors. In summary, we hope that this work could provide more theoretical information for designing and developing more novel and ideal PTP1B inhibitors in the future.


Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model.
The balance between thrombosis and hemostasis is a difficult issue during extracorporeal membrane oxygenation (ECMO) support. The pathogenesis leading to thrombotic complications during ECMO support is not well understood. Neutrophil extracellular traps (NETs) were reported to participate in thrombosis and have a key role in inflammation. This study aimed to explore the role of NETs in thrombosis during ECMO support and investigate NETs as a predictive biomarker for thrombotic complications during ECMO assistance. Ten ovine models of ECMO support were established. Animals were then randomly divided into 2 groups (5 sheep/group): venoarterial (VA) ECMO group and venovenous (VV) ECMO group. The venous blood samples were collected at different time points. Markers of NETs were detected in plasma, neutrophils, and thrombi from the vessels and membrane. Moreover, circulating NETs levels in 8 adults treated in the intensive care unit (ICU) who received VA-ECMO and 8 healthy controls were detected; patient survival was also recorded. In vivo study showed that neutrophils and NETs markers (dsDNA and citH3) levels were significantly elevated 6 h after ECMO compared to baseline. Isolated neutrophils from fresh blood at 6 h could release more NETs. dsDNA and citH3 levels were significantly higher in the VA mode than in the VV mode. NETs were found in thrombi from the vessel and membrane. Clinical data further revealed that dsDNA, citH3, and nucleosomes were higher in patients who received ECMO than in healthy controls. These data suggest NETs might be associated with thrombus during ECMO support, especially in the VA mode. These findings provide new insight into preventing thrombotic complications by targeting NETs. Also, NETs may potentially become an early warning biomarker for thrombosis under ECMO assistance.


Downregulated expression of ADAM9 in anterior polar cataracts.
To determine whether ADAM (a disintegrin and metalloproteinase) is regulated in lens epithelial cells (LECs) of patients with anterior polar cataracts and by transforming growth factor (TGF)-beta 1 in cultured LECs. Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea. Lens epithelial cells attached to the anterior capsules of human cataractous lenses with nuclear and anterior subcapsular cataracts and noncataractous lenses were analyzed by reverse transcribed-polymerase chain reaction for the expression of ADAMs. The effect of TGF-beta 1 on ADAM gene expression was also tested in mouse lens epithelial explants and cultured LEC lines (alpha TN-4 and HLE B-3). Significantly reduced expression of mRNA for ADAM9 was observed in LECs from patients with anterior polar cataracts. The expression of mRNA for ADAM9 was downregulated by TGF-beta 1 in cultured human LECs. Treatment of cultured mouse LECs with TGF-beta 1 led to a reduction in ADAM1 mRNA. ADAMs are expressed and regulated in LECs. The downregulated expression of ADAM9 may serve as a marker for anterior polar cataracts in addition to previously known proteins, fibronectin, alpha-SMA, and beta ig-h3. The functions of this protein in lens pathology require further investigation.


Streptomyces strains producing mitochondriotoxic antimycin A found in cereal grains.
Reasons for mammalian cell toxicity observed in barley and spring wheat grains were sought. Streptomyces sp. isolates from wheat and barley produced heat-stable methanol-soluble substances which inhibited the motility of exposed porcine spermatozoa used as a toxicity indicator. Several barley isolates produced antimycin A (2 to 5 ng/mg wet wt of biomass), a macrolide antibiotic known to block oxygen utilization in mitochondria. The antimycin-producing isolates were members of the Streptomyces albidoflavus group. In in vitro assays with porcine kidney tubular epithelial cells, the specific toxicity of antimycin A towards mitochondria was higher than that of the mycotoxin enniatin B but lower than that of the mitochondriotoxins cereulide and paenilide, produced by food-related Bacillus cereus and Paenibacillus tundrae, respectively. The toxic wheat isolates, related to Streptomyces sedi, did not produce antimycin A and or any other known toxin. Our results suggest that the presence of toxin-producing streptomycetes in stored cereal grains may pose a thus far unrecognized threat for food and feed safety.


Associations of solar activity and related exposures with fetal growth.
Solar and geomagnetic activity have been shown to suppress melatonin and to degrade folate levels, important hormones for fetal development. We examined whether solar and geomagnetic activity were associated with fetal growth. We included 9573 singleton births with 26,879 routine ultrasounds at an academic medical center in Eastern Massachusetts from 2011 through 2016. Sunspot number and Kp index were obtained from the NASA Goddard Space Flight Center. Three exposure windows were considered, including the first 16 weeks of pregnancy, one month prior to fetal growth measurement, and conception until fetal growth measurement (cumulative). Ultrasound scans from which we extracted biparietal diameter, head circumference, femur length, and abdominal circumference measurements were categorized as anatomic (<24 weeks' gestation) or growth scans (≥24 weeks' gestation) based on clinical practice. Ultrasound parameters and birth weight were standardized, and linear mixed models adjusted for long-term trends were fitted. Prenatal exposures were positively associated with larger head parameters measured <24 weeks' gestation, negatively associated with smaller fetal parameters measured ≥24 weeks' gestation, and not associated with birth weight. The strongest associations were observed for cumulative exposure in growth scans, where an interquartile range increase in sunspot number (32.87 sunspots) was associated with a -0.17 (95 % CI: -0.26, -0.08), -0.25 (-0.36, -0.15), and -0.13 (95 % CI: -0.23, -0.03) difference in mean biparietal diameter, head circumference, and femur length z-score, respectively. An interquartile range increase in cumulative Kp index (0.49) was associated with a -0.11 (95 % CI: -0.22, -0.01) and -0.11 (95 % CI: -0.20, -0.02) difference in mean head circumference and abdominal circumference z-score, respectively, in growth scans. Solar and geomagnetic activity were associated with fetal growth. Future studies are needed to better understand the impact of these natural phenomena on clinical endpoints.


