Effectiveness of Carolina rinse solution after cold ischemic storage of rat livers: biochemical and histological analysis using perfusion model.
Using a rat liver perfusion model, the effectiveness of Carolina rinse solution was assessed for the prevention of reperfusion injury after 48 h of cold storage in UW solution. Transaminase levels (GOT, GPT and LDH) of the perfusate were significantly higher in the Ringer group (17 +/- 8, 17 +/- 9 and 191 +/- 97 IU/l, respectively) than in the Carolina group (6 +/- 4, 5 +/- 4 and 21 +/- 20 IU/l) (p < 0.05). The levels of oxygen consumption were also higher in the Carolina group (233 +/- 54 mm Hg) than in the Ringer group (164 +/- 58 mm Hg) (p < 0.05). Histological examination showed severe parenchymal cell damage in the Ringer group, whereas the damage was slight in the Carolina group. Two newly developed monoclonal antibodies, REC16-11 and REC4-1, which specifically react with rat endothelial cells, were used for immunohistochemical studies of the livers. The endothelial cells of central vein and sinusoids were more severely damaged in the Ringer group than in the Carolina group. The present study suggests that Carolina rinse solution is useful for prevention of liver damage from reperfusion injury after cold storage of the graft for organ transplantation.


[Actinobacillus actinomycetemcomitans endocarditis].
Bacterial endocarditis caused by Actinobacillus actinomycetemcomitans (AA) is an extremely rare disease. AA, a gram negative cocco-bacillus, normally resides in the oral cavity. It is involved mostly in local oral cavity infections, but severe systemic infections caused by it have been reported. We describe a 63-year-old man with endocarditis caused by AA which probably originated from a dental abscess. The course of the disease was complicated by acute myocardial ischemia, apparently caused by coronary artery embolism. To enable growth of this bacterium, blood cultures should be maintained for 2-3 weeks in a CO2-rich atmosphere.


Life in a rock pool: Radiation and population genetics of myxozoan parasites in hosts inhabiting restricted spaces.
Intertidal rock pools where fish and invertebrates are in constant close contact due to limited space and water level fluctuations represent ideal conditions to promote life cycles in parasites using these two alternate hosts and to study speciation processes that could contribute to understanding the roles of parasitic species in such ecosystems. Gall bladder and liver samples from five clinid fish species (Blenniiformes: Clinidae) were morphologically and molecularly examined to determine the diversity, prevalence, distribution and host specificity of Ceratomyxa parasites (Cnidaria: Myxozoa) in intertidal habitats along the coast of South Africa. Phylogenetic relationships of clinid ceratomyxids based on the SSU rDNA, LSU rDNA and ITS regions were assessed additionally to the investigation of population genetic structure of Ceratomyxa cottoidii and subsequent comparison with the data known from type fish host Clinus cottoides. Seven Ceratomyxa species including previously described Ceratomyxa dehoopi and C. cottoidii were recognized in clinids. They represent a diverse group of rapidly evolving, closely related species with a remarkably high prevalence in their hosts, little host specificity and frequent concurrent infections, most probably as a result of parasite radiation after multiple speciation events triggered by limited host dispersal within restricted spaces. C. cottoidii represents the most common clinid parasite with a population structure characterized by young expanding populations in the south west and south east coast and by older populations in equilibrium on the west coast of its distribution. Parasite and fish host population structures show overlapping patterns and are very likely affected by similar oceanographic barriers possibly due to reduced host dispersal enhancing parasite community differentiation. While fish host specificity had little impact on parasite population structure, the habitat preference of the alternate invertebrate host as well as tidal water exchange may be additional crucial variables affecting the dispersal and associated population structure of C. cottoidii.


[Characterization of Wood Surface Treated with Electroless Copper Plating by Near Infrared Spectroscopy Technology].
Wood electromagnetic shielding material, which was made by treating wood with electroless plating, not only keep the superior characteristics of wood, but also improve the conductivity, thermal conductivity and electromagnetic shielding properties of wood. The emergence of this material opens the way to the value-added exploitation of wood and widens the processing and application field for the electromagnetic shielding material. In order to explore the feasibility of using NIR technology to investigate the properties of wood electromagnetic shielding material, this study analysis the samples before and after copper plated process by the NIR spectroscopy coupled with principal component analysis (PCA). The results showed that (1) there exist significant differences between samples before and after copper plated process both on the spectral shape and absorption, and the great differences can also be seen in the samples with different treat time, especially for the samples with 5 min treat time; (2) after PCA analysis, six clusters from the samples before and after copper plated process were separately distributed in the score plot, and the properties of untreated wood and sensitized wood were similar, and the properties of samples for 25 and 40 min treat time were also similar in order that these samples were close to each other, all of which might suggest that the NIR spectroscopy reflected major feature information about material treatment; (3) After comparing the PCA performance between NIR and visible spectral region, it could be found that the classification performance of samples before and after copper plated process based on the NIR region were better than that based on the visible region, and the information of color on the surface of samples were preferably reflected in the visible region, which could indicate that there are more information about samples' surface characters using the visible spectroscopy coupled with NIR spectroscopy and it is feasible to use visible-NIR technology to investigate the surface characteristics of natural polymers treated with electroless copper plating.


