Health-Related Quality of Life and Rehabilitation Costs of Patients with Amputated Limb.
The aim of this study was the evaluation of health-related quality of life (HRQoL) and rehabilitation costs of patients with amputated limb. This is a cross-sectional study and the study sample, which was a sample of convenience, included 100 patients with amputated limb. The tools of the survey were the Short Form Questionnaire-36 (SF-36) and the Questionnaire used for measuring rehabilitation costs in trauma patients by Stergiannis et al.Results: The sample of the study consisted of 107 patients with amputation. HRQoL significantly increased (p < 0.001) between all-time points. According to the patients' answers, there were zero costs related to rehabilitation 1 year after the amputation. The type of edge amputation had significant impact on the rate of HRQoL increase. Rehabilitation costs increased over time during the first year. The mean (SD) rehabilitation cost was 1372 (2200) € at the first 6 months and 4774 (9109) € at the second half year. HRQoL was associated with age at all-time points and with costs of purchase of special pharmaceuticals, hospitalization, other expenses, number of medical visits, and cost of phone calls. The economic costs due to the amputation need to be studied as they affect the extent to which an amputated patient can meet his new emerging needs. Therefore, future research should focus in the economic dimension of the amputation in relation with the HRQoL of these patients and their relatives, so that new health policies may be conducted.


The effect of levamisole on postoperative immunosuppression.
Cell mediated immunity was studied before and after surgery in patients with colorectal cancer. Thymus-derived (T) lymphocytes were enumerated and their non-specific activity was measured by assessing phytohaemagglutinin (PHA)-induced blastogenesis. Specific T lymphocyte activity was measured by leucocyte migration inhibition in response to purified protein derivative of tuberculin (PPD) and autochthonous tumour extract. One group of patients received levamisole postoperatively and the other group consisted of controls. There was a more rapid return to preoperative levels of leucocyte migration inhibition to both antigens by the levamisole group. However, levamisole administration had only a marginal effect on the postoperative depression of cell counts and did not restore depressed lymphoblast transformation.


Basic pancreatic trypsin inhibitor has unusual thermodynamic stability parameters.
The stability parameters delta Gst, delta Hst and delta Sst of native basic pancreatic trypsin inhibitor (BPTI) have been characterized by microcalorimetric unfolding studies in various buffer solutions, at different pH values and in the presence of guanidine hydrochloride. The unfolding enthalpy of BPTI, in contrast ot other globular proteins, exhibits a very small dependence on temperature, which results in a characteristic different temperature dependence of the Gibbs energy of stabilization. BPTI has a very high specific Gibbs energy of stabilization, which renders the slow exchange rates of amide protons understandable. Comparison of the unfolding entropy of BPTI at 110 degrees C with corresponding values of other proteins, revealed that the delta S values of BPTI are lower by 2.9 J/(K X residue). This lower value of the unfolding entropy is in good agreement with predictions of a theoretical study by Poland & Scheraga (1965) where the influence of crosslinks on the configurational entropy has been studied. Additionally, we were able to calculate an interaction enthalpy per site of -5.6 kJ/mol based on the measurements of unfolding of BPTI in 6 M-guanidine hydrochloride.


Closing the gap: Novel therapies in treating acute lymphoblastic leukemia in adolescents and young adults.
Acute lymphoblastic leukemia (ALL) is one of the most common cancer diagnoses identified in adolescents and young adults (AYAs). Although most children with ALL are cured of their disease, AYAs have experienced much worse outcomes over time, with event-free survival ranging from 30 to 45%. This survival disparity is likely due to differences in tumor biology, treatment-related toxicities, and nonmedical issues. This review summarizes these differences as well as focusing on the various trials that have demonstrated superior outcomes with pediatric protocols in AYAs with ALL. Even with the widespread use of these protocols, a treatment gap remains, and novel therapies are one way to address this problem. Still, these therapies also have significant toxicities and unique issues that need to be tested further, especially in the AYA population. The development of more AYA-specific trials will be an important way to examine novel therapies and interventions designed to reduce treatment-related toxicities and improve long-term outcomes.


Comparison of steroid-releasing stents vs nonabsorbable packing as middle meatal spacers.
A randomized controlled trial was held to compare nonabsorbable packs to steroid-eluting absorbable stents as middle meatal spacers after endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS). CRS patients were randomly assigned to receive either nonabsorbable Merocel packs wrapped in non-latex glove material (packing type A) or Propel steroid eluting stents (packing type B). Twenty-two-item Sino-Nasal Outcome Test (SNOT-22) scores were collected preoperatively and postoperatively during the initial 4 debridements up to 3 months. Recording of the nasal endoscopy was also collected during all postoperative visits. In addition, Lund-Kennedy scores and middle turbinate lateralization scores, using a new visual analogue scale, were compared between the 2 types of packing. Forty CRS patients were prospectively enrolled in this institutional review board (IRB)-approved study. Patients with packing type A had significantly lower middle turbinate lateralization scores at their first (∼10 days) postoperative visit (p = 0.02 and p = 0.04, for left and right sides, respectively). This difference disappeared by later postoperative visits (from 20 days to 3 months). Overall, patients receiving packing type A had significant lower SNOT-22 scores at 20 days postsurgery (p = 0.05). This difference also disappeared at 1 and 3 months postoperation. There were no statistically significant differences in Lund-Kennedy scores. In this study, nonabsorbable packing materials showed significant superior middle meatal spacing capacities as evidenced by greater middle turbinate medialization capability at the first postoperative visit. Additionally, patients with this type of packing saw improvements in their SNOT-22 scores at the 20-day postoperative visit. This study showed that there was no significant improvement in postoperative outcomes with drug-eluting stents when compared to nonabsorbable packing.


Influence of social factors on patient-reported late symptoms: Report from a controlled trial among long-term head and neck cancer survivors in Denmark.
The incidence of head and neck cancer and morbidity and mortality after treatment are associated with social factors. Whether social factors also play a role in the prevalence of late-onset symptoms after treatment for head and neck cancer is not clear. Three hundred sixty-nine survivors completed questionnaires on late symptoms and functioning. Survivors with short education were more likely to report severe problems than those with medium or long education. In the fully adjusted model, the risk for problems with opening the mouth remained significantly increased (odds ratio [OR] = 3.20; 95% confidence interval [CI] = 1.18-8.63). For survivors who lived alone, the adjusted ORs were significantly increased for physical functioning (2.17; 95% CI = 1.01-4.68) and trouble with social eating (OR = 2.26; 95% CI = 1.14-4.47). Self-reported severe late symptoms were more prevalent in survivors with short education and in those living alone, suggesting differences in perception of late symptoms between social groups. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1713-E1721, 2016.


Efficacy, safety, and tolerability of once-daily abediterol in patients with stable, persistent asthma: a Phase II, randomized, 7-day, crossover study.
Abediterol is a once-daily, long-acting β2 -adrenergic agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. We assessed the efficacy, safety, and tolerability of three dose levels of abediterol, given once daily for 7 days in patients with stable, persistent asthma. This was an ascending-dose, three-period incomplete crossover study design investigating three dose levels of abediterol versus placebo (EudraCT No. 2008-003732-38). Twenty-eight male patients (25-59 years) were randomized to one of four treatment sequences (1:1:1:1). Follow-up was 7 days after final treatment. Spirometry was performed regularly up to 24 h postdose Day 1, up to 36 h postdose Day 7, and at follow-up. Vital signs, 12-lead electrocardiogram, and clinical laboratory tests were recorded throughout. Abediterol 2.5, 5, and 10 μg provided clinically and statistically significant improvements from baseline (predose, Day 1) in trough forced expiratory volume in 1 sec (FEV1 ) versus placebo on Day 7 (primary endpoint) of 334, 365, and 294 mL, respectively (all P < 0.01), and peak FEV1 versus placebo on Day 7 of 364 (P < 0.001), 403 (P < 0.001), and 375 mL (P < 0.01), respectively. Days 1 and 7 area under the curve (AUC) parameters within each abediterol group were similar for AUC0-6 , AUC0-12 , AUC0-24 , and AUC12-24 , with dose-dependent effects observed on Day 1. Abediterol (2.5-10 μg) demonstrated a good safety and tolerability profile. Abediterol 2.5, 5, and 10 μg once daily achieved statistically and clinically significant improvements in pulmonary function versus placebo over 7 days and demonstrated a safety and tolerability profile comparable with placebo.


Arachidonic acid and its metabolites increase cytosolic free calcium in bovine luteal cells.
We studied the effects of arachidonic acid and its metabolites on intracellular free calcium concentrations ([Ca2+]i) in highly purified bovine luteal cell preparations. Corpora lutea were collected from Holstein heifers between days 10 and 12 of the estrous cycle. The cells were dispersed and small and large cells were separated by unit gravity sedimentation and flow cytometry. The [Ca2+]i was determined by spectrofluorometry in luteal cells loaded with the fluorescent Ca2+ probe, Fura-2. Arachidonic acid elicited a dose-dependent increase in [Ca2+]i in both small and large luteal cells, having an effect at concentrations as low as 5 microM; and was maximally effective at 50 microM. Several other fatty acids failed to exert a similar response. Addition of nordihydroguaiaretic acid (NDGA) or indomethacin failed to suppress the effects of arachidonic acid. In fact, the presence of both inhibitors resulted in increases of [Ca2+]i, with NDGA exerting a greater stimulation of [Ca2+]i than indomethacin. Prostaglandin F2 alpha (PGF2 alpha) as well as prostaglandin E2 (PGE2) increased [Ca2+]i in the small luteal cells. These results support the idea that arachidonic acid exerts a direct action in mobilizing [Ca2+]i, in the luteal cells. Furthermore, they demonstrate that the cyclooxygenase (PGF2 alpha and PGE2) and lipoxygenase products of arachidonic acid metabolism also play a role in increasing [Ca2+]i in bovine luteal cells. Since the bovine corpus luteum contains large quantities of arachidonic acid, these findings suggest that this compound may regulate calcium-dependent functions of the corpus luteum, including steroid and peptide hormone production and secretion.


