Block ionomer complexes of PEG-block-poly(4-vinylbenzylphosphonate) and cationic surfactants as highly stable, pH responsive drug delivery system.
A new family of block ionomer complexes (BIC) formed by poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) (PEG-b-PVBP) and various cationic surfactants was prepared and characterized. These complexes spontaneously self-assembled in aqueous solutions into particles with average size of 40-60nm and remained soluble over the entire range of the compositions of the mixtures including stoichiometric electroneutral complexes. Solution behavior and physicochemical properties of such BIC were very sensitive to the structure of cationic surfactants. Furthermore, such complexation was used for incorporation of cationic anti-cancer drug, doxorubicin (DOX), into the core of BIC with high loading capacity and efficiency. The DOX/PEG-b-PVBP BIC also displayed high stability against dilution, changes in ionic strength. Furthermore, DOX release at the extracellular pH of DOX/PEG-b-PVBP BIC was slow. It was greatly increased at the acidic pH mimicking the endosomal/lysosomal environment. Confocal fluorescence microscopy using live MCF-7 breast cancer cells suggested that DOX/PEG-b-PVBP BICs are transported to lysosomes. Subsequently, the drugs are released and exert cytotoxic effect killing these cancer cells. These findings indicate that the obtained complexes can be attractive candidates for delivery of cationic drugs to tumors.


Linking unfolded protein response to inflammation and depression: potential pathologic and therapeutic implications.
Depression is a devastating mental disorder that affects millions of people worldwide. Inflammation has been shown to be a key factor involved in the underlying pathophysiology of depression and has been shown in a substantial proportion of cases of depression. Changes attributed with morphological deformities and immunomodulation in susceptible regions of the depressed brain raised the possibility of altered cellular homeostasis transduced by the intracellular stress response. How emotional stressors can lead to an inflamed brain that directly affects physiology and activity is yet to be fully understood. The unfolded protein response (UPR) has been shown to be active in both models of depression as well as in postmortem brain of depressed individuals. The UPR is the cellular response to stress which results in misfolded proteins. Interestingly, UPR activation is directly linked to both inflammatory cytokine production and Toll-like receptor (TLR) expression. The TLRs are part of the innate immune response which typically reacts to "classic invasions" such as bacteria or viruses as well as trauma. TLRs have also been shown to be upregulated in depression, thus solidifying the connection between inflammation and depression. In this review, we aim to tie the UPR-TLR response and depression, and describe the implications of such an association. We also propose future directions for their role in treatment for depression.


[Early pressure on the gluteus maximus rotation flap in sacral decubitus ulcer].
The myocutaneous gluteus maximus flap in V-Y technique has become the workhorse for covering extensive sacral pressure sores. clinical experience indicates that this flap can sustain pressure prior to the usual three week period. Transcutaneous pO2 measurements permitted us to follow the flaps perfusion and to develop a new mobilization regimen. Patients can lie in the supine position for 30 minutes immediately after surgery for two hourly intervals. Three days postoperatively the usual two-hour repositioning can be resumed. This regimen represents a considerable improvement for paraplegics and has shown a comparable complication rate in 18 cases.


Indications for, and outcomes of, end ileostomy revision procedures.
Ileostomy complications have been reported in >70% of cases. Older studies have shown ileostomy revision to be required in 23%-38% of patients over a 5-10 year period. There is a paucity of recent data addressing ileostomy revision surgery. We aimed to review end ileostomy revisions in a tertiary centre and analyse indications, procedures performed, outcomes and risks for such surgery. This was a retrospective review in a single institution colorectal referral practice. All patients aged >17 years who underwent a revision of an ileostomy at our institution from 2008 to 2019 were included. Indication for ileostomy revision, operative technique (parastomal vs. intra-abdominal) and outcomes including length of stay, readmission rates, wound complications, medical complications and rate of stoma re-revision were assessed. Fifty-three patients who underwent 72 end ileostomy revision procedures were included; 20 (27.8%) were re-revision procedures. The majority (76.4%) had their original ileostomy created for inflammatory bowel disease. Indications for ileostomy revision were stoma retraction (36.1%), prolapse (22.2%), stenosis (18.1%) and parastomal hernia (29.2%). Of stoma revisions, 55.6% were performed by a parastomal approach vs. 44.4% by an intra-abdominal approach. Procedures were a combination of laparotomy, laparoscopy or both. The average length of stay was statistically significantly lower in the parastomal approach revision group (2.3 days) compared to the intra-abdominal approach revision group (10.3 days) (P < 0.001). Readmission and wound complication rates were 6.9% and 15.3%, respectively, in the intra-abdominal approach group alone. Medical complication rates were 20.8%. End ileostomy complications are common and surgical treatment may result in significant morbidity, readmission and reoperation. Patients should be counselled about these possibilities.


Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice.
Nude mice bearing xenografts of MIA PaCa-2 human pancreatic cancer cell line were treated for 4 weeks with AN-51, a somatostatin octapeptide analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) containing methotrexate attached to the alpha-amino group of D-Phe in position 1. Control groups of mice received saline, RC-121 or methotrexate. Drugs were given in equimolar doses by daily s.c. injections. After 7 days of treatment with 25 micrograms/day of AN-51, tumor growth was completely inhibited although the treatment had to be suspended because of toxic side effects, especially on the gastrointestinal tract, accompanied by major weight loss of the animals. Mice were allowed to recover for 1 week and treatment was continued with 12.5 micrograms/day AN-51. After 2 weeks of additional therapy, tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased, compared with controls, only in the group treated with AN-51. Methotrexate and RC-121 also inhibited tumor growth, but their effects were not statistically significant. AN-51 retained its hormonal activity and decreased serum growth hormone levels in mice. Binding affinity of AN-51 for somatostatin receptors on MIA PaCa-2 cells was found to be 2.5-times lower than that of parent compound RC-121. This is the first report on inhibition of human pancreatic cancer growth in vivo by somatostatin analogs carrying cytotoxic radicals.


Lunar soil hydration constrained by exospheric water liberated by meteoroid impacts.
Analyses of samples from the Apollo missions suggest that the Moon formed devoid of native water. However, recent observations by Cassini, Deep Impact, Lunar Prospector and Chandrayaan-1 indicate the existence of an active water cycle on the Moon. Here we report observations of this water cycle, specifically detections of near-surface water released into the lunar exosphere by the Neutral Mass Spectrometer on the Lunar Atmosphere and Dust Environment Explorer. The timing of 29 water releases is associated with the Moon encountering known meteoroid streams. The intensities of these releases reflect the convoluted effects of the flux, velocity and impact location of the parent streams. We propose that four additional detected water releases represent the signature of previously undiscovered meteoroid streams. We show that water release from meteoroid impacts is indicative of a lunar surface that has a desiccated soil layer of several centimetres on top of uniformly hydrated soil. We infer that the Moon is currently in the process of losing water that was either delivered long ago or present at its formation.


Positive and negative regulatory DNA elements including a CCArGG box are involved in the cell type-specific expression of the human muscle dystrophin gene.
The muscle-specific promoter of the dystrophin gene is active in skeletal, cardiac, and smooth muscles and is specifically stimulated during differentiation of myoblasts into multinucleated myotubes. An 850-base pair (bp) DNA fragment upstream from the cap site is able to confer a partial muscle specificity to a reporter gene. The region between -850 and -140 bp includes nonspecific negative and positive regulatory sequences. A continuous stretch of 140 bp upstream from the cap site exhibits a striking conservation between rodents and human (93% homology) and still retains muscle preference of expression. It contains two putative binding sites for factors involved in regulation of other muscle-specific genes, a CCArGG box and an E box. This latter element, however, is unable to confer the ability to be transactivated by MyoD1 to the dystrophin promoter. The -140-bp promoter fragment exhibits antagonist effects contributed by one inhibiting sequence (nucleotide -140/-96), active in all cell types, and one activating region, from nucleotide -96 to the cap site, sufficient to confer a muscle preference of expression, in which the CCArGG box seems to play a major role.


Drying and rewetting induce changes in biofilm characteristics and the subsequent release of metal ions.
Drying and rewetting can markedly influence the microbial structure and function of river biofilm communities and potentially result in the release of metal ions from biofilms containing metals. However, little information is available on the response of metal-enriched biofilms to drying and rewetting over time. In this study, natural biofilms were allowed to develop in four rotating annular bioreactors for 2-11 weeks, followed by drying for 5 days and rewetting for another 5 days. Subsequently, we assessed Zn, Cd, and As desorption from the biofilms and other related parameters (microbial community structure, biofilm morphology, enzyme activity, and surface components as well as characteristics). High-throughput sequencing of the 16 S rRNA gene and confocal laser scanning microscopy revealed that the biofilm architecture and bacterial communities were distinct in different growth phases and under drying and rewetting conditions (permutational multivariate analysis of variance; p = 0.001). Proteobacteria was the dominant bacterial phylum, accounting for 69.7-90.1% of the total content. Kinetic experiments revealed that the drying and rewetting process increased metal desorption from the biofilm matrix. The desorption of heavy metals was affected by the age of the biofilm, with the maximum amount of metal ions released from 2-week-old biofilms (one-way ANOVA, Zn: p < 0.001; Cd: p = 0.008; As: p < 0.001). The modifications in biofilm properties and decreased diversity of the bacterial community (paired t-test, p < 0.05) after drying and rewetting decreased the number of specific binding sites for metal ions. In addition, negatively charged arsenate and other anions in the liquid phase could compete with As ions for adsorption sites to promote the release of As(V) and/or reductive desorption of As(III). The results of this study and their interpretation are expected to help refine the behaviors of heavy metals in the aquatic environment.


Correction to: Computational analysis of viable parameter regions in models of synthetic biological systems.
[This corrects the article DOI: 10.1186/s13036-019-0205-0.].


