The Candida albicans toxin candidalysin mediates distinct epithelial inflammatory responses through p38 and EGFR-ERK pathways.
The fungal pathogen Candida albicans secretes the peptide toxin candidalysin, which damages epithelial cells and drives an innate inflammatory response mediated by the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) pathways and the transcription factor c-Fos. In cultured oral epithelial cells, candidalysin activated the MAPK p38, which resulted in heat shock protein 27 (Hsp27) activation, IL-6 release, and EGFR phosphorylation without affecting the induction of c-Fos. p38 activation was not triggered by EGFR but by two nonredundant pathways involving MAPK kinases (MKKs) and the kinase Src, which differentially controlled p38 signaling outputs. Whereas MKKs mainly promoted p38-dependent release of IL-6, Src promoted p38-mediated phosphorylation of EGFR in a ligand-independent fashion. In parallel, candidalysin also activated the EGFR-ERK pathway in a ligand-dependent manner, resulting in c-Fos activation and release of the neutrophil-activating chemokines G-CSF and GM-CSF. In mice, early clearance events of oral C. albicans infection required p38 but not c-Fos. These findings delineate how candidalysin activates the pathways downstream of the MAPKs p38 and ERK that differentially contribute to immune activation during C. albicans infection.


Screening of monoclonal antibodies using antigens labeled with acetylcholinesterase: application to the peripheral proteins of photosystem 1.
An original immunoenzymatic screening method, based on the use of antigens labeled with the stable enzyme acetylcholinesterase (AChE, EC 184.108.40.206), is described. The high turnover of this enzyme results in a very sensitive detection of antibodies. In this method, monoclonal antibodies from the supernatants of hybridoma cultures are immobilized on a solid phase coated with anti-mouse immunoglobulins and react simultaneously with the appropriate antigen labeled with biotin molecules. In a second step, biotinylated acetylcholinesterase is in turn associated to the system via avidin interactions and subsequently detected by a colorimetric assay. The method appears more sensitive and easier to use than either the corresponding radioimmunological test using a 125I-iodinated antigen or the same type of enzymatic immunoassay performed with biotinylated horseradish peroxidase instead of biotinylated AChE. The combined use of microtiter plates, solid-phase separation, and colorimetric detection allows a high level of automation of the method which makes it very efficient to process a large number of samples. This technique has been successfully applied to the screening of monoclonal antibodies directed against peripheral proteins of the photosystem 1 (PS1) membrane complex in photosynthesis. A complete set of antibodies recognizing these PS1 components was selected. The same technique was also tested in competition immunoassays and appears to be a very precise and useful tool for quantifying PS1 polypeptides in different biological extracts, including sodium dodecyl sulfate-denatured membranes. This can be of special interest for studying the biogenesis of membrane complexes.


Characterization of bovine MHC DRB3 diversity in Latin American Creole cattle breeds.
In cattle, bovine leukocyte antigens (BoLAs) have been extensively used as markers for diseases and immunological traits. However, none of the highly adapted Latin American Creole breeds have been characterized for BoLA gene polymorphism by high resolution typing methods. In this work, we sequenced exon 2 of the BoLA class II DRB3 gene from 179 cattle (113 Bolivian Yacumeño cattle and 66 Colombian Hartón del Valle cattle breeds) using a polymerase chain reaction sequence-based typing (PCR-SBT) method. We identified 36 previously reported alleles and three novel alleles. Thirty-five (32 reported and three new) and 24 alleles (22 reported and two new) were detected in Yacumeño and Hartón del Valle breeds, respectively. Interestingly, Latin American Creole cattle showed a high degree of gene diversity despite their small population sizes, and 10 alleles including three new alleles were found only in these two Creole breeds. We next compared the degree of genetic variability at the population and sequence levels and the genetic distance in the two breeds with those previously reported in five other breeds: Holstein, Japanese Shorthorn, Japanese Black, Jersey, and Hanwoo. Both Creole breeds presented gene diversity higher than 0.90, a nucleotide diversity higher than 0.07, and mean number of pairwise differences higher than 19, indicating that Creole cattle had similar genetic diversity at BoLA-DRB3 to the other breeds. A neutrality test showed that the high degree of genetic variability may be maintained by balancing selection. The FST index and the exact G test showed significant differences across all cattle populations (FST=0.0478; p<0.001). Results from the principal components analysis and the phylogenetic tree showed that Yacumeño and Hartón del Valle breeds were closely related to each other. Collectively, our results suggest that the high level of genetic diversity could be explained by the multiple origins of the Creole germplasm (European, African and Indicus), and this diversity might be maintained by balancing selection.


Heterogeneous alterations in thalamic subfields in major depression disorder.
It is well known that the thalamus is not a unitary and homogeneous entity but a complex and highly connected archeocortical structure. Although many neuroimaging studies have reported alterations in the thalamus in major depressive disorder (MDD), the structural alterations in thalamic subfields remain unclear. This study aimed to investigate changes in gray matter volume (GMV) in thalamic subfields in MDD patients. The present study included structural images of 848 MDD patients and 794 age-matched normal controls (NC) from 17 study sites of the REST-meta-MDD consortium. We performed voxel-based morphometric analyses to calculate the GMV in the entire thalamus and its subfields using three different automated anatomical labeling atlases and subsequently compared the differences between first-episode drug-naïve major depressive disorder (FEDN), recurrent major depressive disorder (RMDD), and NC groups. We also evaluated the relationships between thalamic GMV and clinical symptoms in MDD patients. Compared to NC, the FEDN patients showed increased GMV in thalamic subfields but not in the entire thalamus, while RMDD patients showed no significant alterations in GMV in the entire thalamus and its subfields. Moreover, the mean GMV in the right anterior thalamus and left anteroventral thalamus in RMDD patients were mildly positively correlated with the Hamilton Anxiety Rating Scale scores. The main limitations are a single-modal analysis based on T1-weighted MR images and a cross-sectional design. Our findings suggest that FEDN and RMDD patients show heterogeneous alterations across thalamic subfields, which may help us understand the pathophysiological mechanisms of MDD.


Crustal velocity and interseismic strain-rate on possible zones for large earthquakes in the Garhwal-Kumaun Himalaya.
The possibility of a major earthquake like 2015 Gorkha-Nepal or even greater is anticipated in the Garhwal-Kumaun region in the Central Seismic Gap of the NW Himalaya. The interseismic strain-rate from GPS derived crustal velocities show multifaceted strain-rate pattern in the region and are classified into four different strain-rate zones. Besides compressional, we identified two NE-SW orienting low strain rate (~ 20 nstrain/a) zones; namely, the Ramganga-Baijro and the Nainital-Almora, where large earthquakes can occur. These zones have surface locking widths of ~ 72 and ~ 75 km respectively from the Frontal to the Outer Lesser Himalaya, where no significant surface rupture and associated large earthquakes were observed for the last 100 years. However, strain reducing extensional deformation zone that appears sandwiched between the low strain-rate zones pose uncertainties on the occurences of large earthquakes in the locked zone. Nevertheless, such zone acts as a conduit to transfer strain from the compressional zone (> 100 nstrain/a) to the deforming frontal active fault systems. We also observed a curvilinear surface strain-rate pattern in the Chamoli cluster and explained how asymmetric crustal accommodation processes at the northwest and the southeast edges of the Almora Klippe, cause clockwise rotational couple on the upper crust moving over the MHT.


Microsatellites for Oenothera gayleana and O. hartwegii subsp. filifolia (Onagraceae), and their utility in section Calylophus.
Eleven nuclear and four plastid microsatellite markers were screened for two gypsum endemic species, Oenothera gayleana and O. hartwegii subsp. filifolia, and tested for cross-amplification in the remaining 11 taxa within Oenothera sect. Calylophus (Onagraceae). Microsatellite markers were tested in two to three populations spanning the ranges of both O. gayleana and O. hartwegii subsp. filifolia. The nuclear microsatellite loci consisted of both di- and trinucleotide repeats with one to 17 alleles per population. Several loci showed significant deviation from Hardy-Weinberg equilibrium, which may be evidence of chromosomal rings. The plastid microsatellite markers identified one to seven haplotypes per population. The transferability of these markers was confirmed in all 11 taxa within Oenothera sect. Calylophus. The microsatellite loci characterized here are the first developed and tested in Oenothera sect. Calylophus. These markers will be used to assess whether pollinator foraging distance influences population genetic parameters in predictable ways.


I. Hypoglossal facial anastomosis: its significance for modern facial surgery. II. Combined approach in extratemporal facial nerve reconstruction.
The difficulties encountered in extratemporial facial nerve reconstruction after extensive trauma or following resection of parotid tumors often lead to unsatisfactory functional and cosmetic results. So far it has been common practice to use as a "regenerative nerve," the original facial nerve. Using this procedure, however, frequently only a portion of the peripheral branches can be reanastomosed. Above all, the "autoparalytic syndrome" develops in this situation owing to undirected outgrowth of axons, and an aberration of the blinking-reflex motoneurons occurs. Experience has shown that the isolated use of a cross-face transplant is not suitable for satisfactory functional regeneration. Depending on the individual anatomic situation, a number of possibilities are therefore recommended for a combined approach using several "regenerative nerves." In this connection, the particular physiologic properties of these nerves have to be taken into account which can help to improve considerably the functional and cosmetic results.


Supplemental vibrational force does not reduce pain experience during initial alignment with fixed orthodontic appliances: a multicenter randomized clinical trial.
This prospective randomized trial investigated the effect of supplemental vibrational force on orthodontic pain during alignment with fixed-appliances. Eighty-one subjects < 20 years-old undergoing extraction-based fixed-appliance treatment were randomly allocated to supplementary (20-minutes/day) use of an intra-oral vibrational device (AcceleDent(®)) (n = 29); an identical non-functional (sham) device (n = 25) or fixed-appliances only (n = 27). Each subject recorded pain intensity (using a 100-mm visual-analogue scale) and intake of oral analgesia in a questionnaire, following appliance-placement (T1) and first-adjustment (T2) for 1-week (immediately-after, 4, 24, 72-hours and at 1-week). Mean maximum-pain for the total sample was 72.96 mm [SD 21.59; 95%CI 68.19-77.74 mm] with no significant differences among groups (P = 0.282). Subjects taking analgesics reported slightly higher maximum-pain although this was not significant (P = 0.170). The effect of intervention was independent of analgesia (P = 0.883). At T1 and T2, a statistically and clinically significant increase in mean pain was seen at 4 and 24-hours, declining at 72-hours and becoming insignificant at 1-week. For mean alignment-rate, pain-intensity and use of analgesics, no significant differences existed between groups (P > 0.003). The only significant predictor for mean pain was time. Use of an AcceleDent vibrational device had no significant effect on orthodontic pain or analgesia consumption during initial alignment with fixed appliances.