[Treatment of acute coronary syndrome in older adults and high-risk patients."When the going gets tough…"].
The increasing life expectancy in older adults and the better survival of patients with multiple pathologies require the capability to treat complex clinical conditions with an increased risk of iatrogenic complications. Nevertheless, recent improvements in the pharmacological and interventional treatment of acute coronary syndrome (ACS) have promoted a shift from therapeutic nihilism to a more active management of complex ACS cases. Despite the paucity of specific randomized clinical trials, observational studies seem to show benefit of an early invasive treatment in these patients. This approach requires close cooperation of clinical intensivists, interventional cardiologists and cardiovascular surgeons either in a specialized heart center or in a network of hospitals.


Increasing the use of home medication lists in an outpatient neurorehabilitation clinic.
Medication reconciliation in ambulatory care settings helps prevent adverse drug events. Patient involvement in the process is crucial, as clinicians must verify the reported medication history with other sources such as home medication lists or brown-bagged home medications provided by patients. However, only 47.8% of brain injury and stroke adult outpatients at Toronto Rehabilitation Institute, an academic rehabilitation hospital, bring their medications/medication lists to clinic visits. In turn, missing medication information impacts the clinic by causing delays in treatment and interrupted clinic flow. This project aimed to increase the percentage of patients who bring their medications/medication lists to 80% and decrease the impact on clinic visits caused by missing medication information to 10%. This was a controlled before-after study, with the outpatient rehabilitation assessment (OPRA) clinic as the intervention and the spasticity clinic as the control. The model for improvement was used as the project framework. Process mapping, Ishikawa diagrams, driver diagrams and patient surveys generated the change ideas. Verbal reminders during confirmation phone calls, written reminders and medication list templates were implemented. Data were collected on a biweekly basis and analysed using statistical control charts. After six Plan-Do-Study-Act cycles conducted over 49 weeks, both project aims were achieved. The percentage of OPRA clinic patients who brought medications/medication lists was 81.8% and the impact on clinic visits caused by missing medication information was 9.1% of clinic visits. Special cause variation was detected on the statistical control charts. Conversely, there was no special cause variation for the spasticity clinic (the control) for either aim. Lessons learnt include the importance of prolonged data collection when implementing interventions with long lag time, and that verbal reminders may not be effective for patients with cognitive impairments. Future efforts may focus on implementing the bundle of project interventions for the spasticity clinic.


Characterization of fluorescent sterol binding to purified human NPC1.
Mutations in the NPC1 gene cause Niemann-Pick type C disease, which appears to result from a defect in intracellular cholesterol trafficking. NPC1 is a member of the resistance-nodulation-cell division (RND) permease superfamily and contains a sterol-sensing domain, yet its cellular function and the identity of its substrates remain unknown. FLAG-tagged human NPC1 was purified from NPC1-expressing Chinese hamster ovary cells by solubilization in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), followed by affinity chromatography. Purified NPC1 in detergent solution appeared to be oligomeric as determined by gel filtration fast protein liquid chromatography and was photolabeled by an azido-cholesterol derivative. Fluorescent cholesterol analogs, including dehydroergosterol, cholestatrienol, and 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (NBD-cholesterol), displayed enhanced fluorescence upon binding to NPC1 and also resulted in saturable, concentration-dependent quenching of NPC1 intrinsic Trp fluorescence. The apparent binding affinity for these three sterols was in the 0.5-6 microm range. Binding of NBD-cholesterol to NPC1 at low detergent concentration (2 mm CHAPS) was of high apparent affinity (0.5-0.6 microm) and occurred rapidly (<1 min). However, binding of a BODIPY-labeled cholesterol derivative was very slow, requiring approximately 3 h to reach equilibrium. The apparent NBD-cholesterol binding affinity was greatly reduced at higher detergent concentration. The stoichiometry of NBD-cholesterol binding to NPC1 was approximately 1. Various sterols, including native cholesterol and 25-hydroxycholesterol, inhibited NBD-cholesterol binding, suggesting that they compete for binding to the protein. Dynamic quenching studies showed that bound NBD-cholesterol was almost completely shielded from the aqueous medium, suggesting that it is buried in a deep hydrophobic pocket in NPC1. The use of fluorescent cholesterol analogs provides novel information on the molecular properties of the sterol-binding site in the full-length NPC1 protein.