Oral feeding after total laryngectomy for endolaryngeal cancer.
There is still no agreement about the beginning of oral feedings after total laryngectomy. Some authors begin routine feedings on the 3rd postoperative day, while others delay oral feedings until 12-14 days after surgery. The present study was devised as a prospective randomized clinical trial concerning beginning oral feedings on the 7th or 14th postoperative day in 35 patients following total laryngectomy as treatment for endolaryngeal cancer. There were no differences in risk factors present in either group. Only two pharyngocutaneous fistulae occurred in the overall series (5.7%), with both appearing in the 7-day group and developing on the 18th and 20th postoperative days respectively. There were no statistically significant differences in fistula formation between the two groups (P = 0.49). We conclude that it is not necessary to delay oral feedings more than 7 days in patients without suture line tension.


Understanding evaluation of faces on social dimensions.
People reliably and automatically make personality inferences from facial appearance despite little evidence for their accuracy. Although such inferences are highly inter-correlated, research has traditionally focused on studying specific traits such as trustworthiness. We advocate an alternative, data-driven approach to identify and model the structure of face evaluation. Initial findings indicate that specific trait inferences can be represented within a 2D space defined by valence/trustworthiness and power/dominance evaluation of faces. Inferences along these dimensions are based on similarity to expressions signaling approach or avoidance behavior and features signaling physical strength, respectively, indicating that trait inferences from faces originate in functionally adaptive mechanisms. We conclude with a discussion of the potential role of the amygdala in face evaluation.


Effect of changing the fine particle mass of inhaled beclomethasone dipropionate on intrapulmonary deposition and pharmacokinetics.
Reformulation of beclomethasone dipropionate (BDP) in the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane-134a (HFA) gave the opportunity to produce a solution formulation that provides a greater total mass of fine drug particles than the current CFC suspension metered dose inhaler (MDI). The HFA-BDP MDI was studied in three pharmacokinetic trials in asthmatic patients. Serum levels of BDP plus metabolites [total beclomethasone (total BOH) assay] were used to test whether the increased fine particle mass of HFA-BDP would result in improved intrapulmonary deposition and subsequent differences in serum profiles. Serum levels, maximum serum concentrations and area under the serum concentration-time curves of total BOH following both single and multiple doses of HFA-BDP were similar to those obtained with approximately twice the dose of CFC-BDP. The observed lower bioavailability of CFC-BDP compared with HFA-BDP could be explained if most of each inhaled dose from the CFC-BDP MDI was swallowed and absorbed from the gastrointestinal tract, while most of each inhaled dose from the HFA-BDP MDI was absorbed from the lungs. Deposition studies have confirmed this explanation. These results suggest that asthmatic patients can be treated with lower total daily doses of drug from HFA-BDP extrafine aerosol than from CFC-BDP.


Normative values for the American Urological Association Symptom Index (AUA-7) and short form Urogenital Distress Inventory (UDI-6) in patients 65 and older presenting for non-urological care.
To determine the scores of two commonly used urologic questionnaires in community dwelling elderly patients receiving non-urologic primary care. Patients 65 years and older presenting for routine non-urologic primary care from April to July 2004 were eligible for enrollment. They completed a questionnaire evaluating demographics, AUA-7, UDI-6, and one visual analogue quality of life (QOL) question (range 0, pleased to 10, terrible). Total and question specific scores were analyzed. In addition, correlations among urinary symptoms and QOL scores were performed. In 157 patients who satisfied the study criteria, total and question-specific scores for the AUA-7 and UDI-6 were mildly elevated and similar across age groups in both sexes. Question 1 (frequency) rendered the highest score for both women and men from the UDI-6 questionnaire (mean 1.3 and 0.74, respectively). Question 7 (nocturia) rendered the highest score for both women and men from the AUA-7 questionnaire (mean 1.87 and 0.940, respectively). A total of 32 (27%) of 118 women and 6 (15%) of 39 men were found to have high elevation in QOL scores (>5). The total scores for the AUA-7 and UDI-6 were found to be mildly elevated but stable with age over time in this older population. These data provide useful information for urologists regarding baseline ranges for urinary symptoms in the elderly population. Over one-third of women were found to have a significant elevation in QOL scores (>5) which suggest a need for improvement in identifying and addressing urinary symptoms among elderly women.


Evaluation of bacterial contamination in blood processing.
In the routine deglycerolization of frozen red blood cells, a bottle of solution intended as a final wash (0.8% NaCl, 0.2% dextrose) was found to be abnormally colored and slightly turbid. Close inspection revealed a small crack in the base of the bottle. A pure growth of Klebsiella pneumoniae was cultured. The rabbit pyrogen test on the solution was positive using 2.5 mul as was the limulus amebocyte lysate (LAL) test at a dilution of 1:10-5 for endotoxin. Studies of the growth of this organism are described and the clinical implications are discussed.


Arsenic induces the expressions of angiogenesis-related factors through PI3K and MAPK pathways in SV-HUC-1 human uroepithelial cells.
Arsenic, a well-established human carcinogen, can cause various types of cancers, including bladder cancer. Angiogenesis is a key event for tumor initiation. In this study, several important angiogenesis related factors, including cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α), were up-regulated and PI3K/AKT and MAPK signal pathways were activated in human uroepithelial cell line (SV-HUC-1) treated with NaAsO2 (0, 1, 2, 4, 8 or 10μM) for 24h. Arsenite-induced HIF-1α, VEGF and COX-2 expressions were decreased by PI3K inhibitors. Blockage of the ERK1/2, p38 and JNK down-regulated the VEGF level, while ERK1/2 and p38 inhibitors were more effective than JNK in attenuating arsenite-induced COX-2 expression. HIF-1α expression was only decreased by ERK1/2 inhibitor. It was found that superoxide (O2(-)) generation was involved in arsenite-induced the activation of MAPK and PI3K pathways, which led to the HIF-1α, COX-2 and VEGF overexpressions. In conclusion, arsenite-induced COX-2, VEGF and HIF-1α expressions, mediated partially by reactive oxygen species (ROS), were regulated by MAPK and PI3K/AKT signaling pathways in human uroepithelial cells.


Bilayer technique and nano-filled coating increase success of approximal ART restorations: a randomized clinical trial.
The high-viscosity consistency of glass ionomer cement (GIC) may lead to its incorrect adaptation into the cavity and therefore to restoration failure. To compare two different insertion techniques for GIC in approximal atraumatic restorative treatment (ART) restorations and two different surface protection materials. Approximal caries lesion in primary molars from 208 schoolchildren was randomly assigned into four groups: G1, conventional GIC insertion protected with petroleum jelly (PJ); G2, bilayer technique protected with PJ; G3 conventional GIC insertion protected with nano-filled particles coating for GIC (NPC); G4, bilayer technique protected with NPC. Restorations were evaluated after 1, 6, 12, 18, 24, and 36 months. Kaplan-Meier survival analysis and log-rank test were performed. Cox regression analysis (α = 5%) was used to verify the influence of clinical factors. Restoration survival was 52.8%. Log-rank test indicated a better survival of the bilayer technique restorations, compared to conventional restorations (P = 0.005), whereas the coated conventional restorations presented higher survival than the uncoated ones (P = 0.035). Cox regression analysis showed no influence of any clinical tested variables. The survival rate of the approximal ART restorations is positively influenced by the bilayer technique, and the application of nano-filled coating increases the longevity of the conventional approximal ART restorations.


Design and synthesis of novel 3-substituted-indole derivatives as selective H3 receptor antagonists and potent free radical scavengers.
A series of novel 3-substituted-indole derivatives with a benzyl tertiary amino moiety were designed, synthesized and evaluated as H3 receptor antagonists and free radical scavengers for Alzheimer's disease therapy. Most of these synthesized compounds exhibited moderate to potent antagonistic activities in CREs driven luciferase assay. In particular, compound 2d demonstrated the most favorable H3 receptor antagonistic activity with the IC50 value of 0.049μM. Besides, it also displayed high binding affinity to H3 receptor (Ki=4.26±2.55nM) and high selectivity over other three histamine receptors. Moreover, 2d and other two 3-substituted indole derivatives 1d and 3d exerted potent ABTS radical cation scavenging capacities similar to melatonin. Above results illustrate that 2d is an interesting lead for extensive optimization to explore new drug candidate for AD therapy.


The identification of phage vB_1086 of multidrug-resistant Klebsiella pneumoniae and its synergistic effects with ceftriaxone.
The continued rise of Klebsiella pneumoniae resistance to antibiotics is precipitating a medical crisis. Bacteriophages have been hailed as one possible therapeutic option to enhance the efficacy of antibiotics. This study describes the genomic characterization and biological property of a new bacteriophage vB_1086 and its potential for phage therapy application against Klebsiella pneumoniae. In our study, the double-layer agar plate method isolated a lytic bacteriophage named vB_1086. Besides, we analyzed its biological characteristics and genetic background. Then the antibacterial ability of the bacteriophage vB_1086 combined with antibiotics were analyzed by the combined checkerboard method. The impact on the formation of biofilms was analyzed by crystal violet staining method. vB_1086 is a lytic bacteriophage with stable biological characteristics and clear genetic background, showing good antibacterial activity in combination with ceftriaxone, and the combination of phage and meropenem can effectively inhibit the formation of biofilm. Besides, the combination of bacteriophage and antimicrobials can effectively alleviate the generation of bacterial resistance and reduce the dosage of antimicrobials. vB_1086 is a novel phage. To some extent, these results provide valuable information that phage vB_1086 can be combined with antibiotics to reduce the dosage of antimicrobials and alleviate the generation of bacterial resistance.


Identification of 2-furanmethanethiol contributing to roast aroma in honkaku shochu and awamori.
Honkaku shochu and awamori are traditional Japanese spirits. 2-Furanmethanethiol (2FM), a volatile thiol, was identified as a roast aroma compound in honkaku shochu and awamori. The detection threshold of 2FM in 25% (v/v) ethanol water solutions was determined as 1.6 ng/L. The odor activity values, calculated using the detection threshold suggested that 2FM affects the quality of honkaku shochu and awamori. The odor activity values of 2FM were higher in barley shochu distilled at atmospheric pressure than in sweet potato shochu, rice shochu and awamori; therefore, 2FM is considered to contribute to the characteristics of barley shochu.