[Pulmonary cavitations, late complication of COVID-19].
Patients who have recently suffered from SARS-CoV-2 infections may suffer serious complications, such as pneumothorax or pulmonary cavitations that increase morbi-mortality and imply a challenge for the design of the most appropriate therapeutic strategy to improve their prognosis. Pulmonary cavities are usually associated with secondary complications such as hemoptysis and pneumothorax, and so offer a poor prognosis. We present the case of two patients with COVID-19 disease confirmed by nasopharyngeal PCR who showed satisfactory evolution before readmission with pulmonary involvement compatible with pulmonary cavitation and respiratory failure. Cavitated lesions in the lungs of patients who recently suffered COVID-19 must be identified early in order to discard additional superinfections that may worsen the prognosis.


Kidney regeneration approaches for translation.
The increase in the incidence of chronic kidney diseases that progress to end-stage renal disease has become a significant health problem worldwide. While dialysis can maintain and prolong survival, the only definitive treatment that can restore renal function is transplantation. Unfortunately, many of these patients die waiting for transplantable kidneys due to the severe shortage of donor organs. Tissue engineering and regenerative medicine approaches have been applied in recent years to develop viable therapies that could provide solutions to these patients. Cell-based and cell-free approaches have been proposed to address the challenges associated with chronic kidney diseases. Strategies and progress toward developing alternative therapeutic options will be reviewed.


Mate Retention Behavior and Ejaculate Quality in Humans.
Males of some species use mate retention behavior and investment in ejaculate quality as anti-cuckoldry tactics concurrently while others do so in a compensatory fashion. Leivers, Rhodes, and Simmons (2014) reported that men who performed mate retention less frequently produced higher-quality ejaculates, suggesting that humans use these tactics compensatorily. We conducted a conceptual replication of this research in a sample of 41 men (18-33 years; M = 23.33; SD = 3.60). By self-report, participants had not had a vasectomy and had never sought infertility treatment. We controlled for several covariates known to affect ejaculate quality (e.g., abstinence duration before providing an ejaculate) and found no statistically significant relationships between mate retention behavior and four components of ejaculate quality: sperm velocity, sperm concentration, slow motility, and ejaculate volume. The present results provide little support for the hypothesis that human males deploy mate retention behavior and ejaculate quality investment compensatorily. We discuss the limitations of this study and highlight the need for research to address questions about the nature of anti-cuckoldry tactic deployment in humans, especially concerning investment in ejaculate quality.


Pharmacist monitoring of direct oral anticoagulants for American Indians and Alaska Natives in the outpatient setting.
Direct oral anticoagulants (DOACs) call into question the role of traditional pharmacist-run clinics, and few studies have described the incorporation of DOAC's into traditional anticoagulation management services (AMS) OBJECTIVE: To describe the incorporation of DOACs into a pharmacist-run AMS for American Indian and Alaska Native (AI/AN) patients and determine outcomes related to adherence, follow-up, and pharmacist interventions. Traditional AMS embedded in ambulatory clinic. Warfarin managed by pharmacists under a collaborative practice agreement with supervising physician. DOACs incorporated into AMS by transitioning warfarin patients to rivaroxaban and apixaban and managing new patients with DOAC. Follow-up occurred via phone call and at longer intervals. Single-center, retrospective, observational analysis of AI/AN patients who were followed up by pharmacy AMS. The outcomes measured include adherence to DOAC therapy, number of telephonic encounters versus face-to-face visits, frequency of follow-up, types of interventions made at each visit, and an estimate of face-to-face clinic time savings. A total of 50 patients were included for analysis. The average medication possession ratio was 91%. The majority of visits occurred over the phone (59%), and most follow-up visits occurred every 3 months (62%). The top 3 most frequent interventions were adherence education, initial DOAC education, and education on use of nonsteroidal anti-inflammatory drugs. Traditional AMS can evolve by incorporating DOACs and maintaining follow-up. Pharmacist monitoring of DOACs may promote high levels of adherence and lead to time savings by reducing the amount of time spent in traditional AMS.


Effects of hydroxocobalamin and haemoglobin on no-mediated relaxations in the rat anococcygeus muscle.
1. The effects of hydroxocobalamin (Vitamin B12a) on relaxations produced by nitric oxide (NO), some NO-donating compounds and nitrergic nerve stimulation in isolated preparations of the rat anococcygeus muscle were compared with the effects of haemoglobin. 2. Hydroxocobalamin (30 mumol/L) significantly reduced relaxations induced by NO (0.1-3 mumol/L) and sodium nitroprusside (SNP; 0.01-0.3 mumol/L) but did not affect relaxations induced by glyceryl trinitrate (GTN; 0.01-1 mumol/L), S-nitrosocysteine (0.1-0.3 mumol/L) or stimulation of nitrergic nerves. A higher concentration of hydroxocobalamin (100 mumol/L) slightly reduced nitrergic nerve stimulation-induced relaxations. 3. Haemoglobin (10 mumol/L) blocked relaxation induced by NO and reduced relaxations induced by SNP, GTN, S-nitrosocysteine and nitrergic nerve stimulation. 4. When nitrergic nerve stimulation-induced relaxations had been partially reduced by the NO synthase inhibitor L-NAME (5-10 mumol/L), hydroxocobalamin had only a weak and transient inhibitory effect. 5. Noradrenergic contractions induced by field stimulation were not affected by hydroxocobalamin (30 mumol/L), but were enhanced by haemoglobin (10 mumol/L). 6. The results suggest that the transmitter released from nitrergic nerves in anococcygeus muscles resembles NO-releasing compounds such as S-nitrosocysteine and GTN but not SNP or free NO.


Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease.
Clopidogrel inhibits the ADP subtype P2Y(12) receptor. Recently, polymorphisms of this receptor have been associated with different degrees of platelet aggregation in healthy volunteers and have been suggested to modulate clopidogrel response. However, the role of gene sequence variations of the P2Y(12) receptor in patients treated with clopidogrel has not yet been assessed. The T744C polymorphism of the P2Y(12) receptor gene was assessed in 119 patients: 36 undergoing coronary stenting receiving a 300 mg loading dose (Group A) and 83 on long-term clopidogrel (75 mg/day) treatment (Group B). Patients were divided into 2 subgroups according to the presence or absence of the C allele: carriers (CT heterozygotes and CC homozygotes) and non-carriers (TT homozygotes). Platelet aggregation, assessed by light transmittance aggregometry following ADP, collagen, TRAP and epinephrine stimuli, and platelet activation (GP IIb/IIIa activation and P-selectin expression), assessed by whole blood flow cytometry in ADP and TRAP-stimulated platelets, were performed. Platelet function was assessed at baseline and 4 and 24 h following clopidogrel loading dose in Group A and when patients where on clopidogrel treatment for at least 1 month in Group B. The genotype distribution of Group A was: 22/36 (61.1%) non-carriers and 14/36 (38.9%) carriers of the C allele; Group B: 57/83 (68.7%) non-carriers and 26/83 (31.3%) carriers of the C allele. There were no differences between groups for all the assessed platelet function assays. The T744C polymorphism of the P2Y(12) receptor gene does not modulate platelet response to clopidogrel either in the early or long-term phases of treatment. This specific gene polymorphism alone is therefore unlikely to be the cause of variability in individual response to antiplatelet therapy.


siRNA Versus miRNA as Therapeutics for Gene Silencing.
Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are noncoding RNAs with important roles in gene regulation. They have recently been investigated as novel classes of therapeutic agents for the treatment of a wide range of disorders including cancers and infections. Clinical trials of siRNA- and miRNA-based drugs have already been initiated. siRNAs and miRNAs share many similarities, both are short duplex RNA molecules that exert gene silencing effects at the post-transcriptional level by targeting messenger RNA (mRNA), yet their mechanisms of action and clinical applications are distinct. The major difference between siRNAs and miRNAs is that the former are highly specific with only one mRNA target, whereas the latter have multiple targets. The therapeutic approaches of siRNAs and miRNAs are therefore very different. Hence, this review provides a comparison between therapeutic siRNAs and miRNAs in terms of their mechanisms of action, physicochemical properties, delivery, and clinical applications. Moreover, the challenges in developing both classes of RNA as therapeutics are also discussed.


Occurrence, molecular characterization and antibiotic resistance of Cronobacter spp. isolated from wet rice and flour products in Guangdong, China.
This study explored the prevalence of Cronobacter spp. in wet rice and flour products from Guangdong province, China, the molecular characteristics and antimicrobial susceptibility profiles of the isolates were identified. Among 249 samples, 100 (40.16%) were positive for Cronobacter spp., including 77 wet rice and 23 wet flour products. Eleven serotypes were characterized among 136 isolates with C. sakazakii O2 (n = 32) predominating. Forty-nine MLST patterns were assigned, 15 of which were new. C. sakazakii ST4 (n = 17) was the dominant ST, which is previously reported to have caused three deaths; followed by C. malonaticus ST7 (n = 15), which is connected to adult infections. All strains presented susceptibility to ampicillin/sulbactam, imipenem, aztreonam and trimethoprim/sulfamethoxazole. The isolates showed maximum resistance to cephalothin, and the resistance and intermediate rates were 91.91% and 3.68%, each. Two strains, croM234A1 and croM283-1, displayed resistance to three antibiotics. High contamination level and predominant number of pathogenic STs of Cronobacter in wet rice and flour products implied a potential risk to public healthiness. This survey could provide comprehensive information for establishing more targeted control methods for Cronobacter spp.


The effect of serial in vivo passage on the expression of virulence and DNA stability of an infectious laryngotracheitis virus strain of low virulence.
The effect of 35 serial passages in vivo on an infectious laryngotracheitis virus strain of low virulence was examined in terms of effect on virulence and DNA stability. Within 3 passages in live chickens there was evidence of increasing respiratory distress. Severe respiratory distress (with death in some cases) was observed after the 6th passage, except when there appeared to be a transient decline in pathogenicity following short term storage of the virus inoculum at -70 degrees C. Restriction endonuclease analysis of viral DNA derived from the original inoculum and the final passage did not reveal any genomic alteration. It is postulated that there is a potential for live ILTV vaccines to cause outbreaks of clinical disease in the event of inadequate or incomplete vaccination procedures.