Lack of association between psoriasis vulgaris and red cell acid phosphatase polymorphism.
Polymorphism of red cell acid phosphatase (ACP-1; E.C. 22.214.171.124.) has been studied using the Cellogel technique of Martin et al. (1975) in 102 patients with psoriasis and 102 healthy controls. In contrast to two previous reports, no anomalies in distribution of phenotypes were found in patients or in controls.


Irreversible global DNA hypomethylation as a key step in hepatocarcinogenesis induced by dietary methyl deficiency.
Dietary methyl group deprivation is now well recognized as a model of hepatocarcinogenesis in rodents. In the present study, we examined the effects of feeding a methyl-deficient diet followed by a methyl-adequate diet on the extent of methylation of liver DNA and on the formation and evolution of altered hepatic foci. Male F344 rats were fed a methyl-deficient diet for 9, 18, 24, and 36 weeks, followed by re-feeding a methyl-adequate diet for a total of 54 weeks. Similar to previous findings, the methyl-deficient diet resulted in decreased levels of S-adenosylmethionine (SAM), SAM/SAH ratios, and global DNA hypomethylation. Feeding the methyl-adequate diet restored the liver SAM levels and SAM/SAH ratios to control levels in all experimental groups. In contrast, re-feeding the complete diet restored DNA methylation to normal level only in the group that had been fed the methyl-deficient diet for 9 weeks; in animals exposed to methyl deprivation longer, the methyl-adequate diet failed to reverse the hypomethylation of DNA. Liver tissue of rats exposed to methyl deficiency for 9, 18, 24, or 36 weeks was characterized by the persistent presence of placental isoform of glutathione-S-transferase (GSTpi)-positive lesions despite re-feeding the methyl-adequate diet. The persistence of altered hepatic foci in liver after withdrawal of methyl-deficient diet serves as an indication of the carcinogenic potential of a methyl-deficient diet. Substitution of the methyl-deficient diet with complete diet failed to prevent the expansion of initiated foci and restore DNA methylation in animals exposed to deficiency for 18, 24, or 36 weeks. The association between DNA hypomethylation and expansion of foci suggests that stable DNA hypomethylation is a promoting factor for clonal expansion of initiated cells. These results provide an experimental evidence and a mechanistic basis by which epigenetic alterations may contribute to the initiation and promotion steps of carcinogenesis.


The in vitro passive elastic response of chicken pectoralis muscle to applied tensile and compressive deformation.
The mechanics of passive skeletal muscle are important in impact biomechanics, surgical simulation, and rehabilitation engineering. Existing data from porcine tissue has shown a significant tension/compression asymmetry, which is not captured by current constitutive modelling approaches using a single set of material parameters, and an adequate explanation for this effect remains elusive. In this paper, the passive elastic deformation properties of chicken pectoralis muscle are assessed for the first time, to provide deformation data on a skeletal muscle which is very different to porcine tissue. Uniaxial, quasi-static compression and tensile tests were performed on fresh chicken pectoralis muscle in the fibre and cross-fibre directions, and at 45° to the fibre direction. Results show that chicken muscle elastic behaviour is nonlinear and anisotropic. The tensile stress-stretch response is two orders of magnitude larger than in compression for all directions tested, which reflects the tension/compression asymmetry previously observed in porcine tissue. In compression the tissue is stiffest in the cross-fibre direction. However, tensile deformation applied at 45° gives the stiffest response, and this is different to previous findings relating to porcine tissue. Chicken muscle tissue is most compliant in the fibre direction for both tensile and compressive applied deformation. Generally, a small percentage of fluid exudation was observed in the compressive samples. In the future these data will be combined with microstructural analysis to assess the architectural basis for the tension/compression asymmetry now observed in two different species of skeletal muscle.


