Adolescent RSA responses during an anger discussion task: Relations to emotion regulation and adjustment.
The current study examined associations between adolescent respiratory sinus arrhythmia (RSA) during an angry event discussion task and adolescents' emotion regulation and adjustment. Data were collected from 206 adolescents (10-18 years of age, M age = 13.37). Electrocardiogram (ECG) and respiration data were collected from adolescents, and RSA values and respiration rates were computed. Adolescents reported on their own emotion regulation, prosocial behavior, and aggressive behavior. Multilevel latent growth modeling was employed to capture RSA responses across time (i.e., linear and quadratic changes; time course approach), and adolescent emotion regulation and adjustment variables were included in the model to test their links to RSA responses. Results indicated that high RSA baseline was associated with more adolescent prosocial behavior. A pattern of initial RSA decreases (RSA suppression) in response to angry event recall and subsequent RSA increases (RSA rebound) were related to better anger and sadness regulation and more prosocial behavior. However, RSA was not significantly linked to adolescent aggressive behavior. We also compared the time course approach with the conventional linear approach and found that the time course approach provided more meaningful and rich information. The implications of adaptive RSA change patterns are discussed.


NF-kappaB involvement in the induction of high affinity CAT-2 in lipopolysaccharide-stimulated rat lungs.
Endotoxemia stimulates nitric oxide (NO) biosynthesis through induction of inducible NO synthase (iNOS). Cellular uptake of L-arginine, the sole substrate for iNOS, is an important mechanism regulating NO biosynthesis by iNOS. The isozymes of type-2 cationic amino acid transporters, including CAT-2, CAT-2A, and CAT-2B, constitute the most important pathways responsible for trans-membrane L-arginine transportation. Therefore, regulation of CAT-2 isozymes expression may constitute one of the downstream regulatory pathways that control iNOS activity. We investigated the time course of enzyme induction and the role of nuclear factor-kappaB (NF-kappaB) in CAT-2 isozymes expression in lipopolysaccharide-(LPS) treated rat lungs. Adult male Sprague-Dawley rats were randomly given intravenous injections of normal saline (N/S), LPS, LPS plus NF-kappaB inhibitor pre-treatment (PDTC, dexamethasone, or salicylate), or an NF-kappaB inhibitor alone. The rats were sacrificed at different times after injection and enzyme expression and lung injury were examined. Pulmonary and systemic NO production were also measured. LPS co-induced iNOS, CAT-2, and CAT-2B but not CAT-2A expression in the lungs. Furthermore, NF-kappaB actively participated in LPS-induction of iNOS, CAT-2, and CAT-2B. LPS induced pulmonary and systemic NO overproduction and resulted in lung injuries. Attenuation of LPS-induced iNOS, CAT-2, and CAT-2B induction significantly inhibited NO biosynthesis and lessened lung injury. NF-kappaB actively participates in the induction of CAT-2 and CAT-2B in intact animals. Our data further support the idea that CAT-2 and CAT-2B are crucial in regulating iNOS activity.


A pilot study of the effect of aerobic exercise on people with moderate disability multiple sclerosis.
A pilot study to investigate the effect of aerobic exercise on the mobility and function of people with moderate disability multiple sclerosis (MS). A small group, comparative, pre- and post-intervention study. A gymnasium within a general hospital. Eight subjects, all female, average age 45 years (range 33-61) with moderate disability MS (Kurtzke scale 4-6), were recruited; six completed the study. Intervention consisted of bi-weekly sessions of 30 min cycling on a static bike at their maximal level of exertion for 12 weeks. The stability of each individual's condition was established pre-intervention using three baseline assessments over two weeks. A battery of tests (the 10-metre and 6-min walk tests, the Functional Reach, the Gulick and the Guys Neurological Disability Scale) were completed pre and post intervention. Potential negative effects were recorded on the Fatigue Severity Scale and the Modified Ashworth Scale. An independent rater completed assessments post intervention. Inter-rater reliability was found to be acceptable. Comparisons pre and post intervention (Wilcoxon signed ranked test) showed significant improvement on the Guys Neurological Disability Scale (p = 0.026), with the mean score reducing from 13 to 9, and the 6-min walk test (p = 0.046), with the mean distance increasing from 200 m to 261 m. Other measures failed to reach significance. Findings from this pilot study suggest overall disability and mobility improved with the aerobic training. A positive treatment effect in this small study suggests the need for a larger trial. Knowledge of how to establish predictive heart rate and how to monitor the effects of cycling with people with MS will be used to inform future clinical trials.


Purification and properties of the membrane-bound by hydrogenase from Desulfovibrio desulfuricans.
The membrane-bound hydrogenase from the anaerobic sulphate-reducing bacterium Desulfovibrio desulfuricans (Norway strain) has been purified to homogeneity, with an overall 80-fold purification and a specific activity of 70 mumol of H2 evolved/min per mg of protein. The hydrogenase had a relative molecular mass of 58 000 as determined by gel filtration and was estimated to contain six iron atoms and six acid-labile sulphur groups per molecule. The absorption spectrum of the enzyme was characteristic of an iron-sulphur protein. The E400 and E280 were 28 500 and 109 000 M-1.cm-1 respectively. The e.s.r. of the oxidized protein indicated the presence of [4Fe-4S]3+ or [3Fe-3S]3+, and another paramagnetic centre, probably Ni(III). The hydrogenase was inhibited by heavy-metal salts, carbon monoxide and high ionic strength. However, it was resistant to inhibition by thiol-blocking and metal-complexing reagents. N-Bromosuccinimide totally inhibited the enzyme activity at low concentrations. The enzyme was stable to O2 over long periods and to high temperatures. It catalyses both H2-evolution and H2-uptake with a variety of artificial electron carriers. D. desulfuricans cytochrome C3, its natural electron carrier, had a high affinity for the enzyme (Km = 2 microns). Rate enhancement was observed when cytochrome C3 was added to Methyl Viologen in the H2-evolution assay. The pH optimum for H2-evolution was 6.5.


Telomeres, a busy platform for cell signaling.
Telomeres are the terminal structures at the ends of linear chromosomes that represent a solution to the end replication problem. Specific binding of the six-protein subunit complex shelterin to telomeric, repetitive TTAGGG DNA sequences contributes to the stable architecture and maintenance of telomeres. Proteins involved in the DNA damage response are also localized at telomeres, and play a role in the surveillance and maintenance of telomere integrity. The enzyme responsible for telomere extension is telomerase, a ribonucleoprotein with reverse transcriptase activity. In the absence of telomerase, telomeres shorten to a length threshold that triggers the DNA damage response and replicative senescence. Here, we will summarize the latest findings concerning vertebrate telomere structure and epigenetics, and we present data regarding the impact of short telomeres upon cell signaling. In particular, in murine embryonic stem cells lacking telomerase, we found that distribution of cytosolic/nuclear β-catenin, a key component of the Wnt signaling pathway, changes when telomeres become critically short. We discuss implications and future perspectives of the effect of epigenetic modifications and/or conformational changes of telomeres on cell metabolism and signaling networks. Such an analysis may unveil potential therapeutic targets for pathologies like cancer, where the integrity of telomeres is altered.


Evaluation of the bioequivalence of tablets and capsules containing the novel anticancer agent R115777 (Zarnestra) in patients with advanced solid tumors.
R115777 (Zamestra) is a novel anticancer agent, currently undergoing phase III clinical testing. An open, cross-over trial was performed in 24 patients with solid tumors to compare the bioavailability of a new tablet formulation with the standard capsule formulation. Both dosage forms were administered once daily in doses of 300 or 400 mg. Patients received R115777 as a capsule on day I and as a tablet on day 2, or vice versa. Blood samples were drawn up to 24 hours after drug intake and R115777 levels were measured using a validated high performance liquid chromatography (HPLC) method. The following pharmacokinetic parameters were determined and compared for the two formulations: time to maximal plasma concentration (Tmax), half-life (t 1/2), maximal plasma concentration (Cmax) and area under the curve at twenty-four hours (AUC24h). For the latter two parameters, 90% classical confidence intervals of the ratio tablet/capsule were calculated after a log-transformation, using an Analysis of Variance (ANOVA). For t 1/2 and Tmax, no statistically significant differences were found between tablet and capsule. The point estimates of the ratio's of the log-normalized Cmax and AUC24h were 0.94 and 0.92, respectively, and the 90% confidence intervals were 0.81-1.09 and 0.83-1.03, which is within the critical range for bioequivalence of 0.80-1.25. In conclusion, the established pharmacokinetic parameters demonstrate that the capsule and tablet formulations of R115777 are interchangeable.


Handling Non-Visible Referents in Situated Visualizations.
Situated visualizations are a type of visualization where data is presented next to its physical referent (i.e., the physical object, space, or person it refers to), often using augmented-reality displays. While situated visualizations can be benefcial in various contexts and have received research attention, they are typically designed with the assumption that the physical referent is visible. However, in practice, a physical referent may be obscured by another object, such as a wall, or may be outside the user's visual feld. In this paper, we propose a conceptual framework and a design space to help researchers and user interface designers handle non-visible referents in situated visualizations. We frst provide an overview of techniques proposed in the past for dealing with non-visible objects in the areas of 3D user interfaces, 3D visualization, and mixed reality. From this overview, we derive a design space that applies to situated visualizations and employ it to examine various trade-offs, challenges, and opportunities for future research in this area.


Interrater Reliability of the New Sport-Specific Evidence-Based Classification System for Para Va'a.
The purpose of this study was to examine the interrater reliability of a new evidence-based classification system for Para Va'a. Twelve Para Va'a athletes were classified by three classifier teams each consisting of a medical and a technical classifier. Interrater reliability was assessed by calculating intraclass correlation for the overall class allocation and total scores of trunk, leg, and on-water test batteries and by calculating Fleiss's kappa and percentage of total agreement in the individual tests of each test battery. All classifier teams agreed with the overall class allocation of all athletes, and all three test batteries exhibited excellent interrater reliability. At a test level, agreement between classifiers was almost perfect in 14 tests, substantial in four tests, moderate in four tests, and fair in one test. The results suggest that a Para Va'a athlete can expect to be allocated to the same class regardless of which classifier team conducts the classification.