Validity of the CR-POSSUM model in surgery for colorectal cancer in Spain (CCR-CARESS study) and comparison with other models to predict operative mortality.
To validate and recalibrate the CR- POSSUM model and compared its discriminatory capacity with other European models such as POSSUM, P-POSSUM, AFC or IRCS to predict operative mortality in surgery for colorectal cancer. Prospective multicenter cohort study from 22 hospitals in Spain. We included patients undergoing planned or urgent surgery for primary invasive colorectal cancers between June 2010 and December 2012 (N = 2749). Clinical data were gathered through medical chart review. We validated and recalibrated the predictive models using logistic regression techniques. To calculate the discriminatory power of each model, we estimated the areas under the curve - AUC (95% CI). We also assessed the calibration of the models by applying the Hosmer-Lemeshow test. In-hospital mortality was 1.5% and 30-day mortality, 1.7%. In the validation process, the discriminatory power of the CR-POSSUM for predicting in-hospital mortality was 73.6%. However, in the recalibration process, the AUCs improved slightly: the CR-POSSUM reached 75.5% (95% CI: 67.3-83.7). The discriminatory power of the CR-POSSUM for predicting 30-day mortality was 74.2% (95% CI: 67.1-81.2) after recalibration; among the other models the POSSUM had the greatest discriminatory power, with an AUC of 77.0% (95% CI: 68.9-85.2). The Hosmer-Lemeshow test showed good fit for all the recalibrated models. The CR-POSSUM and the other models showed moderate capacity to discriminate the risk of operative mortality in our context, where the actual operative mortality is low. Nevertheless the IRCS might better predict in-hospital mortality, with fewer variables, while the CR-POSSUM could be slightly better for predicting 30-day mortality. Registered at: ClinicalTrials.gov Identifier: NCT02488161.


To defend or to grow: lessons from Arabidopsis C24.
The emergence of Arabidopsis as a model species and the availability of genetic and genomic resources have resulted in the identification and detailed characterization of abiotic stress signalling pathways. However, this has led only to limited success in engineering abiotic stress tolerance in crops. This is because there needs to be a deeper understanding of how to combine resistances to a range of stresses with growth and productivity. The natural variation and genomic resources of Arabidopsis thaliana (Arabidopsis) are a great asset to understand the mechanisms of multiple stress tolerances. One natural variant in Arabidopsis is the accession C24, and here we provide an overview of the increasing research interest in this accession. C24 is highlighted as a source of tolerance for multiple abiotic and biotic stresses, and a key accession to understand the basis of basal immunity to infection, high water use efficiency, and water productivity. Multiple biochemical, physiological, and phenological mechanisms have been attributed to these traits in C24, and none of them constrains productivity. Based on the uniqueness of C24, we postulate that the use of variation derived from natural selection in undomesticated species provides opportunities to better understand how complex environmental stress tolerances and resource use efficiency are co-ordinated.


Benign ectopic submandibular thyroid with a normotopic multinodular goitre.
Ectopic submandibular thyroid tissue is a rare entity and poses difficult diagnostic and management problems. The first case of ectopic submandibular thyroid with a normotopic multinodular goitre is presented


Quality Improvement Project to Reduce Drug-Related Problems (DRPs) and Potentially Inappropriate Medications (PIMs) in Geriatrics Cardiac Clinic in Saudi Arabia.
Elderly people have a high risk of potentially inappropriate medications (PIMs) and drug-related problems (DRPs) due to polypharmacy, physical and mental limitations, pharmacokinetic, and pharmacodynamics changes. To determine the role of geriatric pharmacists in reducing drug-related problems and potentially inappropriate medication. The observational study was conducted from October 2014 to October 2017 to show the prevalence of DRPs, and PIMs. A total of 375 geriatric cardiology patients (aged ≥ 65) were recruited from Geriatrics Cardiac Clinic in Saudi Arabia. AGS Beers Criteria 2012 and STOPP/START Criteria were used to view the impact of services directed by clinical pharmacists in decreasing DRPs and PIMs including medication review, intervention, and education to junior physicians during multi-disciplinary rounds (MDRs) and by sending e-mail alerts. DRPs were found in 29.6% of patients and PIMs were found in 19% of patients. After medication review, 25% required interventions and the majority (89%) of interventions were accepted by the managing team. DRPs were found in 14.9% of patients and PIMs were found in 9.6% of the patients. DRPs and PIMs were reduced almost by 50% by reviewing the files and educating the involved physicians. This prospective study confirms a high prevalence of DRPs and PIMs in Saudi elderly cardiac patients.