Joint associations of social health and movement behaviours with mortality and cardiovascular disease: an analysis of 497,544 UK biobank participants.
Poor physical activity and excessive sedentary behaviour are well-established risk factors for morbidity and mortality. In the presence of emerging social problems, including loneliness and social isolation, these risks may be even greater. We aimed to investigate the joint effects of social health and movement behaviours on mortality and cardiovascular disease (CVD). 497,544 UK Biobank participants were followed for an average of 11 years. Loneliness and social isolation were measured via self-report. Physical activity was categorised around current World Health Organisation (WHO) guidelines as low (< 600 metabolic equivalent of task [MET]-mins/week), moderate (600 < 1200) and high (≥ 1200). Sedentary behaviour was classified as low (≤ 3.5 h/day), moderate (3.5 ≤ 5) and high (> 5.5). We derived 24 social health-movement behaviour combinations, accordingly. Mortality and hospitalisations were ascertained to May 2020 for all-cause and CVD mortality, and non-fatal cardiovascular events. Social isolation amplified the risk of both all-cause and CVD death across all physical activity and sedentary levels (hazard ratio, 95% confidence interval [HR, 95% CIs] for all-cause mortality; 1.58 [1.49 to 1.68] for low active-isolated vs. 1.26 [1.22 to 1.30] for low active-not isolated). Loneliness was only found to amplify the risk of death from cardiovascular disease among the high active and low sedentary participants. Loneliness and social isolation did not add to the risk of non-fatal cardiovascular events across most activity levels. The detrimental associations of poor physical activity and sedentary behaviour with mortality were consistently amplified by social isolation. Our study supports the need to target the socially isolated as a priority group in preventive public health strategies.


Relationship between NF-κB1 -94 ins/del ATTG polymorphism and susceptibility of multiple sclerosis in Iranian MS patients.
Multiple sclerosis (MS) is one of the most common neurological diseases of the central nervous system (CNS) which is mediated by the autoimmune reactions against myelin sheath. Both genetic and environmental factors are thought to be involved in the pathogenesis of MS. NF-κB1 is one of the most important molecules which regulates the immune functions. NF-κB1 -94 ins/del ATTG promoter polymorphism is a well-studied region in NF-κB1 gene associated with several common autoimmune diseases such as systemic lupus erythematosus (SLE). Our hypothesis was aimed to address the potential association of NF-κB polymorphism and MS. Therefore, we analyzed 200 sex and age matched MS patients along with 200 healthy individuals using PCR-RFLP. The data revealed no significant differences in the frequency of the -94 ins/del ATTG polymorphism in multiple sclerosis patients compared with the control group. To conclude, our study showed no association between -94 ins/del ATTG polymorphism and risk of multiple sclerosis in Iranian patients.


Long-term (56-week) oral administration of probiotic Enterococcus faecium M-74 decreases the expression of sICAM-1 and monocyte CD54, and increases that of lymphocyte CD49d in humans.
To study the effects of long-term probiotic [Enterococcus faecium (EF) M-74 strain] application in humans with respect to adhesion molecules, both soluble forms (sICAM-1, sPECAM-1) and their expression on leukocytes. Double-blinded randomized and placebo controlled study lasting for 60 weeks. A single capsule containing either 2x10(9) of bacteria EF M-74 with 50 microg of organically bound selenium (E-group) or placebo (P-group) was given to volunteers. Peripheral blood was analyzed for the expression of particular adhesive molecules. We observed significant changes in CAMs expression in terms of a decrease in sICAM-1, CD54 on monocytes and CD11b on lymphocytes after one-year administration of Enterococcus faecium M-74 in humans. Anti-adhesion-aimed therapeutic modalities may provide the future approach to prevention and treatment of cardiovascular diseases. Application of probiotics may be part of such strategies. (Tab. 2, Fig. 6, Ref. 41.)


Reported pica behavior in a sample of incident dialysis patients.
In a prospective study, pica behavior was investigated during baseline interviews with a cohort of incident patients (n = 226) who began chronic dialysis therapy in metropolitan Atlanta, GA, during 1996 to 1997. Pica, defined as current pica behavior and/or reported history of pica behavior, was reported by 16% of the sample. Patients reporting pica were significantly more likely to be African American women and were significantly younger than the remainder of the sample. Approximately two thirds of patients who reported pica behaviors craved and excessively consumed ice; the remainder craved and consumed starch, dirt, flour, or aspirin. Among patients reporting pica, average serum albumin values were low and average phosphorus was increased. The average hematocrit of patients reporting ice pica was low. Over half of the hemodialysis patients reporting pica behavior had excessive usual interdialytic weight gain. Potential symptoms/problems affecting quality of life among patients practicing pica, eg, cramps, are shown in a case report. The data indicate the need for targeted education and support for dietitians' increased interaction with dialysis patients involved in pica behaviors.


Structural and functional salvaging of eyes with anterior staphyloma using cyclodialysis with penetrating keratoplasty.
To evaluate the efficacy of a novel technique of anterior segment reconstruction and cyclodialysis in patients with anterior staphyloma. A prospective case series of 8 consecutive patients who underwent anterior segment restoration with penetrating keratoplasty and cyclodialysis was analyzed. The main parameters evaluated were structural success of the graft, improvement in visual acuity, and intraocular pressure. The globe could be salvaged in all the cases, and 75% (6 of 8) of the cases had clear graft at 6-month follow-up. Best-corrected visual acuity (BCVA) ranged from hand motion close to face to 6/12. None of the patients developed glaucoma during the follow-up period. Intraoperative creation of a cyclodialysis cleft can aid in adequate postoperative intraocular pressure (IOP) control and hence decrease the likelihood of graft failure because of raised IOP in eyes predisposed to development of postkeratoplasty glaucoma.