Advances in the management of parkinson's disease.
The treatment of Parkinson's disease today is complex, time-consuming, but rewarding. The introduction of levodopa has not cured the disease, but has provided the most powerful therapy available yet. Its use is limited by side effects and careful titration to optimum dosage, often in combination with other drugs, is required. Despite best therapy, some patients never respond, and others begin to lose benefit after some years of therapy. New problems, such as the "on-off" effect have appeared with long-term treatment, and require careful adjustment of dosage. As with any replacement therapy, a balance between sub-optimal benefit and side effects has to be discovered and maintained by careful and frequent review. New approaches to treatment may offer further improvement in the near future.


Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy.
To determine the safety and efficacy of intravenously administered phytonadione (vitamin K1) in patients on routine oral warfarin anticoagulation. This retrospective cohort study comprised adults who were taking warfarin, were not bleeding, and received intravenous phytonadione anticoagulation therapy before a diagnostic or therapeutic procedure between September 1, 1994, and March 31, 1996. The main outcome measures were adverse reactions to intravenously administered phytonadione, prothrombin-international normalized ratio time values, the incidence of bleeding and thrombosis after the procedure, and the time between the procedure and return to anticoagulation after resumption of warfarin treatment. Two (1.9%) of the 105 patients studied had suspected adverse reactions to intravenous phytonadione (dyspnea and chest tightness during infusion in both). For the 82 patients who underwent a procedure, the median time from phytonadione to procedure onset was 27 hours (range, 0.7-147 hours), which was significantly less for patients receiving an initial phytonadione dose of more than 1 mg (P=.009). None had thromboembolism after surgery, although 2 (2.4%) of the 82 patients had procedure-associated major bleeding. For the 60 patients resuming warfarin therapy after a procedure, the median time to return to therapeutic anticoagulation was 4.1 days (range, 0.8-31.7 days) and was unaffected by the phytonadione dosage. Intravenous phytonadione appears to be safe and is effective for semiurgent correction of long-term oral anticoagulation therapy before surgery. In small doses, it does not prolong the patient's time to return to therapeutic anticoagulation.


Influence of glyphosate on amino acid composition of Egyptian broomrape.
The parasitic plant broomrape is entirely dependent on its host for reduced carbon and nitrogen and is also susceptible to inhibition by glyphosate that is translocated to the parasite through a host. Studies were conducted to examine the effect of broomrape parasitism on amino acid concentrations of two hosts: common vetch that is tolerant of low levels of glyphosate and oilseed rape that has been genetically engineered for glyphosate resistance. The influence of glyphosate on the amino acid content of broomrape and the two hosts was also examined. Amino acid concentrations in leaves and roots of parasitized common vetch plants were generally similar to those of the corresponding tissues of nonparasitized plants. Amino acid concentrations in broomrape were lower than those of the parasitized common vetch root. For common vetch, glyphosate applied at rates that selectively inhibited broomrape growth did not alter individual amino acid concentrations in the leaves, but generally increased amino acid levels at 0.18 kg ha-1. Glyphosate application also increased the amino acid concentrations, with the exception of arginine, of broomrape growing on common vetch and did not generally influence concentrations in leaves or roots of common vetch. In oilseed rape, parasitization by broomrape generally led to higher amino acid concentrations in leaves but lower concentrations in roots of parasitized plants. Broomrape had higher amino acid concentrations than roots of the parasitized oilseed rape. Glyphosate applied at 0.25 and 0.5 kg ha-1 generally increased the amino acid concentrations in oilseed rape leaves, but the 0.75 kg ha-1 application caused the amino acid concentrations to decrease compared to those of untreated plants. In oilseed rape root the general trend was an increase in the concentration of amino acids at the two highest rates of glyphosate. Individual amino acid concentrations in broomrape attachments growing on oilseed rape were generally increased following glyphosate application of 0.25 kg ha-1. These results indicate that low rates of glyphosate alter amino acid profiles in both host and broomrape and raise questions about the regulation of amino acid metabolism in the parasite.


Pulmonary function in young children with alpha 1-antitrypsin deficiency: comparison with matched control subjects.
In this paper we report the initial cross-sectional data from a prospective study of pulmonary function in children with moderately severe and severe alpha 1-antitrypsin deficiency. Using a case-control design, our cases were 19 children 3 to 7 years of age with alpha 1-antitrypsin deficiency, Pi phenotype ZZ or SZ. Control subjects were selected from healthy children participating in a study to establish reference values for functional residual capacity and maximal expiratory flow at functional residual capacity, using a 1:1 match for sex, height, age, and weight. We found no significant difference between the cases and their matched control subjects with respect to functional residual capacity and maximal expiratory flow at functional residual capacity. We conclude that through 7 years of age there is no gross impairment in overall pulmonary function in children with moderately severe and severe alpha 1-antitrypsin deficiency, Pi phenotypes ZZ and SZ.


Arabis watsonii (P.H.Davis) F.K.Mey.: An overlooked cruciferous species from eastern Anatolia and its phylogenetic position.
Arabis watsonii (P.H.Davis) F.K.Mey. was initially reported as Thlaspi watsonii P.H.Davis in Flora of Turkey. Although F.K.Meyer transferred this species to Arabis L., this species has been overlooked and treated as Thlaspi L. in relevant literature for Flora of Turkey. In this study this species was evaluated using molecular (nuclear ITS and plastidic trnL-F sequences) and morphological data. Results clearly show that Arabis watsonii is sister to the Arabis hirsuta aggregate and its relatives. In conclusion, our results increased the number of known Arabis species in Turkey to 23. Furthermore, detailed description and distribution of the species are given and a new IUCN threat category for Arabis watsonii is proposed.


Renal effects of atrial natriuretic factor in primate.
Baboons (Papio hamadryas) were infused intravenously with a nonhypotensive dose (0.1 microgram X min-1 X kg-1) of synthetic human atriopeptin III (ANF) for 60 min. Throughout the infusion in intact animals, ANF significantly increased glomerular filtration rate (GFR) (clearance of inulin) (P less than 0.001), and, to a lesser extent, total renal plasma flow (RPF) [clearance of p-aminohippurate (PAH)] (P less than 0.02) and filtration fraction (P less than 0.02). Concomitant increases in urinary flow rate and in the excretion of osmoles, sodium, chloride, potassium, phosphorus, and calcium were highly significant (less than 0.001 for all). To minimize the hemodynamic impact of ANF on GFR, the same dose of ANF was infused into the same animals 8 wk after uninephrectomy. Base-line single-kidney GFR was then 50% increased. With ANF infusion RPF increased significantly (P less than 0.02), as in intact baboons, but ANF then had only marginally significant effects on GFR (P = 0.06) and insignificant effects on filtration fraction (P = 0.17). Nevertheless, the changes in urinary flow rate and solute excretion rates were highly significant (P less than 0.001 to less than 0.007). In both groups, all changes developed rapidly, were sustained during the infusion of ANF, and were readily reversible within 15 to 30 min of cessation of ANF infusion. The data dissociate in uninephrectomized primate the effects of ANF on water and solute excretion from those on GFR and filtration fraction. Both in intact and in uninephrectomized baboons, the changes in water and solute excretion were associated with small but significant changes in RPF.


Highly enantioselective syntheses of functionalized alpha-methylene-gamma-butyrolactones via Rh(I)-catalyzed intramolecular Alder ene reaction: application to formal synthesis of (+)-pilocarpine.
A highly enantioselective Rh(I)-catalyzed intramolecular Alder ene reaction has been developed. The desired products, 3-vinyl, vinyl acetate, and vinyl ether-substitued alpha-methylene-gamma-butyrolactones were formed in high yields. Aldehydes were produced with the formation of gamma-lactones when alcohols were substituted at allylic position in the substrates. All reactions with listed substrates proceeded in over 99% ee. A formal synthesis of (+)-pilocarpine is an excellent example to demonstrate the synthetic utility of this methodology.


Possible effects of melatonin against rat uterus exposure to bisphenol A during neonatal period.
The aim of this study was to investigate the possible effects of melatonin on rat uterine tissue against exposure with bisphenol A (BPA) in the neonatal period. Twenty-four female rats were divided into four groups, (n=6) per group. Group I was used as a control (sesame oil + ethanol), group II was injected daily with (100 mg/kg) BPA by subcutaneously (sc) daily postnatal days (PND 0-10), group III was injected daily with (10 mg/kg) melatonin by sc for 10 days (PND 20-30), and group IV was injected daily with (100 mg/kg) BPA (PND 0-10) and (10 mg/kg) melatonin (PND 20-30). All rats were sacrificed in the same day of metestrus cycle, approximately PND 70. Histological analyses, immunostaining of B cell lymphoma 2 (Bcl-2), and cytochrome c and TUNEL assays were performed. According to our results, neonatal exposure to BPA accelerates onset of puberty, causes degenerative and morphometric changes on rat uterus, and increases apoptotic reaction rates. The immunoreactivity of Bcl-2 was decreased after BPA administration. In addition, immunoreactivity of Bcl-2 showed an increase after melatonin treatment. However, cytochrome c immunoreactivity was decreased after melatonin administration. Our results suggest that melatonin may have positive effects against BPA-induced degenerative changes on rat uterus.