Evaluation of chemical-physical properties and cytocompatibility of TheraCal LC.
TheraCal LC (TLC, Bisco Inc., Schaumburg, IL, USA) is a light-cured, resin-modified, calcium silicate-filled base/liner material designed for direct and indirect pulp-capping. In this study the result of the evaluation in vitro of the biocompatibility and chemical-physical properties of TLC are reported. TLC specimens were prepared under aseptic conditions in strict compliance with the manufacturer's instructions and sterilized. Osteoblast-like cells (MG63) were used. For different time points, solubility, water uptake, alkalinizing activity and cytotoxicity were evaluated. In ddH20 and in DMEM+FBS, TLC showed a loss of material increasing simultaneously with the absorption capacity. The increase of water uptake of the material promoting the solubilization of mineral ions in medium is a requisite for a bioactive material. The alkalinizing activity is correlated to antimicrobial/bacteriostatic activity and to the ability to favor the formation of apatite deposits. The pH values for water absorption after immersion of the disks ranged between 8 and 9 at each times of evaluation. Cytotoxicity was not observed in MG63 cells treated with TLC and after 5 days, the cells were organized to form a confluent monolayer as demonstrated by fluorescence microscopy observation. TLC showed biocompatibility on MG63 cells allowing a physiologic cell growth and differentiation. The chemical-physical properties and biocompatibility of TLC observed in vitro in the present study, allows considering this cement as an innovative pulp-capping material for the vital pulp therapy.


Home care as a complex experience: a chronological case study.
This case study of an older woman with macular degeneration describes her experience of dispensing daily medications over a 3-year period, during which a home care nurse began and continued visits. Using a phenomenological method, I analyzed data of 9 interviews, discerning the structure of her experience and depicting it in 7 diagrams. The home care experience can have unintended outcomes influenced by family and provider perceptions of clients' abilities, especially when family members and practitioners assume tasks that older women have managed alone. Minimizing intergenerational ambivalence about the need for home care and maximizing client agency should be preeminent foci of home care providers.


[Therapeutic Potential of Targeting Cancer-Associated Fibroblasts in Esophageal Cancer].
Advances in molecular and cellular biochemistry, such as the development of targeted cancer therapy, have dramatically improved the prognosis of cancer patients. Emerging data have suggested that bevacizumab treatment may act by controlling the cancer microenvironment. Many reports have examined the interaction of cancer cells with the tumor microenvironment, and cancer-associated fibroblasts (CAFs) are thought to play a central role in this process. We speculated that the cancer microenvironment and in particular, CAFs, strongly influence the development of esophageal cancer. We have analyzed the signaling pathways of molecular targets. However, inhibition of a single signaling pathway is insufficient to treat cancer effectively. Photoimmunotherapy is a molecular-targeted specific cancer therapy using near-infrared radiation, which was introduced by Mitsunaga et al. in 2011. We are using its specific method of killing cells to target CAFs. We will report the results of its effect on cancer cells in the future.


Three-year safety and two-year effectiveness of etanercept in patients with rheumatoid arthritis in Japan: Results of long-term postmarketing surveillance.
Objectives: To evaluate the real-world safety and effectiveness of etanercept (ETN) in Japanese patients with rheumatoid arthritis. Methods: This postmarketing surveillance study (NCT00503139) assessed the safety and effectiveness of ETN treatment over 3 and 2 years (from June 2007 to September 2011), respectively. Safety was evaluated by occurrence and seriousness of adverse drug reactions (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (ESR) with four variables (swollen and tender joint counts, ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered effective if patients had a good/moderate response by the European League Against Rheumatism response criteria. Results: ADRs occurred in 256/675 (37.9%) patients, the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%). Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100 patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two percent of patients achieved a moderate/good response at 2 years. Conclusion: Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.