Radioiodinated bleomycin: stoichiometry of iodination and structural characterization by 1H-nuclear magnetic resonance.
Bleomycin was iodinated by reaction with iodine monochloride (ICl). A direct relationship was found to exist between the average number of iodine atoms bound per molecule of bleomycin and the ICl: bleomycin molar ratio. Characterization by 1H-NMR analysis denoted that mono, di-, tri- and tetraiodobleomycin are formed when the reacting molar ratios, respectively, are 2:1, 4:1, 6.8:1 and 8.5:1 or greater. The sites of iodination of the bleomycin molecule have been identified to be the imidazole ring which iodinates first, followed by the bithiazole ring system which iodinates last.


Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes.
This study has examined the occurrence of lipid peroxidation in in vivo aged human erythrocyte membranes. Erythrocytes of various ages were separated on discontinuous stractan density gradients. Three erythrocyte fractions were analyzed: (I) Light--erythrocytes staying between stractan densities 1.053 and 1.043 g/ml, (II) predensest--erythrocytes staying between stractan densities 1.081 and 1.111, and (III) densest--erythrocytes passing stractan density 1.111. Peroxidative lipid damage of erythrocytes was assessed by measuring lipid extract fluorescence, by lipid thin-layer chromatography for the presence of adduct of phosphatidylserine (PS), phosphatidylethanolamine (PE) and malondialdehyde, and by thiobarbituric acid-reactivity. Fractions I, II and III contained, respectively, 0.2 +/- 0.1 (S.E.), 1.1 +/- 0.1 and 1.5 +/- 0.1 of phospholipid-malondialdehyde adduct (percent of total phospholipids), and relative lipid fluorescence 22.5 +/- 0.8, 29.3 +/- 0.5, and 33.4 +/- 0.8 per ml packed cells, respectively. Thiobarbituric acid-reactivity of erythrocytes in various fractions was similar. Untreated densest erythrocytes contained significantly reduced PS (12.9 +/- 0.5%), in contrast to light erythrocytes (16.1 +/- 0.1%) and increased PC (31.2 +/- 0.3 versus 27.8 +/- 0.8% of the total phospholipid). This study provides evidence for significant lipid peroxidative damage in the erythrocyte membrane during aging in vivo.


Disease characteristics in patients with and without psoriatic arthritis treated with etanercept.
Patients with psoriasis (PsO) and psoriatic arthritis (PsA) have functional disability, pain and emotional problems, and experience lower quality of life (QoL) than patients with PsO alone. Examine effectiveness of etanercept (ETN) in patients with PsO alone, and with PsA, and determine whether PsA patients on ETN experience rapid QoL improvement. Data from three phase III trials using ETN in adults with moderate-to-severe PsO were pooled. Patients with (n = 523) and without (n = 1330) PsA received ETN 25 mg once weekly to 50 mg twice weekly or placebo for 12-24 weeks. Assessments included Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D), Study 36-item Short Form Health Survey (SF-36) and Hamilton Depression Rating Scale (HAM-D). Baseline PASI, EQ-5D and SF-36 physical component summary scores were worse for PsA patients. With ETN, PASI for PsA and non-PsA groups improved as early as week 2. Scores for both groups converged by week 12. EQ-5D and SF-36 physical component improved faster in PsA patients, with EQ-5D scores converged by week 2. For total DLQI and most components, both groups had similar baseline scores and improved over 24 weeks on ETN. While the PsA group had more depressed patients at baseline, after 24 weeks on ETN it showed a greater reduction in the number of depressed patients than the non-PsA group. In patients with PsO involving ≥10% of body surface area, skin disease and QoL are worse in PsA patients. With ETN, QoL improved rapidly in PsA patients.


Morphology of the acromioclavicular-joint score (MAC).
To date there is no generally accepted specific definition or classification of acromioclavicular (AC) joint osteoarthritis. The aim of this study is to analyze morphological parameters using magnetic resonance imaging (MRI) and to develop a scoring system as a basis for decision making to perform an AC-joint resection. In a retrospective-monocentric matched pair study, healthy and affected subjects were investigated using T2 MRI scans in the transverse plane. There were two groups, group 1 (n = 151) included healthy asymptomatic adults with no history of trauma. In group 2, we included n = 99 patients with symptomatic AC joints, who underwent arthroscopic AC-joint resection. The central and posterior joint space width and the AC angle were measured. Morphological changes such as cartilage degeneration, cysts and bone edema were noted. Malalignment of the joint was defined as: posterior joint space width < 2 mm in conjunction with an AC angle > 12°. A scoring system consisting of the measured morphologic factors was developed. Symptomatic and asymptomatic patients showed significant differences in all measured items. We observed a significant difference in the MAC score for symptomatic and asymptomatic patients (mean 10.4 vs. 20.6, p = 0.0001). The ROC (receiver operator characteristic) analysis showed an excellent AUC of 0.899 (p = 0.001). The sensitivity of the MAC score was 0.81 and the specificity 0.86. The MAC score shows a significant moderate correlation with age (r = 0.358; p = 0.001). The correlation of age and the development of symptoms was only weak (r = 0.22, p = 0.001). Symptomatic patients showed significantly more frequent malalignment compared to asymptomatic patients (p = 0.001), but the positive predictive value that a patient with malalignment is also symptomatic is only 55%. Patients with symptomatic AC joints showed a typical pattern of morphological changes on axial MRI scans with early posterior contact of the joint surfaces, reduction of joint space and malalignment as the basis for the development of a scoring system. The MAC score shows excellent test characteristics, and therefore, proved to be both an appropriate guidance for clinical practice as well as an excellent tool for comparative studies and is superior to the assessment of malalignment alone. Level IV, retrospective diagnostic study.


The Primary Care Respiratory Society-UK Quality Award: development and piloting of quality standards for primary care respiratory medicine.
In an attempt to improve the standards of primary respiratory care in the UK, the Primary Care Respiratory Society-UK (PCRS-UK), in conjunction with other leading respiratory-interested health professional and patient groups, has devised a General Practice Quality Award for Respiratory Medicine. The Award is divided into three modules separated into a total of seven clinical standards (in parentheses): 'Clinical' (prevention, early and accurate diagnosis, acute care, chronic care); 'Organisational' (equipment); and 'The Practice Team' (practice learning needs, educational strategy). Assessment is by submission of a written portfolio of 37 pieces of evidence including audit, reflective learning, patient feedback, and significant event analyses. The Award was piloted in five respiratory-interested practices across the UK. The practices reported improvements in practice organisation, practice teamwork, improved process measures such as improvement in quality of spirometry, and improved patient access to patient services. All practices in the UK are being invited to apply for the Award in 2013. It is hoped that it will provide a framework and stimulus for provision of high-quality primary respiratory care, not only in the UK, but also some aspects of the Award may be applicable on a wider international scale.


Matched comparison of 3 cerebral perfusion strategies in open zone-0 anastomosis for acute type A aortic dissection.
The present study aims to investigate outcomes after the surgical treatment of acute type A aortic dissection in regard to three available selective cerebral perfusion strategies. From 2000 to 2019, patients were selected based on the employment of either retrograde cerebral perfusion (RCP), unilateral antegrade cerebral perfusion (uACP) or bilateral antegrade cerebral perfusion (bACP) during open zone-0 anastomosis. Propensity score TriMatch analysis considering several preoperative and intraoperative variables was used to identify well-balanced triplets. The primary end point of the study was a new cerebral operation-related neurologic deficit. Operative times (operation time, cardiopulmonary bypass time, reperfusion time) were significantly longer in the RCP group, in which deeper hypothermia was applied (27.5 [24-28], 28 [26-28] and 16 [16-17]°C for uACP, bACP and RCP, respectively, P-value <0.001). The RCP group showed higher red blood cell concentrates and fresh frozen plasma transfusion rates. No significant difference of new cerebral operation-related neurologic deficit was observed between the 3 groups (12.9% vs 12.9% vs 11.3% for RCP, uACP and bACP, P-value = 0.86). In addition, 30-day mortality showed similar distribution independently of the cerebral perfusion strategy adopted (17.7% vs 14.5% vs 17.7% for RCP, uACP and bACP, P-value = 0.86). However, based on a small sample size, the comparison showed no relevant differences in terms of neurologic outcome and 30-day mortality, confirming RCP, uACP and bACP as safe and reproducible selective cerebral perfusion strategies in surgery for acute type A aortic dissection.


[Disruption of the electrolyte and microelement composition of gastric juice and bile in patients with chronic diseases of the hepatobiliary system].
A study is presented of 403 patients with chronic diseases of the stomach and biliary tract. It was established that these patients showed disorders of the electrolytic and micro-element composition of the gastric juice and bile depending on the functional state of the stomach and liver.


Factors associated with stunting among children according to the level of food insecurity in the household: a cross-sectional study in a rural community of Southeastern Kenya.
Chronic malnutrition or stunting among children under 5 years old is affected by several household environmental factors, such as food insecurity, disease burden, and poverty. However, not all children experience stunting even in food insecure conditions. To seek a solution at the local level for preventing stunting, a cross-sectional study was conducted in southeastern Kenya, an area with a high level of food insecurity. The study was based on a cohort organized to monitor the anthropometric status of children. A structured questionnaire collected information on the following: demographic characteristics, household food security based on the Household Food Insecurity Access Scale (HFIAS), household socioeconomic status (SES), and child health status. The associations between stunting and potential predictors were examined by bivariate and multivariate stepwise logistic regression analyses. Furthermore, analyses stratified by level of food security were conducted to specify factors associated with child stunting in different food insecure groups. Among 404 children, the prevalence of stunting was 23.3%. The percentage of households with severe food insecurity was 62.5%. In multivariative analysis, there was no statistically significant association with child stunting. However, further analyses conducted separately according to level of food security showed the following significant associations: in the severely food insecure households, feeding tea/porridge with milk (adjusted Odds Ratio [aOR]: 3.22; 95% Confidence Interval [95% CI]: 1.43-7.25); age 2 to 3 years compared with 0 to 5 months old (aOR: 4.04; 95% CI: 1.01-16.14); in households without severe food insecurity, animal rearing (aOR: 3.24; 95% CI: 1.04-10.07); SES with lowest status as reference (aOR range: from 0.13 to 0.22). The number of siblings younger than school age was not significantly associated, but was marginally associated in the latter household group (aOR: 2.81; 95% CI: 0.92-8.58). Our results suggest that measures against childhood stunting should be optimized according to food security level observed in each community.