Atmospheric Deposition of Coal-Related Pollutants in the Pacific Northwest of the United States from 1950 to 2016.
Coal-related elements are toxic and persistent pollutants that have spread globally since the industrial revolution, mainly from point-source emissions. A sediment core was collected from Deep Lake in northeastern Washington State (USA) by the Washington State Department of Ecology, with the aim of assessing recent changes in atmospheric deposition in the US Pacific Northwest. The core was divided into depth intervals and dated by lead-210. A sample from each cross section was digested and analyzed for toxic metals and metalloids using inductively coupled plasma-mass spectrometry. Data show recent increases in the concentrations of arsenic, barium, selenium, and mercury. Comparison with 1993 US Geological Survey ice core data from the Upper Fremont Glacier in Wyoming (USA), Asian coal consumption data, and weather patterns suggests that pollutant inputs to Deep Lake sediments are the result of coal-burning activities in the Asia-Pacific region. Most notably, mercury deposition in Deep Lake has increased from approximately 20 ppb in 1996 to 9470 ppb in 2014 (an ~400-fold increase), and since 1993 when the ice core was analyzed. Environ Toxicol Chem 2020;39:335-342. © 2019 SETAC.


Age, period and cohort models: the use of individual records.
Problems with the interpretation of age-period-cohort models are discussed. If individual records are available for cancer incidence in Scotland, then a solution is obtainable. An example using incidence data for cancers of the lung and larynx in Scotland is presented to illustrate the models.


Oncologic breast surgery: An historical perspective.
Breast cancer (BC) is the most common female cancer worldwide and the second most common cause of cancer-related death in women. BC diagnosis and management have changed dramatically over the years. We recount the historic milestones that have brought the surgical management of breast cancer to its current state.


Accumulation of trace metals in the embryos and hatchlings of Chelonia mydas from Peninsular Malaysia incubated at different temperatures.
A variety of trace metals were measured in the egg contents of three clutches of Chelonia mydas collected from Kuala Terengganu state in Peninsular Malaysia. We quantified Mn, Cu, Zn, Se (essential trace metals) and As (anthropogenic pollutant) at several developmental stages obtained by incubating eggs at two different temperatures (27 °C and 31 °C). The incubation temperatures were chosen because they produce predominantly male or predominantly female hatchlings, respectively. The eggs were removed from the sand and washed before being placed in incubators, to ensure that the only possible source of the detected metals was maternal transfer. Other metals: Mo, Co, Ni, Cd, Sn, Sb, Hg, Tl and Pb (all non-essential metals) were detected at concentrations below the lower limit of quantitation (LLOQ). Trace metal concentrations, particularly [Zn], increased during development, other metals (Cu, As, Se and Cr) accumulated to a lesser degree than zinc but no significant differences were observed between the incubation temperatures at any stage of incubation. To date, only a few studies on trace metals in turtle embryos and hatchlings have been reported; this study will provide basic knowledge on the accumulation of trace metals during development at two different incubation temperatures.


Factors associated with condom use in vaginal intercourse among Spanish adults with intellectual disability: Proposal for an explanatory model.
The prevention of HIV or other STIs in people with intellectual disabilities (ID) is a rarely studied subject even though this population group is at the same risk of infection as the general population. The present study aims to conduct a descriptive analysis of sexual behaviours and condom use frequency in Spanish men and women with intellectual disabilities and identify the combination of variables that best explain condom use in vaginal intercourse. The sample consisted of 253 people (56.1 % male and 43.9 % female) aged between 20 and 64 years (M = 38.52; SD = 10.48). Participants completed the Sexuality Questionnaire for People with Intellectual Disabilities and the Sexual Abuse Risk Screening Scale. The percentage of consistent condom use is 27.7 % for vaginal intercourse. Lack of knowledge about body boundaries constitutes a risk factor contributing to risky sexual behaviour. Knowledge of HIV-transmitting fluids and perceived self-efficacy are protective factors. The proposed model explains between 35.5 % and 46.6 % of the variance. The results highlight the importance of considering the judgements people make about their ability to perform preventive behaviour and the provision of information on sexuality adapted to cognitive abilities to minimise the engagement in risky behaviours.


A framework for assessing the impact of land use policy on community exposure to air toxics.
Our research focuses on the linkage between land use planning policy and the spatial pattern of exposure to air toxics emissions. Our objective is to develop a modeling framework for assessment of the community health risk implications of land use policy. The modeling framework is not intended to be a regulatory tool for small-scale land use decisions, but a long-range planning tool to assess the community health risk implications of alternative land use scenarios at a regional or subregional scale. This paper describes the development and application of an air toxic source model for generating aggregate emission factors for industrial and commercial zoning districts as a function of permitted uses. To address the uncertainty of estimating air toxics emission rates for planned general land use or zoning districts, the source model uses an emissions probability mass function that weights each incremental permitted land use activity by the likelihood of occurrence. We thus reduce the uncertainty involved in planning for development with no prior knowledge of the specific industries that may locate within the land use district. These air toxics emission factors can then be used to estimate pollutant atmospheric mass flux from land use zoning districts, which can then be input to air dispersion and human health risk assessment models to simulate the spatial pattern of air toxics exposure risk. The model database was constructed using the California Air Toxics Inventory, 1997 US Economic Census, and land assessment records from several California counties. The database contains information on more than 200 air toxics at the 2-digit Standard Industrial Classification (SIC) level. We present a case study to illustrate application of the model. LUAIRTOX, the interactive spreadsheet model that applies our methodology to the California data, is available at http://www2.bren.ucsb.edu/~mwillis/LUAIRTOX.htm.


Altered biochemical parameters in saliva of pediatric attention deficit hyperactivity disorder.
Oxidative stress is one of the common causes in etiopathogenesis of attention deficit hyperactivity disorder (ADHD). Hence, the salivary levels of protein thiols, ceruloplasmin, magnesium and pseudocholinesterase were estimated in children with ADHD. The symptoms of ADHD were identified using Conner's rating and DSM IV criteria. Saliva was collected and assessed for the levels of protein thiols, ceruloplasmin, magnesium and pseudocholinesterase, spectrophotometrically. It was also checked for pH and the flow rate was noted down. There was a significant increase (P < 0.001) in the salivary protein thiols and pseudocholinesterase levels in ADHD children when compared to controls. Ceruloplasmin levels did not show any significant change. Magnesium levels were significantly decreased (P < 0.001) in cases when compared to controls. Further, a receiver operating characteristic curve for validity of the biochemical parameters in saliva of ADHD children indicated a sensitivity and specificity above 90% for protein thiols and magnesium values. Our study shows that protein thiols, magnesium, and pseudocholinesterase might have a role in the pathogenesis of ADHD and saliva can be effectively used as a non-invasive tool for evaluation of such children.


N-[(E)-4-Bromo-benzyl-idene]-2,3-di-methyl-aniline.
The title compound, C15H14BrN, has an E conformation about the C=N bond and the dihedral angle between the benzene rings is 50.7 (2)°. In the crystal, mol-ecules are linked via C-H⋯π inter-actions, forming columns propagating along [010].


Structure-activity relationships in the beta-lactam family: an impossible dream.
The difficulty of establishing structure-activity relationships in the beta-lactam family of antibiotics stems from the fact that: (1) The targets in various bacteria exhibit widely different sensitivities. (2) Some bacteria produce beta-lactamases, enzymes capable of destroying the antibiotics. The rates of the reactions with the beta-lactamases and the target enzymes are not necessarily related. (3) In Gram-negative bacteria, the diffusion rate through the outer membrane varies independently from the two other factors.


A cultural evolutionary model of the interaction between parental beliefs and behaviors, with applications to vaccine hesitancy.
Health perceptions and health-related behaviors can change at the population level as cultures evolve. In the last decade, despite the proven efficacy of vaccines, the developed world has seen a resurgence of vaccine-preventable diseases (VPDs) such as measles, pertussis, and polio. Vaccine hesitancy, which is influenced by historical, political, and socio-cultural forces, is believed to be a primary factor responsible for decreasing vaccine coverage, thereby increasing the risk and occurrence of VPD outbreaks. Behavior change models have been increasingly employed to understand disease dynamics and intervention effectiveness. However, since health behaviors are culturally influenced, it is valuable to examine them within a cultural evolution context. Here, using a mathematical modeling framework, we explore the effects of cultural evolution on vaccine hesitancy and vaccination behavior. With this model, we shed light on facets of cultural evolution (vertical transmission, community influences, homophily, etc.) that promote the spread of vaccine hesitancy, ultimately affecting levels of vaccination coverage and VPD outbreak risk in a population. In addition, we present our model as a generalizable framework for exploring cultural evolution when humans' beliefs influence, but do not strictly dictate, their behaviors. This model offers a means of exploring how parents' potentially conflicting beliefs and cultural traits could affect their children's health and fitness. We show that vaccine confidence and vaccine-conferred benefits can both be driving forces of vaccine coverage. We also demonstrate that an assortative preference among vaccine-hesitant individuals can lead to increased vaccine hesitancy and lower vaccine coverage.


Liver and spleen MRI findings in virus-associated hemophagocytic syndrome in a patient with acute lymphocytic leukemia.
Virus-associated hemophagocytic syndrome is characterized by the phagocytosis of erthythrocytes and other blood elements in multiple organ systems, especially the liver and spleen. Magnetic resonance imaging (MRI) can suggest this diagnosis in the proper clinical setting by demonstrating multiple, rounded signal voids in the spleen corresponding to hemosiderin deposition. We report a patient with virus-associated hemophagocytic syndrome during the course of acute lymphocytic leukemia and MRI findings that suggested the preoperative diagnosis.


Immunoreactive epidermal growth factor concentrations in follicular fluid obtained from in vitro fertilization.
Immunoreactive epidermal growth factor (EGF) was measured in follicular fluid (FF) obtained at the time of oocyte retrieval for in vitro fertilization from cycles with (91 follicles) and without (128 follicles) the gonadotropin-releasing hormone agonist leuprolide acetate (LA). Follicular fluid immunoreactive EGF levels in the non-LA cycles correlated with androstenedione but not estradiol or progesterone levels from follicles with prophase I oocytes or from all follicles taken together, but not from metaphase I or metaphase II oocyte containing follicles alone. In non-LA cycles, FF immunoreactive EGF levels were lower in follicles that contained metaphase I or II oocytes than prophase I oocytes. Additionally, FF immunoreactive EGF levels were lower in follicles containing metaphase I or II oocytes from non-LA than LA cycles. We conclude that immunoreactive EGF is present in FF. Leuprolide acetate may affect FF immunoreactive EGF levels.