Small-animal PET of steroid hormone receptors predicts tumor response to endocrine therapy using a preclinical model of breast cancer.
Estrogen receptor-α (ERα) and progesterone receptor (PR) are expressed in most human breast cancers and are important predictive factors for directing therapy. Because of de novo and acquired resistance to endocrine therapy, there remains a need to identify which ERα-positive (ERα(+))/PR-positive (PR(+)) tumors are most likely to respond. The purpose of this study was to use estrogen- and progestin-based radiopharmaceuticals to image ERα and PR in mouse mammary tumors at baseline and after hormonal therapy and to determine whether changes in these imaging biomarkers can serve as an early predictive indicator of therapeutic response. Mammary adenocarcinomas that spontaneously develop in aged female mice deficient in signal transducer and activator of transcription-1 (STAT1) were used. Imaging of ERα and PR in primary tumor-bearing mice and mice implanted with mammary cell lines (SSM1, SSM2, and SSM3) derived from primary STAT1-deficient (STAT1(-/-)) tumors was performed. Hormonal treatments consisted of estradiol, an ER agonist; letrozole, an aromatase inhibitor; and fulvestrant, a pure ER antagonist. Small-animal PET/CT was performed using (18)F-fluoroestradiol ((18)F-FES) for ER, (18)F-fluoro furanyl norprogesterone ((18)F-FFNP) for PR, and (18)F-FDG for glucose uptake. Tracer uptake in the tumor was quantified and compared with receptor concentration determined by in vitro assays of resected tumors. Primary STAT1(-/-) mammary tumors and implanted SSM2 and SSM3 tumors showed high (18)F-FES and (18)F-FFNP uptake and were confirmed to be ERα(+)/PR(+). Classic estrogen-induced regulation of the progesterone receptor gene was demonstrated by increased (18)F-FFNP uptake of estradiol-treated SSM3 tumors. Treatment with fulvestrant decreased (18)F-FFNP, (18)F-FES, and (18)F-FDG uptake and inhibited growth of SSM3 tumors but decreased only (18)F-FES uptake in SSM2 tumors, with no effect on growth, despite both tumors being ERα(+)/PR(+). Decreased (18)F-FFNP uptake by SSM3 tumors occurred early after initiation of treatment, before measurable tumor growth inhibition. Using small-animal PET, a profile was identified that distinguished fulvestrant-sensitive from fulvestrant-resistant ERα(+)/PR(+) tumors before changes in tumor size. This work demonstrates that imaging baseline tumoral (18)F-FES uptake and initial changes in (18)F-FFNP uptake in a noninvasive manner is a potentially useful strategy to identify responders and nonresponders to endocrine therapy at an early stage.


Role of T channels in cardiovascular function.
Although two types of Ca2+ channels are found to occur in the cardiovascular system, very little is known about one of them, primarily because a pharmacological blocking agent has been lacking. The enigmatic transient (T)-type Ca2+ channel has finally been recognized by a selective Ca2+ antagonist. The novel tetralol Ca2+ antagonist, mibefradil, is a selective T-type Ca2+ channel blocker that produces effective vasodilatation with additional inhibitory actions on blood vessel wall and left ventricular thickening. The availability of a blocking agent has begun to reveal the significance of T-type Ca2+ channel signals. Selective T-type Ca2+ channel blockade characteristics include vascular selectivity, freedom from negative cardiac inotropism, consistent and predictable reduction in heart rate, reduction in subendothelial proliferation, and increased survival of severely hypertensive and heart failure animal models. Mibefradil increases coronary blood flow without increasing myocardial oxygen consumption, and by decreasing heart rate and thus time spent in diastole, improves subendocardial perfusion. Improved perfusion of the myocardial wall and lowered heart rate appear to normalize the underlying pathophysiological factors, improve heart failure, and provide long-term protection. Thus, T-type Ca2+ channel blockade offers significant new cardiovascular protective benefits, even in the presence of critical pathophysiological elements (i.e. increased heart rate and neurohumors in the presence of decreased ejection fraction and contractility) found in heart failure.


Unrecognized anomalous origin of the left coronary artery from the pulmonary artery as a cause of ventricular fibrillation after patent ductus arteriosus ligation in an infant.
We present a case of an infant who developed ventricular fibrillation after patent ductus arteriosus (PDA) ligation. The infant had unrecognized anomalous origin of the left coronary artery from the pulmonary artery before PDA ligation. Acute reduction in systemic pulmonary artery pressures after PDA ligation resulted in an abrupt reduction in left main coronary artery blood flow. After prompt resuscitation, cardiac catheterization confirmed the diagnosis of anomalous origin of the left coronary artery from the pulmonary artery. The infant subsequently underwent coronary artery translocation and recovered uneventfully.


The association between prenatal environment and children's mental health trajectories from 2 to 14 years.
The prenatal period is recognised as a critical period for later behavioural development. This study aimed to elucidate how an adverse prenatal environment, as defined by the presence of a number of known prenatal risk factors, would influence mental health trajectories in children to 14 years of age. The Raine Study provided comprehensive data from 2,900 pregnancies. Offspring were followed up at ages 2, 5, 8, 10, and 14 years using the Child Behaviour Checklist (CBCL). We used linear mixed regression models with random intercept and slope (random effects models) to examine the extent to which the predictor variables considered influenced changes in continuous CBCL total, internalising, and externalising T scores from ages 2 to 14. In the final multivariate models, increased offspring CBCL T scores were significantly predicted by the mother not finishing high school, smoking during pregnancy, having a total family income below the poverty line, being diagnosed with gestational hypertension and experiencing stressful life events during pregnancy. Conversely, as maternal age increased, CBCL T scores were significantly decreased. Child age also significantly interacted with maternal education, total family income, and maternal stressful life events, such that these variables predicted increases in CBCL scores from age 2 to age 10, and from age 2 to age 14 years. In the Raine Study sample, children who experienced adverse prenatal environments experienced increased levels of problem behaviours in childhood, and more problematic mental health trajectories. Maternal health risk behaviours and other psychosocial variables more commonly affected child behaviour than obstetric complications.