Exercise capacity assessed with the one-minute sit-to-stand test (1-min STST) and echocardiographic findings in patients with heart failure with preserved ejection fraction (HFpEF).
Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Precise risk stratification remains challenging. The one-minute sit-to-stand-test (1-min STST), a quick, objective test of functional capacity may be helpful for stratification of clinical profile in HFpEF patients. The aim of this initial investigation was to prospectively examine whether the 1-min STST can be used for the evaluation of exercise capacity in HFpEF patients and whether it is in line with echocardiographic as well as quality of life (QoL) findings. 39 HFpEF patients were prospectively studied. Functional performance was examined with the 1-min STST and QoL with the CAMPHOR questionnaire. Clinical parameters including echocardiographic measurements [estimated pulmonary artery systolic pressure (ePASP), tricuspid regurgitation velocity (TRV)] were obtained. Patients were divided into two groups based on their number of 1-min STST repetitions (Group I: ≤50% of predicted 1-min STST repetitions using the norm-reference values developed by Strassmann et al. for healthy people, N=24; Group II: >50% of predicted 1-min STST repetitions, N=15). Patients in group I with limited 1-min STST performance showed worse echocardiographic parameters [higher ePASP (p=0.038), higher TRV (p=0.018) and more reduced tricuspid annular plane systolic excursion (TAPSE) (p=0.001)], worse six-minute walk test (6MWT) (p<0.001) and worse QoL (p<0.001) compared to patients in group II. Our study shows potential usefulness of the 1-min STST as an evaluative tool for exercise capacity in HFpEF patients, because patients with worse 1-min STST performance have worse clinical parameters and QoL.


Efficacy analysis and research progress of complementary and alternative medicines in the adjuvant treatment of COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan.


Interval between injury and lingual nerve repair as a prognostic factor for success using type I collagen conduit.
The purpose of the present study was to investigate the role of a type I collagen nerve conduit in the repair of lingual nerve injuries compared with those lingual nerve repairs performed without a collagen membrane and to identify the prognostic factors for functional sensory recovery (FSR). This was a retrospective cohort study evaluating a sample derived from the population of patients who had undergone lingual nerve microsurgery from March 17, 2000, to February 23, 2010 by the same surgeon (V.B.Z.) with complete records available, including follow-up assessments. The primary outcome variable was the interval to successful FSR according to the British Medical Research Council criteria for FSR. The predictor variables were categorized into demographic, surgical, and clinical sensory testing. Appropriate descriptive statistics and univariate and multivariate Cox proportional hazards survival statistics were computed in analyzing the patient age at lingual nerve injury repair (in years), gender, timing of surgical intervention, mechanism of injury, specific surgical procedures, and application of a type I collagen conduit. The study cohort included 41 patients with 42 lingual nerve injuries who underwent surgical repair. Their mean age was 28.3 ± 8.3 years (range 13 to 44), with 88% females (n = 32). In the multivariate model, the injury to surgery interval per 1-month increase (hazard ratio 1.23, 95% confidence interval 1.02 to 1.48, P = .029) and injury to surgery interval of 9 months or longer (hazard ratio 4.67, 95% confidence interval 1.04 to 20.87, P = .04) remained significantly associated statistically with successful FSR. The results of the present study have demonstrated that the injury to surgery interval is the most significant prognostic factor in the repair of lingual nerve injuries. The use of the collagen membrane demonstrated a greater level of FSR compared with those treated without the use of the membrane. However, the results from the collagen conduit were not statistically significant.


Hypothetical reasons of the HIV1-AIDS "tritherapy" failure. A challenging model.
Daily journals in France recently published a declaration of eight AIDS-assistance associations stating, because of already established resistance of most of types of HIV1 to the so called "tritherapies" 8,000 subjects in France will soon be "in condition of treatment failure". This tritherapeutic "flat note" is a double flat, for relative and absolute reasons: a) relative indeed was the case of well-known results: the tritherapies initially performed better than bitherapies, which had done better than monotherapies; b) absolute is their failure, which induce, as the other types, toxicity, resistance and relapses. Toxicity and resistance are due to the fact that, as the T1/2 of the virus is very short, virostatics must be applied continuously. But in AIDS groups tritherapies are applied not only in a continuous fashion, but in an identical form and for an undefined time, the process which is used in experimental cancer chemotherapy to induce resistant cell lines. Applying them in sequences of 3 weeks (a duration chosen with the knowledge that resistance may occur in about 12 weeks), we have shown in AIDS not only an absence of toxicity, but also an absence of resistance in patients treated with four drugs affecting four different targets. There is indeed another point to underline: AIDS group tritherapies are comprised of three drugs, but whatever the choices of these drugs they affect only two targets: retrotranscriptase and HIV1-protease. We had obtained in the best murine model of HIV1-infection (Friend's virus infection) eradication with a combination of three drugs, AZT, acriflavine (ACF) and the ellipticine analogue methyl-hydroxy-ellipticine (MHE); (the two last were discovered to be rather more efficient that AZT in our virostatic screening). This combination affects three virus targets (AZT, retrotranscriptase; MHE, topoisomerase 2; and ACF, integrated and proviral DNA). The next article will show that sequential drug combinations of three virostatics chosen from ten drugs available, affecting four targets, are more efficient in HIV1-AIDS than three drug combinations affecting three targets because they were chosen from a pool of only five drugs. It will, however, be shown that the same type of sequential combinations with four drug rotations chosen among the ten available ones affecting four targets rapidly reduced, and for years maintained, the viral load at undetectable levels. This level has been < 200 RNA copies/mL during the trial and is, at the end of the study, < 20 RNA copies/mL.