Coplanar and non-coplanar congener-specificity of PCB bioaccumulation and immunotoxicity in sea stars.
The sea star Asterias rubens (L.), a representative species of the North Sea benthic environment, was exposed to a mixture of 10 selected PCB congeners (3 coplanar or c-PCBs, and 7 non-coplanar) via experimentally contaminated sediments. Both the degree of bioaccumulation and subsequent immunotoxic effects of these PCBs were determined. A strong congener-specificity for both bioaccumulation and immunotoxicity was found as well as a probable induction of a congener-specific detoxification mechanism resulting in the dramatic decrease in body levels of the three coplanar congeners tested (PCBs 77, 126 and 169). Moreover, a correlation was found between the bioaccumulation of c-PCBs and their immunotoxic effects. These findings suggest that coplanar congeners should be included in the list of congeners recommended to be analyzed for biological impact-oriented marine monitoring programmes.


Somatostatin fibers and their relationship to specific cell types (GH and TSH) in the rat anterior pituitary.
Fibers immunocytochemically stained for somatostatin (growth hormone-release-inhibiting hormone) were localized in the anterior pituitaries of rats. Initial studies of fiber localization involved the use of thick frozen (30 micron) sections which allowed visualization of fibers as they coursed along the periphery of the anterior lobe in the sagittal plane and along blood vessels throughout the lobe. Fibers were observed most often at the rostral, caudal, and lateral poles. In thinner (1-3 micron) paraffin sections, stained somatostatin fibers could be localized in close proximity to cells that were stained for growth hormone or thyroid stimulating hormone in a double stain with a second peroxidase substrate. These and our previous light microscopic studies show that a few neuronal processes containing neurotransmitters extent beyond the level of the median eminence (or perhaps from a peripheral source), penetrate the anterior lobe in specific regions, and lie in close proximity to cells known to be controlled by the transmitter.


Clinical research on the efficacy and safety of thread-embedding acupuncture for treatment of herniated intervertebral disc of the lumbar spine: a protocol for a multicenter, randomized, patient-assessor blinded, controlled, parallel, clinical trial.
A lumbar herniated intervertebral disc (LHIVD) is a common problem that usually causes lower back pain and neurological symptoms that manifest as radiating pain. Several studies have reported that thread-embedding acupuncture (TEA) is effective in the treatment of LHIVD. However, these studies were of low quality and there is therefore little clinical evidence for the effectiveness of TEA in this regard. The aim of the present study is to establish the clinical evidence regarding the efficacy and safety of TEA in the treatment of pain, function, and quality of life in patients with LHIVD. The study uses a rigorously designed, full-scale, randomized clinical trial (RCT) protocol. This is a multicenter, randomized, patient-assessor blinded, sham-controlled trial with two parallel arms. Seventy patients with LHIVD who have lower back pain more severe than 40 mm on the 100-mm visual analogue scale (VAS), and who are aged 19-70 years, will be recruited and randomly allocated to a TEA group and sham TEA (STEA) group. Both groups will receive treatment on 23 predefined acupoints once a week for eight weeks; needles with the thread removed will be used in the STEA group, while normal TEA will be employed in the TEA group. Changes in the 100-mm VAS for lower back pain after eight weeks will be assessed as the primary outcome. Furthermore, the 100-mm VAS for radiating pain, Oswestry Disability Index, Roland-Morris disability questionnaire, EuroQol 5 Dimensions 5 Levels, and global perceived effect will be measured and analyzed as secondary outcomes. All outcomes will be assessed at baseline and at 4, 8, 12, and 16 weeks after screening. The results of this trial will help to establish the clinical evidence regarding TEA in the treatment of patients with LHIVD. ClinicalTrials.gov, NCT03236753 . Registered on August 2, 2017. Clinical Research Information Service of the Republic of Korea, KCT0002439 . Registered on August 1, 2017.


Rapid re-establishment of top-down control at a no-take artificial reef.
Establishment of artificial reefs and no-take areas are management measures available for restoring deteriorated marine ecosystems, compensating for habitat loss and strengthening harvested populations. Following the establishment of no-take artificial reefs in western Sweden to compensate for hard bottoms lost to a shipping lane, we detected rapid positive effects on crustaceans and demersal fish compared to fished reference areas. The relative abundance and size structure of European lobster (Homarus gammarus) increased strongly in the no-take area indicating more than doubled and tripled egg production in 5 and 10 years, respectively. For benthic fish and crustacean communities, the abundances of gadoids and wrasses increased and the abundances of small decapod crustaceans decreased in the no-take area, likely indicating cascading effects of increased predation. The study demonstrates that relatively small no-take areas, enhanced by artificial reefs, can rapidly invigorate populations of lobster and fish that in turn may re-initiate local top-down control.


Developing a modified directly observed therapy intervention for hepatitis C treatment in a methadone maintenance program: implications for program replication.
Hepatitis C virus (HCV) is a prevalent chronic blood-borne infection among opioid-dependent patients on methadone maintenance treatment (MMT). Despite case reports and case-control studies, a randomized controlled trial (RCT) examining HCV treatment adherence in methadone-maintained patients is lacking and was the impetus for this ongoing RCT examining modified directly administered therapy for HCV treatment integrated within a MMT. Subjects were randomized 1:1 to receive HCV treatment as modified directly observed therapy (mDOT) into the MMT program or at a liver specialty clinic as self-administered therapy (SAT). Randomization was stratified based on HIV status and HCV genotype. Twenty-one subjects to date have enrolled in this pilot study. The mDOT subjects have had greater success in starting treatment and 10 of the 12 mDOT subjects achieved early virologic response (EVR) at week 12 and 6 of those 10 achieved sustained virologic response (SVR). Of the nine SAT subjects, only three achieved EVR at week 12 and only one achieved SVR despite not completing the treatment. Hepatitis C treatment can be successfully integrated into a methadone maintenance clinic, and mDOT can be implemented with a methadone clinic's existing nursing and medical staff. Patients struggling with concurrent substance use and mental illness comorbidity may be successfully addressed in such settings and facilitate access to and completion of treatment through the utilization of on-site clinical services for HCV treatment and adherence support with mDOT. The exact importance of site of services and adherence support remains a significant area for future investigation.


Clinical outcomes of chemotherapy in cancer patients with different ethnicities.
Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup. Pharmacogenomics, the study of how an individual's genes impact the processing and action of a drug, can optimize drug responsiveness and reduce toxicities by creating a customized medication regimen. However, these differences are rarely considered in the initial determination of standardized chemotherapeutic protocols and treatment algorithms. Because pharmacoethnicity is influenced by both genetic and nongenetic variables, clinical data highlighting disparities in the frequency of polymorphisms between different ethnicities is steadily growing. Recent data suggests that ethnic variations in the expression of allelic variants may result in different pharmacokinetic properties of the anti-cancer medication. In this article, the clinical outcomes of various chemotherapy classes in patients of different ethnicities were reviewed. Genetic and nongenetic variables contribute to the interindividual variability in response to chemotherapeutic drugs. Considering pharmacoethnicity in the initial determination of standard chemotherapeutic protocols and treatment algorithms can lead to better clinical outcomes of patients of different ethnicities.


A unidirectional mapping of ICD-8 to ICD-10 codes, for harmonized longitudinal analysis of diseases.
Periodic revisions of the international classification of diseases (ICD) ensure that the classification reflects new practices and knowledge; however, this complicates retrospective research as diagnoses are coded in different versions. For longitudinal disease trajectory studies, a crosswalk is an essential tool and a comprehensive mapping between ICD-8 and ICD-10 has until now been lacking. In this study, we map all ICD-8 morbidity codes to ICD-10 in the expanded Danish ICD version. We mapped ICD-8 codes to ICD-10, using a many-to-one system inspired by general equivalence mappings such that each ICD-8 code maps to a single ICD-10 code. Each ICD-8 code was manually and unidirectionally mapped to a single ICD-10 code based on medical setting and context. Each match was assigned a score (1 of 4 levels) reflecting the quality of the match and, if applicable, a "flag" signalling choices made in the mapping. We provide the first complete mapping of the 8596 ICD-8 morbidity codes to ICD-10 codes. All Danish ICD-8 codes representing diseases were mapped and 5106 (59.4%) achieved the highest consistency score. Only 334 (3.9%) of the ICD-8 codes received the lowest mapping consistency score. The mapping provides a scaffold for translation of ICD-8 to ICD-10, which enable longitudinal disease studies back to and 1969 in Denmark and to 1965 internationally with further adaption.


A murine plasmacytoma with a variant (15;16)(D2/3;B1) translocation that involves the c-myc and lambda light chain gene-carrying chromosomes.
A murine plasmacytoma (MPC) with a reciprocal translocation between chromosomes 15 and 16 with breakpoints in 15D2/3 and 16B1 is reported. The breakpoint on chromosome 15 is identical to the breakpoint in the MPC-associated typical (12;15) and kappa variant (6;15) translocation. Therefore it probably involves the c-myc gene as well. Unlike the Burkitt lymphoma (BL) system, a lambda/myc variant translocation has not been described in the MPC system. Chromosome 16 is known to carry the lambda gene. Therefore, the 15;16 translocation probably represents the "missing" lambda/myc variant in MPC, suggesting that the lambda gene is localized at 16B1.


Overview of technical solutions and assessment of clinical usefulness of capsule endoscopy.
The paper presents an overview of endoscopic capsules with particular emphasis on technical aspects. It indicates common problems in capsule endoscopy such as: (1) limited wireless communication (2) the use of capsule endoscopy in the case of partial patency of the gastrointestinal tract, (3) limited imaging area, (4) external capsule control limitations. It also presents the prospects of capsule endoscopy, the most recent technical solutions for biopsy and the mobility of the capsule in the gastrointestinal tract. The paper shows the possibilities of increasing clinical usefulness of capsule endoscopy resulting from technological limitations. Attention has also been paid to the current role of capsule endoscopy in screening tests and the limitations of its effectiveness. The paper includes the author's recommendations concerning the direction of further research and the possibility of enhancing the scope of capsule endoscopy.