An integrated view of precambrian eumetazoan evolution.
The eumetazoan clade of modern animals includes cnidarians, acoels, deuterostomes, and protostomes. Stem group eumetazoans evolved in the late Neoproterozoic, possibly before the Marinoan glaciation, according to a variety of different kinds of evidence. Here, we combine this evidence, including paleontological observations, results from molecular and morphological phylogeny, and paleoecological considerations, with deductions from the organization of the gene regulatory networks that underlie development of the bilaterian body plan. Eumetazoan body parts are morphologically complex in detail, and modern knowledge of gene regulatory network structure shows that the control circuitry required for their development is hierarchical and multilayered. Among the consequences is that the kernels of the networks that control the early allocation of spatial developmental fate canalize the possibilities of downstream evolutionary change, a mechanism that can account for the appearance of distinct clades in early animal evolution. We reconstruct preeumetazoan network organization and consider the process by which the eumetazoan regulatory apparatus might have been assembled. A strong conclusion is that the evolutionary process generating the genomic programs responsible for developmental formulation of basic eumetazoan body plans was in many ways very different from the evolutionary changes that can be observed at the species level in modern animals.


The strength of B cell immunity in female rhesus macaques is controlled by CD8+ T cells under the influence of ovarian steroid hormones.
To understand more clearly how mucosal and systemic immunity is regulated by ovarian steroid hormones during the menstrual cycle, we evaluated the frequency of immunoglobulin- and antibody-secreting cells (ISC, AbSC) in genital tract and systemic lymphoid tissues of normal cycling female rhesus macaques. The frequency of ISC and AbSC was significantly higher in tissues collected from animals in the periovulatory period of the menstrual cycle than in tissues collected from animals at other stages of the cycle. The observed changes were not due to changes in the relative frequency of lymphocyte subsets and B cells in tissues, as these did not change during the menstrual cycle. In vitro, progesterone had a dose-dependent inhibitory effect, and oestrogen had a dose-dependent stimulatory effect on the frequency of ISC in peripheral blood mononuclear cell (PBMC) cultures. The in vitro effect of progesterone and oestrogen on ISC frequency could not be produced by incubating enriched B cells alone with hormone, but required the presence of CD8+ T cells. Following oestrogen stimulation, a CD8+ enriched cell population expressed high levels of IFN-gamma and IL-12. The changes in B cell Ig secretory activity that we document in the tissues of female rhesus macaques during the menstrual cycle is due apparently to the action of ovarian steroid hormones on CD8+ T cells. Thus, CD8+ T cells control B cell secretory activity in both mucosal and systemic immune compartments. Understanding, and eventually manipulating, the CD8+ regulatory cell-B cell interactions in females may produce novel therapeutic approaches for autoimmune diseases and new vaccine strategies to prevent sexually transmitted diseases.


Anesthesia for bronchoscopic laser surgery.
Choice of anesthesia for bronchoscopic laser surgery depends on the surgical technique. Fiberoptic bronchoscopy can be managed with either topical or general anesthesia, while rigid bronchoscopy usually requires general anesthesia. In either case precautions for laser surgery must be taken. Preoperative evaluations should include cardiovascular status and the anatomy of the lesion. Preoperative medication should include an anticholinergic agent. The influence of total intravenous vs. inhaled anesthetics on prolonged respiratory depression is discussed, and the techniques for providing controlled vs. spontaneous respiration are described. Finally, postoperative care, including the management of airway obstruction and hemorrhage, is outlined.