The journey to birth: medical and geographical patterns of births to women of a rural Kentucky county, 1911-1980.
A relative lack of medical services is common in rural areas, and it has been suggested that the number of births in the mother's county of residence reflects both the availability of obstetric services as well as attitudes toward local and nonlocal medical care. In order to better understand these relationships, we analyzed the evolution of medical and geographical patterns of births to women of a rural Kentucky county in the context of both a changing philosophy and a changing availability of medical care. Specifically, using archival data, we assessed the locus (i.e., home versus hospital) and location (i.e., county) of births to Robertson County women from 1911 to 1980. Without a hospital for the entire period and with the number of physicians declining, the percentage of in-county home births increased steadily, reaching virtually 100 percent by 1950. During this same period, the number of physicians practicing there decreased from 22 to 2. Subsequent delivery patterns reflect the acceptance by the physicians and women of the "principle" of hospital delivery formally enounced in 1945. By 1965, home births had been eliminated, and Robertson County women were, of necessity, traveling the 25-30 miles to the several hospitals in contiguous counties. In the past 15 years, a substantial proportion (almost 20 percent) have elected to travel to hospitals even farther (55-60 miles) from Robertson County. Generally, the Robertson County experience reflects the "lag" observed in the rural-urban, home versus hospital birth experience. Nevertheless, since 1966, all recorded births to Robertson County women have occurred in hospitals.(ABSTRACT TRUNCATED AT 250 WORDS)


[Comparative analysis of the interaction of protein A from Staphylococcus aureus with native, reduced and aggregated IgG].
In a comparative study the affinity of rabbit and human IgG, native, reduced and aggregated by various methods, to protein A obtained from the cell wall of Staphylococcus aureus was determined. For this purpose the method of the passive hemagglutination inhibition test was developed. The affinity to protein A was found to grow considerably after specific or non-specific IgG aggregation and to decrease by 60% after local damage affecting the structure of the IgG molecule waist as a result of the dissolution of the disulfide bond between its heavy chains. The problem of similarity between such effector properties of IgG as its ability to activate the complement system and to combine with protein A is considered, as well as the problem of the pathogenetic role of immune complexes bound with protein A.


Substrate interactions during anaerobic biodegradation of BTEX by the mixed cultures under nitrate reducing conditions.
The enriched BTEX-degrading bacteria were used to investigate the substrate interactions during anaerobic biodegradation of all the possible BTEX binary combinations. Beneficial and detrimental substrate interactions were observed in comprehensive mixtures of benzene, toluene, ethylbenzene, o-xylene, m-xylene and p-xylene. The amendment of toluene or ethylbenzene could stimulate benzene degradation. Lower concentrations of m-xylene would enhance the degradation of benzene, whereas degradation of benzene was inhibited with higher concentrations of m-xylene. The simultaneous presence of toluene and ethylbenzene could stimulate the degradation of each other. The addition of toluene stimulated o-xylene degradation, whereas the amendment of ethylbenzene inhibited the degradation of o-xylene. Lower concentrations of toluene or ethylbenzene would enhance the degradation of m-xylene and p-xylene, whereas higher concentrations of toluene or ethylbenzene had a slight inhibitory effect on m-xylene and p-xylene degradation. The amendment of benzene, m-xylene or p-xylene would inhibit the degradation of other BTEX compounds. When the concentration of BTEX mixtures was over 150 mg/l, the degradation of benzene, o-xylene, m-xylene and p-xylene was severely inhibited.


Lamotrigine as adjunctive therapy in patients with refractory epilepsy and mental retardation.
This study evaluated the effects of lamotrigine as adjunctive therapy for refractory epilepsy in patients with mental retardation. Patients with epilepsy and mental retardation having uncontrolled seizures despite treatment with other antiepileptic drugs were eligible (n=67). The open-label study comprised a Baseline Phase, an Escalation Phase during which lamotrigine was titrated to a target dose, an 8-week Maintenance Phase during which doses of lamotrigine and concomitant antiepileptic drugs were maintained, and a 12-week Optimization Phase during which doses of lamotrigine and other antiepileptic drugs could be adjusted. Almost half (44%) of patients experienced a 50% reduction in seizure frequency during the Maintenance Phase after addition of lamotrigine; 15% of patients became seizure-free. A similar pattern of results was reported for the Optimization Phase. Investigator-rated clinical status was improved relative to baseline in 66 and 74% of patients at the end of the Maintenance and Optimization Phases, respectively. Most patients experienced improvements in seizure frequency, duration, and intensity during the Maintenance Phase (62 to 72%) and the Optimization Phase (65 to 74%). Many patients were rated as having improved social functioning during the Maintenance Phase (42%) and the Optimization Phase (46%). The Aberrant Behavior Checklist score for lethargy and the mean Habilitative Improvement Scale score were improved at the ends of the Maintenance and Optimization Phases relative to baseline (P< or =0.04). One limitation of this study is its open-label design, which limits the ability definitively to attribute the clinical improvements to lamotrigine. Adjunctive lamotrigine in patients with refractory epilepsy and mental retardation appears to decrease seizure frequency and improve behavior while permitting a reduction in dose of concomitant antiepileptic drugs.


Clathrin: a good view of a shapely leg.
The crystal structure of an amino-terminal fragment of the clathrin heavy chain has recently been determined, revealing a globular beta-propeller domain attached by an alpha-zig-zag connecting rod to the heavy chain's distal segment. The structure sheds interesting new light on the design features of this versatile protein.


Orthodontic correction of a skeletal Class II malocclusion with severe gummy smile by total intrusion of the maxillary dentition.
A 22-year-old woman visited the hospital complaining of lip protrusion, crowded teeth, and a gummy smile. The clinical examination showed a convex profile with a hyperdivergent mandible and a severe gummy smile in both anterior and posterior regions. The unstable mandible position was considered during treatment planning, and a targeted mechanic system was carefully designed. Temporary skeletal anchorage devices in the posterior dental region and a transpalatal arch were introduced as anchorage for the intrusion of the entire maxillary dentition and controlled retraction of the anterior teeth. Based on effective and simple mechanisms, we successfully eliminated the severe gummy smile and improved the facial aesthetics with the aid of conventional appliances. This approach provided an alternative option to orthognathic surgery or bulky invasive miniscrews for treatment of skeletal Class II malocclusion with severe gummy smile.


Diagnostic Performance of Left Atrial Diameter Measurement in Computed Tomography to Detect Increased Left Atrial Volume.
The left atrium (LA) is frequently imaged in cardiac computed tomographic (cCT) examinations. The LA volume can be accurately measured with three-dimensional (3D) volumetry but this method is time consuming and thus not routinely used in clinical practice. Accordingly, increased LA size may be overlooked although volume enlargement is associated with adverse cardiovascular events. We evaluated the accuracy of LA diameter measurement in cCT and in transthoracic echocardiography (TTE) in the diagnosis of LA enlargement using 3D cCT as the reference standard. Altogether, 146 patients with suspected cardiogenic stroke underwent cCT and TTE. LA volume by cCT was determined for all patients. LA diameter was measured in both modalities. Furthermore, 40 healthy controls were analyzed in order to assess the cut-off values for normal LA volume. Diagnostic performance of cCT and conventional TTE diametrical measurements for detecting enlarged LA volume were analyzed and compared using Cohen's kappa (κ). In controls, the mean LA volume was 59.8±15.3 ml and the mean LA diameter was 30.4±5.0 mm by cCT. The mean value plus twice the standard deviation, which was considered the upper limit, for normal LA volume and diameter were 90.4 ml and 40.4 mm, respectively. Age- and gender-matched patients with stroke had statistically significantly (p<0.001) larger LA volumes (85.5±21.1 vs. 59.8±15.3 ml) and diameters (37.6±5.7 vs. 30.4±5.0 mm) than controls. LA diameter measurement by cCT was more reliable in detecting an LA volume enlargement than the corresponding measurement with TTE (κ=0.489 vs. 0.234; p=0.002). An enlarged LA diameter measured by cCT was more reliable than TTE at detecting enlarged LA volume.


Glucose increases extracellular [Ca2+] in rat insulinoma (INS-1E) pseudoislets as measured with Ca2+-sensitive microelectrodes.
Secretory granules of pancreatic β-cells contain high concentrations of Ca2+ ions that are co-released with insulin in the extracellular milieu upon activation of exocytosis. As a consequence, an increase in the extracellular Ca2+ concentration ([Ca2+]ext) in the microenvironment immediately surrounding β-cells should be expected following the exocytotic event. Using Ca2+-selective microelectrodes we show here that both high glucose and non-nutrient insulinotropic agents elicit a reversible increase of [Ca2+]ext within rat insulinoma (INS-1E) β-cells pseudoislets. The glucose-induced increases in [Ca2+]ext are blocked by pretreatment with different Ca2+ channel blockers. Physiological agonists acting as positive or negative modulators of the insulin secretion and drugs known to intersect the secretory machinery at different levels also induce [Ca2+]ext changes as predicted on the basis of their described action on insulin secretion. Finally, the glucose-induced [Ca2+]ext increase is strongly inhibited after disruption of the actin web, indicating that the dynamic [Ca2+]ext changes recorded in INS-1E pseudoislets by Ca2+-selective microelectrodes occur mainly as a consequence of exocytosis of Ca2+-rich granules. In conclusion, our data directly demonstrate that the extracellular spaces surrounding β-cells constitute a restricted domain where Ca2+ is co-released during insulin exocytosis, creating the basis for an autocrine/paracrine cell-to-cell communication system via extracellular Ca2+ sensors.


Clinical significance of serum bilirubin in primary Sjögren syndrome patients.
The purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS). A total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed. Serum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = -.406, P < .001; r = -.206, P = .026; r = -.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR. This study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow-up visits of the patients with pSS.