Evaluation of sex difference in tissue repair following acute carbon tetrachloride toxicity in male and female Sprague-Dawley rats.
Cellular regeneration and tissue repair greatly influence the outcome of acute carbon tetrachloride (CCl4) hepatotoxicity. This study examined the temporal kinetics of cellular regeneration and tissue repair processes in male and female Sprague Dawley (SD) rats following an acute CCl4 exposure (0.8 ml/kg, i.p.). In female rats, hepatic damage peaked at 24 h following the treatment and was approximately 2.5-fold (AST 2.7-fold, ALT 2.3 fold) greater than the damage observed in male rats. The hepatic damage in male rats appeared to peak by 3 h post-exposure and did not significantly change through the 36-h time-point. The activity of cytochrome P 4502E1 was 20% greater in male rats and did not correlate with the magnitude of hepatic damage. Morphometric analysis of cell cycle indices revealed that cellular regeneration was significantly greater in female rats as compared to male rats at 48 h and corresponded proportionally to the extent of liver damage. This study demonstrated that female SD rats respond more severely to acute CCl4 hepatotoxicity than male SD rats and the extent of tissue repair and cellular regeneration was greater in female rats. Furthermore, our results suggest that tissue repair is unlikely to result in accounting for the different responses exhibited by male and female SD rats to CCl4 hepatotoxicity.


Initial clinical experience with infrared-reflecting skin markers in the positioning of patients treated by conformal radiotherapy for prostate cancer.
To evaluate an infrared (IR) marker-based positioning system in patients receiving conformal radiotherapy for prostate cancer. During 553 treatments, the ability of the IR system to automatically position the isocenter was recorded. Setup errors were measured by means of orthogonal verification films and compared to conventional positioning (using skin drawings and lasers) in 184 treatments. The standard deviation of anteroposterior (AP) and lateral setup errors was significantly reduced with IR marker positioning compared to conventional: 2 vs. 4.8 mm AP (p < 0.01) and 1.6 vs. 3.5 mm laterally (p < 0.01). Longitudinally, the difference was not significant (3.5 vs. 3.0 mm). Systematic errors were on the average smaller AP and laterally for the IR method: 4.1 vs. 7.8 mm AP (p = 0.01) and 3.1 vs. 5.6 mm lateral (p = 0.07). Longitudinally, the IR system resulted in somewhat larger systematic errors: 5.0 vs. 3.4 mm for conventional positioning (p = 0.03). The use of an off-line correction protocol, based on the average deviation measured over the first four fractions, allowed virtual elimination of systematic errors. Inability of the IR system to correctly locate the markers, leading to an executional failure, occurred in 21% of 553 fractions. IR marker-assisted patient positioning significantly improves setup accuracy along the AP and lateral axes. Executional failures need to be reduced.


Pelvic floor muscle exercises alleviate symptoms and improve mental health and rectal function in patients with low anterior resection syndrome.
Pelvic floor rehabilitation has been reported to be effective in improving fecal incontinence. The aim of this study was to prospectively evaluate the effectiveness of combined pelvic floor muscle exercises (PFMEs) and loperamide treatment on rectal function and mental health for low anterior resection syndrome (LARS) patients after sphincter-saving operation (SSO) for rectal cancer. A total of 60 inpatients diagnosed with LARS were enrolled and randomly assigned to one of two groups: patients in Group A (n = 30) were treated with a PFME intervention and those in Group B (n = 30) with a control intervention for 4 weeks. High-resolution anorectal manometry (HRAM) was performed for all LARS patients. Demographic information was collected for all patients, and they subsequently also completed several questionnaires, including the Hospital Anxiety and Depression Scale (HADS), a measure of Wexner score, a measure of stool frequency per day, and the Bristol Stool Form Scale (BSFS). No significant differences between the groups were observed in baseline data. With regard to rectal function, we found significant improvements at week 4 in maximal resting pressure (MRP) (39.93 ± 5.02 vs. 28.70 ± 5.40 mmH2O, p < 0.001) and maximal squeeze pressure (MSP) (132.43 ± 8.16 mmH2O vs. 113.33 ± 9.87 mmH2O, p < 0.001) among Group A patients compared to Group B patients. Additionally, Wexner scores were significantly lower in Group A than in Group B at week 4 (8.10 ± 1.24 vs. 9.87 ± 1.29 ml, p = 0.018), as were stool frequency (6.47 ± 0.90 vs. 7.83 ± 0.93, p < 0.001) and BSFS scores (5.17 ± 0.65 vs. 6.10 ± 0.80, p = 0.020). Notably, HADS scores were also significantly lower in Group A than in Group B at week 4 (8.25 ± 2.36 vs. 10.48 ± 3.01, p < 0.001). Additionally, both anxiety scores (4.16 ± 1.38 vs. 5.33 ± 1.69, p < 0.001) and depression scores (4.09 ± 1.56 vs. 5.15 ± 1.89, p < 0.001) were significantly lower in Group A than in Group B at week 4. Pelvic floor muscle exercises are an effective treatment that can alleviate symptoms and improve rectal function and mental health in patients with low anterior resection syndrome.


Light emitting diode (LED) photobiomodulation therapy on murine macrophage exposed to Bothropstoxin-I and Bothropstoxin-II myotoxins.
The light-emitting diode (LED) is considered a therapeutic tool due to its anti-inflammatory, analgesic, and wound-healing effects, which occur through angiogenesis, decrease in IL-1β and IL-6 secretion, and acceleration of the cicatricial process. Snakebites are an important public health problem in tropical regions of the world. LED treatment is a therapeutic tool associated with serum therapy used to minimize the local effects of snakebites, including decrease in creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations, myonecrosis, and inflammatory and haemorrhagic responses. In this study, we analysed the photobiomodulation effect of LED on the activation of murine macrophages induced by BthTX-I or BthTX-II isolated from Bothrops jararacussu venom. Photobiomodulation caused an increase in mitochondrial metabolism and a considerable decrease in cytotoxicity in murine macrophages. Moreover, it induced a decrease in reactive oxygen species and nitrogen liberation. However, photobiomodulation caused an increase in macrophage phagocytic capacity and lipid droplet formation. The results of this study corroborated with those of others in an unprecedented way and provide a better understanding of the mechanism of action of photobiomodulation, besides offering a coadjuvant action treatment for the local effects of snakebites, not achieved with serum therapy alone.


Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic β-cell dysfunction.
Severe malnutrition is a major health problem in developing countries and can present as kwashiorkor or marasmus. Kwashiorkor is associated with septicaemia, profound metabolic changes including hepatic steatosis, altered protein metabolism and increased oxidative stress. Limited data suggest that children with kwashiorkor have an impaired glucose tolerance and insulin secretion. Our objective was to determine glucose tolerance in children with kwashiorkor compared to marasmus and its relation to insulin secretion and sensitivity. Six children with kwashiorkor and 8 children with marasmus were studied. We were also able to include 3 healthy children for comparison. They received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6-(2)H(2)]glucose for 4 h with serial blood sampling. In addition, an oral glucose tolerance test (OGTT) was performed with labeled 10 mg/g [U-(13)C]glucose. Glucose clearance was determined using mathematical modeling. Glucose clearance rates during the OGTT were -392 (range 309) mL/kg in children with kwashiorkor, -156 (426) mL/kg in marasmus and 279 (345) mL/kg in the control group. Glucose clearance rates correlated with plasma albumin concentrations (r=0.67, P=.001). Insulin responses were strongly impaired in both kwashiorkor and marasmus. There was no indication of peripheral or hepatic insulin resistance in the malnourished groups. We show that glucose clearance rates are affected in both children with marasmus as well as kwashiorkor, which correlate with plasma albumin concentrations. The disturbed glucose clearance in malnutrition is related to an impairment in insulin availability.


The locus controlling liver GM1(NeuGc) expression is mapped 1 cM centromeric to H-2K.
The polymorphic variation of liver GM1 (NeuGc) ganglioside was found in inbred strains of the mouse. The genetic analysis using C57BL/10 (GM1-negative) and SWR (GM1-positive) mice revealed that a single autosomal gene (Ggm-1) was involved in the expression of liver GM1(NeuGc) and that C57BL/10 mice lacking GM1(NeuGc) expression carried a defective gene on Ggm-1. Since our previous study on H-2 congenic mice indicated that Ggm-1 was linked to the H-2 complex, in this study we measured recombination frequencies among Ggm-1, Glo-1 and H-2K in the backcross progeny between (C57BL/10 X SWR)F1 and C57BL/10. Ggm-1 was mapped 1 cM centromeric to H-2K on chromosome 17.


Influence of a Stay-At-Home Order on Trauma Volume and Injury Patterns at a Level I Trauma Center in Ohio.
Changes in injury patterns during the COVID pandemic have been reported in other states. The objective was to explore changes to trauma service volume and admission characteristics at a trauma center in northeast Ohio during a stay-at-home order (SAHO) and compare the 2020 data to historic trauma census data. Retrospective chart review of adult trauma patients admitted to a level I trauma center in northeast Ohio. Trauma admissions from January 21 to July 21, 2020 (COVID period) were compared to date-matched cohorts of trauma admissions from 2018 to 2019 (historic period). The COVID period was further categorized as pre-SAHO, active-SAHO, and post-SAHO. The SAHO was associated with a reduction in trauma center admissions that increased after the SAHO (P = .0033). Only outdoor recreational vehicle (ORV) injuries (P = .0221) and self-inflicted hanging (P = .0028) mechanisms were increased during the COVID period and had substantial effect sizes. Glasgow Coma Scores were lower during the COVID period (P = .0286) with a negligible effect size. Violence-related injuries, injury severity, mortality, and admission characteristics including alcohol and drug testing and positivity were similar in the COVID and historic periods. The SAHO resulted in a temporary decrease in trauma center admissions. Although ORV and hanging mechanisms were increased, other mechanisms such as alcohol and toxicology proportions, injury severity, length of stay, and mortality were unchanged.


Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells.
There are some successful reports of kidney generation by utilizing the natural course of kidney development, namely, the use of an artificially treated metanephros, blastocyst or ureteric bud. Under a novel concept of cellular interactions via conditioned media (CMs), we have attempted in vivo nephron generation from tubular epithelial cells (TECs) or mesenchymal stem cells (MSCs). Here we used 10× CMs of vascular endothelial cells (VECs) and TECs, which is the first to introduce a CM into the field of organ regeneration. We first present stimulative cross-talks induced by these CMs between VECs and TECs on cell proliferation and morphological changes. In MSCs, TEC-CM suppressed these changes, however, induced cytokeratin expression, indicating the differentiation of MSCs into TECs. As a result, glomerular and tubular structures were created following the implantation of TECs or MSCs with both CMs. Our findings suggest that the cellular interactions via CMs might induce in vivo nephron generation from TECs or MSCs. As a promoting factor, CMs could also be applied to the regeneration of other organs and tissues.


Managing the unexpected: Carcinosarcoma of the kidney parenchyma A case with the longest follow-up.
We present the management of the second reported case of carcinosarcoma of the kidney parenchyma with malignant degeneration of both epithelial and mesenchymal components. A 36-year-old woman came to our attention for an incidental sonographic finding of a lesion in the lower pole of the left kidney. A contrasted computed tomography scan confirmed the presence of a 50 × 52 mm2 contrasted lesion in the left lower kidney pole. The patient underwent a challenging laparoscopic left partial nephrectomy and para-aortic lymphadenectomy. The histological examination led to the diagnosis of a carcinosarcoma of the kidney parenchyma with malignant degeneration of both epithelial and mesenchymal components. The patient underwent adjuvant chemotherapy with paclitaxel at 175 mg/m2 plus carboplatin area under the curve 6 intravenously for six cycles. At a follow-up of 42 months, the patient is alive and does not show any local recurrences or distant metastases. A multi-disciplinary therapeutic approach, combined with an adequate doctor-patient relationship and a close and detailed follow-up, is of fundamental importance in obtaining good outcomes in such rare and challenging cases.


Effect of space flight on the behavior of human retinal pigment epithelial ARPE-19 cells and evaluation of coenzyme Q10 treatment.
Astronauts on board the International Space Station (ISS) are exposed to the damaging effects of microgravity and cosmic radiation. One of the most critical and sensitive districts of an organism is the eye, particularly the retina, and > 50% of astronauts develop a complex of alterations designated as spaceflight-associated neuro-ocular syndrome. However, the pathogenesis of this condition is not clearly understood. In the current study, we aimed to explore the cellular and molecular effects induced in the human retinal pigment ARPE-19 cell line by their transfer to and 3-day stay on board the ISS in the context of an experiment funded by the Agenzia Spaziale Italiana. Treatment of cells on board the ISS with the well-known bioenergetic, antioxidant, and antiapoptotic coenzyme Q10 was also evaluated. In the ground control experiment, the cells were exposed to the same conditions as on the ISS, with the exception of microgravity and radiation. The transfer of ARPE-19 retinal cells to the ISS and their living on board for 3 days did not affect cell viability or apoptosis but induced cytoskeleton remodeling consisting of vimentin redistribution from the cellular boundaries to the perinuclear area, underlining the collapse of the network of intermediate vimentin filaments under unloading conditions. The morphological changes endured by ARPE-19 cells grown on board the ISS were associated with changes in the transcriptomic profile related to the cellular response to the space environment and were consistent with cell dysfunction adaptations. In addition, the results obtained from ARPE-19 cells treated with coenzyme Q10 indicated its potential to increase cell resistance to damage.


Assessment of mutagenic activity of repeatedly used deep-frying fats.
Mutagenic activity of repeatedly used deep-frying fats was evaluated in relation to chemical characteristics. Deep-frying fat samples were collected from local restaurants and snack bars after sensory indication of abuse. A total of 20 deep-frying fat samples and 2 unused control fat samples was tested. Fat samples were fractionated into non-polar and polar compounds by column chromatography. Amounts of polar compounds obtained ranged from 2% (by weight) for unused fat to 44% for used deep-frying fat. Levels of di- and polymeric triglycerides (DPTG) were determined using gel-permeation chromatography. DPTG concentrations of 13 used deep-frying fat samples exceeded the threshold level of 10% above which fats are rejected for use. In addition thiobarbituric acid-reactive substances (TBA-RS) were measured. Amounts of TBA-RS were just above detection levels for most fat samples. Five used fat samples, however, contained relatively high concentrations of TBA-RS, ranging from 82 to 177 nmoles malondialdehyde/g. Non-polar and polar fractions were screened for mutagenic activity using the Ames mutagenicity assay. Mutagenic activity was found predominantly in polar fractions at doses higher than 1 mg/plate in strains TA97, TA100 and TA104, variously with and without metabolic activation. The highest number of mutagenic samples was detected by strain TA97, which appeared to be most sensitive. Some samples exhibited toxic effects. Chromatography blanks, consisting of solvents processed according to the same procedures as used for fat samples, were not mutagenic. Mutagenic activity was also detected in polar material obtained from unused frying fat. Non-polar fractions of unused frying fats showed no mutagenicity. A frying experiment carried out under laboratory conditions indicated that during repeated and prolonged use of deep-frying fat mutagenic polar substances were formed. Fat samples taken after 20 and 40 h of frying contained increasing amounts of polar compounds. Mutagenic activity was highest after 20 h of frying but was slightly decreased after 40 h of frying. At this stage, however, mutagens also appeared in the non-polar fraction. Mutagenic activity of polar fractions of used deep-frying fats in strain TA97 was positively correlated with levels of TBA-RS, which may indicate the involvement of lipid oxidation products in mutagenicity of used deep-frying fats. No significant correlations were found with other chemical characteristics. In the process of deep-fat frying numerous degradation products are formed, which may include mutagenic heterocyclic amines and other pyrolysates.(ABSTRACT TRUNCATED AT 400 WORDS)


A randomized, controlled trial to test the efficacy of an online, parent-based intervention for reducing the risks associated with college-student alcohol use.
Alcohol consumption among college students remains a major public health concern. Universal, Web-based interventions to reduce risks associated with student alcohol consumption have been found to be effective in changing their alcohol-related behavior. Recent studies also indicate that parent-based interventions, delivered in booklet form, are effective. A parent-based intervention that is also Web-based may be well suited to a dispersed parent population; however, no such tool is currently available. The purpose of this study was to test the efficacy of an online parent-based intervention designed to (1) increase communication between parents and students about alcohol and (2) reduce risks associated with alcohol use to students. A total of 558 participants, comprising 279 parent-teen dyads, were enrolled in the study. The findings suggested that parents who participated in the online intervention were more likely to discuss protective behavioral strategies, particularly those related to manner of drinking and stopping/limiting drinking, with their teens, as compared with parents in an e-newsletter control group. Moreover, students whose parents received the intervention were more likely to use a range of protective behavioral strategies, particularly those related to manner of drinking and stopping/limiting drinking, as compared with students whose parents did not receive the intervention. A universal, online, parent-based intervention to reduce risks associated with student alcohol consumption may be an efficient and effective component of a college's overall prevention strategy.


Regulatory and other rheumatoid factors in rheumatoid arthritis patients with active disease or in remission.
Previously, we identified a regulatory rheumatoid factor (regRF), the production of which provides rats with resistance to collagen-induced arthritis (CIA). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces symptoms of CIA. The aim of this study was to determine whether there is a link between regRF levels and rheumatoid arthritis (RA) activity in humans in order to assess the potential of regRF as a therapeutic biotarget in RA. The variability of rheumatoid factor (RF) specificities present in the blood of RA patients was also studied. The regRF were studied in RA patients with active disease and in remission. Variability in the specificities of RF associated with RA was studied by concurrent inhibition of RF latex fixation by variants of modified IgG. Patients in remission had regRF levels higher than in healthy subjects. The regRF in remission was characterized by tight binding to its antigen, as in healthy subjects. The regRF levels in patients with active RA varied dramatically, and regRF binding to its antigen was weak. The exacerbation of Still's disease coincided with low regRF levels and affinity, while an improvement in patient condition was associated with an increase in regRF levels and affinity. The RF specific to RA, which was detected by the RF latex-fixation method, was a nonhomogeneous population of antibodies that included RF to lyophilized IgG, to IgG immobilized on polystyrene, and to rabbit IgG. Stimulating regRF production might enable improved RA therapy.


Renal impairment and hydronephrosis in a premature infant following morphine infusion: case report.
This is a case report of an association between morphine administration and occurrence of hydronephrosis with acute renal failure. This premature female infant born at 27 weeks of gestation had moderate hydronephrosis with acute renal impairment while receiving morphine infusion for pain management after chest-tube insertion. All these findings were reversed after stopping morphine and urinary catheterization. Follow-up renal ultrasound and voiding cystourethrogram showed resolution of hydronephrosis with no evidence of vesicoureteral reflux. Morphine is associated with reversible hydronephrosis and renal impairment in premature infants.


The group I intron of apocytochrome b gene from Chlamydomonas smithii encodes a site-specific endonuclease.
The mitochondrial DNA molecules of two interfertile algal species, Chlamydomonas smithii and C. reinhardtii, are co-linear except for a 1075 bp intron (the alpha-insert) that is present in the cob gene of C. smithii. The alpha-insert, a group I intron (Cs cob.1) containing an open reading frame (ORF) which encodes a basic, hydrophilic protein of 237 amino acids, is unidirectionally transmitted to all diploid progeny during interspecific crosses. In this report, we show that the Cs cob.1-encoded protein is a site-specific endonuclease (I-Csm I) which could mediate the intron transfer via the gene conversion mechanism. The Cs cob.1 ORF was cloned into the vector pMALcr1 and over-expressed as a hybrid protein fused to maltose-binding protein (MBP). This fusion protein exhibited an in vivo endonuclease activity which specifically cleaved the intron homing site within the intronless cob gene.


Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients.
It is uncertain if nucleos(t)ide analogue (NA)-induced hepatitis B surface antigen (HBsAg) seroclearance is durable. We investigated the impact of hepatitis B surface antibody (anti-HBs) and duration of consolidation antiviral therapy on the durability of HBsAg seroclearance. A territory-wide cohort study was conducted using data from the Hospital Authority, Hong Kong. We identified all subjects with positive HBsAg between January 1, 2000 and August 31, 2016. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was confirmed HBsAg seroclearance, defined least two negative HBsAg test results, with the last HBsAg test being negative in patients with chronic hepatitis B (CHB). A total of 4,080 CHB patients were included for analysis. In patients with spontaneous HBsAg seroclearance (n=3,563), 1,771 patients (49.7%) had confirmed HBsAg seroclearance and 75 patients (2.1%) had HBsAg seroreversion. In patients with NA-induced HBsAg seroclearance (n=475), 320 patients (67.4%) had confirmed HBsAg seroclearance and 14 patients (2.9%) had HBsAg seroreversion. The five-year cumulative probability of confirmed HBsAg seroclearance was comparable in patients with spontaneous and NA-induced HBsAg seroclearance (88.1% vs. 92.2%; Log-rank test, p=0.964); it was also similar in patients with or without anti-HBs in NA-treated patients (95.4% vs. 95.5%, Log-rank test, p=0.602). HBsAg seroreversion was only observed in 3 (2.0%) patients who had received consolidation therapy for 6-12months and none of those who had received it for ≥12months. NA-induced HBsAg seroclearance is as durable as spontaneous HBsAg seroclearance. NA-treated patients may not need to have positive anti-HBs before stopping treatment. Longer consolidation NA treatment may result in more durable HBsAg seroclearance. We investigated 4,080 patients with hepatitis B surface antigen (HBsAg) seroclearance. HBsAg seroreversion occurred in 2.1% of patients with spontaneous and 2.9% of those with nucleos(t)ide analogues-induced HBsAg seroclearance.


Intravitreal implants manufactured by supercritical foaming for treating retinal diseases.
Chronic retinal diseases, such as age-related macular degeneration (AMD), are a major cause of global visual impairment. However, current treatment methods involving repetitive intravitreal injections pose financial and health burdens for patients. The development of controlled drug release systems, particularly for biological drugs, is still an unmet need in prolonging drug release within the vitreous chamber. To address this, green supercritical carbon dioxide (scCO2) foaming technology was employed to manufacture porous poly(lactic-co-glycolic acid) (PLGA)-based intravitreal implants loaded with dexamethasone. The desired implant dimensions were achieved through 3D printing of customised moulds. By varying the depressurisation rates during the foaming process, implants with different porosities and dexamethasone release rates were successfully obtained. These implants demonstrated controlled drug release for up to four months, surpassing the performance of previously developed implants. In view of the positive results obtained, a pilot study was conducted using the monoclonal antibody bevacizumab to explore the feasibility of this technology for preparing intraocular implants loaded with biologic drug molecules. Overall, this study presents a greener and more sustainable alternative to conventional implant manufacturing techniques, particularly suited for drugs that are susceptible to degradation under harsh conditions.


Secreted phospholipase A2 inhibitor modulates fatty acid composition and reduces obesity-induced inflammation in Beagle dogs.
Secreted phospholipase A2 inhibitor (sPLA2i) has been reported to have an anti-inflammatory function by blocking the production of inflammatory mediators. Obesity is characterized by low-grade inflammation and oxidative stress. The aim of this study was to investigate the effects of dietary supplementation of sPLA2i on inflammation, oxidative stress and serum fatty acid profile in dogs. Seven obese and seven lean Beagle dogs were used in a 28-day double blind cross-over design. Dogs were fed a control diet without supplemental sPLA2i or an sPLA2i supplemented diet. The sPLA2i diet decreased plasma fibrinogen levels and increased the protein:fibrinogen ratio in obese dogs to levels similar to those of lean dogs fed the same diet. Obese dogs had a higher plasma concentration of the lipophilic vitamin A with potential antioxidative capacity and a lower ratio of retinol binding protein 4:vitamin A compared to lean dogs, independent of the diets. A higher proportion of myristic acid (C14:0) and a lower proportion of linoleic acid (C18:2n-6) were observed in the dogs fed with the sPLA2i diet compared to dogs fed with the control diet. Furthermore, a higher ratio of n-6 to n-3, a lower proportion of n-3 polyunsaturated fatty acids and lower omega-3 index were observed in obese compared to lean dogs. The results indicate that obese dogs are characterized by a more 'proinflammatory' serum fatty acid profile and that diet inclusion of sPLA2i may reduce inflammation and alter fatty acid profile.


The impact of occlusal function on structural adaptation in alveolar bone of the growing pig, Sus Scrofa.
this study investigated the effects of growth and tooth loading on the structural adaptation of the developing alveolar bone adjacent to the tooth root as the tooth erupted into function. Growth and occlusal function were expected to lead to increased alveolar bone density. Meanwhile, the supporting alveolar bone was expected to develop a dominant trabecular orientation (anisotropy) only after occlusal loading. minipigs with erupting and occluding mandibular first molars (M(1)'s) were used to study the effects of growth and occlusal function on developing alveolar bone structure through comparison of alveolar bone surrounding M(1)'s. A second minipig model with one side upper opponent teeth extracted prior to occlusal contact with the M(1) was raised until the non-extraction side M(1)'s developed full occlusal contact. The comparisons between extraction and non-extraction side M(1) alveolar bone were used to emphasize the impact of occlusal loading on alveolar bone structure. Specimens were scanned on a Scanco Medical μCT 20 at a 22μm voxel resolution for structural analysis. with growth and occlusal function a distinct alveolar bone proper tended to develop immediately adjacent to the tooth root. The cancellous bone had thicker but fewer and more separated trabeculae after growth or occlusal loading. On the other hand, occlusal function did not lead to increased alveolar structural anisotropy. during tooth eruption, growth and masticatory loads effect structural change in alveolar bone. The impact of occlusal function on cancellous bone anisotropy may need a more extensive period of time to demonstrate.


Spurious oscillations reduction in transient diffusion and wave propagation problems discretized with the Finite Element Method.
This work presents a new method, the SOR_FEM, spurious oscillation reduction-FEM, that uses analytical solutions of simple problems to find numerical solutions of more complex problems to reduce the spurious oscillations that occur due to solution discontinuity. With the proposed method it is possible to find numerical solutions without spurious oscillations of problems submitted to impulsive point sources without using any approximation for the Dirac delta function. To validate the proposed method, linear problems of heat diffusion and wave propagation in homogeneous and heterogeneous media are solved with the Finite Element Method (FEM).


A bird's eye view on the flat and conic band world of the honeycomb and Kagome lattices: towards an understanding of 2D metal-organic frameworks electronic structure.
We present a thorough tight-binding analysis of the band structure of a wide variety of lattices belonging to the class of honeycomb and Kagome systems including several mixed forms combining both lattices. The band structure of these systems are made of a combination of dispersive and flat bands. The dispersive bands possess Dirac cones (linear dispersion) at the six corners (K points) of the Brillouin zone although in peculiar cases Dirac cones at the center of the zone [Formula: see text] point) appear. The flat bands can be of different nature. Most of them are tangent to the dispersive bands at the center of the zone but some, for symmetry reasons, do not hybridize with other states. The objective of our work is to provide an analysis of a wide class of so-called ligand-decorated honeycomb Kagome lattices that are observed in a 2D metal-organic framework where the ligand occupy honeycomb sites and the metallic atoms the Kagome sites. We show that the p x -p y graphene model is relevant in these systems and there exists four types of flat bands: Kagome flat (singly degenerate) bands, two kinds of ligand-centered flat bands (A2 like and E like, respectively doubly and singly degenerate) and metal-centered (three fold degenerate) flat bands.


Long Non-Coding RNA LINC00491 Contributes to the Malignancy of Non-Small-Cell Lung Cancer via Competitively Binding to microRNA-324-5p and Thereby Increasing Specificity Protein 1 Expression.
A long non-coding RNA termed as long intergenic non-protein coding RNA 491 (LINC00491) has been validated as an oncogene to promote cancer progression in colon adenocarcinoma. The goal of this study was to determine the expression and carcinogenic functions of LINC00491 in non-small-cell lung cancer (NSCLC). Besides, it was aimed to understand how LINC00491 affects the malignant processes of NSCLC cells. The expression of LINC00491 in NSCLC was investigated by bioinformatic analysis and reverse transcription-quantitative PCR. After LINC00491 knockdown, cell counting kit-8 assay, flow cytometry, migration and invasion detection assays as well as nude mice xenograft assay were conducted to test the roles of LINC00491 in NSCLC cells. Two online databases, StarBase 3.0 and miRDB, were utilized to determine the putative target miRNA of LINC00491, and the prediction was subsequently confirmed by luciferase reporter assay, RNA immunoprecipitation assay, reverse transcription-quantitative PCR, Western blotting, and rescue assays. LINC00491 was overexpressed in both NSCLC tissues and cell lines. Functional investigation revealed that depleted LINC00491 facilitated cell apoptosis and decreased cell proliferation, migration, and invasion in vitro. Additionally, the downregulation of LINC00491 impaired NSCLC cell tumor growth in vivo. Mechanistically, LINC00491 functioned as a competing endogenous RNA by sponging microRNA-324-5p (miR-324-5p) in NSCLC cells. miR-324-5p was weakly expressed in NSCLC and exerted tumor-suppressing actions during cancer progression. Furthermore, specificity protein 1 (SP1) was validated as the direct target of miR-324-5p in NSCLC and was under the regulation of LINC00491 via sponging miR-324-5p. Rescue experiments reconfirmed that miR-324-5p inhibition and SP1 overexpression both abrogated the suppressive roles of LINC00491 deficiency in NSCLC cells. LINC00491 promoted the oncogenicity of NSCLC via serving as a miR-324-5p sponge, which further upregulated the expression of SP1. The LINC00491/miR-324-5p/SP1 pathway disclosed a new mechanism of NSCLC pathogenesis and may provide effective targets for better NSCLC treatment.