[Effect of intracoronary dipyridamole administration on the incidence of restenosis after PTCA. A prospective randomized study].
Restenosis after PTCA remains a serious long-term complication of balloon angioplasty occurring in 30 to 50% of patients. Platelets play a crucial role in the pathogenesis of restenosis following PTCA. Dipyridamole has been shown to inhibit platelet aggregation in humans. Its action as an antithrombotic drug can be attributed to different mechanisms including inhibition of platelet phosphodiesterase and inhibition of the cellular uptake of adenosine. The purpose of the following study was to investigate the effect of an intracoronary infusion of dipyridamole on the incidence of angiographic and clinical restenosis. In 763 balloon angioplasties patients were randomly allocated to receive either conventional pretreatment (heparin 15000 IE, aspirin 500 mg i.v.) or an additional intracoronary infusion of dipyridamole (0.5 mg/kg body weight). Conventional pretreatment was performed in 388 interventions (61 interventions in women, age 60.5 +/- 8.7 years; 47 interventions for acute coronary syndromes); in 375 interventions additional intracoronary dipyridamole was infused (58 interventions in women, age = 59.6 +/- 9.6 years; 57 interventions for acute coronary syndromes). As compared to conventional pretreatment intracoronary dipyridamole application was associated with a reduction in angiographic restenosis from 43.0% to 36.8% and a reduction of target vessel revascularisation by 15.5% but failed to reach statistical significance. These results were due to an increase in net gain following dipyridamole application. Intracoronary pretreatment with dipyridamole prior to PTCA fails to reduce the incidence of angiographic restenosis and target vessel revascularisation significantly. However, a moderate improvement of long-term follow-up can be achieved.


Dietary intake of Spirulina platensis alters HSP70 gene expression profiles in the brain of rats in an experimental model of mixed stress.
Spirulina platensis has gradually gained more attention for its therapeutic, antioxidant, and anti-inflammatory potential worldwide. However, the current molecular knowledge about the effects of spirulina on stress-related genes is rather limited. The effects of dietary intake of spirulina on the HSP70 gene expression were assessed in a controlled in vivo experimental design. Moreover, alterations in serum corticosterone levels, IL-2, IL-4, IFN-Υ, triglyceride, ALT, AST, relative gene expression values, and the correlations between them were evaluated. A total of 36 rats were divided into four groups: control group, stress-only group, spirulina group, and spirulina+stress group. To control the dose administration, S. platensis was applied by a gastric gavage in stress groups. Crowded environment stress and hosting alone stress were applied to the stress-only group and spirulina + stress group. RNA was extracted from brain samples using TRIpure and the relative gene expression assessment was performed using Roche-LightCycler-480-II real-time PCR-System. Gene expression values were remarkably different among the four experimental groups. The differences between stress-only and the spirulina groups were statistically significant (P<0.05). The correlation between the HSP70 gene expression and the IFN-Υ was found to be statistically significant (P<0.05; r=0.50). Results indicate a novel effect of spirulina on the HSP70 expression related to the stress-response. Data presented in this study may be useful for further studies to define not only the molecular genetic aspects through dietary S. platensis but also the effects of spirulina on stress-response and animal welfare.


[Feeding gastrostomy--last possibility for a palliative operation in malignant stenoses of the esophagus-cardia].
From 1960-1980 we operated 326 patients suffering from a malignant stenosis of the esophagus-cardia region. We had to establish a nutritional fistula as a palliative operation in 56 patients (17.2%). The operative tactics and the final results are described. The postoperative lethality with these dangerously ill patients is up to 23.9%.


A single homozygous point mutation in a 3'untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy.
Mutations in the SEPN1 gene encoding the selenoprotein N (SelN) have been described in different congenital myopathies. Here, we report the first mutation in the selenocysteine insertion sequence (SECIS) of SelN messenger RNA, a hairpin structure located in the 3' untranslated region, in a patient presenting a classical although mild form of rigid spine muscular dystrophy. We detected a significant reduction in both mRNA and protein levels in the patient's skin fibroblasts. The SECIS element is crucial for the insertion of selenocysteine at the reprogrammed UGA codon by recruiting the SECIS-binding protein 2 (SBP2), and we demonstrated that this mutation abolishes SBP2 binding to SECIS in vitro, thereby preventing co-translational incorporation of selenocysteine and SelN synthesis. The identification of this mutation affecting a conserved base in the SECIS functional motif thereby reveals the structural basis for a novel pathological mechanism leading to SEPN1-related myopathy.


Spatiotemporal characterization of atrial activation in persistent human atrial fibrillation: multisite electrogram analysis and surface electrocardiographic correlations--a pilot study.
The mechanisms of persistent human atrial fibrillation (AF) are not well understood. The purpose of this study was to examine whether left atrial (LA) drivers are present in persistent AF by performing a comprehensive evaluation of atrial activation frequency and organization using multisite atrial recordings and correlating the findings with atrial waveform frequency and organization on surface ECG. Nine patients undergoing catheter ablation for persistent AF were studied. Electrograms were recorded from at least 10 sites in each atrium, tagged to an electroanatomic map, and subjected to spectral analysis. Dominant frequency (DF) and regularity index were calculated at each site. Surface ECG recordings were analyzed to obtain precordial lead DFs and AF vector stability index. Mean, maximum, and minimum DF and mean regularity index were higher in LA than right atrium (RA). DF was correlated with regularity index (R = 0.59, P <.0001) and negatively correlated with distance from maximal DF site (R = -0.80, P <.0001). Precordial lead DFs were highly correlated with atrial DFs. Vector stability index was 0.39 +/- 0.12 (P <.01 vs predicted if AF vector direction was random). LA-RA DF gradient and vector stability index were negatively correlated (R = -0.83, P <.05). The existence of LA-RA frequency gradients in most patients in this study along with the regularity of LA activation and centrifugal dissipation of activation frequency suggest that LA drivers are often present in persistent AF. Analysis of AF vectors from surface ECG demonstrates spatial stability and correlates with intracardiac recordings. These findings may have implications for catheter ablation of persistent AF.


Gene structure of rat cathepsin H.
The gene structure of rat cathepsin H was determined. It comprises at least 12 exons of various lengths (32-433 bp) spanning in total more than 17.5 kbp. The gene structure does not correspond well to the functional unit of the proteinase. The region around the active site Cys residue, the most conserved region among cysteine proteinases, is split by an intron. This is a common characteristic among the gene structures of cysteine proteinases.


Effect of Astaxanthin on the Antioxidant Capacity and Intestinal Microbiota of Tsinling Lenok Trout (Brachymystax lenok tsinlingensis).
Astaxanthin (Ast) has been shown to be beneficial for the antioxidant capacity, immune system, and stress tolerance of fish. This study was conducted to investigate the effects of dietary supplementation of Ast on the antioxidant capacity and intestinal microbiota of tsinling lenok trout. We formulated four diets with 0 (CT), 50 (A50), 100 (A100), and 150 (A150) mg/kg Ast. The results showed that Ast increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), lysozyme (LZM), and catalase (CAT) activities. Malondialdehyde (MDA) content was lower in A150 and A100 than in CT (P < 0.05). Furthermore, the activities of acid phosphatase (ACP) were higher in A100 and A150 than in CT (P < 0.05). We harvested the midgut and applied next-generation sequencing of 16S rDNA. Compared to the control group, the Ast group had a greater abundance of Halomonas. Functional analysis showed that polycyclic aromatic hydrocarbon degradation was significantly higher with Ast, while novobiocin biosynthesis and C5-branched dibasic acid metabolism were significantly lower with Ast. In conclusion, Ast could enhance the antioxidant capacity, non-specific immunity, and intestinal health of tsinling lenok trout.


The transjugular intrahepatic portosystemic stent-shunt (TIPSS): results of a pilot study.
The new concept of TIPSS (Transjugular Intrahepatic Portosystemic Stent-Shunt) using the Palmaz iliac stent was successfully accomplished in 9 patients with severe portal hypertension (7 alcoholic, 2 postinfectious liver cirrhosis) and histories of multiple life-threatening upper GI bleeding. All patients were considered noncandidates for surgical portal decompression. An intrahepatic central connection was made transjugularly between the right hepatic vein and the right portal vein in 8 patients and the left portal vein in 1. The portosystemic gradient dropped from an average of 29 +/- 7.2 mmHg to 17.8 +/- 2.9 mmHg immediately after, and to 15.7 +/- 2.8 mmHg at the latest follow-up control after the procedure. Seven patients survived the procedure and progressed to Child's A stage during the observation period of 1-10 months (mean 5 months). One patient died as a direct complication from the procedure, and another patient 11 days after the procedure from a severe nosocomial infection. In none of the surviving patients has bleeding from varices recurred or encephalopathic coma developed. In one patient the shunt diameter was moderately increased by a routine PTA catheter to further decrease the portosystemic gradient (23 to 14 mmHg) 3 months after the primary procedure. Autopsy in the two patients who died demonstrated open stent-shunts with early neoendothelial incorporation.


Prescribed fire maintains host plants of a rare grassland butterfly.
As grassland ecosystems transform globally due to anthropogenic pressures, improvements in our understanding of the effect of management on rare and threatened species in such landscapes has become urgent. Although prescribed fire is a very efficient tool for habitat restoration and endangered species management on fire-adapted ecosystems, the specific mechanisms underlying potential effects of burning on population dynamics of butterfly host plants are poorly understood. We analyzed a 12-year dataset (2004-2015), combining violet abundance, habitat physiognomy and fire history data from a fire-managed system, to determine factors influencing the spatiotemporal distribution and abundance of violets (Viola spp.), the host plants of the threatened eastern regal fritillary (Speyeria idalia idalia) butterfly. Our results demonstrate a critical role for fire in driving both presence and abundance of violets, suggesting management with prescribed fires can effectively promote butterfly host plants. In addition, we determined the character of habitats associated with violet presence and abundance, in particular a strong positive association with biocrusts. These results provide a roadmap for efficient site selection to increase the effectiveness of restoration efforts, including assessment of potential reintroduction sites for regal fritillary and other grassland butterflies and actions to promote the re-establishment of host plants in these sites.


6'-Bromo-1'H-spiro-[cyclo-hexane-1,2'-pyrido[2,3-d]pyrimidin]-4'(3'H)-one.
The title compound, C(12)H(14)BrN(3)O, is built up from two fused six-membered rings and one six-membered ring linked through a spiro C atom. The hydro-pyrimidine ring has an envelope conformation and the cyclo-hexane ring is in a chair conformation. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds, forming a mol-ecular tape along the b axis.