Sofosbuvir initial therapy abandonment and manufacturer coupons in a commercially insured population.
To describe rates of sofosbuvir initial medication adherence as a function of the insurer-required member cost (ie, out-of-pocket cost) and to determine how manufacturer coupons affect insurer-required member cost. Observational cross-sectional analysis. Administrative pharmacy claims data from 13 million commercially insured members were used to identify sofosbuvir new starts between January 2014 and September 2014. Members were categorized as either sofosbuvir initial adherence or as abandoning therapy. A multivariate logistic regression model adjusting for sociodemographic characteristics, severity of illness, and total drug costs (health insurer plus member amount) for non-sofosbuvir pharmacy claims in 2014 was used to evaluate the association between insurer-required member cost and initial medication adherence. In a sub-analysis, sofosbuvir index claims with coupon data available were analyzed to determine how coupon use impacted insurer-required member cost. A total of 67.3% of members had a pre-coupon member cost of < $250 for their index sofosbuvir claim. Just 201 (5.0%) members were exposed to a member cost of more than $10,000. The logistic regression model demonstrated an association between member cost and abandonment starting at $2500 to < $5000 (odds ratio: 1.9; 95% CI, 1.01-3.43; P = .0393). The average member sofosbuvir index claim cost was $1349 before coupon was applied, and $28 after. Overall, coupons offset the member amounts paid by 98%: $771,593 of the $787,860 member cost requested by the insurer. These findings indicate that a 30-day supply sofosbuvir member cost of > $2500 was associated with increased initial therapy abandonment, and that manufacturer coupons substantially reduced sofosbuvir insurer-required member cost. Insurers and policy makers should consider the impact of member cost on medication adherence and the impact coupons have on the actual member cost.


Time- and dose-dependent inhibition of neutrophil extracellular trap formation by blocking of the interleukin-1 receptor.
Besides performing phagocytosis and degranulation, neutrophils are capable of eliminating microorganisms by releasing neutrophil extracellular traps (NETs). NET formation was found to be associated with increased mortality in sepsis. During sepsis levels of interleukin 1β (IL-1β), a cytokine, increases significantly and also was associated with increased mortality. Blocking of the interleukin 1 (IL-1) receptor by anakinra leads to less NET formation in gout patients. However, NET formation is crucial during infection by trapping pathogens and thereby slowing the process. Total or early blocking of cascades leading to NETs may lead to aggravation of infection in otherwise mild cases. The dose- and time-dependent effect of the IL-1 receptor antagonist anakinra was tested on spontaneous, lipopolysaccharide (LPS)-induced and phorbol-12-myristate 13-acetate (PMA)-induced formation of NETs in vitro. Quantitative detection of NETs was performed for NETspecific proteins and cell-free DNA. Immunostained microscopy imaging was used for visualization. Our study shows a dose- and time-dependent inhibitory effect of anakinra that involves the change of intracellular calcium mobilization on the formation of NETs in vitro for PMA-stimulated neutrophils but not for LPS-stimulated neutrophils. It may be useful for treatment of sepsis as part of a multimodal treatment concept, but it seems that timing and dose need to be carefully chosen.


Correlation between patterns of antral contractility and gastric emptying of radiopaque markers.
Gastric clearance of radiopaque markers (ROMs) has been proposed as an easy and noninvasive technique for assessment of gastric emptying. This study was conducted to evaluate the role of antral obliterating contractions in gastric emptying of ROMs in healthy volunteers. Fifteen healthy volunteers, 12 males and three females, aged 21-38 yr, were enrolled in this study. Simultaneous recording of scintigraphic solid phase gastric emptying, gastric clearance of ROMs, and gastric manometry were performed after an overnight fast. The data of scintigraphic solid phase gastric emptying were expressed by half-emptying time (t1/2). The ROMs remaining in the stomach were counted fluoroscopically 2.5 and 4.5 h after the test meal. The time for the appearance of antral obliterating contractions after the meal was calculated. Six subjects (40%) passed all 10 ROMs after 4.5 h of recording. Among these six subjects, five had antral obliterating contractions 190-251 min (mean 232.2 +/- 24.3 min) after the test meal. There was no significant difference in t1/2 between subjects with or without antral obliterating contractions within the 4.5 h of recording. There was a considerable intersubject variation in the time of first antral obliterating contraction after the test meal. In the healthy volunteers, all ROMs were passed when there was a postprandial antral obliterating contraction. However, some of the ROMs still passed from the stomach in the absence of antral obliterating contractions.


Feigned intellectual deficits on the Wechsler Adult Intelligence Scale-Revised.
To examine whether individuals instructed to fake intellectual impairment on the WAIS-R employed common faking tactics and to assess the accuracy of detection of faking tactics employed. Two groups of participants were instructed to fake 'mental handicap' on the WAIS-R. The first group included incarcerated young offenders and the second group included postgraduate students and research fellows from a university psychology department. Both groups produced faked mean IQ scores within the 'mental retardation' range. There were, however, unusual features in the answers of both groups, including unusual error types. The faking tactics employed were readily detected. The results suggest that an individual's WAIS-R performance should be interpreted with due consideration given to both the quantitative and the qualitative aspects of their presentation.