Pseudo Bartter Syndrome in anorexia nervosa.
Anorexia nervosa is a psychiatric disorder with various non-psychiatric manifestations that arise from the self-imposed malnourishment and possible purging behaviors. These medical manifestations or complications may mimic non psychiatric disorders and difficult the diagnosis of an eating disorder. We report the case of a patient with a binge-eating/purging subtype of anorexia nervosa, whose purges consisted in diuretic abuse. She kept her purges secret and during more than 1 year she was admitted several times in the emergency room for, sometimes life-threatening, hypokalemia. Furthermore, she consulted practitioners from different specialties and was hospitalized in a nephrology service to investigate chronic hypokalemia and other metabolic and hydroelectrolytic disturbances. A Bartter Syndrome was suspected, and she underwent genetic testing. Eventually she started psychiatric follow up and was admitted as an inpatient under the care of a specialized eating disorders unit. This patient presented a series of metabolic disturbances secondary to the diuretic abuse, that mimicked the manifestations of hereditary tubulopathies like Bartter Syndrome. Coincidentally it was found that the patient had a mutation in a gene linked to Bartter Syndrome, that wasn't enough to justify this diagnosis. So, a Pseudo Bartter Syndrome secondary to the diuretic abuse was evident. The focus on medical manifestations delayed the recognition of the anorexia nervosa and the associated diuretic abuse as the main cause of the electrolyte and metabolic disturbances. This case emphasizes the importance of being familiarized with the non-psychiatric manifestations of eating disorders, so they may be rapidly recognized and managed. Level V, Case Report.


Cytotoxicity and immunological responses following oral vaccination of nanoencapsulated avian influenza virus H5 DNA vaccine with green synthesis silver nanoparticles.
DNA formulations provide the basis for safe and cost effective vaccine. Low efficiency is often observed in the delivery of DNA vaccines. In order to assess a new strategy for oral DNA vaccine formulation and delivery, plasmid encoding hemagglutinin (HA) gene of avian influenza virus, A/Ck/Malaysia/5858/04 (H5N1) (pcDNA3.1/H5) was formulated using green synthesis of sliver nanoparticles (AgNP) with polyethylene glycol (PEG). AgNP were successfully synthesized uniformly dispersed with size in the range of 4 to 18 nm with an average size of 11 nm. Cytotoxicity of the prepared AgNP was investigated in vitro and in vivo using MCF-7 cells and cytokine expression, respectively. At the concentration of -5 log₁₀AgNP, no cytotoxic effects were detected in MCF-7 cells with 9.5% cell death compared to the control. One-day-old specific pathogen-free (SPF) chicks immunized once by oral gavage with 10 μl of pcDNA3.1/H5 (200 ng/ml) nanoencapsulated with 40 μl AgNP (3.7×10⁻² μg of Ag) showed no clinical manifestations. PCR successfully detect the AgNP/H5 plasmid from the duodenum of the inoculated chicken as early as 1h post-immunization. Immunization of chickens with AgNP/H5 enhanced both pro inflammatory and Th1-like expressions, although no significant differences were recorded in the chickens inoculated with AgNP, AgNP/pcDNA3.1 and the control. In addition, serum samples collected from immunized chickens with AgNP/H5 showed rapidly increasing antibody against H5 on day 14 after immunization. The highest average antibody titres were detected on day 35 post-immunization at 51.2±7.5. AgNP/H5 also elicited both CD4+ and CD8+ T cells in the immunized chickens as early as day 14 after immunization, at 7.5±2.0 and 20±1.9 percentage, respectively. Hence, single oral administrations of AgNP/H5 led to induce both the antibody and cell-mediated immune responses as well as enhanced cytokine production.


Flavonoids modulate liposomal membrane structure, regulate mitochondrial membrane permeability and prevent erythrocyte oxidative damage.
In the present work, we investigated the interaction of flavonoids (quercetin, naringenin and catechin) with cellular and artificial membranes. The flavonoids considerably inhibited membrane lipid peroxidation in rat erythrocytes treated with tert-butyl hydroperoxide (700 μM), and the IC50 values for prevention of this process were equal to 9.7 ± 0.8 μM, 8.8 ± 0.7 μM, and 37.8 ± 4.4 μM in the case of quercetin, catechin and naringenin, respectively, and slightly decreased glutathione oxidation. In isolated rat liver mitochondria, quercetin, catechin and naringenin (10-50 μM) dose-dependently increased the sensitivity to Ca2+ ions - induced mitochondrial permeability transition. Using the probes TMA-DPH and DPH we showed that quercetin rather than catechin and naringenin strongly decreased the microfluidity of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomal membrane bilayer at different depths. On the contrary, using the probe Laurdan we observed that naringenin transfer the bilayer to a more ordered state, whereas quercetin dose-dependently decreased the order of lipid molecule packing and increased hydration in the region of polar head groups. The incorporation of the flavonoids, quercetin and naringenin and not catechin, into the liposomes induced an increase in the zeta potential of the membrane and enlarged the area of the bilayer as well as lowered the temperature and the enthalpy of the membrane phase transition. The effects of the flavonoids were connected with modification of membrane fluidity, packing, stability, electrokinetic properties, size and permeability, prevention of oxidative stress, which depended on the nature of the flavonoid molecule and the nature of the membrane.