Membrane-bound potassium and magnesium ion-stimulated inorganic pyrophosphatase from roots and cotyledons of sugar beet (Beta vulgaris L).
1. The 25 000-30 000 X g fraction from sugar beet leaf or roots contains, together with (Na+ plus K+)-activated ATPase, also K+-stimulated inorganic pyrophosphatase. 2. This inorganic pyrophosphatase is also stimulated by Rb+ and to a lesser degree by Li+ and Na+. 3. Na+ is at the same time an inhibitor to the K+-stimulation of the inorganic pyrophosphatase. 4. No signs of synergism for (Na+ plus K+) were found. 5. Optimum pH was at about 8.5.


Na+/Ca2+ exchanger: target for oxidative stress in salt-sensitive hypertension.
The Na+/Ca2+ exchanger regulates intracellular calcium ([Ca2+]i), and attenuation of Na+/Ca2+ exchange by oxidative stress might lead to dysregulation of [Ca2+]i. We have shown that the Na+/Ca2+ exchanger differs functionally and at the amino acid level between salt-sensitive and salt-resistant rats. Therefore, the purpose of these studies was to determine how oxidative stress affects the activities of the 2 Na+/Ca2+ exchangers that we cloned from mesangial cells of salt-resistant (RNCX) and salt-sensitive (SNCX) Dahl/Rapp rats. The effects of oxidative stress on exchanger activity were examined in cells expressing RNCX or SNCX by assessing 45Ca2+ uptake (reverse mode) and [Ca2+]i elevation (forward mode) in the presence and absence of H2O2 and peroxynitrite. Our results showed that 45Ca2+ uptake in SNCX cells was attenuated at 500 and 750 micromol/L H2O2 (63+/-12% and 25+/-7%, respectively; n=16) and at 50 and 100 micromol/L peroxynitrite (47+/-9% and 22+/-9%, respectively; n=16). In RNCX cells, 45Ca2+ uptake was attenuated at only 750 and 100 micromol/L H2O2 and peroxynitrite (61+/-9% and 63+/-6%, respectively; n=16). In addition, the elevation in [Ca2+]i was greater in SNCX cells than in RNCX cells in response to 750 micromol/L H2O2 (58+/-5.5 vs 17+/-4.1 nmol/L; n=13) and 100 micromol/L peroxynitrite (33+/-5 vs 11+/-6 nmol/L; n=19). The enhanced impairment of SNCX activity by oxidative stress might contribute to the dysregulation of [Ca2+]i that is found in this model of salt-sensitive hypertension.


Universality in RNA and DNA deformations induced by salt, temperature change, stretching force, and protein binding.
Nucleic acid deformations play important roles in many biological processes. The physical understanding of nucleic acid deformation by environmental stimuli is limited due to the challenge in the precise measurement of RNA and DNA deformations and the complexity of interactions in RNA and DNA. Magnetic tweezers experiments provide an excellent opportunity to precisely measure DNA and RNA twist changes induced by environmental stimuli. In this work, we applied magnetic tweezers to measure double-stranded RNA twist changes induced by salt and temperature changes. We observed RNA unwinds when lowering salt concentration, or increasing temperature. Our molecular dynamics simulations revealed the mechanism: lowering salt concentration or increasing temperature enlarges RNA major groove width, which causes twist decrease through twist-groove coupling. Combining these results with previous results, we found some universality in RNA and DNA deformations induced by three different stimuli: salt change, temperature, and stretching force. For RNA, these stimuli first modify the major groove width, which is transduced into twist change through twist-groove coupling. For DNA, these stimuli first modify diameter, which is transduced into twist change through twist-diameter coupling. Twist-groove coupling and twist-diameter coupling appear to be utilized by protein binding to reduce DNA and RNA deformation energy cost upon protein binding.


Solitary keratoacanthoma of the conjunctiva.
Two ranch workers had rapidly-growing crateriform conjunctival nodules excised without recurrence. Histopathologically, these lesions consisted of acanthotic epithelium characterized by prominent keratin formation both within cells and in horn pearls. Although both clinically and histologically they resemble squamous cell carcinoma, keratoacanthomas are benign tumors commonly thought to arise in hair follicles. The presence of these lesions on conjunctiva and other epithelia without hair in the two cases described was evidence against this hypothesis.


Long noncoding RNA expression patterns in lymph node metastasis in colorectal cancer by microarray.
To profile the long noncoding RNA (lncRNA) expression patterns in normal lymph node (NLN) of colorectal cancer compared with paired metastatic lymph node (MLN). MLN, NLN lncRNA and messenger RNA (mRNA) expression levels were determined by microarray in three patients; quantitative reverse transcription-polymerase chain reaction validation of 3 differentially expressed lncRNAs was conducted in another 26 patients. The lncRNAs' functions were predicted through coexpressed mRNA annotations. A total of 1133 lncRNA transcripts transcripts were dysregulated in metastatic lymph node, compared with normal lymph node. The expressions of the 3 chosen lncRNAs were validated by quantitative reverse transcription-polymerase chain reaction. Functional analysis suggests that several groups of lncRNAs may participate in biological pathways related to colorectal cancer by cis- and/or trans-regulation of protein-coding genes. This study constitutes the first report of lncRNA expression patterns in human MLN, NLN of colorectal cancer. More than 1000 dysregulated lncRNA transcripts are found by microarray.


Structural alterations of double-stranded DNA in complex with the adenovirus DNA-binding protein. Implications for its function in DNA replication.
The Adenovirus DNA-binding protein (DBP) binds to single-stranded (ss) DNA as well as to double-stranded (ds) DNA and forms multimeric protein-DNA complexes with both. Gel retardation assays indicate rapid complex formation for both DNAs. DBP rapidly dissociates from dsDNA, indicating a dynamic equilibrium, whereas the ssDNA-DBP complex is much more stable. We investigated the complex between DBP and dsDNA in more detail. Electron microscopical analysis shows thick filament-like and beaded structures in which the length of the DNA is not significantly altered. Cryo-electron micrographs suggest the presence of interwound protein fibres around the DNA. Ligase-mediated cyclization, but not linear multimerization, of DBP-saturated DNA fragments exceeding the persistence length was severely inhibited. This suggests that DNA may be organized by DBP into a rigid structure. Under those conditions, DBP induces distinct changes in the circular dichroism spectrum of the DNA, indicative of structural DNA changes. No bending or twisting of the complex was observed. Hydroxyl radical footprinting showed that the breakdown pattern of DNA at saturating DBP concentrations is much more regular than the protein-free DNA. This suggests the removal of tertiary structures, which may be related to the effects of DBP on enhanced NFI binding and chain elongation during Adenovirus DNA replication. Using purified proteins in an in vitro replication system, we correlate the structural changes with the effects of DBP on enhancement of NFI-binding as well as on DNA replication.


The role of organoids in cancer research.
Organoids are established through in vitro 3D culture, and they can mimic the structure and physiological functions of organs or tissues in vivo. Organoids have attracted much attention in recent years. They can provide a reliable technology platform for cancer research and treatment and are a valuable preclinical model for academic research and personalized medicine. A number of studies have confirmed that organoids have great application prospects in new drug development, drug screening, tumour mechanism research, and precision medicine. In this review, we mainly focus on recent advances in the application of organoids in cancer research. We also discussed the opportunities and challenges facing organoids, hoping to indicate directions for the development of organoids in the future.


Long-term effects of natalizumab on MRI activity and clinical outcomes in Japanese patients with relapsing-remitting multiple sclerosis.
Relapsing-remitting multiple sclerosis (RRMS) is the most common phenotype of multiple sclerosis (MS), and its active stage is characterized by active T2 lesions with or without gadolinium (Gd) enhancement on magnetic resonance imaging (MRI). Natalizumab is indicated as monotherapy in adults with active RRMS in Japan. The main objective of this study was to investigate the long-term effect of natalizumab on disease progression in Japanese patients with RRMS using MRI data. This retrospective, chart review study was conducted at a single center in Japan. The main study outcome was the yearly proportion of patients with active T2-weighted image lesions detected with or without Gd enhancement on brain MRI (incidence rate) after treatment initiation for up to 5 years. Additional endpoints included annual relapse rate (ARR) and expanded disability status scale (EDSS) score. This study included data from 85 patients with RRMS who had received natalizumab for ≥ 1 year; of these, 65 (76.5%) were female and the mean ± standard deviation (SD) age at baseline was 37.5 ± 10.0 years. The incidence rate of active T2 lesions was 52.9% (45/85) in the year prior to natalizumab treatment (Year - 1), which decreased to 2.4% and 1.6% in Year 0.5-1.5 and Year 1.5-2.5, respectively. No active T2 lesions were detected in Year 2.5-5.5 in patients who continued natalizumab treatment. EDSS score was stable, improved, and worsened in 61.8%, 26.3%, and 11.8% of patients, respectively. The median (range) EDSS score was 2.0 (0.0-7.0) at baseline (n = 85) and remained within a similar range (median score between 1.0 and 2.25 during Years 1-5). ARR decreased from 1.12 relapses per year at baseline to 0.12 relapses per year during Year 1 and remained below 0.15 relapses per year up to Year 5. The results of this first long-term study evaluating the effect of natalizumab on MRI activity and clinical outcomes in Japanese patients with RRMS suggest that natalizumab markedly reduced disease activity and maintained effectiveness over several years.


Biogeochemical characterisation of a coal tar distillate plume.
The distillation of acidified coal tars for up to 50 years has given rise to a phenol plume approximately 500 m long, 50 m deep and containing up to 15 g l(-1) dissolved organic carbon (DOC) in the Triassic Sandstones aquifer. A conceptual biogeochemical model based on chemical and microbiological analysis of groundwater samples has been developed as a preliminary to more detailed studies of the controls on natural attenuation. While the development of redox zones and the production of methane and carbon dioxide provide evidence of natural attenuation, it appears that degradation is slow. The existence of sulphate in the plume indicates that this electron acceptor has not been depleted and that consequently methanogenesis is probably limited. Based on a simple estimate of sulphate input concentration, a half-life of about 15 years has been estimated for sulphate reduction. Geochemical modelling predicts that increased alkalinity within the plume has not led to carbonate precipitation, and thus within the limits of accuracy of the measurement, alkalinity may reflect the degree of biodegradation. This implies a loss of around 18% of the DOC over a 30-year period. Despite limited degradation, microbial studies show that there are diverse microbial communities in the aquifer with the potential for both anaerobic and aerobic biodegradation. Microbial activity was found to be greatest at the leading edge of the plume where DOC concentrations are 60 mg l(-1) or less, but activity could still be observed in more contaminated samples even though cells could not be cultured. The study suggests that degradation may be limited by the high phenol concentrations within the core of the plume, but that once diluted by dispersion, natural attenuation may proceed. More detailed studies to confirm these initial findings are identified and form the basis of associated papers.