Difficulties in translating in vitro hazards of local acute irritants to relevant human risk: Learnings from Captan and Folpet.
In order to assess the regulatory value of New Approach Methodologies (NAMs), authors should provide their opinion on the physiological and exposure relevance of observed in vitro effects for correlation with predicted in vivo effects. Further, peer-reviewers should be encouraged to request such information during review. This is critical to scientifically transition to animal-free, reliable, robust and -- most importantly -- relevant regulatory toxicology and risk assessment approaches. Recently published studies using NAMs for the fungicides Captan and Folpet illustrate the difficulties and limitations of applying NAMs to adequately assess the toxicological relevance of these substances.


Physical and Chemical Enhancement of and Adaptive Resistance to Irreversible Electroporation of Pancreatic Cancer.
Irreversible electroporation (IRE) can be used to treat cancer by electrical pulses, with advantages over traditional thermal approaches. Here we assess for the first time the IRE response of pancreatic cancer, one of the deadliest forms of cancer, both in vitro and in vivo. We demonstrate that both established and primary cancer cell lines can be destroyed by IRE, but with differential susceptibility and thresholds. We further demonstrate in vitro that viability for a given IRE dose can vary with the local chemistry as outcomes were shown to depend on suspending medium and reduction of glucose in the media significantly improved IRE destruction. Data here also demonstrate that repeated IRE treatments can lead to adaptive resistance in pancreatic carcinoma cells thereby reducing subsequent treatment efficacy. In addition, we demonstrate that physical enhancement of IRE, by re-arranging the pulse sequences without increasing the electrical energy delivered, achieve reduced viability in vitro and decreased tumor growth in an in vivo xenograft model. Together, these results show that IRE can destroy pancreatic cancer in vitro and in vivo, that there are both chemical and physical enhancements that can improve tumor destruction, and that one should guard against adaptive resistance when performing repeated treatments.


Serial studies of serum dopamine-B-hydroxylase and urinary vanillylmandelic and homovanillic acids in neuroblastoma.
Recent reports have suggested that elevations of serum dopamine-B-hydroxylase (DBH) activity may correlate with diagnosis in neuroblastoma patients excreting vanillylmandelic acid (VMA). We have serially studied serum DBH and urinary homovanillic acid (HVA) and VMA excretion during the disease course of five patients with neuroblastoma. DBH activities did not indicate clinical course, therapies, or prognosis. Dilution studies revealed an age-related alteration in DBH effectors and they suggest that these may be different in neuroblastoma.


Can fetishism occur in transsexuals?
The literature concerning the relationships between transsexualism and transvestism and their association with fetishism is reviewed. Sexual activity, including sexual arousal to women's clothes, is frequently reported in histories of transsexuals. Characteristics are reported of 12 male subjects who have shown sexual arousal to women's clothes and who have a sustained cross-gender identity combined with a desire for a change-of-sex operation. Diagnostic categories alternative to transsexualism for subjects who cross-dress are inadequate to classify at least some of the 12 subjects reported. Restricting the definition of transsexualism so as to exclude those who have shown fetishistic features is considered premature.


History of convulsions and use of pertussis vaccine.
Data on 2062 reports from the Monitoring System for Adverse Events Following Immunization, Centers for Disease Control (CDC), were analyzed to compare the risk of a personal or family history of convulsions in children who had a neurologic adverse event after receipt of diphtheria-tetanus-pertussis (DTP) vaccine with those who had a nonneurologic adverse event. Children with a neurologic event after DTP vaccine had a 7.2 times higher risk for personal history of convulsions (95% confidence limits 4.5 to 11.5) and a 4.5 times higher risk for family history of convulsions (95% confidence limits 3.1 to 6.7) than did children with an adverse event that did not affect the nervous system. Children with either a febrile or nonfebrile convulsion after receipt of DTP were significantly more likely to have a personal history of convulsions than children with a nonneurologic adverse event (P less than 0.0001). Children with a febrile convulsion after receipt of DTP but not children with nonfebrile convulsions were significantly more likely to have a family history of convulsions than those with a nonneurologic adverse event. It is recommended that pertussis vaccination be deferred in children with a personal history of a convulsion until it can be determined that an evolving neurologic disorder is not present. If such disorders are found, these children should be given the combined pediatric diphtheria and tetanus toxoids (DT) vaccine to complete the series.


Outcome and survival in canine sick sinus syndrome and sinus node dysfunction: 93 cases (2002-2014).
To evaluate the clinical presentation, diagnosis, treatment, and outcomes of a group of dogs with sinoatrial node abnormalities. Ninety-three client-owned dogs at a referral institution. Medical records were reviewed for clinical history, diagnostic testing, and medical or permanent artificial pacemaker (PAP) treatment. Owners or veterinarians were contacted for long-term follow-up. Sixty-one dogs were symptomatic for their bradyarrhythmia and were diagnosed with sick sinus syndrome (SSS). Thirty-two dogs were asymptomatic for their bradyarrhythmia and were diagnosed with sinus node dysfunction (SND). Miniature Schnauzers, West Highland White terriers, Cocker spaniels, and female dogs were overrepresented. Medical management with positive chronotropic drugs successfully controlled syncope long-term in 54% of SSS dogs, and acted as a bridge to PAP in 20%. Positive atropine response predicted medical treatment success. Forty-six percent of SSS dogs eventually underwent PAP implantation. Median survival time was approximately 18 months in SND and SSS dogs regardless of treatment strategy. Congestive heart failure (CHF) associated with progressive valvular heart disease occurred commonly in all groups, particularly in dogs with bradycardia-tachycardia syndrome. Sinus node dysfunction and SSS represent a spectrum of sinoatrial node disease, which for some dogs may also involve a component of autonomic dysfunction. Dogs with SND do not require treatment. Dogs with SSS often require treatment to reduce the frequency of syncope; medical management is often useful, particularly in atropine responsive dogs. Prognosis of SSS with treatment is good, though development of CHF does not appear to be mitigated by treatment.


Primary renal lymphoma presenting as acute renal failure.
Diffuse bilateral infiltration of the kidneys by lymphoma cells is a rare but well-documented cause of acute renal failure (ARF). Only 51 such cases have been reported, 15 of which had ARF as the initial presentation of lymphoma. The clinical and pathologic features of these 15 cases and of two additional cases reported herein are reviewed. The diagnosis should be suspected in a patient with ARF, bilateral enlargement of the kidneys, minimal proteinuria, nonspecific findings on urinalysis, and absence of features of allergic tubulointerstitial nephritis. Renal imaging techniques may suggest the possibility of lymphomatous infiltration, but only renal biopsy or autopsy can provide a definitive diagnosis. Although modern chemotherapy and/or radiation therapy usually leads to a dramatic normalization of renal function, almost all patients eventually die of widespread recurrent lymphoma, despite the absence of clinical or pathologic involvement of the kidneys at the time of death.


Psychomotor symptoms in depressed elderly patients: assessment of the construct validity of the Dutch CORE by accelerometry.
Psychomotor symptoms are putative distinguishing features of melancholia that may guide treatment decisions. Hence, there is a need for valid instruments to assess psychomotor symptoms. The objective of this study is to examine the construct validity of the CORE, an observational instrument designed to quantify psychomotor symptoms in depression. Associations between CORE scores and levels of motor activity measured by accelerometry were examined in a sample of 25 elderly depressed in-patients, for various time intervals, during 24h of follow-up. Total CORE scores (as well as CORE retardation and agitation sub-scale scores) were negatively correlated with activity scores, with depression severity increasing the correlational strength substantively. For total CORE scores and retardation sub-scale scores, the highest associations were quantified across morning intervals. Given the nature of the study mild levels of depression were overrepresented, monitoring of motor activity lasted only 24h and non-motor activity items in the CORE were not measured. Associations between CORE total scores and retardation sub-scale scores support the validity of the CORE as well as quantifying associations between severity of psychomotor disturbance and clinical depression severity. Study results also support the application of accelerometry tools in quantifying components of clinical depression.


Evaluation of Postmortem Cerebrospinal Fluid S100B Protein and Serotonin Levels: Comparison of Suicidal Versus Nonsuicidal Deaths in Konya, Turkey.
Although suicide is a preventable public health problem, objective assays for suicide risk are limited. In this study, it was aimed to determine levels of S100B protein and serotonin as a marker for risk of suicide. S100B protein and serotonin levels were investigated with ELISA method in the cerebrospinal fluid (CSF) in medicolegal autopsy cases, including those of suicide cases (n = 32) and nonsuicide cases (n = 56). The CSF S100B levels were higher (9.3 ± 2.9 ng/mL vs. 5.4 ± 2.0 ng/mL), and serotonin levels were lower (10.4 ± 4.9 ng/mL vs. 19.0 ± 5.7 ng/mL) in suicide group than nonsuicide group (p < 0.05). There was no correlation between S100B protein and serotonin levels with gender, age groups, postmortem interval, and cause of death. It is concluded that both S100B protein and serotonin in CSF may be useful for determination of suicide risk.


The influence of ultraviolet reflectance differs between conspicuous aposematic signals in neotropical butterflies and poison frogs.
Warning signals are often characterized by highly contrasting, distinctive, and memorable colors. Greater chromatic (hue) and achromatic (brightness) contrast have both been found to contribute to greater signal efficacy, making longwave colored signals (e.g., red and yellow), that are perceived by both chromatic and achromatic visual pathways, particularly common. Conversely, shortwave colors (e.g., blue and ultraviolet) do not contribute to luminance perception yet are also commonly found in warning signals. Our understanding of the role of UV in aposematic signals is currently incomplete as UV perception is not universal, and evidence for its utility is at best mixed. We used visual modeling to quantify how UV affects signal contrast in aposematic heliconiian butterflies and poison frogs both of which reflect UV wavelengths, occupy similar habitats, and share similar classes of predators. Previous work on butterflies has found that UV reflectance does not affect predation risk but is involved in mate choice. As the butterflies, but not the frogs, have UV-sensitive vision, the function of UV reflectance in poison frogs is currently unknown. We found that despite showing up strongly in UV photographs, UV reflectance only appreciably affected visual contrast in the butterflies. As such, these results support the notion that although UV reflectance is associated with intraspecific communication in butterflies, it appears to be nonfunctional in frogs. Consequently, our data highlight that we should be careful when assigning a selection-based benefit to the presence of UV reflectance.


Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.
Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.


Crystallization and preliminary X-ray crystallographic analysis of the rhesus macaque MHC class I molecule Mamu-B*17 complexed with an immunodominant SIVmac239 Env epitope.
Long-term nonprogression during simian immunodeficiency virus (SIV) infection has been strongly associated with the major histocompatibility complex (MHC) class I allele Mamu-B*17. Here, a complex of rhesus macaque Mamu-B*17 with rhesus macaque β2-microglobulin (β2m) and an immunodominant peptide (SIVmac239 Env241-251; LRCNDTNYSGF; Env LF11) derived from the SIV Env protein was crystallized by the hanging-drop method using PEG 3350 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P2, with unit-cell parameters a = 68.3, b = 45.0, c = 81.5 Å, β = 96.5°. Assuming the presence of one molecule in the asymmetric unit, the Matthews coefficient and solvent content were calculated to be 2.96 Å(3) Da(-1) and 58.5%, respectively.


Regulation of feeding by galnon.
Galanin is a neuropeptide that has been implicated in multiple bioactivities, inter alia eating disorders. In this study, we have examined the effects of galnon, a novel low molecular weight galanin receptor ligand. Previous studies have shown that galnon acts as a systemically active, blood-brain barrier crossing agonist on galanin signaling both in vitro and in vivo, inhibiting pentylenetetrazole-induced seizures. Here, intracerebroventricular (10-20 microg) and intraperitoneal (1.5-5 mg/kg) administration of galnon induced a strong, dose-dependent reduction of food intake in rats and mice. This reduction in feeding occurred without reducing general activity and was shown to be attenuated by an intracerebroventricular administration of M35, a peptide galanin antagonist. These data demonstrate that galnon is a promising tool for studies of the involvement of galanin in feeding disorders and other behavioral processes.


Significance of Tyr302, His235 and Asp194 in the α-amylase from Bacillus licheniformis.
The calcium-binding residues, Tyr302 and His235, and the sodium-binding residue, Asp194, on the activity of Bacillus licheniformis α-amylase were investigated using site-directed mutagenesis. Tyr302 and His235 were replaced by Asn and Asp, respectively, to produce the mutants Y302N and H235D; Asp194 was replaced by Ala to produce D194A. The mutant amylases were purified to homogeneity; each was ~53 kDa. The specific activity of the D194A was 236 U mg(-1), lower than the specific activity of the wild-type enzyme by 55%. No significant changes of thermostability, optimum temperature, and optimum pH level were observed in D194A. Mutant amylases with H235D and Y302N significantly improved their specific activity by 43% (754 U mg(-1)) and 7% (563 U mg(-1)), respectively, compared with the wild-type enzyme. H235D substitution decreased its optimum pH by approx. 0.5-1 pH unit.


Hepatitis--Bs antigen in an isolated Indian population of southern Venezuela: a family study.
A genetic analysis of the presence of HBsAg in a population of which 7.2% of the members were positive is presented. Though the ratios of carriers: non-carriers were generally in good agreement with expectation if the carrier state were determined by homozygosity for a single recessive gene, the two examples of mating most critical to a test of the hypothesis, carrier X carrier, yielded 2 normal children among 4 in one family, and one normal child, the only offspring, in the second family. Other investigators have reported similar findings. We conclude that the hypothesis of simple recessive inheritance cannot be sustained.


Carbon isotope ratios and crop analyses of Arphia (Orthoptera: Acrididae) species in southeastern Wyoming Grassland.
Food habits of Arphia conspersa Scudder and Arphia pseudonietana (Thomas) were studied along an altitudinal transect in southeastern Wyoming shortgrass mixed prairie. Stable carbon isotope ratios indicated that diets were significantly different between study sites, between species, and between sexes. These differences were found to be primarily related to the availability of different food plants along the transect, although species with the C3 pathway of photosynthesis were consumed in greater proportion than their availability in the habitat. The preference for C3 species is presumably related to their higher nutritional value and digestibility, in spite of the fact that more time and energy must be spent to locate these food plants in some of the habitats studied. This study demonstrates the utility of the carbon isotope method in studying plant-animal interactions in habitats containing both C3 and C4 plants.


Endoscopic extraperitoneal repair of a Grynfeltt hernia.
There are three types of lumbar hernia: congenital, acquired, and incisional hernias. Acquired hernia can appear in two forms: the inferior (Petit) type and the superior type, first described by Grynfeltt in 1866. We report endoscopic extraperitoneal repair of a Grynfeltt hernia. A 46-year-old woman presented with a painful swelling in the left lumbar region that had caused her increasing discomfort. The diagnosis of Grynfeltt's hernia was made, and she underwent surgery. With the patient in a left-side decubitus position, access to the extraperitoneal space was gained by inserting a 10-mm inflatable balloon trocar just anteriorly to the midaxillary line between the 12th rib and the superior iliac crest through a muscle-splitting incision into the extraperitoneal space. After the balloon trocar had been removed a blunt-tip trocar was inserted. Using two 5-mm trocars, one above and another below the 10-mm port in the midaxillary line, the hernia could be reduced. A polypropylene mesh graft was introduced through the 10-mm trocar and tacked with spiral tackers. The patient could be discharged the next day after requiring only minimal analgesics. At this writing, 2 (1/2) years after the operation, there is no sign of recurrence. This Grynfeltt hernia could safely be treated using the extraperitoneal approach, which obviates opening and closing the peritoneum, thereby reducing operative time and possibly postoperative complications.


Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions.
The 72-kDa gelatinase/type IV collagenase, a metalloproteinase thought to play a role in metastasis and in angiogenesis, forms a noncovalent stoichiometric complex with the tissue inhibitor of metalloproteinase-2 (TIMP-2), a potent inhibitor of enzyme activity. To define the regions of the 72-kDa gelatinase responsible for TIMP-2 binding, a series of NH2- and COOH-terminal deletions of the enzyme were constructed using the polymerase chain reaction technique. The full-length and the truncated enzymes were expressed in a recombinant vaccinia virus mammalian cell expression system (Vac/T7). Two truncated enzymes ending at residues 425 (delta 426-631) and 454 (delta 455-631) were purified. Like the full-length recombinant 72-kDa gelatinase, both COOH-terminally truncated enzymes were activated with organomercurial and digested gelatin and native collagen type IV. In contrast to the full-length enzyme, delta 426-631 and delta 455-631 enzymes were less sensitive to TIMP-2 inhibition requiring 10 mol of TIMP-2/mol of enzyme to achieve maximal inhibition of enzymatic activity. The activated but not the latent forms of the delta 426-631 and delta 455-631 proteins formed a complex with TIMP-2 only when excess molar concentrations of inhibitor were used. We also expressed the 205-amino acid COOH-terminal fragment, delta 1-426, and found that it binds TIMP-2. In addition, a truncated version of the 72-kDa gelatinase lacking the NH2-terminal 78 amino acids (delta 1-78) of the proenzyme retained the ability to bind TIMP-2. These studies demonstrate that 72-kDa gelatinases lacking the COOH-terminal domain retain full enzymatic activity but acquire a reduced sensitivity to TIMP-2 inhibition. These data suggest that both the active site and the COOH-terminal tail of the 72-kDa gelatinase independently and cooperatively participate in TIMP-2 binding.


Treatment Withdrawal Following Remission in Juvenile Idiopathic Arthritis: A Systematic Review of the Literature.
Early diagnosis and treatment of juvenile idiopathic arthritis (JIA) with conventional and biologic disease-modifying anti-rheumatic drugs have vastly improved outcomes for children with these diseases. Currently, a large proportion of children with JIA are able to achieve clinical inactive disease and remission. With this success, important questions have arisen about when medications can be stopped and how to balance the risks and benefits of continuing medications versus the potential for flare after stopping. The aim was to conduct a systematic review of the available literature to summarize current evidence about medication withdrawal for JIA in remission. We conducted a systematic literature search in PubMed and Embase from 1990 to 2019. References were first screened by title and then independently screened by title and abstract by two authors. A total of 77 original papers were selected for full-text review. Data were extracted from 30 papers on JIA and JIA-associated uveitis, and the quality of the evidence was evaluated using National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) tools. Studies on biochemical and radiologic biomarkers were also reviewed and summarized. Most studies investigating treatment withdrawal in JIA have been observational and of poor or fair quality; interpretations of these studies have been limited by differences in study populations, disease and remission durations, the medications withdrawn, approaches to withdrawal, and definitions of disease outcomes. Overall the data suggest that flares are common after stopping JIA medications, particularly biologic medications. Clinical characteristics associated with increased risks of flare have not been consistently identified. Biochemical biomarkers and ultrasound findings have been shown to predict outcomes after stopping medications, but to date, no such predictor has been consistently validated across JIA populations. Studies have also not identified optimal strategies for withdrawing medication for well-controlled JIA. Promising withdrawal strategies include discontinuing methotrexate before biologic medications in children receiving combination therapy, dose reduction for children on biologics, and treat-to-target approaches to withdrawal. These and other strategies require further investigation in larger, high-quality studies. The published literature on treatment withdrawal in JIA has varied in design and quality, yielding little conclusive evidence thus far on the management of JIA in remission. Given the importance of this question, international collaborative efforts are underway to study clinical and biologic predictors of successful medication withdrawal in JIA. These efforts may ultimately support the development of personalized approaches to withdrawing medication in children with JIA in remission.


Bovine virus diarrhoea virus induces in vitro a proliferative response of peripheral blood mononuclear cells from cattle immunized by infection.
The ability of bovine peripheral blood mononuclear cells (PBMC) to mount a proliferative response to bovine virus diarrhoea virus (BVDV) in vitro was examined. After culturing PBMC in the presence of a non-cytopathic strain of BVDV for 6 days, the magnitude of PBMC proliferation was measured as incorporation of radiolabelled thymidine, present during the last 18 h. Live, but not heat-inactivated, BVDV evoked a proliferative response of PBMC obtained from cattle seropositive to the virus. However, PBMC from seronegative or persistently BVDV-infected animals were not stimulated by BVDV. The presence of live BVDV did not alter the proliferative response of PBMC to stimulation with concanavalin A.