AANA journal course: update for nurse anesthetists--medical gases, hospital pipelines, and medical gas cylinders: how safe are they?
Medical gases which hospital personnel are familiar with include oxygen, nitrous oxide, medical air, carbon dioxide, and nitrogen. Their composition and packaging is defined by the Code of Federal Regulations and the United States Pharmacopeia/National Formulary. Unfortunately, numerous safety issues and even cases of death occur each year that relate to the use of these gases in medical settings. This review documents incidents of near hits and deaths of patients from pipeline and gas cylinder use and describes the key role that anesthesia and healthcare personnel play in verifying the integrity of gases used and the systems which deliver them.


Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease.
As tissue macrophages of the central nervous system (CNS), microglia constitute the pivotal immune cells of this organ. Microglial features are strongly dependent on environmental cues such as commensal microbiota. Gut bacteria are known to continuously modulate microglia maturation and function by the production of short-chain fatty acids (SCFAs). However, the precise mechanism of this crosstalk is unknown. Here we determined that the immature phenotype of microglia from germ-free (GF) mice is epigenetically imprinted by H3K4me3 and H3K9ac on metabolic genes associated with substantial functional alterations including increased mitochondrial mass and specific respiratory chain dysfunctions. We identified acetate as the essential microbiome-derived SCFA driving microglia maturation and regulating the homeostatic metabolic state, and further showed that it is able to modulate microglial phagocytosis and disease progression during neurodegeneration. These findings indicate that acetate is an essential bacteria-derived molecule driving metabolic pathways and functions of microglia during health and perturbation.


Taphonomic alterations by the rodent species woodland vole (Microtus pinetorum) upon human skeletal remains.
This forensic case report describes the taphonomic effects of woodland vole (Microtus pinetorum) upon a set of skeletonized human remains recovered in Massachusetts, USA. Remains of an individual of this rodent species were discovered where it had been nesting inside the human cranium. Fine, parallel grooves indicative of small rodent gnawing were noted on multiple postcranial elements, and all isolated grooves were consistent in size with the incisors of this species. Other taphonomic alterations to these remains include some gnawing damage and dispersal by large carnivores. This case represents the first report of this rodent species affecting human remains.


In vitro evaluation of antifilarial effect of Azadirachta indica leaves extract in different solvents on the microfilariae of Setaria cervi.
Polar solvent extracts of Azadirachta indica leaves were investigated to evaluate in vitro anthelmintic activity on the microfilariae of Setaria cervi. Four extracts of A. indica leaves were prepared with different solvents in increasing order of polarity (diethyl ether < chloroform < ethanol < methanol). Stock solution of the extract of A. indica leaves was prepared in Ringer's solution at the concentrations of 50, 100 and 200 μg/ml and used against microfilariae in three replicates. Ringer's solution was used as experimental control. Mortality rates of microfilariae were recorded for each concentration after 45, 90 and 135 min, respectively. All the solvent extracts show significant anthelmintic activity at the concentration of 200 μg/ml after 135 min of incubation. Highest mortality rate of microfilariae was observed in methanol and ethanol extracts throughout the incubation period compared to chloroform and diethyl ether extracts which showed low mortality rates. Dose dependent effect of ethanol and chloroform showed highest and lowest ranking when analyzed by regression values and correlation of regression. Solvents extracts of A. indica leaves showed anthelmintic effect and therefore may be used as phytopharmacological agents in future.


Handling obese patients takes toll on staff health.
About 1,000 NHS workers have been injured while caring for obese patients over the past five years, freedom of information data show.


Spindle cell and pleomorphic lipoma: an immunohistochemical study and histogenetic analysis.
Twenty-two spindle cell lipomas and seven pleomorphic lipomas were investigated immunohistochemically in order to study the differentiation of the non-adipocytic elements. In all cases, neither spindle cells nor pleomorphic cells reacted with antibodies to a monocyte/macrophage antigen (MAC-387), fibronectin, laminin or type IV collagen. The absence of demonstrable basement membrane material argues against the possible prelipoblastic nature of these cells. With the antibody to S-100 protein, spindle cells were immunonegative, whereas pleomorphic cells sometimes revealed an intracytoplasmic weak to moderate staining reaction. In the light of what is known about the development of adipose tissue, our results would support the hypothesis of Bolen and Thorning (Am J Surg Pathol 1981; 5: 435-441) that spindle cell lipoma is composed of adipocytes and non-fat storing immature mesenchymal cells. It would appear that pleomorphic lipoma is similarly derived but that in some cases adipocytic differentiation is also abnormal. The characteristic clinical distribution of these two types of tumour may be of relevance in determining the cause of these unusual benign patterns of differentiation.