Viewpoints: diet and dietary adaptations in early hominins: the hard food perspective.
Recent biomechanical analyses examining the feeding adaptations of early hominins have yielded results consistent with the hypothesis that hard foods exerted a selection pressure that influenced the evolution of australopith morphology. However, this hypothesis appears inconsistent with recent reconstructions of early hominin diet based on dental microwear and stable isotopes. Thus, it is likely that either the diets of some australopiths included a high proportion of foods these taxa were poorly adapted to consume (i.e., foods that they would not have processed efficiently), or that aspects of what we thought we knew about the functional morphology of teeth must be wrong. Evaluation of these possibilities requires a recognition that analyses based on microwear, isotopes, finite element modeling, and enamel chips and cracks each test different types of hypotheses and allow different types of inferences. Microwear and isotopic analyses are best suited to reconstructing broad dietary patterns, but are limited in their ability to falsify specific hypotheses about morphological adaptation. Conversely, finite element analysis is a tool for evaluating the mechanical basis of form-function relationships, but says little about the frequency with which specific behaviors were performed or the particular types of food that were consumed. Enamel chip and crack analyses are means of both reconstructing diet and examining biomechanics. We suggest that current evidence is consistent with the hypothesis that certain derived australopith traits are adaptations for consuming hard foods, but that australopiths had generalized diets that could include high proportions of foods that were both compliant and tough.


Enhanced capabilities of current ICU ventilators: do they really benefit patients?
The current-generation mechanical ventilators are certainly enhanced in performance, style, and cost. Many of these enhancements appear to benefit both the patient (eg, reduced work of breathing, wider range of operation) and the hospital (eg, reduced maintenance costs). Although vast areas for refinements remain, my plea is that efforts be made to learn about and take advantage of the current technology, before embarking upon new technology. As we have learned, you have to have the right tool for the right job. Unfortunately, it's not the right tool, if you don't know how to use it.


Relationship of injection drug use, antiretroviral therapy resistance, and genetic diversity in the HIV-1 pol gene.
To determine if a history of injection drug use influences genotypic protease inhibitor (PI) resistance to antiretroviral agents. We assessed the presence of resistance mutations in PI-naive injection drug users (IDUs) and non-IDUs participating in the Women's Interagency HIV Study. Eighteen HIV-infected participants who reported injection drug use before study enrollment and 32 HIV-infected non-IDUs contributed a total of 34 and 65 person-visits, respectively, to analyses. Based on data from multiple clones obtained from different time points from each individual, we determined that primary PI resistance mutations were more frequent among person visits contributed by IDUs (24%) than non-IDUs (8%, P = 0.05). Although neither reached statistical significance, diversity was higher within the protease region among study visits carrying PI-resistant clones at both the nucleotide level (2.66 vs. 2.35; P = 0.08) and at the amino acid level (1.60 vs. 1.32; P = 0.23). Most of the primary resistance mutations could not be detected using the standard population sequencing employed in the clinical setting. Five of 6 individuals in whom clones encoding PI resistance mutations were identified failed PI-containing highly active antiretroviral therapy within 12 months of therapy initiation. Our findings indicate that more aggressive sampling for resistance mutations among viral clones before highly active antiretroviral therapy initiation might permit selection of more effective treatment, particularly in IDUs.


Danish Hip Arthroscopy Registry: an epidemiologic and perioperative description of the first 2000 procedures.
Danish Hip Arthroscopy Registry (DHAR) was initiated in 2012 as a web-based prospective registry. The purpose of this study was to evaluate and report the epidemiologic and perioperative data of the first 2000 procedures in a Danish hip arthroscopy population and to describe the development of DHAR. We describe the use of various Patient Related Outcome Measures related to non-arthritic hip patients. The 2000 procedures consisted of 56% females and 44% males. Mean age 37.5 years, mean surgical time was 86.5 min and mean traction time 50.5 min. The most frequently performed procedure was CAM and Pincer resection in 93.5% of the cases. Labral refixation or repair was done in 70.3% of the cases. The most common type of acetabular chondral damage was grade II lesions (36.6%). Grade III and IV changes were seen in 36.1% of the cases. The preoperative iHOT12 was 45 (mean) based on all 12 items. EQ-5D was 0.65 and HAGOS sub-scores were 51 (pain), 49 (symptoms), 53 (ADL), 35 (sport), 20 (physical activity) and 29, respectively. We conclude that patients undergoing hip arthroscopy report considerable pain, loss of function, reduced level of activity and reduced quality-of-life prior to surgery. The problems with development and maintaining a large clinical registry are described and further studies are needed to validate data completeness. We consider the development of a national clinical registry for hip arthroscopy as a successful way of developing and maintaining a valuable clinical and scientific tool.


Women with a recent history of early-onset pre-eclampsia have a worse periodontal condition.
Pre-eclampsia is a complication of pregnancy characterized by systemic vascular dysfunction and pathological changes in placental arteries. Growing evidence of chronic infection as an aetiological factor in vascular diseases prompted us to study maternal periodontal disease in subjects with early-onset pre-eclampsia (<34 weeks). A case-control study was carried out on 17 early-onset pre-eclamptic women and 35 controls with uncomplicated pregnancies in a period of 3-28 months postpartum. All were Caucasians. Full-mouth periodontal examinations were performed to determine the periodontal condition. Subgingival-plaque samples were analysed by anaerobic culture techniques for the presence of seven bacterial periodontal pathogens. Potential confounders as age, smoking, educational level and body mass index were determined. Severe periodontal disease was found in 82% of the pre-eclamptic and in 37% of the control group (p=0.009). After adjusting for age, smoking and educational level, the odds ratio was 7.9 (95% CI: 1.9-32.8). The periodontopathic microorganism Micromonas micros was more prevalent in the case group (p=0.040) while Campylobacter rectus was more prevalent in the control group (p=0.047). These results indicate that Caucasian women with a recent history of early-onset pre-eclampsia have a worse periodontal condition, as compared with women with uncomplicated deliveries.


High-order Cerenkov laser gain.
Cerenkov free-electron lasers have primarily operated on the fundamental guided mode of the dielectric waveguide. Higher-order generation would allow short wavelength emission in a relatively large scale resonator. In comparison to the fundamental mode, we find that gain on higher-order modes can be significant in a planar geometry. This analysis is presented with a discussion of practical limits.


A murine hybridoma with large cytoplasmic inclusions of kappa light chains.
A murine hybridoma cell line has been established that consistently forms large cytoplasmic inclusions. These structures bind antibody specific for mouse kappa L chain when stained in situ. SDS-PAGE analysis of isolated inclusion bodies produce a single protein band of approximately 26,000 Mr that reacts with anti-kappa antibody when transferred to nitrocellulose. No carbohydrate was detected in association with the purified protein. These data are consistent with the intracellular retention and deposition of complete kappa L chain protein.


Perforated peptic ulcer - an update.
Peptic ulcer disease (PUD) affects 4 million people worldwide annually. The incidence of PUD has been estimated at around 1.5% to 3%. Perforated peptic ulcer (PPU) is a serious complication of PUD and patients with PPU often present with acute abdomen that carries high risk for morbidity and mortality. The lifetime prevalence of perforation in patients with PUD is about 5%. PPU carries a mortality ranging from 1.3% to 20%. Thirty-day mortality rate reaching 20% and 90-d mortality rate of up to 30% have been reported. In this review we have summarized the current evidence on PPU to update readers. This literature review includes the most updated information such as common causes, clinical features, diagnostic methods, non-operative and operative management, post-operative complications and different scoring systems of PPU. With the advancement of medical technology, PUD can now be treated with medications instead of elective surgery. The classic triad of sudden onset of abdominal pain, tachycardia and abdominal rigidity is the hallmark of PPU. Erect chest radiograph may miss 15% of cases with air under the diaphragm in patients with bowel perforation. Early diagnosis, prompt resuscitation and urgent surgical intervention are essential to improve outcomes. Exploratory laparotomy and omental patch repair remains the gold standard. Laparoscopic surgery should be considered when expertise is available. Gastrectomy is recommended in patients with large or malignant ulcer.


Venous and neural invasion as predictors of recurrence in rectal adenocarcinoma.
After radical surgery for rectal adenocarcinoma, the presence of venous and neural invasion of tumor cells was correlated with the pattern of treatment failure, local in the pelvis or distant. Of 128 operation specimens, venous and neural invasion was demonstrated in 22 percent and 32 percent, respectively. A significant decrease of the distant recurrence-free 5-year survival (Kaplan-Meier method) was seen when venous invasion was demonstrated (32.9 percent vs. 84.3 percent; P less than 0.0001), whereas more local failures were registered in patients with neural invasion. The local recurrence-free 5-year survival in patients with neural invasion was 64.3 percent, compared with 81.1 percent when neural invasion was not demonstrated (P = 0.03). Their prognostic value was then studied in a Cox regression model including stage and grade. Neural invasion had the strongest association with local recurrences, whereas venous invasion was found to be the third strongest independent predictor of metastasis, after lymph node status and extent of local tumor infiltration. We conclude that examining for the presence of venous and neural invasion gives reliable prediction of recurrences after radical resection of rectal cancer. Recording of tumor recurrence pattern may lead to a better selection of patients for adjuvant therapy after surgery.


Prospect of immunotherapy in neoadjuvant/adjuvant treatment for early breast cancer.
Immunotherapy is revolutionary and changing the cancer therapy of multiple solid tumors. Immunotherapy began with discovering the proteins of immune checkpoints such as programmed death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4). Breast cancer, unlike cancers with high tumor mutation burden, is generally considered to be of intermediate immunogenicity; therefore, the efficacy of checkpoint monotherapy is limited. Among breast cancer subtypes, triple negative breast cancer (TNBC) is considered to be the most immunogenic and is mainly evaluated in clinical trials. Some trials have demonstrated that checkpoint inhibitors when combined with chemotherapy improve the survival of TNBC patients. When investigating new drugs, a neoadjuvant setting is preferred because drug efficacy can be evaluated earlier using pathological complete response (pCR) as an alternative endpoint for survival. The strategy is based on the accumulated results that pCR after neoadjuvant therapy significantly correlates with both progression free survival (PFS) and overall survival (OS). We aimed to review relevant articles, and discuss the current position of immunotherapy and future prospects of immunotherapy as neoadjuvant/adjuvant therapy in breast cancer based on our conclusions from the findings in the current literature.