FOXO in B-cell lymphopoiesis and B cell neoplasia.
FOX O family transcription factors are important for differentiation and function of multiple cell types. In B lymphocytes they play a critical role. The activity of FOXOs is directly regulated both by signaling from B cell receptor (BCR) and cytokine receptors. FOXO1 action controls the transition between differentiation stages of B cell development. In comparison to other FOXO family members, FOXO1 plays a superior role in the regulation of early stages of B-cell differentiation. Although being known as a negative regulator of cell proliferation and therefore potential tumor suppressor, FOXO1 is downregulated only in Hodgkin lymphoma (HL) subtypes. In non-Hodgkin lymphoma (NHL) entities its expression is maintained at significant levels, raising the question on the role of FOXO-transcription factors in the proliferation and survival programs in the process of B cell differentiation as well as their contribution to the oncogenic programs of B-cell lymphomas. In particular, we discuss molecular mechanisms that might determine the switch between pro-apoptotic and pro-survival effects of FOXO1 and their interplay with specific differentiation programs.


Accuracy of antenatal ultrasound signs in predicting the risk for bowel atresia in patients with gastroschisis.
Evaluate accuracy of prenatal ultrasound findings in predicting the risk of bowel atresia in patients with gastroschisis. A retrospective study was conducted on 18 fetuses with a prenatal diagnostic of gastroschisis treated at University hospital of Saint Etienne France between 2002 and 2012. Ultrasound abnormalities were used to classify them into three groups: no ultrasound abnormality (n=4), oligohydramnios (n=9), intra-abdominal bowel dilatation ≥20.5mm (n=5). Postnatal outcomes were compared between groups. The threshold value of 20.5mm for the prediction of atresia was determined through the receiver operator characteristics curve. In the group with oligohydramnios, intra uterine growth restriction were significantly more frequent (p=0.015) and three newborns had serositis including two with secondary complications after the initial surgery. In the group with major intra-abdominal bowel dilatation, all had a narrow defect <10mm significantly more than other fetuses (p=0.002). Intra-abdominal bowel dilatation reaching 20.5mm started at a mean gestational age significantly lower than that of the other fetuses (23.3 versus 29.7 weeks p=0.02). On the five fetuses presented intra-abdominal bowel dilatation ≥20.5mm, four showed atresia and no other newborn has this complication (p=0.0016). The threshold value of 20.5mm has a sensitivity of 100% and a specificity of 92.9%. The area under the curve was equal to 96.4%. Intra-abdominal bowel dilatation ≥20.5mm seems to be associated with the risk of postnatal atresia. MRI could help to clarify a complicated or uncertain ultrasound aspect.


A portable microfluidic device-based Fe3O4-urease nanoprobe-enhanced colorimetric sensor for the detection of heavy metals in fish tissue.
A portable microfluidic device with highly sensitive enzyme nanoprobe (Fe3O4 MNPs-urease, average size 34.6 nm) was demonstrated for the analysis of heavy metals ions (Hg2+, Cd2+ and Pb2+) in fish gill and muscle tissue. The immobilized urease nanoprobe (Km = 0.05 mM) exhibited twofold sensitivity over the free enzyme assay (apparent Km = 0.1 mM). The nanoprobe was characterized using SEM, EDAX, PSA and FT-IR. The inhibition measurements were carried out for individual as well as the mixture of metal ions (CRM standards of 9 elements (CRMmix-9)). The lower limit of quantification (LOQ) (0.5, 0.1, and 0.1 ng L-1 for Hg2+, Cd2+, and Pb2+) and lower limit of detection (LOD) was achieved at 0.1 ng L-1 with sensitivity 8-14% per decade for Hg2+, Cd2+, and Pb2+ ions. A visual result can be observed by the naked eye through the microfluidic device as well as with 96 transparent microwell plates. The order of relative inhibition was found to be CRMmix-9 > (Hg2+ + Cd2+ + Pb2+) > (Cd2+ + Pb2+) > (Pb2+ + Hg2+) > (Hg2+ + Cd2+) > Pb2+ > Cd2+ > Hg2+, respectively. The recovery % in fish tissues were found to be 88-98% for Hg2+, Cd2+ and Pb2+ ions.


Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin.
The chromosomal localization of genes for parathyroid hormone (PTH), beta-globin cluster, c-Ha-ras-1, and insulin, all of which have previously been assigned to the short arm of chromosome 11, generated considerable interest because of their association with development of disease states. Furthermore, the availability of recombination data from family studies made the determination of their physical location on the chromosome necessary. Several investigators have attempted this; however, controversy has arisen concerning the location of beta-globin, insulin, and c-Ha-ras-1 genes. Thus, while the results of some investigators suggested that all three genes are situated in the 11p15 region, data of other investigators placed the beta-globin and insulin genes close to the centromere and c-Ha-ras-1 in a more proximal region than 11p15. The subchromosomal position of the PTH gene remains to be determined. We have performed in situ hybridization of meiotic pachytene bivalents with 3H-labeled cloned genomic probes of PTH, beta-globin, and insulin genes and find their germ-line positions to be the following: PTH at 11p11.21, beta-globin at 11p11.22, and insulin at 11p14.1. These data, when considered with our recent germ-line assignment of the c-Ha-ras-1 gene to 11p14.1, indicate the following relative order on 11p: cen-PTH-beta-globin-c-Ha-ras-insulin or cen-PTH-beta-globin-insulin-c-Ha-ras. The former order is consistent with genetic evidence from linkage analysis of DNA polymorphisms adjacent to these genes segregating in families.


[Epidemiology of thromboembolic diseases: atrial fibrillation, venous thromboembolic disease and acute coronary syndrome].
Thromboembolic diseases include atrial fibrillation, venous thromboembolism and acute coronary syndrome. The incidence and prevalence of these diseases are high and show an increasing trend over the years. There are differences according to age, gender, ethnicity and other factors. Hypertension, diabetes and metabolic syndrome have been proven to be key risk factors for these diseases, which cause high morbidity and mortality. Epidemiological studies have shown the changing demographics of thromboembolic diseases and have highlighted their serious personal, social, economic and global health consequences, demonstrating the importance of further work on prevention, early diagnosis and improved treatment.


A perspective on the role of uncertainty in sustainability science and engineering.
The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.


[Genetic divergence of sympatric charrs of the genus Salvelinus from Nachikinskoe Lake (Kamchatka)].
We studied genetic differentiation of two charr species, Dolly Varden Salvelinus malma malma Walbaum and resident lacustrine charr Salvelinus sp., which sympatrically inhabit Nachikinskoe Lake (the Bol'shaya River basin) in southwestern Kamchatka Peninsula. Using restriction analysis (RFLP), three mitochondrial DNA fragments (ND1/ND2, ND5/ND6, and Cytb/D loop) amplified in polymerase chain reaction (PCR) were compared. The divergence of the mtDNA sequences between Salvelinus sp. and S. malma malma was 2.8%; Salvelinus sp. and S. taranetzi, 0.36%; Salvelinus sp. and S. krogiusae, 0.21%; Salvelinus sp. and S. alpinus, 3.0%. These results point to reproductive isolation of charrs in Nachikinskoe Lake and support the earlier suggestion on a close relationship between Salvelinus sp., S. taranetzi, and S. krogiusae.


Neuropilin-1 Expression on CD4 T Cells Is Atherogenic and Facilitates T Cell Migration to the Aorta in Atherosclerosis.
Neuropilin 1 (Nrp1) is a type I transmembrane protein that plays important roles in axonal guidance, neuronal development, and angiogenesis. Nrp1 also helps migrate thymus-derived regulatory T cells to vascular endothelial growth factor (VEGF)-producing tumors. However, little is known about the role of Nrp1 on CD4 T cells in atherosclerosis. In ApoE-/- mice fed a Western diet for 15 wk, we found a 2-fold increase in Nrp1+Foxp3- CD4 T cells in their spleens, periaortic lymph nodes, and aortas, compared with chow-fed mice. Nrp1+Foxp3- CD4 T cells had higher proliferation potential, expressed higher levels of the memory marker CD44, and produced more IFN-γ when compared with Nrp1- CD4 T cells. Treatment of CD4 T cells with oxLDL increased Nrp1 expression. Furthermore, atherosclerosis-susceptible mice selectively deficient for Nrp1 expression on T cells developed less atherosclerosis than their Nrp1-sufficient counterparts. Mechanistically, we found that CD4 T cells that express Nrp1 have an increased capacity to migrate to the aorta and periaortic lymph nodes compared to Nrp1- T cells, suggesting that the expression of Nrp1 facilitates the recruitment of CD4 T cells into the aorta where they can be pathogenic. Thus, we have identified a novel role of Nrp1 on CD4 T cells in atherosclerosis. These results suggest that manipulation of Nrp1 expression on T cells can affect the outcome of atherosclerosis and lower disease incidence.


Structure-activity relationships of a pigment-dispersing crustacean neurohormone.
This study evaluated the effects of N-terminal sequence deletion and of chemical modifications on the melanophore pigment dispersing activity of a crustacean neuropeptide (DRPH: Asn-Ser-Gly-Met-Ile-Asn-Ser-Ile-Leu-Gly-Ile-Pro-Arg-Val-Met-Thr-Glu-Ala-NH2). Sustained biological activity was not demonstrated by peptides smaller than the tridecapeptide DRPH (6-18). N-terminal extension of this peptide led to a steady increase in activity, with the DRPH (1-18) showing the maximum activity. Carboxyl group modification had no effect, but acetylation, oxidation, cyanogen bromide, and trypsin caused a decrease in activity. Phenylglyoxal modification of Arg-13 in DRPH led to a 14-fold increase in activity. It is concluded that the N-terminus and the methionine residues are important for full activity and that the phenylglyoxal-induced potentiation is due to protection of the peptide from proteolysis in vivo.