Individual trail marking by larvae of the scarce swallowtail Iphiclides podalirius L. (Lepidoptera; Papilionidae).
Starting from permanent resting sites covered with silk, the solitary and territorial larvae of I. podalirius spin silk trails leading to feeding sites. It is shown that the silk contains a volatile trail marker. The larvae recognize their own trails and prefer them to those laid by conspecific caterpillars. Trail marking appears to be widespread among larvae of Lepidoptera.


Stimulation and inhibition of the protein synthetic process by NAD+ in lysed rabbit reticulocytes.
NAD+ at 0.16 mM stimulates the initiation step of the protein synthetic process in lysed rabbit reticulocytes. This conclusion is based on the stimulation of (i) the transfer of formylmethionine from f[35S]Met-tRNAfMet into polypeptide, (ii) the accumulation of the initial dipeptide, methionylvaline, in the presence of pactamycin, and (iii) the formation of the 40 S initiation complex. The effect of NAD+ changes from a stimulatory role on protein synthesis to an inhibitory role at concentrations greater than 0.16 mM. At 4.0 mM NAD+, protein synthesis is inhibited. This has been demonstrated experimentally by using the same three assays described above. In addition, 4.0 mM NAD+ inhibits MettRNAfMet.initiation factor.GTP ternary complex formation. The elongation and termination steps of polypeptide synthesis are not affected by 0.16 to 4.0 mM NAD+. The data presented clearly show that the stimulatory activity of 0.16 mM NAD+ and the inhibitory activity of 4.0 mM NAD+ affects the initiation step of the protein synthetic process in lysed rabbit reticulocytes.


Retroperitoneal fibrosis and schistosomiasis: a causal relationship?
Retroperitoneal fibrosis (RPF) is characterized by replacement of the normal tissue of the retroperitoneum with fibrosis and/or chronic inflammation. About two-thirds of cases of RPF are idiopathic and one-third is secondary to drugs, infections (tuberculosis, syphilis, actinomycosis, fungal infections), retroperitoneal hemorrhage, or malignancy. We report the case of a patient who was diagnosed as having RPF and schistosomiasis caused by Schistosoma haematobium with histological documentation. He was treated with praziquantel and afterwards with corticosteroids with remission of RPF. To our knowledge, the association between schistosomiasis and RPF has not been described in the literature. We postulate that there is a causal relationship between these two conditions.


[Prostacyclin inhalation in pulmonary failure following smoke inhalation].
A 42 year-old man was admitted to hospital due to smoke inhalation. Thirty-three hours after admission arterial oxygen saturation was 80-90% with FiO2 = 1.0. Inhalation with prostacyclin was commenced with a dose rate of 7 ng/kg/min with an immediate effect, i.e. SATaO2 increased to 100%. Prostacyclin was terminated after 24 hours, when FiO2 was reduced to 0.5. It is concluded that prostacyclin inhalation therapy may have effect in patients following pulmonary smoke injury.


The effects of a rust infection on fitness components in a natural population of Tolumnia variegata (Orchidaceae).
The effects of a rust infection (Sphenosphora saphena, Basidiomycetes) on several fitness components of the orchid Tolumnia (Oncidium) variegata were quantified in a subtropical moist forest of Puerto Rico. Infected and uninfected plants of two size categories were observed and manipulated by increasing natural levels of fruit production to determine the effects of infection on short and long-term sexual reproduction, subsequent vegetative and reproductive growth, and mortality. Under artificially high levels of fruit production, infection had no effect on short or long-term reproduction through male or female function except for a modest decline in seed viability in small plants. Under natural levels of fruit production, infection was only related to a reduction in the number of leaves per shoot. At artificially high levels of fruit production, infection reduced leaf length, leaf width, and the number of live shoots. Survival was not associated with rust occurrence. The rust appears to have minor ecological impact on this orchid population.


Metformin influences on respiratory system in obese mice induced by postnatal overnutrition.
Many studies have confirmed the merits of metformin to treat type 2 diabetes, but few studies have addressed its effect on the respiratory system. Moreover, vascular endothelial growth factor (VEGF) is critical to many lung functions. In this way, we evaluated the metformin impact on the lung in treated obese Swiss mice, induced by postnatal overnutrition. Glucose and insulin were detected and the insulin resistance index (HOMA) was calculated; inflammatory cells and nitrite/nitrate concentration (NOx) was quantified from bronchoalveolar lavage, collagen and lung VEGF-a was analysed in the lung tissue and lung mechanics were evaluated by methacholine-induced bronchoconstriction. Values of glucose, insulin, HOMA; VEGF-a and collagen demonstrate the partial ability of metformin to improve the effects of obesity. However, metformin is ineffective in re-establishing the inflammation, shows no effects on NOx and does not restore bronchoconstriction in obese mice. In conclusion, metformińs beneficial effects on lung are questionable in the postnatal overnutrition model of obesity.