Metabolite profiling as an aid to metabolic engineering in plants.
The past decade has seen some impressive successes in the metabolic engineering of biotechnologically important plant pathways. However, plant metabolic engineering currently proceeds more by trial and error than by intelligent system design. A change in philosophy away from studying pathways in isolation and towards studying metabolism as a network is necessary. To support this development, improvements in technologies for metabolic analysis, a wider adoption of metabolite-profiling approaches and significant innovations in data analysis methodologies are required.


PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification.
Molecular classification of gliomas is a major challenge in the effort to improve therapeutic decisions. The plasminogen activator system, including plasminogen activator inhibitor type 1 (PAI-1), plays a key role in tumor invasion and neoangiogenesis. Epidermal growth factor receptor (EGFR) is involved in the control of proliferation. The contribution of PAI-1 and EGFR to the survival of gliomas was retrospectively investigated. Fifty-nine adult gliomas treated by neurosurgery and conventional irradiation were analyzed, including 9 low-grade (2) and 50 high-grade (3-4) tumors (WHO classification). PAI-1 was measured on cytosols and EGFR on solubilized membranes using ELISA methods. High PAI-1 levels were strongly associated with high histologic grade (p < 0.001) and histologic necrosis (p < 0.001). PAI-1 also correlated positively with patient age (p = 0.05) and negatively with Karnofsky index (p = 0.01). By univariate analysis of the high-grade population, higher PAI-1 (p < 0.0001) and EGFR values (p = 0.02) were associated with shorter overall survival. Only PAI-1 was an independent factor in multivariate analysis. Grade 3 tumors with low PAI-1 (100% 3-year overall survival rate) presented the same clinical outcome as the low-grade tumors. In this prognostic study, PAI-1 and EGFR expression revealed similarities and differences between high-grade gliomas that were not apparent by traditional clinical criteria. These data strongly support that biologic factors should be included in glioma classification and the design of clinical trials to treat more homogeneous populations.


Testing Feasibility of a Mobile Application to Monitor Fatigue in People With Multiple Sclerosis.
Fatigue is a significant and burdensome symptom for patients with multiple sclerosis and is associated with other symptoms, signs, and decreased quality of life. A prospective pilot study was conducted with a convenience sample (n = 34) of patients with relapsing-remitting multiple sclerosis using a phone application, FatigueApp.com, to collect data on patient-reported outcome measures (Patient-Reported Outcomes Measurement Information System [PROMIS]). FatigueApp feasibility was good, with the ability to collect data on self-reported fatigue and other symptoms using PROMIS measures. This study showed that using a phone application with PROMIS may be useful in the future to provide estimates of fatigue and other variables to facilitate clinical monitoring of fatigue for neurology clinic settings.


The Interplay Between Pattern Recognition Receptors and Autophagy in Inflammation.
Pattern recognition receptors (PRRs) are sensors of exogenous and endogenous "danger" signals from pathogen-associated molecular patterns (PAMPs), and damage associated molecular patterns (DAMPs), while autophagy can respond to these signals to control homeostasis. Almost all PRRs can induce autophagy directly or indirectly. Toll-like receptors (TLRs), Nod-like receptors (NLRs), retinoic acid-inducible gene-I-like receptors (RLRs), and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway can induce autophagy directly through Beclin-1 or LC3-dependent pathway, while the interactions with the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1), CD91/Calreticulin, and TLRs/HSPs are achieved by protein, Ca2+, and mitochondrial homeostasis. Autophagy presents antigens to PRRs and helps to clean the pathogens. In addition, the induced autophagy can form a negative feedback regulation of PRRs-mediated inflammation in cell/disease-specific manner to maintain homeostasis and prevent excessive inflammation. Understanding the interaction between PRRs and autophagy in a specific disease will promote drug development for immunotherapy. Here, we focus on the interactions between PRRs and autophagy and how they affect the inflammatory response.


Correlation of apparent diffusion coefficient at 3T with prognostic parameters of retinoblastoma.
Pathologic prognostic parameters for retinoblastoma have been defined. Our purpose was to correlate ADC values at 3T with prognostic parameters of retinoblastoma. This study included 72 children (30 boys and 42 girls, mean age 19 ± 2.6 months) with retinoblastoma. Pretreatment diffusion-weighted MR imaging was performed on a 3T scanner with b factors of 0, 500, and 1000 seconds/mm(2). ADC values were calculated and pathologic specimens were analyzed. ADC values of the tumors were then correlated with prognostic parameters, including degree of histologic differentiation, tumor size, bilaterality, choroidal invasion, and optic nerve extension. The mean ADC value of retinoblastoma was 0.49 ± 0.12 × 10(-3) mm(2)/s. The ADC values of well- and moderately differentiated tumors were significantly different (P = .007) from poorly and undifferentiated retinoblastoma. There was also a significant difference in the ADC value among small, medium, and large tumors (P = .015), as well as between unilateral and bilateral retinoblastoma (P = .001), and this was independent of the degree of differentiation. The ADC value was also significantly lower (P = .003) when optic nerve invasion was present. There was no correlation of ADC value with growth pattern or choroidal invasion (P = .640 and 0.661, respectively). The ADC value of retinoblastoma was well correlated with the degree of differentiation of the tumor (r = 0.87, P = .007) and inversely correlated with the size of the tumor (r = -0.68, P = .015). ADC correlated with some of the accepted parameters of poor prognosis for retinoblastoma and may serve as a noninvasive prognostic parameter for assessment of newly diagnosed retinoblastoma.


The role of glycosylation in protein antigenic properties.
Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate' the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific T cell clones.


Porcine lymphoblastoid cell lines of B-cell origin.
Two lymphoblastoid cell lines were isolated from different pigs and were maintained in culture for over 100 passages or 20 months. These cell lines were characterized by their cell surface antigens, ability to stimulate a mixed lymphocyte reaction and production of immunoglobulin. When tested against a panel of monoclonal anti-cell surface antigen antibodies, only those monoclonal antibodies which detect porcine class I or II molecules reacted against the lymphoblastoid cell lines in a microcytotoxicity assay. The two pig cell lines could stimulate peripheral blood mononuclear cells in a mixed lymphocyte reaction. P-SC(1) and P-16(2) also demonstrated a dependency upon the presence of 2-mercaptoethanol for cell division. The secretion of pig immunoglobulin by P-SC(1) or P-16(2) was first demonstrated by ELISA using a polyclonal anti-swine IgG (heavy and light chain) serum. By the use of monoclonal anti-IgA, IgG or IgM antibodies in an enzyme-linked assay on Western blots of P-SC(1) or P-16(2) lysate/supernatant, the two cell lines were demonstrated to be producing a whole monomeric IgA molecule and a mu chain.


Reverse transcription of Drosophila mobile dispersed genetic element RNAs: detection of intermediate forms.
DNA-RNA complexes were detected in cultured Drosophila melanogaster cells. These complexes are practically perfect hybrid molecules of mobile dispersed genes DNA (mdg1 and mdg3) and suitable poly(A)+RNA. Three species of single-stranded DNA have been found in hybrid molecules: full-sized mdg DNA containing either one or two LTRs (both minus strands) and single LTR sequences (plus strand). The properties of hybrid molecules are consistent with those being expected from the model of reverse transcription pathway of transposition and amplification of mdg elements.


Disparities in cancer mortality patterns: A comprehensive examination of U.S. rural and urban adults, 1999-2020.
Cancer mortality rates overall in the U.S. have decreased significantly; however, the rate of decline has not been uniform across sociodemographic groups. We aimed to compare trends in cancer mortality rates from 1999 to 2020 between rural and urban individuals and to examine whether any rural-urban differences are uniform across racial and ethnic groups. We used U.S.-wide data from the National Center for Health Statistics, for all cancer deaths among individuals aged 25 years or older. We estimated average annual percentage change (AAPC) in age-standardized cancer mortality rates in the U.S. by cancer type, rural-urban status, sex, and race and ethnicity. There was a larger reduction in cancer mortality rates among individuals from urban (males: AAPC, -1.96%; 95% CI, -2.03, -1.90; females: AAPC, -1.56%; 95% CI, -1.64, -1.48) than rural (males: AAPC, -1.43%; 95% CI, -1.47, -1.39; females: AAPC, -0.93; 95% CI, -1.03, -0.82) areas. AAPCs for cancer types were uniformly higher among urban areas compared with rural areas. Despite overall decreases, deaths rates for liver and pancreas cancers increased, including in the most recent period among males (2012-2020, APC, 1.34; 95% CI, 0.49, 2.20) and females (2013-2020, APC, 1.52; 95% CI, 0.03, 3.02) in rural areas. Cancer death rates decreased in all racial and ethnic populations; however, the rural-urban differences varied by race/ethnicity. The rate of decline in mortality rates were lower in rural areas and death rates for liver and pancreas cancers increased, particularly for individuals living in rural America.


Synthesis and in vitro modeling and characterization of self-assembling drug conjugates for targeted medicinal application.
A number of conjugates tend to self-associate in a transient or permanent fashion and this has formed the basis of considerable intense scientific and commercial investigation over recent years. This article considers a variety of strategic formulations, their flaws and advantages. Working practices and groundbreaking developmental activities within the sphere of self-assembling drug conjugates are also reviewed.


Enhancement of aromatic amino acid-nucleic acid base stacking interaction by metal coordination to base: fluorescence study on a tryptophan-Pt(II)-guanine ternary complex.
In order to investigate the effect of the Pt(II) ion on the stacking interaction between tryptophan and a guanine base, the quenching of Trp fluorescence was monitored for some systems in the absence and presence of the metal ion, and the association constants were obtained by the analysis of Eadie-Hofstee plots. All spectral data suggested that the stacking interaction is enhanced by the Pt(II) coordination to the guanine N7 atom. The result indicates the importance of the metal ion as a bookmark in the specific recognition of a nucleic acid base by an aromatic amino acid residue.