Re-Examination of Some Carbocations. Structures, Energies, and Charge Distributions.
Chemists have had a long-standing interest in reactive intermediates such as carbenes, carbon radicals, carbanions, and carbocations. Carbocations are an interesting part of this group because of their tendency to undergo rearrangement, sometimes forming bridged ions, as well as their ability in many cases of spreading out the positive charge over several atoms. We have re-examined some of these cases using high-level compound procedures, W1BD and G4, as well as by considering the charge distributions making use of the Hirshfeld method that has been shown to uniquely correlate with several types of experimental data.


Strategies for reducing EFL learners' foreign language anxiety in online classes: Investigating teachers' teaching credentials and experience.
Foreign Language Anxiety (FLA) has been studied by researchers interested in educational psychologists and applied linguists. Researchers suggested coping strategies for reducing EFL learners' FLA. However, the coping strategies which EFL learners use to reduce the foreign language learners' FLA in online classes have not been well explored. This study examined Chinese EFL teachers' coping strategies to mitigate Chinese English learners' FLA in online classes. The study also addressed the role of Chinese English language teachers' teaching credentials and teaching experience. A mixed-method research design was employed. In the qualitative phase, the researchers interviewed 23 teachers selected through theoretical sampling and explored the most frequently used coping strategies. The results if the thematic analysis of the interviews with the teachers showed that Chinese EFL teachers in online classes used 26 coping strategies. In the quantitative phase, a researcher-developed questionnaire of 26 items was used and administered to 200 Chinese EFL teachers who were selected through convenience sampling. The data were analyzed using factor analysis, Cronbach's alpha, and independent samples-t-tests. The results showed that the questionnaire enjoyed acceptable reliability and construct validity. Results also showed that the experienced and certified teachers used coping strategies more frequently than did the less experienced and non-certified teachers. Findings have theoretical implications for educational psychologists and researchers interested in applied linguistics. Results have a practical the implication for less experienced and non-certified EFL teachers to learn more about the coping strategies for reducing EFL learners' FLA.


Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy.
Cationic liposomes (CLs) have been regarded as the most promising gene delivery vectors for decades with the advantages of excellent biodegradability, biocompatibility, and high nucleic acid encapsulation efficiency. However, the clinical use of CLs in cancer gene therapy is limited because of many uncertain factors in vivo. Extracellular barriers such as opsonization, rapid clearance by the reticuloendothelial system and poor tumor penetration, and intracellular barriers, including endosomal/lysosomal entrapped network and restricted diffusion to the nucleus, make CLs not the ideal vector for transferring extrinsic genes in the body. However, the obstacles in achieving productive therapeutic effects of nucleic acids can be addressed by tailoring the properties of CLs, which are influenced by lipid compositions and surface modification. This review focuses on the physiological barriers of CLs against cancer gene therapy and the effects of lipid compositions on governing transfection efficiency, and it briefly discusses the impacts of particle size, membrane charge density, and surface modification on the fate of CLs in vivo, which may provide guidance for their preclinical studies.


Contact lens user statistics in Okada eye clinic.
To investigate the relationships between contact lens wearers, their lens wear, and treatment to provide correct instructions for use. A total of 55,056 consumers, who purchased contact lenses in the two institutions of Okada Eye Clinic in the 1-year period from April 1, 2002 to March 31, 2003, were analyzed with regard to age, sex, contact lens brands, treatments and lens-solution combinations purchased, and patterns of wear. The 2-week frequent-replacement soft contact lenses were the most popular type of contact lens, and most wearers of these lenses were those in their 20s. Saline solution was the treatment purchased most often with conventional soft contact lenses. Hard contact lens wearers tended to buy treatments of the same brand as their hard contact lenses. Hydrogen peroxide was the most purchased product with the 2-week frequent-replacement soft contact lenses and multipurpose treatment the next, especially with consumers in their 20s. There were no significant sex gaps. The survey was conducted on a wide age range of more than 50,000 people and can be assumed to accurately reflect the tendencies of contact lens wearers in Japan. The results clearly show the actual use of contact lenses and treatments of each age group and will be useful in instructing wearers to the correct use of their treatments.


Effect of Connexin43 on Mechanical Tension-stimulated Osteogenic Transcription Factors of Human Periodontal Ligament Fibroblasts.
To investigate the expression and effect of Connexin43 (Cx43) on tensile tension-stimulated osteogenic transcription factors of human periodontal ligament fibroblasts (hPDLFs). After hPDLFs were treated with 5% elongation tension for 1 h, 2 h, 4 h, 8 h, and 24 h, we examined the expressions of Cx43, Osterix, and RUNX2 at the mRNA level. After Cx43 expression was suppressed by siRNA or 18α-GA, the changes The mRNA in hPDLFs of Osterix and RUNX2 were observed. The expressions of Cx43, Osterix, and RUNX2 mRNA in hPDLFs increased in a time-dependent fashion following tensile strain (all P<0.05), with the highest level at 5% elongation for 24 h. After Cx43 expression was blocked by two different methods, the increasing expressions of Osterix and RUNX2 were inhibited. 5% cyclic tension upregulates Cx43 expression and promotes the expression of Osterix and RUNX2 in a time-dependent manner. Cx43 may be involved in the osteogenic response of hPDLFs to mechanical tension.


Isolated liver metastasis from a renal cell carcinoma 12 years after nephrectomy: report of a case and literature review.
We present a rare case of isolated liver metastasis from renal cell carcinoma 12 years after complete resection of the primary site. Such abnormal behavior of renal cell carcinoma has been reported elsewhere in the literature; thus, careful long-term surveillance should be performed in patients with a past history of renal cell carcinoma, even after radical resection of the primary site. We present also contrast-enhanced sonographic findings for this case.


Resonant characteristics of the human head in relation to temporomandibular joint sounds.
Frequency analysis of the sounds produced by the temporomandibular joint (TMJ) has been claimed to be of diagnostic value. In this study the resonant behaviour of the human skull has been characterized. Assuming that impact is one major mechanism generating the sound, it is shown that the frequencies seen in TMJ sounds relate to the resonant modes of the skull. Where the rise time of the impact is sufficiently short, higher resonant modes are excited.


Correcting Neuromuscular Deficits With Gene Therapy in Pompe Disease.
We have recently reported on the pathology of the neuromuscular junction (NMJ) in Pompe disease, reflecting disruption of neuronal and muscle homeostasis as a result of glycogen accumulation. The aim of this study was to examine how the alteration of NMJ physiology contributes to Pompe disease pathology; we performed molecular, physiological, and histochemical analyses of NMJ-related measures of the tibialis anterior muscles of young-, mid-, and late-stage alpha-glucosidase (GAA)-deficient mice. We performed intramuscular injection of an adeno-associated virus (AAV)9 vector expressing GAA (AAV9-hGAA) into the tibialis anterior muscle of Gaa(-/-) mice at early, mid, and severe pathological time points. We analyzed expression of NMJ-related genes, in situ muscle force production, and clearance of glycogen in conjunction with histological assessment of the NMJ. Our data demonstrate that AAV9-hGAA is able to replace GAA to the affected tissue and modify AChR mRNA expression, muscle force production, motor endplate area, and innervation status. Importantly, the degree of restoration for these outcomes is limited by severity of disease. Early restoration of GAA activity was most effective, whereas late correction of GAA expression was not effective in modifying parameters reflecting NMJ structure and function nor in force restoration despite resolution of glycogen storage in muscle. Our data provide new mechanistic insight into the pathology of Pompe disease and suggest that early systemic correction to both neural and muscle tissues may be essential for successful correction of neuromuscular function in Pompe disease. Ann Neurol 2015;78:222-234.


A large conformational change couples the ATP binding site of SecA to the SecY protein channel.
In bacteria, the SecYEG protein translocation complex employs the cytosolic ATPase SecA to couple the energy of ATP binding and hydrolysis to the mechanical force required to push polypeptides through the membrane. The molecular basis of this energy transducing reaction is not well understood. A peptide-binding array has been employed to identify sites on SecYEG that interact with SecA. These results along with fluorescence spectroscopy have been exploited to characterise a long-distance conformational change that connects the nucleotide-binding fold of SecA to the transmembrane polypeptide channel in SecY. These movements are driven by binding of non-hydrolysable ATP analogues to a monomer of SecA in association with the SecYEG complex. We also determine that interaction with SecYEG simultaneously decreases the affinity of SecA for ATP and inhibitory magnesium, favouring a previously identified active state of the ATPase. Mutants of SecA capable of binding but not hydrolysing ATP do not elicit this conformationally active state, implicating residues of the Walker B motif in the early chain of events that couple ATP binding to the mobility of the channel.


The ponerine ant Pachycondyla (=Ophthalmopone) berthoudi Forel carries loads economically.
The energy cost of running and carrying a load were measured in the termitophagus ponerine ant Pachycondyla (=Ophthalmopone) berthoudi. This ant species uses the individual foraging method in which there is no cooperation between the foragers in the search for or retrieval of prey items. The foragers also transport workers and brood between the nests of the polydomous colony. Pachycondyla berthoudi foragers ran voluntarily in a running tube respirometer at 25 degrees C. Some of the foragers ran in the running tube carrying their termite load, which enabled the metabolic costs of carrying immobilized prey to be determined. This included the costs of maintaining the prey in the mandibles and of stabilization during running. The minimum cost of unladen running was 165.9 J kg-1 m-1, while that of laden running was 136.1 J kg-1 m-1. The mass used to calculate the cost of laden running included body mass of ant and mass of load carried. Pachycondyla berthoudi foragers carry their loads very cheaply. Load carriage costs were calculated to be about 40% as much as body carriage per unit mass, which is the lowest yet found for ants. Low cost of load carriage could have been selected for in P. berthoudi due to its life history.


The nature of the substance P-containing nerve fibres in taste papillae of the rat tongue.
The nature of the association of substance P (SP) with taste buds in the rat tongue was investigated by immunohistochemical and radioimmunoassay techniques. Both the circumvallate and fungiform papillae were found to receive a rich innervation by substance P-containing fibres. Although these fibres were closely associated with the taste buds in these structures, they assumed a perigemmal rather than an intragemmal location. Bilateral lesions of the glossopharyngeal nerve resulted in the depletion of taste buds from the vallate papilla and a large reduction in substance P immunoreactive fibres in this area. Lesions of the chorda tympani, which led to the degeneration of taste buds in fungiform papillae, had no effect on the immunohistochemical appearance of substance P in these papilla or on the substance P levels in the anterior part of the tongue. Lesions of the mandibular division of the trigeminal nerve or neonatal capsaicin treatment had no effect on the structural integrity of taste buds in fungiform papillae but led to the depletion of substance P-immunoreactive fibres from these papillae. Both of these procedures caused a 71% reduction in the substance P content of the anterior tongue, ipsilaterally after the nerve lesion and bilaterally after capsaicin treatment. The results are discussed in relation to the possible functional role of substance P-containing fibres within nerves supplying taste structures of the tongue.