Blockade of integrin α3 attenuates human pancreatic cancer via inhibition of EGFR signalling.
The prognosis of pancreatic cancer remains dismal despite continuous and considerable efforts. Integrins (ITGs) are highly expressed in various malignant cancers. However, very few studies investigated the role of integrin α3 (ITGα3) in malignant cancers. Here, we determined the functional role of ITGα3 in pancreatic cancer. Analysis of public microarray databases and Western blot analysis indicated a unique expression of ITGα3 in human pancreatic cancer. Silencing ITGα3 expression significantly inhibited the viability and migration of human pancreatic cancer cells. Notably, ablation of ITGα3 expression resulted in a significant decrease of epidermal growth factor receptor (EGFR) expression compared with transfection of control-siRNA through an increased number of leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) expression. In addition, ablating ITGα3 inhibited tumour growth via blockade of EGFR signalling in vivo. Furthermore, the highly expressed ITGα3 led to a poor prognosis of pancreatic cancer patients. Our results provide novel insights into ITGα3-induced aggressive pancreatic cancer.


Coated pits, coated vesicles, and receptor-mediated endocytosis.
Proteins and peptides can enter cells by receptor-mediated endocytosis, a coupled process by which selected extracellular proteins or peptides are first bound to specific cell surface receptors and then rapidly internalised by the cell. Internalisation follows clustering of the receptors in specialised regions of the cell surface called coated pits that invaginate to form intracellular coated vesicles. It is now recognised that receptor-mediated endocytosis has a fundamental role in the growth, nutrition and differentiation of animal cells.


Racism as trauma: Experiences of Aboriginal and Torres Strait Islander Australian child protection practitioners.
Aboriginal and Torres Strait Islander children are disproportionately represented in the statutory child protection system across Australia. A strategy gaining traction to address this disproportionate representation is to recruit more Indigenous practitioners into statutory child protection work. However, the experiences of Indigenous people who undertake child protection work have not been explored thoroughly, particularly in an Australian research context. While it has been established in contemporary literature that exposure to trauma is an expected occupational hazard of undertaking statutory child protection work, the experience of racism as a potential source of traumatic stress for practitioners has not been explicitly explored. This paper reports on results from a recent doctoral study which explored the experiences of Indigenous child protection practitioners based in Queensland, Australia. This research relied on the stories of participants, shared through qualitative in-depth semi-structured interviews, to answer the primary research question: what are the experiences of Indigenous child protection workers? The findings emerged from a research design that was underpinned by critical theory and decolonisation frameworks, which placed the participants as experts of their own experiences. The experiences of the research participants tell the story of a deficiency within the statutory child protection system to meet the wellbeing needs of Indigenous workers and provide a workplace environment that is culturally safe. Participants described recurrent experiences of racist behaviour displayed by non-Indigenous colleagues and a lack of support that acknowledges the distinctive experience of Indigenous people who undertake child protection work.


Demyelinating polyneuropathy associated with monoclonal IgM-paraproteinaemia. Histological, ultrastructural and immunocytochemical studies.
Histological, ultrastructural and immunocytochemical findings of sural nerve biopsies from 2 patients with monoclonal IgM-paraproteinaemia are presented. In both cases the pathological IgM antibodies reacted with a myelin antigen which was identified as myelin-associated glycoprotein (MAG) by immunoelectroblot . Histology and electron microscopy showed typical features of a chronic demyelinating neuropathy with accompanying axonal degeneration. Immunohistochemical studies demonstrated IgM in the vicinity of endoneurial vessels and on some of the myelinated fibres. The localisation of IgM on the myelin sheath showed a typical pattern, which was similar to that found in binding studies with the patients sera on control nerves. It resembled the characteristic immunocytochemical staining pattern of MAG. Binding studies with the patients' sera on human and canine CNS material exhibited a clear labelling of white matter and certain, as yet unidentified structures within the cerebral and cerebellar cortex. In mixed glial cell cultures, the sera of both patients bound specifically to oligodendrocytes. Our observations are interpreted as immunohistochemical evidence that the anti-MAG antibodies of the patients' sera had bound to their antigenic target in the peripheral nerves. Because the antibodies clearly react to central myelin, oligodendrocytes and other not yet identified cortical structures, CNS involvement in such disorders should be considered.


Invasive brown widow spiders avoid parasitism despite high densities.
Invasive species are sometimes less susceptible to natural enemies compared to native species, but the mechanism is often unclear. Here we tested two potential mechanisms for lower parasitism of invasive species: density-dependent parasitism and preference for human-dominated habitats. We investigated how variation in host density and habitat type affect egg sac parasitism in two widow spider species (family Theridiidae). We compared parasitism on the egg sac of the brown widow, Latrodectus geometricus, an urban invasive species, and the white widow, Latrodectus pallidus, a species native to Israel. To investigate variation in host and parasitoid density, we measured nearest-neighbor distance between spider webs and parasitism rates in 16 sites, and in a single site monthly throughout a year. In L. pallidus, denser sites were more heavily parasitized (up to 55%) and parasitism rate increased with population density throughout the season. Extremely dense L. geometricus populations, however, had very low rates of parasitism (0-5%). We then conducted an egg sac transplant experiment in human-dominated and natural habitats. We found no parasitism of either species in the human-dominated habitat, compared to 30% parasitism of both species in the natural habitat. In addition, we found evidence for higher predation of L. pallidus than of L. geometricus egg sacs, particularly in the natural habitat. These combined results suggest that the human-dominated habitats inhabited by L. geometricus have a lower abundance of predators and parasites. We conclude that lower parasitism and predation in human-dominated habitats could contribute to the invasion success of L. geometricus.