Evaluation of a Novel Mitochondrial Pan-Mucorales Marker for the Detection, Identification, Quantification, and Growth Stage Determination of Mucormycetes.
Mucormycosis infections are infrequent yet aggressive and serious fungal infections. Early diagnosis of mucormycosis and its discrimination from other fungal infections is required for targeted treatment and more favorable patient outcomes. The majority of the molecular assays use 18 S rDNA. In the current study, we aimed to explore the potential of the mitochondrial rnl (encoding for large-subunit-ribosomal-RNA) gene as a novel molecular marker suitable for research and diagnostics. Rnl was evaluated as a marker for: (1) the Mucorales family, (2) species identification (Rhizopus arrhizus, R. microsporus, Mucor circinelloides, and Lichtheimia species complexes), (3) growth stage, and (4) quantification. Sensitivity, specificity, discriminatory power, the limit of detection (LoD), and cross-reactivity were evaluated. Assays were tested using pure cultures, spiked clinical samples, murine organs, and human paraffin-embedded-tissue (FFPE) samples. Mitochondrial markers were found to be superior to nuclear markers for degraded samples. Rnl outperformed the UMD universal® (Molyzm) marker in FFPE (71.5% positive samples versus 50%). Spiked blood samples highlighted the potential of rnl as a pan-Mucorales screening test. Fungal burden was reproducibly quantified in murine organs using standard curves. Identification of pure cultures gave a perfect (100%) correlation with the detected internal transcribed spacer (ITS) sequence. In conclusion, mitochondrial genes, such as rnl, provide an alternative to the nuclear 18 S rDNA genes and deserve further evaluation.


Enduring social and behavioral effects of exposure to military combat in vietnam.
PURPOSE: To assess current social and behavioral outcomes among Vietnam veterans up to 35 years after exposure to military combat.METHODS: A cohort of 1,315 American Legion members whose combat experiences were assessed with a standard quantitative measure in 1984 were followed-up through 1998 for current health and psychosocial status. Another 2,260 Legionnaires who served outside Vietnam during the same period were used as a comparison group. Outcomes included smoking and drinking habits as health risk indicators, income, measures of marital and general happiness and life satisfaction, and the Columbia Univerity PERI (Psychiatric Epidemiology Research Instrument) scales for psychological well-being: anxiety, depression, helplessness/hopelessness, anger and irritation, and physical symptoms of depression. Combat intensity was classified as high, medium, and low.RESULTS: Income was significantly lower in the high-combat group by $4,000 per year compared to the low- and medium-combat groups and the non-Southeast Asia veterans, whose incomes were similar to each other. Marital happiness, life happiness, general life satisfaction, decreased with increasing combat, while smoking prevalence increased with combat score. The PERI scale components were strongly dose-related to combat intensity. Furthermore, the anger/irritation score for the low-combat group was significantly higher than for the non-SEA group.CONCLUSIONS: Although practically all veterans in this study last saw combat prior to 1971, the detrimental effects of having experienced combat which were strongly apparent when this group was surveyed in the 1980s continue to exert an adverse effect on many aspects of their lives almost three decades after the war.


Analysing chemical-induced changes in macroinvertebrate communities in aquatic mesocosm experiments: a comparison of methods.
Mesocosm experiments that study the ecological impact of chemicals are often analysed using the multivariate method 'Principal Response Curves' (PRCs). Recently, the extension of generalised linear models (GLMs) to multivariate data was introduced as a tool to analyse community data in ecology. Moreover, data aggregation techniques that can be analysed with univariate statistics have been proposed. The aim of this study was to compare their performance. We compiled macroinvertebrate abundance datasets of mesocosm experiments designed for studying the effect of various organic chemicals, mainly pesticides, and re-analysed them. GLMs for multivariate data and selected aggregated endpoints were compared to PRCs regarding their performance and potential to identify affected taxa. In addition, we analysed the inter-replicate variability encountered in the studies. Mesocosm experiments characterised by a higher taxa richness of the community and/or lower taxonomic resolution showed a greater inter-replicate variability, whereas variability decreased the more zero counts were encountered in the samples. GLMs for multivariate data performed equally well as PRCs regarding the community response. However, compared to first axis PRCs, GLMs provided a better indication of individual taxa responding to treatments, as separate models are fitted to each taxon. Data aggregation methods performed considerably poorer compared to PRCs. Multivariate community data, which are generated during mesocosm experiments, should be analysed using multivariate methods to reveal treatment-related community-level responses. GLMs for multivariate data are an alternative to the widely used PRCs.


Ion fluxes in giant excised cardiac membrane patches detected and quantified with ion-selective microelectrodes.
We have used ion-selective electrodes (ISEs) to quantify ion fluxes across giant membrane patches by measuring and simulating ion gradients on both membrane sides. Experimental conditions are selected with low concentrations of the ions detected on the membrane side being monitored. For detection from the cytoplasmic (bath) side, the patch pipette is oscillated laterally in front of an ISE. For detection on the extracellular (pipette) side, ISEs are fabricated from flexible quartz capillary tubing (tip diameters, 2-3 microns), and an ISE is positioned carefully within the patch pipette with the tip at a controlled distance from the mouth of the patch pipette. Transport activity is then manipulated by solution changes on the cytoplasmic side. Ion fluxes can be quantified by simulating the ion gradients with appropriate diffusion models. For extracellular (intrapatch pipette) recordings, ion diffusion coefficients can be determined from the time courses of concentration changes. The sensitivity and utility of the methods are demonstrated with cardiac membrane patches by measuring (a) potassium fluxes via ion channels, valinomycin, and Na/K pumps; (b) calcium fluxes mediated by Na/Ca exchangers; (c) sodium fluxes mediated by gramicidin and Na/K pumps; and (d) proton fluxes mediated by an unknown electrogenic mechanism. The potassium flux-to-current ratio for the Na/K pump is approximately twice that determined for potassium channels and valinomycin, as expected for a 3Na/2K pump stoichiometery (i.e., 2K/charge moved). For valinomycin-mediated potassium currents and gramicidin-mediated sodium currents, the ion fluxes calculated from diffusion models are typically 10-15% smaller than expected from the membrane currents. As presently implemented, the ISE methods allow reliable detection of calcium and proton fluxes equivalent to monovalent cation currents <1 pA in magnitude, and they allow detection of sodium and potassium fluxes equivalent to <5 pA currents. The capability to monitor ion fluxes, independent of membrane currents, should facilitate studies of both electrogenic and electroneutral ion-coupled transporters in giant patches.


Integrated antibody and cellular immunity monitoring are required for assessment of the long term protection that will be essential for effective next generation vaccine development.
The COVID pandemic exposed the critical role T cells play in initial immunity, the establishment and maintenance of long term protection, and of durable responsiveness against novel viral variants. A growing body of evidence indicates that adding measures of cellular immunity will fill an important knowledge gap in vaccine clinical trials, likely leading to improvements in the effectiveness of the next generation vaccines against current and emerging variants. In depth cellular immune monitoring in Phase II trials, particularly for high risk populations such as the elderly or immune compromised, should result in better understanding of the dynamics and requirements for establishing effective long term protection. Such analyses can result in cellular immunity correlates that can then be deployed in Phase III studies using appropriate, scalable technologies. Measures of cellular immunity are less established than antibodies as correlates of clinical immunity, and some misconceptions persist about cellular immune monitoring usefulness, cost, complexity, feasibility, and scalability. We outline the currently available cellular immunity assays, review their readiness for use in clinical trials, their logistical requirements, and the type of information each assay generates. The objective is to provide a reliable source of information that could be leveraged to develop a rational approach for comprehensive immune monitoring during vaccine development.


Superior protective effects of in vitro propagated green garlic against hydrogen peroxide-induced cytotoxicity in human hepatoma cells.
Garlic is a valuable source material for medicines due to its known antitumor, hypolipidaemic, antioxidant, and immunomodulatory effects. This study compares the protective effects of conventionally grown (CG) and in vitro propagated garlic (PG) against hydrogen peroxide-induced cytotoxicity in HepG2 cells and their antioxidant activity. Garlic used in this study was obtained by planting garlic cloves or by planting the transplants of PG directly in the field. At the end of the vegetation period, CG and PG were sampled and extracts prepared for the experiment. Compared to conventionally grown garlic bulbs, PG leafy part yielded significantly higher content of polyphenols, flavonoids and alliin, and also showed equal or higher antioxidant activity, measured by the cell viability test, GSH and ROS level. Moreover, PG can be produced in less time (shorter vegetation period) and with significantly less material (cloves). Significantly higher content of alliin, polyphenols, and flavonoids and significantly higher yield of plant biomass in PG has a great potential to become a new production model with improved garlic properties as a medicine material.


[Morphologic changes of the lesser gastric curvature after segmental gastrectomy associated to proximal gastric vagotomy. Experimental study in dogs].
The segmental gastrectomy of the body of the stomach, combined with proximal gastric vagotomy, has been indicated in the treatment of duodenal ulcer, especially in patients with major risk of the recurrent ulceration. To evaluate the histopathologic changes, secondaries to combined corporeal segmental gastrectomy and proximal gastric vagotomy, in the lesser curvature of the stomach. Thirty-six adult mongrel dogs weighing between 10 to 20 kg were divided into three groups of twelve animals each: Group I animals (control) were submitted to laparotomy and gastric manipulation; Group II, animals underwent proximal gastric vagotomy; and Group III, animals underwent corporeal segmental gastrectomy combined with proximal gastric vagotomy. Each group was subdivided into two subgroups of six animals each, and according to the subgroup, the animals were then sacrificed on the third or in the eighth postoperative day. A fragment of the lesser curvature was removed from each stomach for microscopic study. Regarding edema, vascular congestion, inflammatory exudate, fibrosis and cell damage; histopathologic changes found in animals sacrificed in the same postoperative day were slight in Group I, moderate in Group II and intense in the group III. Although nonspecific, the character and site of the lesions were similar to the ones occurring in ischemic process. It was also observed a directly proportional relation between severity of morphologic changes and ischemic potentiality of surgical procedure. The segmental gastrectomy probably aggravated the arterial blood supply of the remnant of lesser curvature of the stomach, which was already compromised by devascularization consequent to proximal gastric vagotomy.


Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood.
Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3',4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain.


Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward.
Targeting the prostaglandin (PG) pathway is potentially a critical intervention for the prevention and treatment of cancer. Central to PG biosynthesis are two isoforms of cyclooxygenase (COX 1 and 2), which produce prostaglandin H(2) (PGH(2)) from plasma membrane stores of fatty acids. COX-1 is constitutively expressed, whereas COX-2 is an inducible isoform upregulated in many cancers. Differences between COX-1 and COX-2 catalytic sites enabled development of selective inhibitors. Downstream of the COX enzymes, prostaglandin E(2) synthase converts available PGH(2) to prostaglandin E(2) (PGE(2)), which can stimulate cancer progression. Significant research efforts are helping identify more selective targets and fully elucidate the downstream targets of prostaglandin E(2)-mediated oncogenesis. Nonetheless, as a key rate-limiting control point of PG biosynthesis, COX-2 continues to be an important anticancer target. As we embark upon a new era of individualized medicine, a better understanding of the individual risk and/or benefit involved in COX-2 selective targeting is rapidly evolving. This review endeavors to summarize developments in our understanding of COX-2 and its downstream targets as vital areas of anticancer research and to provide the current status of an exciting aspect of molecular medicine.


Macro- and microstructural changes in patients with spinocerebellar ataxia type 6: assessment of phylogenetic subdivisions of the cerebellum and the brain stem.
Site-specific degeneration patterns of the infratentorial brain in relation to phylogenetic origins may relate to symptoms in patients with spinocerebellar degeneration, but the patterns are still unclear. We investigated macro- and microstructural changes of the infratentorial brain based on phylogenetic origins and their correlation with symptoms in patients with spinocerebellar ataxia type 6. MR images of 9 patients with spinocerebellar ataxia type 6 and 9 age- and sex-matched controls were obtained. We divided the infratentorial brain on the basis of phylogenetic origins and performed an atlas-based analysis. Comparisons of the 2 groups and a correlation analysis assessed with the International Cooperative Ataxia Rating Scale excluding age effects were performed. A significant decrease of fractional volume and an increase of mean diffusivity were seen in all subdivisions of the cerebellum and in all the cerebellar peduncles except mean diffusivity in the inferior cerebellar peduncle in patients compared with controls (P < .0001 to <.05). The bilateral anterior lobes showed the strongest atrophy. Fractional volume decreased mainly in old regions, whereas mean diffusivity increased mainly in new regions of the cerebellum. Reflecting this tendency, the International Cooperative Ataxia Rating Scale total score showed strong correlations in fractional volume in the right flocculonodular lobe and the bilateral deep structures and in mean diffusivity in the bilateral posterior lobes (r = 0.73 to ±0.87). We found characteristic macro- and microstructural changes, depending on phylogenetic regions of the infratentorial brain, that strongly correlated with clinical symptoms in patients with spinocerebellar ataxia type 6.


Molecular modeling of organophosphorous agents and their aqueous solutions.
Using molecular dynamics simulations, we modeled solvation and diffusion in aqueous solutions of organophosphorous compounds, including nerve G-agents sarin and soman (methylphosphonofluoridates) and their common simulants DMMP (dimethyl methylphosphonate) and DIFP (diisopropyl fluorophosphate). The aqueous solutions of the organophosphorous compounds were found to display complex molecular scale structures and dynamic properties due to competing interactions between strongly hydrophobic and hydrophilic groups. The mixing of agents with water was proved to be exothermic with negative excess mixing volume, indicating a strongly hydrophilic solvation. This effect was confirmed in a specially performed experiment. We discuss to what extent DMMP and DIFP are suitable simulants for G-agents in experimental studies, as far as their interactions with water are concerned. We also focus on the relevance of the structural features and mobilities of agents in water to their interactions with permselective polyelectrolyte membranes that may be employed as protective barriers against chemical warfare agents.


Management of Anticoagulants and Antiplatelet Agents During Colonoscopy.
Colonoscopy frequently is performed for patients who are taking aspirin, nonsteroidal anti-inflammatory drugs, antiplatelet agents, and other anticoagulants. These colonoscopies often involve polypectomy, which can be complicated by bleeding. The risks of precipitating thromboembolic complications if anticoagulants are stopped must be weighed against the risk of postpolypectomy bleeding if these agents are continued. This article systematically reviews the management of anticoagulation during elective and emergency colonoscopy. For patients undergoing colonoscopic polypectomy, the overall risk of postpolypectomy bleeding is <0.5%. Risk factors for postpolypectomy bleeding include large polyp size and anticoagulant use, especially warfarin and thienopyridines. For patients who do not stop aspirin or other nonsteroidal anti-inflammatory drugs prior to colonoscopy, the rate of postpolypectomy bleeding is not significantly different from that for patients who do not take those medications. For patients who continue thienopyridines and undergo polypectomy, the risk of delayed postpolypectomy bleeding is approximately 2.4%. Even for patients who interrupt warfarin, the risk of postpolypectomy bleeding is increased. The direct oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) have a rapid onset and offset of action, and periprocedural bridging generally is not necessary. For the thienopyridines, warfarin, and the direct oral anticoagulants, the decision to interrupt or continue these agents for endoscopy will involve considerable exercise of clinical judgment.


Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia.
Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.


Transtemporal approach to hypothalamic hamartomas in children: report of 3 cases.
The surgical approach to hypothalamic hamartomas (HHs) associated with medically refractory epilepsy is challenging because of these lesions' deep midline or paramedian location. Whether the aim is resection or disconnection, the surgical corridor dictates how complete a procedure can be achieved. Here, the authors report a transtemporal approach suitable for Delalande type I, inferior extraventricular component of type III, and type IV lesions. This approach provides optimal visualization of the plane between the hamartoma and the hypothalamus with no manipulation to the pituitary stalk and brainstem, allowing for extensive disconnection while minimizing injury to adjacent neurovascular structures.Through a 1-cm corticectomy in the middle temporal gyrus, a surgical tract is developed under neuronavigational guidance toward the plane of intended disconnection. On reaching the mesial temporal pia-arachnoid margin, it is opened, providing direct visualization of the hamartoma, which is then disconnected or resected as indicated. Critical neurovascular structures are generally not exposed through this approach and are preserved if encountered.Three patients (mean age 4.9 years) with intractable epilepsy were treated using this technique as part of the national Children's Epilepsy Surgery Service. Following resection, the patient in case 1 (Delalande type I) is seizure free off medication at 3 years' follow-up (Engel class IA). The patient in case 2 (Delalande type III) initially underwent partial disconnection through a transcallosal interforniceal approach and at first had significant seizure improvement before the seizures worsened in frequency and type. Complete disconnection of the residual lesion was achieved using the transtemporal approach, rendering this patient seizure free off medication at 14 months postsurgery (Engel class IA). The patient in case 3 (Delalande type IV) underwent incomplete disconnection with a substantial reduction in seizure frequency at 3 years' follow-up (Engel class IIIC). There were no surgical complications in any of the cases.The transtemporal approach is a safe and effective alternative to more conventional surgical approaches in managing HHs with intractable epilepsy.


Inhibition of oral carcinogenesis by citrus flavonoids.
Six citrus flavonoids were tested for antineoplastic activity. The hamster cheek pouch model was utilized, and the solutions of the flavonoids (2.0-2.5%) and the solution of the carcinogen, 7,12-dimethylbenz[a]anthracene (0.5%), were applied topically to the pouches. The pouches of the positive controls were treated with the solvent used to dissolve the flavonoids and the solution of the carcinogen. The data show that 4 flavonoids (hesperetin, neohesperidin, tangeretin, and nobiletin) were inactive. The results with naringin and naringenin show that both of these flavonoids significantly lowered tumor number [5.00 (control group), 2.53 (naringin group), and 3.25 (naringenin group)]. Naringin also significantly reduced tumor burden [269 mm(3)(control group) and 77.1 mm(3)(naringin group)]. The data suggest that naringin and naringenin, 2 flavonoids found in high concentrations in grapefruit, may be able to inhibit the development of cancer.


Store-specific grocery-shopping patterns and their association with objective and perceived retail food environments.
To explore store-specific grocery shopping patterns and assess associations with the objective and perceived retail food environment (RFE). This cross-sectional study used principal component analysis and hierarchical cluster analysis to identify grocery shopping patterns, and logistic regression models to assess their associations with the RFE, while adjusting for household characteristics. The Montpellier Metropolitan Area, in France. To be eligible for inclusion participants had to be 18 years of age or older and reside in the Montpellier Metropolitan Area. Analyses were carried out on 415 households. Households of cluster "Supermarket" (49% of households) primarily shopped at supermarkets, and were less likely to live near a convenience store. Households of cluster "Diversified" (18%) shopped mostly at organic stores, markets, specialized stores, and from producers, and were more likely to have a market in their activity space. Households of cluster "Discount" (12%) primarily shopped at discounters, and were less likely to perceive a producer in their activity space. Households of cluster "Convenience" (12%) mostly shopped online or in convenience stores. Finally, households of cluster "Specialized" (9%) had high expenditures in greengrocers and in other specialized food stores, and were more likely to live near a specialized food store. This study highlighted the importance of considering both perceived and objective RFE indicators, as well as assessments around the home and in activity space. Understanding how people buy food and interact with their RFE is crucial for policymakers seeking to improve urban food policies.