Activation of NF-kappaB in lymphocytes and increase in serum immunoglobulin in hyperthyroidism: possible role of oxidative stress.
This study evaluated oxidative stress, serum IgM and IgG, and nuclear factor (NF)-kappaB signaling in lymphocytes of hyperthyroidism patients. GSH content in lymphocytes was significantly lower and serum malondialdehyde, IgM and IgG levels were significantly higher in hyperthyroidism as compared to controls. In lymphocytes, the NF-kappaB signaling pathway was studied by western blot analysis of p65 and p-IkappaBalpha. Density of p-IkappaBalpha and p65 (in nuclear fraction) was significantly higher in hyperthyroidism as compared to controls. The density of p-IkappaBalpha and p65 had significant positive correlation with serum malondialdehyde level and negative correlation with lymphocyte GSH level in hyperthyroid cases. The serum IgG and IgM levels were correlated significantly with density of p-IkappaBalpha and p65. As immunoglobulin production is regulated by the NF-kappaB pathway, we conclude that the oxidative stress-induced activation of the NF-kappaB pathway might play a role in the rise of serum immunoglobulin level in hyperthyroidism.


Direct interaction between GluR2 and GAPDH regulates AMPAR-mediated excitotoxicity.
Over-activation of AMPARs (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors) is implicated in excitotoxic neuronal death associated with acute brain insults, such as ischemic stroke. However, the specific molecular mechanism by which AMPARs, especially the calcium-impermeable AMPARs, induce neuronal death remains poorly understood. Here we report the identification of a previously unrecognized molecular pathway involving a direct protein-protein interaction that underlies GluR2-containing AMPAR-mediated excitotoxicity. Agonist stimulation of AMPARs promotes GluR2/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) complex formation and subsequent internalization. Disruption of GluR2/GAPDH interaction by administration of an interfering peptide prevents AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia.


Human leukocyte antigen typing using buccal swabs as accurate and non-invasive substitute for venipuncture in children at risk for celiac disease.
Human leukocyte antigen (HLA) typing is an important step in the diagnostic algorithm for celiac disease (CD) and is also used for screening purposes. Collection of blood is invasive and accompanied with emotional impact especially in children. Genetic technological progress now enables HLA typing from buccal cell samples. This study evaluated the reliability and feasibility of HLA typing for CD-associated HLA polymorphisms using buccal swabs as routine test in high-risk individuals. Blood and buccal swabs of 77 children and adolescents with high risk for CD were prospectively collected in this cohort study. Buccal swab collection was performed either by the investigator at the outpatient clinic or by the patient or its parents at home. To evaluate the possibility of self-administration, three families performed the test at home. DNA was extracted using an adapted QIAamp method. Quantity, quality, and purity of DNA were recorded. HLA-DRB1, HLA-DQA1, and HLA-DQB1 typing was examined on buccal cell-derived and blood-derived DNA at low and, if necessary, high resolution level, using sequence-specific oligonucleotide and sequence-based typing, respectively. DNA isolation using buccal swabs yielded a good quality and sufficient quantity of DNA to perform HLA-DQ typing in all individuals. HLA typing results on buccal cell-derived DNA were identical to typing on blood-derived DNA, also for the self-administered samples. Introduction of the buccal swab test for HLA typing of CD risk in routine diagnostics can omit the current venipuncture and enables self-administration at home. Therefore, the buccal swab test is beneficial for individuals with a clinical suspicion for CD, as well as for screening purposes in high-risk populations.


Hearing in Whales and Dolphins: Relevance and Limitations.
Understanding the hearing of marine mammals has been a priority to quantify and mitigate the impact of anthropogenic sound on these apex predators. Yet our knowledge of cetacean hearing is still limited to a few dozen species, therefore compromising any attempt to design adaptive management strategies. The use of auditory evoked potentials allows scientists to rapidly and noninvasively obtain the hearing data of species rarely available in captivity. Unfortunately, many practical and ethical reasons still limit the availability of large whales, thus restricting the possibility to effectively ensure that anthropogenic sounds have minimum effects on these species. The example of a recent Blainville's beaked whale (Mesoplodon densirostris) audiogram collected after a stranding indicated, for instance, very specialized hearing between 40 and 50 kHz, which corresponded to the frequency-modulated upsweep signals used by this species during echolocation. The methods used during a stranding event are presented along with the major difficulties that have slowed down the scientific community in measuring the audition of large whales and the potential value in obtaining such results when successful.


Influence of curve magnitude and other variables on operative time, blood loss and transfusion requirements in adolescent idiopathic scoliosis.
Posterior spinal instrumentation and fusion for correction of adolescent idiopathic scoliosis (AIS) typically requires lengthy operating time and may be associated with significant blood loss and subsequent transfusion. This study aimed to identify factors predictive of duration of surgery, intraoperative blood loss and transfusion requirements in an Irish AIS cohort. A retrospective review of 77 consecutive patients with AIS who underwent single-stage posterior spinal instrumentation and fusion over a two-year period at two Dublin tertiary hospitals was performed. Data were collected prospectively and parameters under analysis included pre- and postoperative radiographic measurements, intraoperative blood loss, surgical duration, blood products required, laboratory blood values and perioperative complications. Mean preoperative primary curve Cobb angle was 62.3°; mean surgical duration was 5.6 h. The perioperative allogeneic red blood cell transfusion rate was 42.8 % with a median requirement of 1 unit. Larger curve magnitudes were positively correlated with longer fusion segments, increased operative time and greater estimated intraoperative blood loss. Preoperative Cobb angles greater than 70° [Relative Risk (RR) 4.42, p = 0.003] and estimated intraoperative blood loss greater than 1400 ml (RR 3.01, p = 0.037) were independent predictors of red blood cell transfusion risk. Larger preoperative curve magnitudes in AIS increase operative time and intraoperative blood loss; preoperative Cobb angles greater than 70(o) and intraoperative blood loss greater than 1400 ml are predictive of red blood cell transfusion requirement in this patient group.


Anaesthetic efficacy of supplemental lingual infiltration of mandibular molars after inferior alveolar nerve block plus buccal infiltration in patients with irreversible pulpitis.
To investigate the effect of supplemental lingual infiltration (LI) of mandibular molars following an inferior alveolar nerve block (IANB) plus buccal infiltration (BI) in patients with irreversible pulpitis. Eighty adult patients diagnosed with irreversible pulpitis participated in this prospective study. All patients received standard IANB via injection of 4 mL of 2% lidocaine with 1 : 100,000 epinephrine. Ten minutes after the IANB, patients with numbness of the lower lip were randomly divided into two groups. In the BI group, 40 patients received supplemental BI of 0.9 mL of 4% articaine with 1 : 100,000 epinephrine. In the buccal plus lingual infiltration (BLI) group, 40 patients received supplemental BI of 0.9 mL of 4% articaine with 1 : 100,000 epinephrine and, subsequently, LIs with the same anaesthetic solution and dose. Endodontic access cavity preparation began 15 min after the IANB. Pain during treatment was recorded using a Heft-Parker visual analogue scale. Success was defined when pain was 'none' or 'mild' on endodontic access and initial instrumentation. The pain was estimated and statistically analysed by the chi-squared test (α = 0.05). The success rates for the BI and BLI groups were 70% and 62.5%, respectively. No statistical difference was found between the two groups (P = 0.478). Supplemental LIs are not recommended for administration in mandibular molars with irreversible pulpitis, because they do not improve the anaesthetic success after IANB plus BI.


Febrile seizures in rural Tanzania: hospital-based incidence and clinical characteristics.
Febrile seizures may contribute to epilepsy later in life, but data in sub-Saharan Africa are scarce. We, therefore, conducted a hospital-based study on clinical characteristics of children with febrile seizures. Over 2 years, we screened all pediatric admissions of Haydom Lutheran Hospital, northern Tanzania, and recruited 197 children with febrile seizures. The incidence of febrile seizures was 4% of all admitted children aged <10 years, with a mortality of almost 4%. The peak age at the first febrile seizure was 2 years. One of five children experienced repeated episodes, and the majority of children showed features of complex seizures. Approximately 20% of children had a positive family history of febrile seizures or epilepsy. Febrile seizures represent a frequent cause for admission of children, bearing a rather high mortality. Most children exhibit complex febrile seizures, which may contribute to the development of epilepsy later in life.


Quercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy.
Quercetin, a bioflavonoid abundant in grapefruit, onion, berries, etc., has vast therapeutic potential, especially against Type 2 diabetes and its complications. Quercetin showed similar effects as that of metformin, (widely prescribed antidiabetic drug) in cell lines models (Sajan et al., 2010; Dhanya et al., 2017). In vivo findings also showcase it as a promising agent against diabetes and its pathophysiological complications. Quercetin can be produced on a large scale through a novel fermentation-based glycosylation strategy from cheap substrates and can be utilized as a dietary supplement. The review focuses on the mounting evidence pointing to Quercetin as a promising candidate for managing type 2 diabetes and its oxidative stress mediated pathophysiological complications. Quercetin acts on multiple targets of diabetes and regulates key signalling pathways which improve the symptoms as well as the complications of Type 2 diabetes. However further studies are needed to improve the bioavailability and to establish a dosing regimen for Quercetin.


Current grading of gall bladder cholecystitis and management guidelines: Is it sufficient?
•These two cases highlight the limitations in current grading systems, particularly in the context of gallbladder size.•We propose modifications to the PGS to include not only abnormal anatomy but instances of distorted gallbladder anatomy due to inflammation and/or the large to giant size in order to account for the increased risk of complications.•Both distorted gallbladder anatomy and giant gallbladder size can make laparoscopic cholecystectomy a challenge, and thus warrant contribution to overall clinical grade.•While the PGS, Tokyo Guidelines, and AAST grading scales are validated grading scales for acute cholecystitis, additional modifications can further characterize different types of acute cholecystitis to better guide patient management.