Antibiotics in the non-surgical treatment of peri-implantitis.
Four electronic databases (MEDLINE via Pubmed; EMBASE via Ovid; EBSCO Dentistry and Oral Science Source), in addition to six related journals (Clinical Implant Dentistry and Related Research; Clinical Oral Implants Research; International Journal of Oral and Maxillofacial Implants; International Journal of Oral Implantology; Journal of Clinical Periodontology; Journal of Periodontology), were searched for publications until 2022. Randomised controlled trials (RCTs), evaluating the effectiveness of local or systemic antibiotics as an adjunct in the non-surgical treatment (NST) for peri-implantitis (PI), were assessed. The eligibility criteria included RCTs with a parallel group, split-mouth design and appropriate NST interventions over a three to twelve month period. Data were extracted from RCTs to capture a multitude of primary outcomes, including: implant success rate, radiographic marginal bone loss rate, periodontal health changes and PI resolution. Risk of bias assessments were made using the Cochrane Collaboration's tool, by two authors independently and in duplicate. RCTs with similar observation periods and interventions were included in the meta-analyses. Random-effects meta-analyses of mean differences or relative risks with 95% confidence intervals were calculated, in additional to data heterogeneity calibration through I2 statistics. Following the screening of 270 papers, six RCTs were included, which resulted in the evaluation of 391 patients (375 implants). Adjunctive local antibiotic therapy at disease sites showed statistically significant periodontal outcomes; improvements in success rate (risk ratio = 9.89; 95% CI 2.39-40.84), probing pocket depth (mean difference (MD) = 0.6 mm; 95% CI 0.42-0.78) and bleeding on probing (MD = 0.15%; 95% CI 0.10-0.19). Conversely, adjunctive systemic antibiotics improved probing pocket depths (MD = 1.15 mm; 95% CI 0.31-1.99) and probing attachment levels only (MD = 1.10 mm; 95% CI 0.13-2.08). Across the six included RCTs, the bone loss rate and PI resolution rate determined no significant differences between the groups; mirrored in the single studies and in the meta-analysis. Disease resolution ranged from 2 to 65%. Two of the studies were found to be at low risk of bias and four presented with some concerns. Adjunctive antibiotics aid NST. However, the heterogeneity of study methods and low quality of current RCTs evidenced, deem their role in NSTs of PI as inconclusive.


Non-invasive tear break-up time in normal Malays.
Tear stability in normal Malays with consideration of gender and age has not been reported. In this study, we measured tear stability in normal Malays using the non-invasive tear break-up time (NIBUT). Forty-eight Malay subjects aged seven to 60 years were recruited from among the staff, their children and students of the faculty. NIBUT was measured by noting the time taken for distortions to appear in a reflected image of a grid pattern formed on the corneal surface. The mean NIBUT of the sample was 15.8 +/- 9.4 (SD) seconds. The median was 14.6 seconds with range of 4.2 seconds to 48.6 seconds. The majority (73 per cent) of subjects had NIBUT values between six and 20 seconds. There was no significant difference in NIBUT values between males and females but there was a decrease of NIBUT with age. The NIBUT values found in this study are comparable to those reported for Asian populations but much less than those of Western populations. Our findings point to the need for local clinical studies in contact lens and contact lens-related research as tear physiology of the local population may not be the same as in Western populations.


Variations of Essential Oil Constituents in Oregano (Origanum vulgare subsp. viridulum (= O. heracleoticum) over Cultivation Cycles.
Oregano is-probably-the most appreciated and widespread aromatic plant in Sicily. With the aim of evaluating the modifications of oregano's essential oil composition over time, between 2013 and 2015 six weekly samplings of three different oregano plantations were carried out, from the beginning of flowering (early May) until the traditional harvest moment (end of June). Samples were hydrodistilled and the obtained essential oils (EOs) were evaluated by means of a combination of GC-FID and GC-MS. The Origanum plants under study were demonstrated to belong to the high-yielding, thymol-type biotypes, with thymol, γ-terpinene and p-cymene as three main components, among the total of about 50 of the evaluated EOs. In each location, EO yields were found to increase throughout survey dates. Significant variations were found in many EO components, both across years and throughout harvest dates within locations. The choice of the harvest moment was confirmed to be crucial in assessing quality aspects of oregano.


The role of nitric oxide in anticonvulsant and proconvulsant effects of morphine in mice.
Acute subcutaneous administration of lower doses of morphine (0.5, 1 and 3 mg/kg) increase the threshold of seizures induced by pentylenetetrazole (PTZ) in mice, whereas higher doses of morphine (15, 30 and 60 mg/kg) have proconvulsant effects. The effect of systemic administration of nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-L-arginine (L-NNA) and nitric oxide synthase (NOS) L-arginine on biphasic effect of morphine was investigated. Acute administration of both L-NAME (1, 3 and 10 mg/kg) and L-NNA (1 and 10 mg/kg) as well as chronic pretreatment with L-NAME (1 and 10 mg/kg, 4 days) dose-dependently inhibited both the anticonvulsant and proconvulsant effects of morphine (1 and 30 mg/kg, respectively). The inhibition was complete for anticonvulsant effect while partial for proconvulsant effect. L-arginine at doses that did not affect seizure threshold per se (acute, 30 and 60 mg/kg; chronic, 60 mg/kg) potentiated both anticonvulsant and proconvulsant properties of less potent doses of morphine (0.5 and 15 mg/kg, respectively). The L-arginine induced potentiation of both phases of morphine effect was blocked by L-NAME (0.5-30 mg/kg). Moreover, low and per se non-effective doses of naloxone (0.1 mg/kg) and L-NAME (0.3, 0.5 or 1 mg/kg) showed additive effects in inhibiting both phases of morphine effects. These results support the involvement of L-arginine/nitric oxide pathway in the modulation of seizure threshold by morphine.


Seed predation in the legume Crotalaria : II. Correlates of interplant variability in predation intensity.
Correlates of individual plant escape from seed predation were investigated for an East African population of the shrub Crotalaria pallida (Papilionaceae) in which seed mortality due to chewing insects is high and varies among neighboring individuals. Several plant properties expected to influence phytophagous insect host choice or fitness were measured simultaneously and their contribution to variance in predation examined with multiple regression analysis. Microhabitat, seed pyrrolizidine alkaloid concentration, and parasitoid load on the seed predators are the best predictors of predation intensity; plant size, distance from conspecifics, and infructescence characteristics do not appear to affect predation probabilities. However, predictions of the direction of microhabitat effects were only partially successful, and contrary to expectation, plants with higher seed alkaloid levels experienced greater seed predation; several hypotheses are advanced to account for these results. Higher parasitoid loads are associated with lower predation intensity, probably due in part to interference between lepidopteran larvae and the less voracious hymenopteran seed predators or their parasitoids.


High-speed autoradiography of 3H-thymidine-labelled nuclei.
High-speed autoradiography with stripping film of 3H-thymidine-labelled cells was tested. The tests involved: (a) various times of immersion of emulsion-covered cell preparations in the mixture of dioxane-PPO-POPOP, at 20 degrees C, (b) exposure of cell preparations and blanks for various times at either -70 degrees C or +20 degrees C, with different humidity levels. Autoradiographs of good quality could be produced by 2-min immersion in the scintillator, exposure time greater than or equal to 1 h at either temperature and relative humidity 20--30%. A linear relationship between autoradiographic efficiency and exposure time of 1--7 h was found at either temperature, although the efficiency of autoradiographs exposed at -70 degrees C was by approximately 30% higher than that of autoradiographs exposed at +20 degrees C. Background values of autoradiographs dried with a fan and exposed for 1/4--7 h at either -70 degrees C or +20 degrees C were 0.6--0.8 grain/100 micron2. Theoretical calculations and experimental data showed that high-speed autoradiographs are 30--50 times more efficient as compared with conventional stripping film autoradiographs, thus allowing a shortening of the respective exposure time. Theoretical aspects of efficiency and resolution of high-speed autoradiography are considered.


Harnessing dislocation motion using an electric field.
Dislocation motion, an important mechanism underlying crystal plasticity, is critical for the hardening, processing and application of a wide range of structural and functional materials. For decades, the movement of dislocations has been widely observed in crystalline solids under mechanical loading. However, the goal of manipulating dislocation motion via a non-mechanical field alone remains elusive. Here we present real-time observations of dislocation motion controlled solely by using an external electric field in single-crystalline zinc sulfide-the dislocations can move back and forth depending on the direction of the electric field. We reveal the non-stoichiometric nature of dislocation cores and determine their charge characteristics. Both negatively and positively charged dislocations are directly resolved, and their glide barriers decrease under an electric field, explaining the experimental observations. This study provides direct evidence of dislocation dynamics controlled by a non-mechanical stimulus and opens up the possibility of modulating dislocation-related properties.


A natural feeding experiment on a declining snowshoe hare population.
A snowshoe hare (Lepus americanus) population on a 9-ha area was supplied with extra natural food by chopping down large white spruce (Picea glauca) and aspen (Populus tremuloides) trees throughout 3 winters from 1981 to 1984. Hares fed vigorously on the downed trees, but the phase of decline of the ten-year cycle occurred equally on control and experimental grids from 1981-1983, and we could detect no improvement in survival or reproduction on the food area. Growth rates were improved on the food grid during the first winter of the decline (1981-82). We concluded that food shortage is not necessary for the cyclic decline of snowshoe hares in the southern Yukon.


Educating teachers of nursing: a survey of the opinions of students.
In this paper an account of an opinion survey is reported, which was carried out in order to determine how student teachers of nursing rated aspects of their course. The opinion survey included questions on pedagogical and education studies, teaching practice, research methods, statistics, related science and supporting studies. In the last section the method of course assessment is evaluated. Finally there is a discussion about the implications and limitations of the survey.


Evaluation of the Efficacy of Titanium Mesh Cages with Posterior C1 Lateral Mass and C2 Pedicle Screw Fixation in Patients with Atlantoaxial Instability.
Atlantoaxial fusion is a surgical technique that is performed for the treatment of atlantoaxial instability. The standard surgical procedure is fixation of the atlantoaxial complex via a C1 lateral mass and C2 pedicle screw with posterior wiring. Bone grafting material may still be biomechanically suboptimal, such as autologous bone obtained from osteoporotic patients, and may result in collapse and loosening of posterior wiring. Fourteen patients with C1 lateral mass and C2 pedicle fixation as a result of atlantoaxial instability were included in this study. All patients were treated by a single surgeon using a titanium mesh cage with demineralized bone matrix packing. Patient clinical history, imaging data, and medical records were reviewed. To evaluate bony fusion, measurement of the atlantodental interval and computed tomography were performed in the preoperative period, immediate postoperative period, and at 1, 3, 6, and 12 months postoperatively. The Wilcoxon signed-rank test was used to compare differences in the radiologic evaluation at 1 and 12 months postoperatively. Bone fusion was achieved in all patients (100%). Of the 14 patients, 11 had rheumatoid arthritis and 3 had trauma. The mean atlantodental interval of patients with rheumatoid arthritis was 1.85 mm in the immediate postoperative period, 1.96 mm at 1 month postoperatively, 1.98 mm at 3 months postoperatively, 1.96 mm at 6 months, and 1.93 mm at 12 months. Hardware failure and other complications were not observed. The titanium mesh cage has several advantages compared with bone autografts, including reduced donor-site morbidity, immediate rigid fixation, and successful bone fusion.