Cryptosporidiosis: From Prevention to Treatment, a Narrative Review.
Cryptosporidiosis is a water- and food-borne zoonotic disease caused by the protozoon parasite of the genus Cryptosporidium. C. hominis and C. parvum are the main two species causing infections in humans and animals. The disease can be transmitted by the fecal-oral route as well as the respiratory route. The infective stage (sporulated oocysts) is resistant to different disinfectants including chlorine. Currently, no effective therapeutic drugs or vaccines are available to treat and control Cryptosporidium infection. To prevent cryptosporidiosis in humans and animals, we need to understand better how the disease is spread and transmitted, and how to interrupt its transmission cycle. This review focuses on understanding cryptosporidiosis, including its infective stage, pathogenesis, life cycle, genomics, epidemiology, previous outbreaks, source of the infection, transmission dynamics, host spectrum, risk factors and high-risk groups, the disease in animals and humans, diagnosis, treatment and control, and the prospect of an effective anti-Cryptosporidium vaccine. It also focuses on the role of the One Health approach in managing cryptosporidiosis at the animal-human-environmental interface. The summarized data in this review will help to tackle future Cryptosporidium infections in humans and animals and reduce the disease occurrence.


Metabolite Biomarkers of Leishmania Antimony Resistance.
Leishmania parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. Leishmania exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using L. tropica promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using 1H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite's efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.


Incontinentia pigmenti achromians (Ito) in a West African.
Incontinentia pigmenti achromian is a very rare cutaneous disorder of pigmentation which has been reported from Japan, the United States of America, the Caribbean countries, Mexico and India. A case with coarse hair and associated with atopic dermatitis in a West African girl is presented in this brief report. The case, to the authors' knowledge, is the first documented in Africa.


Hyperglycemia and microangiopathy in the eel.
When female eels, fasting and sexually mature, were progressively adapted to cold water (2-4 degrees C), their blood sugar concentration rose to values averaging 600 mg/dl. Control eels, kept in warm water (18-20 degrees C), had a mean blood sugar concentration of 100 mg/dl. After a period of 5-6 mo, the blood capillaries of the rete mirabile in the swimbladder were examined in both control, low blood sugar eels, and in cold-adapted, high blood sugar eels. In the latter, the basal laminae of the capillaries were thickened; their amino acids composition was altered and the in vitro glucose carbon incorporation into basal laminae glycoproteins was increased over a wide range of medium glucose concentrations. Furthermore, the diffusion capacity of the rete, as measured with tracer molecules during steady-state conditions in a countercurrent perfusion system, was increased in the hyperglycemic eel. It is concluded that chronic hyperglycemia in the cold-adapted eel is associated with a microangiopathy characterized by morphologic, biochemical, and functional alterations.


B cell depletion and signs of sepsis-acquired immunodeficiency in bone marrow and spleen of COVID-19 deceased.
In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified. This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden. In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events. Signs of sepsis-acquired immunodeficiency were found in the setting of an abscess-forming superinfection of viral COVID-19 pneumonia. Furthermore, a severe B cell loss was observed in the bone marrow and/or spleen in 64% of COVID-19 patients. This was reflected by lymphocytopenia in the peripheral blood. As compared to B cell preservation, B cell loss was associated with a higher pulmonary SARS-CoV-2 burden and only a marginal decrease of of T cell counts. The results of this study suggest the presence of sepsis-related immunodeficiency in severe COVID-19 pneumonia with superinfection. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, which might impede the durability of the humoral immune response to SARS-CoV-2.


The Contribution of Neuromuscular Stimulation in Elucidating Muscle Plasticity Revisited.
Studies carried out during the past 45 years on the effects of chronic low-frequency stimulation on skeletal muscle have revealed a multiplicity of adaptive changes of muscle fibres in response to increased activity. As reflected by induced changes in the metabolic properties, protein profiles of the contractile machinery and elements of the Ca2+-regulatory system, all essential components of the muscle fibre undergo pronounced changes in their properties that ultimately lead to their reversible transformation from fast-to-slow phenotype. The chronic low-frequency stimulation experiment thus allows exploring many aspects of the plasticity of mammalian skeletal muscle. Moreover it offers the possibility of elucidating molecular mechanisms that remodel phenotypic properties of a differentiated post-mitotic cell during adaptation to altered functional demands. The understanding of the adaptive potential of muscle can be taken advantage of for repairing muscle damage in various muscle diseases. In addition it can be used to prevent muscle wasting during inactivity and aging. Indeed, pioneering studies are still the sound grounds for the many current applications of Functional Electrical Stimulation and for the related research activities that are still proposed and funded.


Prevalence of back pain in chiropractors.
An epidemiological survey was made of the prevalence of back pain in a sample of 320 Canadian chiropractors. In addition, demographic, postural and other variables were studied to determine their effect on back pain. The overall prevalence of back pain was 87%. Low back pain was claimed by 74% of responding chiropractors. It was found that male chiropractors complained most frequently of lumbar pain, while among female respondents thoracic pain was most common. No apparent correlation was found between back pain and operating postures or table heights. Yet, 82% of the chiropractors that believed their back pain was aggravated by practice made these kinds of changes to avoid pain.


Outcomes after heart transplantation for amyloid cardiomyopathy in the modern era.
We conducted a review of patients undergoing heart transplantation (HT) at our institution for amyloid cardiomyopathy (ACM) between 2008 and 2013. Complete follow-up was available for all patients. Nineteen patients with ACM underwent HT during the study period, accounting for 9.4% of all HT performed at our institution during this period. Amyloid subtype was light chain (AL) in 9 patients and transthyretin (ATTR) in 10 (2 wild-type, 7 familial, 1 unknown). Eight of nine patients with AL amyloidosis began chemotherapy prior to HT, six have resumed chemotherapy since HT, and five have undergone autologous stem cell transplantation. Most recent free light chain levels in AL patients decreased by a median of 85% from peak values. Only one patient developed recurrent graft amyloidosis, occurring at 3.5 years post-HT and asymptomatic. After a median follow-up of 380 days, 17 (89.5%) patients are alive. To our knowledge, this is the largest single-center series reported of ACM patients undergoing HT in the modern era. Our results suggest that acceptable outcomes following HT can be achieved in the short-to-intermediate term and that this is a feasible option for end-stage ACM with careful patient selection and aggressive control of amyloidogenic light chains in AL patients.


Ultradian rhythms in performance on tests of specialized cognitive function.
Performance on cognitive tasks cycled at ultradian frequencies for 24 males over a test period of eight hours. The verbal task of written word production cycled at 80 minutes; the spatial task of locating points in space cycled at 96 minutes. Multiple cycles were seen for a perceptual speed task that factor loads on both the verbal and spatial task. Replication of the results for the first 12 and second 12 subjects demonstrated their robustness. The verbal and spatial tasks were chosen to reflect specialized functions of the left and right cerebral hemispheres, respectively. Accordingly, the results are interpreted as evidence that specialized task performances are associated with independent neurochemical systems. In addition, blood samples were taken at task performance to assess cyclicity of hormone levels. Luteinizing hormone had a period of 120 minutes, testosterone and cortisol were inconsistent and none seemed to be related to the cognitive tasks. However when subjects were divided according to a winter or summer testing schedule, the spatial periodicity was absent for the summer group and the verbal periodicity was absent for the winter peak.


Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.
Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators.


[The influence of thyroid and antithyroid preparations on the development of induced breast cancer].
Research Institute of Endocrinology and Hormone Chemistry, Khar'kov It was shown that realization of a neoplastic process in the breast is determined, in particular, by the chemical structure of agents employed and their dosage. So 1-thyroxine, depending on the dosage used, may stimulate the development of tumor process in mammary glands, but exert no influence on it (an effect of "the effect extinction"), and finely suppress tumor development. Among the determining factors the activity of thyreotropic function of the hypophysis and a concentration of an albumin bound form of thyroxine in blood are of special importance.


Bacterial Expression of a Single-Chain Variable Fragment (scFv) Antibody against Ganoderic Acid A: A Cost-Effective Approach for Quantitative Analysis Using the scFv-Based Enzyme-Linked Immunosorbent Assay.
Due to the highly specific binding between an antibody and its target, superior analytical performances was obtained by immunoassays for phytochemical analysis over conventional chromatographic techniques. Here, we describe a simple method for producing a functional single-chain variable fragment (scFv) antibody against ganoderic acid A (GAA), a pharmacologically active metabolite from Ganoderma lingzhi. The Escherichia coli BL21(DE3) strain produced a large amount of anti-GAA scFv. However, in vitro refolding steps, which partially recovered the reactivity of the scFv, were required. Interestingly, the functional scFv was expressed as a soluble and active form in the cytoplasm of an engineered E. coli SHuffle® strain. Purified anti-GAA scFv, which yielded 2.56 mg from 1 L of culture medium, was obtained from simple and inexpensive procedures for expression and purification. The anti-GAA scFv-based indirect competitive enzyme-linked immunosorbent assay (icELISA) exhibited high sensitivity (linearity: 0.078-1.25 µg/mL) with precision (CV: ≤6.20%) and reliability (recovery: 100.1-101.8%) for GAA determination. In summary, the approach described here is an inexpensive, simple, and efficient expression system that extends the application of anti-GAA scFv-based immunoassays. In addition, when in vitro refolding steps can be skipped, the cost and complexity of scFv antibody production can be minimized.