Novel indole-thiazole and indole-thiazolidinone derivatives as DNA groove binders.
In this study, we report the synthesis of eight novel indole-thiazole and indole-thiazolidinone derivatives, as well as their ability to interact with DNA, analysed through the UV-vis absorption, fluorescence, circular dichroism (CD), viscosity techniques and molecular docking. The ctDNA interaction analysis demonstrated different spectroscopic effects and the affinity constants (Kb) calculated by the UV-vis absorption method were between 2.08 × 105 and 6.99 × 106 M-1, whereas in the fluorescence suppression constants (Ksv) ranged between 0.38 and 0.77 × 104 M-1 and 0.60-7.59 × 104 M-1 using Ethidium Bromide (EB) and 4',6-Diamidino-2-phenylindole (DAPI) as fluorescent probes, respectively. Most derivatives did not alter significantly the secondary structure of the ctDNA according to the CD results. None of the compounds was able to change the relative viscosity of the ctDNA. These results prove that compounds interact with ctDNA via groove binding, which was confirmed by A-T rich oligonucleotide sequence assay with compound JF-252, suggesting the importance of both the phenyl ring coupled to C-4 thiazole ring and the bromo-unsubstituted indole nucleus.


Temperature-dependent block of capacitative Ca2+ influx in the human leukemic cell line KU-812.
The mechanism by which depletion of intracellular Ca2+ stores activates Ca2+ influx is not understood. We recently showed that primaquine, an inhibitor of vesicular transport, blocks the activation of the calcium release-activated calcium current (ICRAC) in rat megakaryocytes (Somasundaram, B., Norman, J. C., and Mahaut-Smith, M. P. (1995) Biochem. J. 309, 725-729). Since it is well established that vesicular transport is temperature-sensitive, we have investigated the effect of temperature on both the activation and maintenance of store-mediated Ca2+ and Mn2+ influx in the human leukemic cell line KU-812 using a combination of whole cell ICRAC recordings and measurements of Mn2+ photoquench of fura-2. Activation of ICRAC was temperature-sensitive, showing a nonlinear reduction when the temperature was lowered from 27 to 17 degrees C with an abrupt change at 21-22 degrees C and complete inhibition at 17 degrees C. Once activated, ICRAC also displayed an abrupt reduction at 21-22 degrees C but was not completely blocked even when the temperature was reduced to 14 degrees C, suggesting that at least one of the temperature-sensitive components is exclusively involved in ICRAC activation. Activation of store-mediated Mn2+ influx also showed similar nonlinear temperature sensitivity and complete inhibition at 19 degrees C. However, in contrast to ICRAC measurements, lowering the temperature following maximal activation of the influx pathway at 37 degrees C did not result in any detectable residual Mn2+ entry below 19 degrees C. We conclude that the mechanism of store-mediated Ca2+ influx involves temperature-dependent steps in both its maintenance and activation, suggesting dependence on a lipid membrane environment.


Brain Functional Alterations in Long-term Unilateral Hearing Impairment.
The rate of patients with unilateral hearing impairments (UHI) increase with age and are characterized by asymmetric auditory afferents in which auditory information is asymmetrically transmitted to the brain. Long-term bilateral hearing imbalance can cause abnormal functional changes in the cerebral cortex. However, the relationship between functional alterations in the brain and the severity of the hearing impairment remains unclear. This study included 33 patients with UHI (left-sided impairment in 17 and right-sided impairment in 16) and 32 healthy patients. All participants underwent resting-state, blood oxygen level dependent functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuation (fALFF) values were calculated after data preprocessing and compared among the left-sided and right-sided impairment groups and the control group. Pure tone audiometry was used to evaluate patients' hearing impairment level. The correlation between fALFF values of abnormal brain regions and the duration and severity of hearing impairment was analyzed. Results provide evidence for altered resting-state functional activities in the brain of patients with left or right long-term UHI, with significantly increased fALFF values in the Heschl's gyrus, superior temporal gyrus, and insula were observed. Moreover, complicated networks reorganization involved in the visual, cognitive, sensorimotor and information transmission functions except for the auditory function and some brain regions exhibited functional changes only in the one-sided impairment group. In addition, the severity of hearing impairment is related with the functional activities in the bilateral Heschl's gyrus, bilateral insula, right superior temporal gyrus, and left middle frontal gyrus. In conclusion, alterations in functional activity are observed in the brains of patients with long-term hearing impairments and multiple brain regions within different functional networks are involved in the brain functional remodeling. The brain reintegration mechanism appears to be asymmetrical and the lateralization pattern in the contralateral brain hemisphere for auditory information processing related with the severity of hearing impairment.


Can bismuth film screen printed carbon electrodes be used to study complexation?
Ex- situ bismuth film on commercial screen-printed carbon electrodes (BiSPCE) has been used for the first time for the analysis of the complexation of Cd(2+) by thiol containing compounds as glutathione (GSH) and phytochelatin (γ-Glu-Cys)2-Gly (PC2). Reproducibility of data is quite satisfactory and allows their treatment by multivariate curve resolution by alternating least squares (MCR-ALS). Unitary voltammograms and concentration profiles provided by MCR-ALS confirm the formation of 1:1 and 1:2 Cd(2+):GSH and 1:2 Cd(2+):PC2 complexes. These results are in agreement with those previously obtained by mercury electrodes, and allow us to propose the use of BiSPCE for further studies on complexation.


An individual-based rurality measure and its health application: A case study of Latino immigrants in North Florida, USA.
Rurality has been frequently noted by researchers as pathways to understand human health in rural and remote areas. Current measures of rurality are mostly oriented to places, not individuals, and have not accounted for individual mobility, thus inappropriate for studying health and well-being at an individual level. This research proposed a new concept of individual-based rurality by integrating personal activity spaces. A feasible method was developed to quantify individuals' rural experience using household travel surveys and geographic information systems (GIS). For illustration, the proposed method was applied to understand the well-being and social isolation among rural Latino immigrants, who had participated in a community-based participatory research (CBPR) study in North Florida, USA. The resulting individuals' rurality indices were paired with their scores of well-being and social isolation to identify potential associations. The correlation analysis showed that the proposed rurality can be related to the social isolation, mental and physical well-being of individuals in different gender groups, and hence could be a suitable tool to investigate rural health issues.


Cell polarity linked to gravity sensing is generated by LZY translocation from statoliths to the plasma membrane.
Organisms have evolved under gravitational force, and many sense the direction of gravity by means of statoliths in specialized cells. In flowering plants, starch-accumulating plastids, known as amyloplasts, act as statoliths to facilitate downstream gravitropism. The gravity-sensing mechanism has long been considered a mechanosensing process by which amyloplasts transmit forces to intracellular structures, but the molecular mechanism underlying this has not been elucidated. We show here that LAZY1-LIKE (LZY) family proteins involved in statocyte gravity signaling associate with amyloplasts and the proximal plasma membrane. This results in polar localization according to the direction of gravity. We propose a gravity-sensing mechanism by which LZY translocation to the plasma membrane signals the direction of gravity by transmitting information on the position of amyloplasts.


In vitro shearing force testing of the Australian zirconia-based ceramic Begg bracket.
The purpose of this study was to investigate the condition of bond failure of the Australian zirconia-based ceramic Begg bracket (Elipse bracket) in comparison with that of a small-base metal Begg bracket (Solitaire bracket) under various environmental conditions. Shear tests were performed and sites of bond failure were also recorded. The results showed that (1) mean shear force of the bonded Elipse ceramic bracket is significantly higher than the metal one (2) shearing force at failure in both ceramic and metal groups, is considered clinically acceptable, (3) thermocycling (1000 cycles) had no significant additional effect on shearing force with both groups, (4) failure sites of the bonding were more likely to be at enamel/resin interfaces, and (5) there was no instance of fracture of the ceramic bracket and the enamel. A particular distinction is noted concerning the test results that measured shearing force rather than shear strength. It is questioned whether some published reports referring to "shear strength" have adequately accounted for bond surface area estimation necessary for proper calculation of strength values.


Evidence of functional cellular immune impairment in an adult Belgian with visceral leishmaniasis acquired in Spain.
An adult Belgian patient with visceral leishmaniasis acquired while on holiday in Spain is described. This patient's cellular immunity was assessed by skin testing using six different antigens and was normal just before leaving for Spain. During the leishmaniasis, skin tests with the same antigens showed complete anergy. Lymphocyte transformation tests to antigens and mitogens were severely impaired but normal T cell subsets determined by OKT monoclonal antibodies were found. Immune complexes, containing antibodies to Leishmania antigen were isolated during the patient's illness. It is most likely that visceral leishmaniasis caused the functional cellular immune impairment of the patient.


Effect of psyllium husk and wheat mill bran fractions on the microstructure and mixograph characteristics of Arabic bread.
When psyllium husk, wheat bran and germ was added, Incorporation of psyllium and wheat bran may affect the dough structure, dough rheology as well as the final quality of baked Arabic flat bread, which, thus, became important for this study. Scanning Electron Micrographs (SEM) taken on Arabic bread, depicted both intact small and the large starch granules on the outer crust area. This was mainly due to the rapid loss of moisture from the Arabic bread surface during intense baking operation leaving less moisture for gelatinization to take place. With psyllium added to WWF at 0, 3, and 5 % level, the peak time was increased from 3 to 4.5 min. The ascending and descending angle values were more or less identical in all the samples except with wheat germ addition, whereas much lower values (51 to 58°) for these parameters were observed, indicating a faster rate of dough breakdown. With psyllium, fine- and coarse bran addition to WWF, a corresponding increase in peak time was observed. Ascending and descending angles showed similar trends to that of the WWF and psyllium combinations. Use of falling number apparatus is an indirect method of measuring the diastatic enzyme activity in cereal flours. WGF showed lower falling-number values (502 s) than the WWF (607 s). Addition of fine bran to WWF lowered the falling number (607 to 563 s) whereas with coarse wheat bran and germ, these values were increased.


Smoking and experiences with tobacco cessation among men who have sex with men: New Orleans, 2011.
Smoking continues to be a problem in the United States, particularly among men who have sex with men (MSM). The current study assesses the prevalence of current and lifetime smoking as well as cessation experiences in a sample of MSM. Two-thirds of the sample had ever smoked tobacco and 50 % of MSM were current smokers. Prevalence of current smoking in this sample was higher than comparative data obtained from HIV positive patients at a local clinical population. Smoking was found to be associated with HIV status, race, age, education, income and alcohol use. A high proportion of MSMs social networks were smokers especially among current smokers. Continued efforts targeting or linking MSM into tobacco cessation efforts are recommended.