The neurologist as a true philosopher.
This work is produced in the hope that the neurologist will learn to assert his commanding position (from the nature of his training and the special observations of human beings which his work is constantly providing) of that of the scientific philosopher. At present the discipline of neurology is toward divisive over-specialization, with a loss of that form of broader, even universal, vision of behaviour, of "living", which our professional observations are ever providing. Professor Dr. Bruyn may serve as an admirable model for us to emulate.


Application of Toxicity Identification Evaluation (TIE) procedures for the characterization and management of dredged harbor sediments.
This study refers to the performance of Phase I Toxicity Identification Evaluation (TIE) procedures to identify the contaminants (i.e. organic compounds, metals and ammonia) exerting toxicity in marine sediments from the Pasaia harbor (Oiartzun estuary, northern Spain). The effectiveness of the manipulations to reduce toxicity was proved with the marine amphipod survival test (whole-sediment) and the sea urchin embryo-larval assay (elutriates). By means of TIEs it was concluded that organic compounds were the major contaminants exerting toxicity, although toxic effects by metals was also demonstrated. Additionally, the combination of Phase I treatments allowed to investigate the toxicity changes associated to the mobility of contaminants during dredging activities. Therefore, the performance of TIE procedures as another line of evidence in the decision-making process is recommended. They show a great potential to be implemented at different steps of the characterization and management of dredged harbor sediments.


[Non-immunologic hydrops fetalis (NIHF)--case report of double partial trisomy 15q and 17q resulting from familial translocation 15/17 and cytogenetic findings in 50 cases with hydrops fetalis].
We report the first case of non-immune hydrops fetalis (NIHF) with trisomy 15q11/17q22.5 resulting from a familial translocation 15/17. Furthermore the cytogenetic findings of 50 cases with hydrops fetalis are presented. Of the 30 cytogenetic analyzable cases 7 showed chromosomal abnormalities (4x45,X; 2x47,XY,+21; 1x47,XY,+13). In every case of NIHF a chromosomal analysis should be performed if possible from different tissues.


Expression of the endogenous and heterologous clavulanic acid cluster in Streptomyces flavogriseus: why a silent cluster is sleeping.
Clusters for clavulanic acid (CA) biosynthesis are present in the actinomycetes Streptomyces flavogriseus ATCC 33331 and Saccharomonospora viridis DSM 43017. These clusters, which are silent, contain blocks of conserved genes in the same order as those of the Streptomyces clavuligerus CA cluster but assembled in a different organization. S. flavogriseus was grown in nine different media, but clavulanic acid production was undetectable using bioassays or by high-performance liquid chromatography analyses. Reverse-transcriptase polymerase chain reaction (RT-PCR) of S. flavogriseus CA biosynthesis genes showed that the regulatory genes ccaR and claR and some biosynthetic genes were expressed whereas expression of cyp, orf12, orf13, and oppA2 was undetectable. The ccaR gene of S. clavuligerus was unable to switch on CA production in S. flavogriseus::[Pfur-ccaR C], but insertion of a cosmid carrying the S. clavuligerus CA cluster (not including the ccaR gene) conferred clavulanic acid production on S. flavogriseus::[SCos-CA] particularly in TBO and YEME media; these results suggests that some of the S. flavogriseus CA genes are inactive. The known heptameric sequences recognized by CcaR in S. clavuligerus are poorly or not conserved in S. flavogriseus. Quantitative RT-PCR analysis of the CA gene clusters of S. clavuligerus and S. flavogriseus showed that the average expression value of the expressed genes in the former strain was in the order of 1.68-fold higher than in the later. The absence of CA production by S. flavogriseus can be traced to the lack of expression of the essential genes cyp, orf12, orf13, orf14, and oppA2. Heterologous expression of S. clavuligerus CA gene cluster in S. flavogriseus::[SCos-CA] was 11- to 14-fold lower than in the parental strain, suggesting that the genetic background of the host strain is important for optimal production of CA in Streptomyces.


Square one: zygote polarity and early embryogenesis in flowering plants.
In the last two decades, work on auxin signaling has helped to understand many aspects of the fundamental process underlying the specification of tissue types in the plant embryo. However, the immediate steps after fertilization including the polarization of the zygote and the initial body axis formation remained poorly understood. Valuable insight into these enigmatic processes has been gained by studying fertilization in grasses. Recent technical advances in transcriptomics of developing embryos with high spatial and temporal resolution give an emerging picture of the rapid changes of the zygotic developmental program. Together with the use of live imaging of novel fluorescent marker lines, these data are now the basis of unraveling the very first steps of the embryonic patterning process.


A new generation of direct X-ray detectors for medical and synchrotron imaging applications.
Large-area X-ray imaging is one of the most widely used imaging modalities that spans several scientific and technological fields. Currently, the direct X-ray conversion materials that are being commercially used for large-area (> 8 cm × 4 cm without tiling) flat panel applications, such as amorphous selenium (a-Se), have usable sensitivities of up to only 30 keV. Although there have been many promising candidates (such as polycrystalline HgI2 and CdTe), none of the semiconductors were able to assuage the requirement for high energy (> 40 keV) large-area X-ray imaging applications due to inadequate cost, manufacturability, and long-term performance metrics. In this study, we successfully demonstrate the potential of the hybrid Methylammonium lead iodide (MAPbI3) perovskite-based semiconductor detectors in satisfying all the requirements for its successful commercialization in synchrotron and medical imaging. This new generation of hybrid detectors demonstrates low dark current under electric fields needed for high sensitivity X-ray imaging applications. The detectors have a linear response to X-ray energy and applied bias, no polarization effects at a moderate bias, and signal stability over long usage durations. Also, these detectors have demonstrated a stable detection response under BNL's National Synchrotron Light Source II (NSLS-II) 70 keV monochromatic synchrotron beamline.


Viral Impact on Prokaryotic and Microalgal Activities in the Microphytobenthic Biofilm of an Intertidal Mudflat (French Atlantic Coast).
This is the first report on viriobenthos activity within the microbial biofilm located at the top-surface of the intertidal mudflat during emersion in Marennes-Oléron Bay (France). By combining in situ and ex situ approaches, the viral production (VP) was linked to the dynamics of prokaryotes and microphytobenthos (MPB). VP averaged 2-4 × 10(8) viruses ml(-1) h(-1). VP correlated positively with the Virus to Prokaryote Ratio, and both were correlated negatively with the water content. The virus-induced mortality of prokaryotes was lower in winter than in summer (6.8 vs. 39.7% of the production) and the C-shunting may supply 2-12% of their Carbon Demand, respectively. VP accounted for 79% of loss in Prokaryotes but the response was delayed compared to the increase in VP suggesting a simultaneous release of viruses of MPB origin. This hypothesis is supported by capsid-sizing of virions by transmission electronic microscopy and bioassays. Harvesting and ex situ maintenance of top-surface sediments was carried out to monitor the dynamics of viruses, prokaryotes and MPB after inoculation with benthic or planktonic viruses. Benthic viruses modified the prokaryotic and MPB dynamics and decreased the photosynthesis efficiency in contrast to planktonic viruses that impacted MPB but not the prokaryotes.


Acoustic vibration of the amphibian eardrum studied by white noise analysis and holographic interferometry.
The motion of the amphibian eardrum under free-field acoustic stimulation was investigated using time-averaged holography. We show that the amplitude is linearly related to sound pressure up to +/- 1000 nm. The frequency response of the eardrum shows broad resonance characteristics with a main peak between 1200-2200 Hz. The velocity of the tympanic membrane's motion at its resonance frequency matches the acoustic velocity of air particles. The resonance characteristics of the eardrum are also revealed by white noise stimulation. The power spectrum obtained by Fourier transformation of the autocorrelation of the response to noise resembles closely that obtained by holography.


Fully Textured, Production-Line Compatible Monolithic Perovskite/Silicon Tandem Solar Cells Approaching 29% Efficiency.
Perovskite/silicon tandem solar cells are promising avenues for achieving high-performance photovoltaics with low costs. However, the highest certified efficiency of perovskite/silicon tandem devices based on economically matured silicon heterojunction technology (SHJ) with fully textured wafer is only 25.2% due to incompatibility between the limitation of fabrication technology which is not compatible with the production-line silicon wafer. Here, a molecular-level nanotechnology is developed by designing NiOx /2PACz ([2-(9H-carbazol-9-yl) ethyl]phosphonic acid) as an ultrathin hybrid hole transport layer (HTL) above indium tin oxide (ITO) recombination junction, to serve as a vital pivot for achieving a conformal deposition of high-quality perovskite layer on top. The NiOx interlayer facilitates a uniform self-assembly of 2PACz molecules onto the fully textured surface, thus avoiding direct contact between ITO and perovskite top-cell for a minimal shunt loss. As a result of such interfacial engineering, the fully textured perovskite/silicon tandem cells obtain a certified efficiency of 28.84% on a 1.2-cm2 masked area, which is the highest performance to date based on the fully textured, production-line compatible SHJ. This work advances commercially promising photovoltaics with high performance and low costs by adopting a meticulously designed HTL/perovskite interface.


Childhood respiratory infections and hospital admissions for COPD.
Chronic Obstructive Pulmonary Disease (COPD) exacerbations are associated with viral infections. We wished to determine if respiratory viral infection of children in the community was associated with hospital admissions of patients with exacerbations of COPD. We collected data over a 45-month period from the Northern Ireland Regional Virus Laboratory and from a general hospital in the same locality. We studied the relationship between upper respiratory infections in children and COPD admissions. We also examined the role of school holidays. Correlations were seen between the frequency of all viral infections in children and the number of adult COPD hospitalizations (P<0.005). Subgroup analysis showed distinct relationships with epidemics of; influenza A (P<0.001), influenza B (P<0.05), adenovirus (P=0.05), respiratory syncytial virus (P<0.005) and hospital admissions of patients with COPD. There were significantly fewer COPD admissions in the week after the start of a school holiday period (P<0.05). When children are hospitalized with viral respiratory infection there is an associated rise in adult COPD admissions. This suggests exacerbations of COPD are associated with epidemics of respiratory viruses. When children are on school holidays there is a reduction in COPD admissions in the community. This provides further support for respiratory viruses in the pathogenesis of COPD exacerbations.