New classification of HLA-DRB1 alleles in rheumatoid arthritis susceptibility: a combined analysis of worldwide samples.
Rheumatoid arthritis (RA) is a complex polygenic disease of unknown etiology. HLA-DRB1 alleles encoding the shared epitope (SE) (RAA amino acid pattern in positions 72 to 74 of the third hypervariable region of the DRbeta1 chain) are associated with RA susceptibility. A new classification of HLA-DRB1 SE alleles has been developed by Tezenas du Montcel and colleagues to refine the association between HLA-DRB1 and RA. In the present study, we used RA samples collected worldwide to investigate the relevance of this new HLA-DRB1 classification in terms of RA susceptibility across various Caucasoid and non-Caucasoid patients. Eighteen subsamples were defined from a total number of 759 cases and 789 controls and grouped in 10 samples on the basis of their ethnic origin. HLA-DRB1 alleles were divided into five groups (S1, S2, S3D, S3P, and X) according to the new HLA-DRB1 allele classification. The whole analysis was performed by comparing carrier frequencies for the five HLA-DRB1 allele groups between RA patients and controls across the 10 Caucasoid and non-Caucasoid samples. The Mantel-Haenszel method of meta-analysis provided a global odds ratio (OR) estimate with 95% confidence interval (CI). A positive association with RA susceptibility was found for S2 allele carriers (OR 2.15, 95% CI 1.54 to 3.00; p < 10(-5)) and S3P allele carriers (OR 2.74, 95% CI 2.01 to 3.74; p < 10(-5)). A negative association was found for S1 alleles (OR 0.60, 95% CI 0.48 to 0.76; p < 10(-4)) and X alleles (OR 0.58, 95% CI 0.39 to 0.84; p = 4 x 10(-3)). No significant association was highlighted for the S3D group of alleles (OR 0.89, 95% CI 0.69 to 1.14; p = 0.89). The complementary genotype analysis fit with the genotype risk hierarchy previously reported in Caucasoid RA patients. So far, the present study is the first attempt to investigate the relevance of this new HLA-DRB1 classification in terms of RA susceptibility on both Caucasoid and non-Caucasoid samples. Our results support the hypothesis of a differential role played by different HLA-DRB1 allele groups in RA susceptibility across different ethnic backgrounds and confirm the interest of such an HLA-DRB1 classification in differentiating predisposing and protective alleles.


Hypoxia and ischaemia in buffer-perfused toad hearts.
Previous studies on the effects of ischaemia or hypoxia in ectothermic vertebrate hearts have generally used preparations that were not performing at physiological levels of pressure and flow. The conclusions that ischaemia or hypoxia are not stressful to these organisms were examined in another species, Bufo marinus, in which a buffer-perfused heart was performing physiological levels of work. The in situ preparation demonstrated the Frank-Starling relationship and mechanical characteristics similar to the hearts of intact animals. The hearts recovered from 60 min of ischaemia and reperfusion with no reduction in pressure, flow or heart rate parameters. Hearts exposed to 30 min of hypoxia at physiological filling and diastolic afterload pressures ceased generating a continuous cardiac output during the hypoxia. In most cases, there was a gradual reduction of cardiac output to zero, but in 27% of the hearts studied, intermittent beating was observed. During reoxygenation, the hearts recovered 50-90% of their prehypoxic function and were damaged. Hearts exposed to hypoxia with reduced filling and diastolic afterload continued to develop a cardiac output throughout the hypoxia and demonstrated an overshoot phenomena with the onset of reoxygenation. If demand is in the normal range at the onset of hypoxia, the hearts intrinsically reduce demand either by reducing pressure development or by conversion to intermittent beating. Toad hearts appear not to be damaged by ischaemia, a condition in which demand is low.


[Radiometric study of the decarboxylating activity of desert soil microflora].
Employment of growth media containing salts of organic acids, labelled with 14C, gave a rapid and intensive signal concerning the decarboxylating activity of microorganisms from desert soils. The value of the signal was higher than that during the decomposition of uniformly labelled glucose. The results of these studies would help to select the optimal growth medium for carrying out exobiological experiments.


Neurocognitive Correlates of Attention-Deficit Hyperactivity Disorder Symptoms in Children Born at Extremely Low Gestational Age.
Compared with children born near term, those born extremely preterm (EP) are at much higher risk for attention-deficit hyperactivity disorder (ADHD). Little information is available about differences in neuropsychological outcomes among EP children with and without ADHD. Our analyses aimed to evaluate the neuropsychological correlates of ADHD symptoms in extremely low gestational age newborns (ELGANs). We obtained Child Symptom Inventory-4 reports from parents (n = 871) and teachers (n = 634) of 10-year-old children born before the 28th week of gestation. Participants completed standardized assessments of neurocognitive and academic functioning. In the total sample, children who screened positive for ADHD symptoms were at increased risk for neurocognitive limitations. These associations were weaker when the sample was limited to those with intelligence quotient (IQ) ≥70 or ≥85. Even those with IQ ≥85 who screened positive for ADHD symptoms were more likely than their peers to have deficits on the DAS-II Working Memory Cluster and the NEPSY-II Auditory Response subtest. The risks for impaired academic performance (Z ≤ -1) on components of the WIAT-III were 2-to-3 times higher in this group than among ELGANs not classified as having ADHD symptoms. Among children born EP, those with ADHD symptoms are more likely to have global neurocognitive impairment. When IQ is within normal limits, ADHD symptoms are associated with deficits in executive functioning skills. These findings highlight a group at risk for executive functioning deficits and related academic difficulties, even in the absence of intellectual disability.


6,12-Bis[(tri-cyclo-hexyl-sil-yl)ethyn-yl]indeno-[1,2-b]fluorene.
The title compound, C60H76Si2, a formally anti-aromatic system containing 20-π electrons, contains a rare p-xylylene motif. This is displayed by the alternating short and long bonds. The outer rings possess nearly homogenous bond lengths. In the crystal, the molecules forms layers perpendicular to the c axis and within these layers there are two one-dimensional stacks with one stack that has a sp (2) carbon contact of 3.283 (6) Å, less than the sum of the van der Waals radii. The center of the mol-ecule sits on an inversion center.


Gypenosides Production and Spermatogenesis Recovery Potentials of Extracts from Cell Suspension Cultures of Gynostemma pentaphyllum.
Gynostemma pentaphyllum (GP), also called Giao-co-lam, is a traditional Vietnamese herb, also known as the "Herb of Immortality", that grows throughout Asian countries and is used for the treatment of hematuria, edema in the pharynx and neck, tumors, and trauma. In this study, we investigated the effects of culture conditions on cell growth and total gypenoside accumulation in the GP suspension cells. Cells were cultured on Murashige and Skoog (MS) medium supplemented with 2.0 mg/L KIN and 0.5 mg/L IBA, and different inoculum sizes (2-4 g) for 10-24 days. The results showed that the optimum inoculum size and shaking speed were 3 g of callus and 120 rpm, respectively. The highest cell biomass reached was 5.833 g of fresh weight, corresponding to 0.136 g of dry weight after 20 days of culture. The total gypenoside and Rb1 accumulation was the highest after 18 days of culture, with 46.498 mg/g and 0.038 mg/g dry weight, respectively. In addition, the crude extract from GP cell suspension cultures remarkably improved pathological changes in mouse testicular tissue after scrotal heat exposure. Blood testosterone levels were significantly increased in heat-exposed mice treated with the GP cell suspension culture extract. Taken together, these results suggest that GP bio-mass production by cell suspension cultures leads to the accumulation of gypenosides in large amounts, and provides the potential for the recovery of spermatogenesis following heat stress.


A gastrin-releasing peptide receptor antagonist blocks D-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats.
The gastrin-releasing peptide receptor (GRPR) has emerged as a novel molecular target in neurological and psychiatric disorders, and previous animal studies suggest that GRPR antagonists might display cognitive-enhancing and antipsychotic properties. Hyperlocomotion produced by administration of D-amphetamine (D-AMPH) to rats has been put forward as a model of the manic phase of bipolar disorder (BD). In the present study, we examined the effects of a single systemic administration of the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095) on hyperlocomotion induced by a single systemic injection of D-AMPH in male rats. We also evaluated the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of rats treated with D-AMPH and RC-3095. Administration of RC-3095 at any of the doses used blocked D-AMPH-induced hyperlocomotion. Specific doses of RC-3095 increased the levels of NGF and BDNF in the dorsal hippocampus. Administration of D-AMPH did not affect NGF or BDNF levels by itself, but blocked the RC-3095 effects. The results suggest that GRPR antagonists might display anti-manic activity.


Autophagy in the lung.
Autophagy is a cellular process for the disposal of damaged organelles or denatured proteins through a lysosomal degradation pathway. By reducing endogenous macromolecules to their basic components (i.e., amino acids, lipids), autophagy serves a homeostatic function by ensuring cell survival during starvation. Increased autophagy can be found in dying cells, although the relationships between autophagy and programmed cell death remain unclear. To date, few studies have examined the regulation and functional significance of autophagy in human lung disease. The lung, a complex organ that functions primarily in gas exchange, consists of diverse cell types (i.e., endothelial, epithelial, mesenchymal, inflammatory). In lung cells, autophagy may represent a general inducible adaptive response to injury resulting from exposure to stress agents, including hypoxia, oxidants, inflammation, ischemia-reperfusion, endoplasmic reticulum stress, pharmaceuticals, or inhaled xenobiotics (i.e., air pollution, cigarette smoke). In recent studies, we have observed increased autophagy in mouse lungs subjected to chronic cigarette smoke exposure, and in pulmonary epithelial cells exposed to cigarette smoke extract. Knockdown of autophagic proteins inhibited apoptosis in response to cigarette smoke exposure in vitro, suggesting that increased autophagy was associated with epithelial cell death. We have also observed increased morphological and biochemical markers of autophagy in human lung specimens from patients with chronic obstructive pulmonary disease (COPD). We hypothesize that increased autophagy contributes to COPD pathogenesis by promoting epithelial cell death. Further research will examine whether autophagy plays a homeostatic or maladaptive role in COPD and other human lung diseases.


Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy.
Increasing prevalence of type 2 diabetes in women of childbearing age has led to a higher incidence of diabetes-associated birth defects. We established a model of type 2 diabetic embryopathy by feeding 4-week-old female mice a high-fat diet (HFD) (60% fat). After 15 weeks on HFD, the mice showed characteristics of type 2 diabetes mellitus (DM) and were mated with lean male mice. During pregnancy, control dams fed a normal diet (10% fat) were maintained on either normal diet or HFD, serving as a control group with elevated circulating free fatty acids. DM dams produced offspring at a rate of 11.3% for neural tube defect (NTD) formation, whereas no embryos in the control groups developed NTDs. Elevated markers of oxidative stress, endoplasmic reticulum stress, caspase activation, and neuroepithelial cell apoptosis (causal events in type 1 diabetic embryopathy) were observed in embryos of DM dams. DM dams treated with 200 mg/kg metformin in drinking water ameliorated fasting hyperglycemia, glucose intolerance, and insulin resistance with consequent reduction of cellular stress, apoptosis, and NTDs in their embryos. We conclude that cellular stress and apoptosis occur and that metformin effectively reduces type 2 diabetic embryopathy in a useful rodent model.


Phenology and spatial distribution of native and exotic Tetropium longhorned beetles (Coleoptera: Cerambycidae).
The co-existence of two closely related Tetropium species in eastern Canada, invasive T. fuscum and native T. cinnamopterum (TF and TC, respectively), provides a model system to investigate seasonal and spatial demographic parameters of biological invasions at the interspecific level. In this study, we take advantage of the similar semiochemical communication of TF and TC to evaluate the abundance of adults of the two species concurrently using grids of traps baited with pheromone and host volatiles in stands of spruce. Adult TF emerged on average 2 wk before TC both in the field and under controlled laboratory conditions. This observation, combined with the early reproduction of emergent females, implies that the smaller (younger) larvae of native TC may be at increased risk of intra-guild predation by TF. The high spatial association between male and female TF in dense, aggregated populations suggests that the rate of mate encounter is depressed in sparse populations toward the edge of the invasive range. The higher level of spatial aggregation for TF than TC, particularly at high population density, suggests a higher propensity of adult TF to congregate at "landmarks." Considering the broader range of host conditions, earlier seasonal emergence, and presumably more effective mate encounter for TF than TC, the exotic TF may be a superior competitor with the potential to displace or reduce the abundance of TC.


The Nottingham Fatigue after Stroke (NotFAST) study: factors associated with severity of fatigue in stroke patients without depression.
To identify factors associated with post-stroke fatigue in a sample of stroke survivors without depression. Cross-sectional cohort study. Recruitment was from four stroke units in the UK. Participants were assessed within four to six weeks of first stroke; those with high levels of depressive symptoms (score ⩾7 Brief Assessment Schedule Depression Cards) were excluded. Participants were assessed after stroke on the Fatigue Severity Scale of the Fatigue Assessment Inventory, the Rivermead Mobility Index, Nottingham Extended Activities of Daily Living scale, Beck Anxiety Index, Sleep Hygiene Index, 6m walk test, and measures of cognitive ability. Of the 371 participants recruited, 103 were excluded and 268 were assessed. Of the latter, the mean age was 67.7 years (SD 13.5) and 168 (63%) were men. The National Institutes of Health Stroke Scale mean score was 4.96 (SD 4.12). Post-stroke fatigue was reported by 115 (43%) of participants, with 71 (62%) reporting this to be a new symptom since their stroke. Multivariate analysis using the Fatigue Severity Scale as the outcome variable found pre-stroke fatigue, having a spouse/partner, lower Rivermead Mobility Index score, and higher scores on both the Brief Assessment Schedule Depression Cards and Beck Anxiety Index were independently associated with post-stroke fatigue, accounting for approximately 47% of the variance in Fatigue Severity Scale scores. Pre-stroke fatigue, lower mood, and poorer mobility were associated with post-stroke fatigue.


A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine.
Genetic pressure in animal breeding is sparking the interest of breeders for selecting elite boars with higher sperm quality to optimize ejaculate doses and fertility rates. However, the molecular basis of sperm quality is not yet fully understood. Our aim was to identify candidate genes, pathways and DNA variants associated to sperm quality in swine by analysing 25 sperm-related phenotypes and integrating genome-wide association studies (GWAS) and RNA-seq under a systems biology framework. By GWAS, we identified 12 quantitative trait loci (QTL) associated to the percentage of head and neck abnormalities, abnormal acrosomes and motile spermatozoa. Candidate genes included CHD2, KATNAL2, SLC14A2 and ABCA1. By RNA-seq, we identified a wide repertoire of mRNAs (e.g. PRM1, OAZ3, DNAJB8, TPPP2 and TNP1) and miRNAs (e.g. ssc-miR-30d, ssc-miR-34c, ssc-miR-30c-5p, ssc-miR-191, members of the let-7 family and ssc-miR-425-5p) with functions related to sperm biology. We detected 6128 significant correlations (P-value ≤ 0.05) between sperm traits and mRNA abundances. By expression (e)GWAS, we identified three trans-expression QTL involving the genes IQCJ, ACTR2 and HARS. Using the GWAS and RNA-seq data, we built a gene interaction network. We considered that the genes and interactions that were present in both the GWAS and RNA-seq networks had a higher probability of being actually involved in sperm quality and used them to build a robust gene interaction network. In addition, in the final network we included genes with RNA abundances correlated with more than four semen traits and miRNAs interacting with the genes on the network. The final network was enriched for genes involved in gamete generation and development, meiotic cell cycle, DNA repair or embryo implantation. Finally, we designed a panel of 73 SNPs based on the GWAS, eGWAS and final network data, that explains between 5% (for sperm cell concentration) and 36% (for percentage of neck abnormalities) of the phenotypic variance of the sperm traits. By applying a systems biology approach, we identified genes that potentially affect sperm quality and constructed a SNP panel that explains a substantial part of the phenotypic variance for semen quality in our study and that should be tested in other swine populations to evaluate its relevance for the pig breeding sector.


Aquaporin 4 IgG serostatus and outcome in recurrent longitudinally extensive transverse myelitis.
Studies focused on recurrent longitudinally extensive transverse myelitis (rLETM) are lacking. To determine the aquaporin 4 (AQP4) IgG detection rate using recombinant human APQ4-based assays in sequential serum specimens collected from patients with rLETM categorized as negative by first-generation tissue-based indirect immunofluorescence (IIF) assay and to define the clinical characteristics and motor disability outcomes in AQP4-IgG-positive rLETM. A search of the Mayo Clinic computerized central diagnostic index (October 1, 2005, through November 30, 2011), cross-linked with the Neuroimmunology Laboratory database, identified 48 patients with rLETM, of whom 36 (75%) were positive and 12 (25%) negative for neuromyelitis optica (NMO) IgG (per IIF of serial serum specimens). Stored serum specimens from "seronegative" patients were retested with recombinant human AQP4-based assays, including enzyme-linked immunosorbent, transfected cell-based, and fluorescence-activated cell-sorting assays. Control patients included 140 AQP4-IgG-positive patients with NMO, of whom a subgroup of 20 initially presented with 2 attacks of transverse myelitis (rLETM-onset NMO). AQP4-IgG serostatus, clinical characteristics, and Expanded Disability Status Scale score. Six patients with negative IIF results were reclassified as AQP4-IgG positive, yielding an overall AQP4-IgG seropositivity rate of 89%. Fluorescence-activated cell-sorting, cell-based, and enzyme-linked immunosorbent assays improved the detection rate to 89%, 85%, and 81%, respectively. The female to male ratio was 2:3 for AQP4-IgG-negative rLETM and 5:1 for AQP4-IgG-positive patients. The AQP4-IgG-positive patients with rLETM or rLETM-onset NMO were similar in age at onset, sex ratio, attack severity, relapse rate, and motor disability. From Kaplan-Meier analyses, 36% of AQP4-IgG-positive patients with rLETM are anticipated to need a cane to walk within 5 years after onset. For patients with rLETM-onset NMO, the median time from onset to first optic neuritis attack (54 months) was similar to the median disease duration for AQP4-IgG-positive patients with rLETM (59 months). The median number of attacks was 3 for AQP4-IgG-positive patients with rLETM (range, 2-22), and the first optic neuritis attack for those with rLETM-onset NMO followed a median of 3 myelitis attacks (range, 2-19). Immunosuppressant therapy reduced the relapse rate in both AQP4-IgG-positive and AQP4-IgG-negative patients with rLETM. Recombinant antigen-based assays significantly increase AQP4-IgG detection in patients with rLETM, and AQP4-IgG-negative adults with rLETM are rare. Evolution to NMO can be anticipated in AQP4-IgG-positive patients. Early initiation of immunotherapy may result in a more favorable motor outcome.


[Benign thyroid nodule: what is the treatment? Personal experience].
Solitary thyroid nodule is an important pathology with an incidence of 2-5% in the Italian population. The diagnosis was based on clinical exam, laboratory tests and ultrasonographic evaluation. The study undertook has the purpose to assess the usefulness between lobe-isthmusectomy (with corresponding risk of possible relapse and complications for reintervention) and total thyroidectomy (with corresponding post-surgical treatment complications), for benign thyroid disease with solitary nodule, on selected cases for disease and corresponding risk factors, in the retrospective clinical study, using laboratory tests and ultrasonographic evaluation. The study was conducted on 80 patients admitted from 1994 to 2000 with diagnosis of benign thyroid nodule and operated with lobe-isthmusectomy. In seven patients the operation had to be converted in total thyroidectomy. Operative mortality was nil and long-term results at a mean follow-up of three years are encouraging. The main advantages of lobe-isthmusectomy for benign solitary thyroid nodule consist in less postoperative complications and less hospital stay. Therefore our experience has carried us to consider the lobectomy which treatment of choice for all those benign thyroid diseases with solitary nodule.