Migration enhancement by tuftsin of human mononuclear cells and its effect on the migration inhibition factor test with tumor antigens.
Tuftsin, a physiological tetrapeptide which stimulates the phagocytic activity of polymorphonuclear neutrophils and macrophages, is found to enhance the migration of normal and sensitized human mononuclear cells. Furthermore, it abrogates the migration inhibition effect of human malignant melanoma antigen. This finding may represent a possible explanation for the unexpected migration enhancement often observed when the migration inhibition test is employed.


Anti-oxidant, anti-apoptotic, and mitochondrial regulatory effects of selenium nanoparticles against vancomycin induced nephrotoxicity in experimental rats.
Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment against multi-resistant Gram-positive bacteria. The present research aimed to investigate the ability of selenium nanoparticles (SeNPs) to protect against VCM-induced nephrotoxicity in rats. Experimental rats were divided into five groups; the first was the normal control, the second was treated with VCM (200 mg/kg twice/day, i.p.) for 7 days. The third, fourth, and fifth groups were treated orally with SeNPs (0.5, 1, and 2 mg/kg/day); respectively. SeNPs were administered for 12 days before VCM, 1 week simultaneously with VCM, and for another 1 week after its administration. Levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and kidney injury molecule-1 (KIM-1) were significantly increased in kidney tissue after VCM administration. Expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), Bcl-2 associated X protein (Bax), caspase 3 and caspase 9 in kidney tissue was significantly increased, while the antioxidant enzymes, mitochondrial complexes, the ATP levels and B-cell lymphoma protein 2 (Bcl-2) were decreased in kidney in the VCM-treated rats compared to the normal control group. Treatment with SeNPs significantly decreased levels of MDA, iNOS, NO, TNF-α, and KIM-1 in the kidney tissue. Administration of SeNPs also downregulated the expression of the proapoptotic agents and enhanced the activities of the antioxidant enzymes and the mitochondrial enzyme complexes in the kidney. SeNPs alleviated VCM-induced nephrotoxicity through their anti-oxidant, anti-inflammatory, anti-apoptotic and mitochondrial protective effects.


Studies on combined effects of organophosphates or carbamates and morsodren in birds. II. Plasma and cholinesterase in quail fed morsodren and orally dosed with parathion or carbofuran.
The degree of interaction between mercury and cholinesterase inhibiting pesticides was determined by comparing enzyme responses to sublethal dosages of parathion or carbofuran in quail fed 0.05, 0.5, or 5.0 ppm morsodren for 18 weeks. A statistically significant interaction was defined as greater brain cholinesterase inhibition in morsodren-fed than in clean-fed birds following pesticide dosage. The tissue residues of mercury that accumulated before significant mercury-parathion interactions occurred were higher than levels that might be expected in natural populations, but significant mercury-carbofuran interactions occurred in birds that had only accumulated 1.0 ppm liver mercury. The results indicate that indiscriminate usage of cholinesterase inhibiting pesticides are dangerous, since natural populations of fish-eating birds oftentimes contain this magnitude of mercury.


The influence of subjective factors on temporary threshold shifts after exposure to music and noise of equal energy.
The present study examined the influence of subjective factors on temporary threshold shifts (TTS) after exposure to noise and music. Two groups of subjects, those who indicated liking and those who indicated disliking pop/rock music, were exposed to both noise and music on separate occasions. Subjects who liked the music exhibited less TTS following music than noise. They also exhibited less TTS in music than the subjects who disliked the music. Those who disliked the music evidenced greater magnitude of TTS in music than noise.


Transthyretin is synthesized in the mammalian eye.
Transthyretin (TTR, prealbumin) is a 55 kDa protein which plays an important role in the plasma transport of thyroxine and retinol. Although the liver and choroid plexus are the two major known sites of TTR synthesis, several lines of evidence suggest the possibility of a separate ocular source of TTR. We report the presence of TTR mRNA in rat and bovine eye and of TTR in rat eye. Preliminary immunohistochemical data indicate that the retinal pigment epithelium is a major site of TTR immunoreactivity in the rat. While the functional significance of ocular TTR synthesis is unclear, TTR may be involved in the ocular translocation and processing of retinol. The finding of TTR synthesis in the eye may explain ocular involvement in the familial amyloidotic polyneuropathies.


Changes in blood parameters in rhesus monkeys (Macaca mulatta) during the first trimester of gestation.
Regarding the good practice in the laboratory work, it is essential to have a broad spectrum of biochemical and hematological references in pregnant females to determine the health status of the colony. To establish reference values to reveal changes in hematology and blood chemistry in pregnant rhesus monkeys (Macaca mulatta) in their first trimester of pregnancy. Twenty-eight females in reproductive stage were used, divided into two groups: 14 pregnant macaques in their first trimester and 14 non-pregnant used as the control group. Blood samples were collected for the hematological test and blood chemistry. The results showed significant difference in the blood chemistry for the following parameters: glucose, total bilirubin, and total protein. The hematological evaluation revealed significant difference in leukocytes and neutrophils. These findings offer a reference range and provide a basis for improvement in techniques and refinement of clinical processes in these specimens.


Neutrophil-macrophage cooperation in the host defence against mycobacterial infections.
CD-1 mice inoculated intraperitoneally with Mycobacterium avium, M. bovis, M. microti or M. kansasii showed a persistent peritoneal granulocytosis (above 10(6) cells, i.e. more than 15% of total cells) throughout the 3 month period of infection studied. By contrast, in mice inoculated with the non-pathogenic M. aurum or with heat-killed M. avium the number of granulocytes decreased progressively after the first 15 days. No mycobacteria were found in granulocytes except in the first 2 days of infection. The mycobacteria-induced chronic granulocytosis was accompanied by phagocytosis of granulocytes by macrophages. Throughout the 3 months of infection, macrophages were found to contain intracellular lactoferrin. Macrophages with lactoferrin were also found in subcutaneous infection caused by M. marinum and in systemic infection caused by M. avium or M. kansasii. The in vitro activity of mouse peritoneal macrophages against M. avium and M. microti was increased after ingestion of granulocyte material by macrophages. These results lead us to propose that granulocytes participate in the host response to mycobacterial infections, not as phagocytes but rather through an indirect mechanism, as a source for the macrophages of molecules involved in antimicrobial mechanisms (e.g., lactoferrin and myeloperoxidase) lacking in the mature macrophage.


Protein repellent anti-coagulative mixed-charged cellulose derivative coatings.
This study describes the formation of cellulose based polyelectrolyte charge complexes on the surface of biodegradable polycaprolactone (PCL) thin films. Anionic sulphated cellulose (CS) and protonated cationic amino cellulose (AC) were used to form these complexes with a layer-by-layer coating technique. Both polyelectrolytes were analyzed by charge titration methods to elucidate their pH-value dependent protonation behavior. A quartz crystal microbalance with dissipation (QCM-D) in combination with X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to follow the growth, stability and water content of up to three AC/CS bi-layers in aqueous environment. This was combined with coagulation studies on one, two and three bilayers of AC/CS, measuring the thrombin formation rate and the total coagulation time of citrated blood plasma with QCM-D. Stable mixed charged bilayers could be prepared on PCL and significantly higher masses of AC than of CS were present in these complexes. Strong hydration due to the presence of ammonium and sulphate substituents on the backbone of cellulose led to a significant BSA repellent character of three bilayers of AC/CS coatings. The total plasma coagulation time was increased in comparison to neat PCL, indicating an anticoagulative nature of the coatings. Surprisingly, a coating solely composed of an AC layer significantly prolonged the total coagulation time on the surfaces although it did not prevent fibrinogen deposition. It is suggested that these cellulose derivative-based coatings can therefore be used to prevent unwanted BSA deposition and fibrin clot formation on PCL to foster its biomedical application.


Correlation between nutritional status and oral health quality of life, self-efficacy of older inpatients and the influencing factors.
This study explores the relationship between nutritional status and oral health quality of life, the self-efficacy of older inpatients and the correlative factors. In this study, the convenience sampling method was used to select 307 older inpatients in the southern section of the Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October to December 2020 as the main research participants. A mini nutritional assessment questionnaire was used to assess nutritional status, and the Chinese version of a geriatric oral health assessment index questionnaire was used to determine the oral health quality of life. Self-efficacy was assessed by a general self-efficacy scale questionnaire. Descriptive statistics were used to analyse data using the SPSS 22.0 software. Pearson correlation and multiple linear regression analysis were applied to explore the correlation between variables and factors concerned with nutritional status, respectively. The results of this study showed that the self-efficacy and oral health quality of life of older inpatients were at a moderate level. Among the patients, 263 had one or more tooth defects, and only 128 had oral restorations or wore dentures. The risk of malnutrition in hospitalised older patients was 37.1%, and the incidence of malnutrition was 13.4%. The risk factors of nutritional status of older patients were age, oral-related quality of life, prealbumin index, self-efficacy, chronic disease, monthly income and tooth defect (P < 0.05). The incidence of malnutrition and malnutrition risk in hospitalised older patients is relatively high. The main associated factors include age, tooth defect, oral health quality of life, self-efficacy, chronic disease status and monthly income. Therefore, older inpatients, especially those with prosthodontic problems, should carry out nutritional assessments, intervention and graded management as soon as possible to improve their self-efficacy, improve their nutrition and health status and reduce the incidence of a poor prognosis.


Can the product of the theta gene be a real globin?
A new member (theta 1, or psi alpha) of the alpha-globin gene family has recently been identified in a number of species. In higher primates the theta 1 gene has all the structural features apparently necessary for expression, and it appears to have long been under strong selective constraints which suggests that it could still be, or recently have been, a functional gene. No corresponding 'globin' has yet been identified, however. In some other species, galago and rabbit for example, the theta 1 and psi alpha genes have accumulated enough inactivating mutations for them to be considered genuine pseudogenes. Horses also have an alpha-like gene (psi alpha), in a 3' position identical to the other species in relation to the functional alpha genes, and this also appears to have the elements required for a functional gene. The predicted amino-acid sequence, however, suggests that any 'globin' product is likely to be non-viable because it has a number of seriously deleterious amino-acid replacements. Some of these amino-acid changes are shared with the rabbit and primate sequences, indicating that they predate the mammalian radiation, and that if indeed any of these genes are still functional, they are unlikely to be making haemoglobin.