Physiological and life history changes associated with seasonal adaptation in the cactophilic Drosophila mojavensis.
Many insects inhabiting temperate climates are faced with changing environmental conditions throughout the year. Depending on the species, these environmental fluctuations can be experienced within a single generation or across multiple generations. Strategies for dealing with these seasonal changes vary across populations. Drosophila mojavensis is a cactophilic Drosophila species endemic to the Sonoran Desert. The Sonoran Desert regularly reaches temperatures of 50°C in the summer months. As individuals of this population are rare to collect in the summer months, we simulated the cycling temperatures experienced by D. mojavensis in the Sonoran Desert from April to July (four generations) in a temperature- and light-controlled chamber, to understand the physiological and life history changes that allow this population to withstand these conditions. In contrast to our hypothesis of a summer aestivation, we found that D. mojavensis continue to reproduce during the summer months, albeit with lower viability, but the adult survivorship of the population is highly reduced during this period. As expected, stress resistance increased during the summer months in both the adult and the larval stages. This study examines several strategies for withstanding the Sonoran Desert summer conditions which may be informative in the study of other desert endemic species.


Nasal Symptom Questionnaire: Our Proposed Scoring System and Prognostic Factors in Chronic Rhinosinusitis.
We aimed to verify the usefulness of our proposed nasal symptom questionnaire (NSQ) scoring system and to determine predictors linked to the improvement in nasal symptoms in chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). Ninety-one CRS patients undergoing ESS and 144 volunteers with results of NSQ available were enrolled. The NSQ consists of 10 items. Receiver-operating-characteristic (ROC) curve, area under the ROC curve (AUC), internal consistency, and test-retest reproducibility of the NSQ were analyzed. The relationship of the NSQ score with the visual analogue scale (VAS) was examined. After classifying into two groups, i.e., (i) "improvement group" and (ii) "no-improvement group," factors linked to the improvement in NSQ after ESS were investigated. ROC-AUC (0.9318), the Cronbach α coefficient (0.8696), and the test-retest coefficient (0.8131) showed high reliability. NSQ score significantly correlated with VAS in both pre- (p < 0.0001, rs = 0.6007) and postoperative stages (p < 0.0001, rs = 0.5975). The postoperative NSQ scores significantly decreased compared with baseline levels (p < 0.0001). In multivariate analysis, the computed tomography (CT) score by the Lund-Mackay scoring system revealed to be significant (p = 0.0481). Our proposed NSQ scoring system was well verified. The CT score can be helpful for predicting the improvement in nasal symptoms after ESS in CRS patients.


Variant specific antigens of Trypanosoma brucei exist in solution as glycoprotein dimers.
Purified variant specific antigens of Trypanosoma brucei were shown to exist in solution as dimers, and occasionally as higher oligomers, as judged by gel filtration and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis after treatment with bifunctional cross-linking reagents.


Real-time simulation of the transplanted tooth using model order reduction.
The biomechanics of transplanted teeth remain poorly understood due to a lack of models. In this context, finite element (FE) analysis has been used to evaluate the influence of occlusal morphology and root form on the biomechanical behavior of the transplanted tooth, but the construction of a FE model is extremely time-consuming. Model order reduction (MOR) techniques have been used in the medical field to reduce computing time, and the present study aimed to develop a reduced model of a transplanted tooth using the higher-order proper generalized decomposition method. The FE model of a previous study was used to learn von Mises root stress, and axial and lateral forces were used to simulate different occlusions between 75 and 175N. The error of the reduced model varied between 0.1% and 5.9% according to the subdomain, and was the highest for the highest lateral forces. The time for the FE simulation varied between 2.3 and 7.2 h. In comparison, the reduced model was built in 17s and interpolation of new results took approximately 2.10-2s. The use of MOR reduced the time for delivering the root stresses by a mean 5.9 h. The biomechanical behavior of a transplanted tooth simulated by FE models was accurately captured with a significant decrease of computing time. Future studies could include using jaw tracking devices for clinical use and the development of more realistic real-time simulations of tooth autotransplantation surgery.


[Mechanism of Jiawei Huangqin decoction for treating ulcerative colitis in mice: the role of STAT3/NF-kB/IL-6 pathway].
To investigate the therapeutic effect of Jiawei Huangqin (JWHQ) decoction on ulcerative colitis (UC) and the regulation of STAT3/NF-kB/IL-6 pathway. Forty-eight mice were randomized into blank control group, model group, positive control (Sulfasalazine) group, and low-, moderate- and high-dose JWHQ Decoction groups (n=8). In all but the blank control groups, the mice were given 3% DSS in drinking water to induce UC, followed 7 days later by treatment with saline (blank control and model groups) or JWHQ Decoction by gavage (10 mL/k) for 7 consecutive days. After the treatment, the mice were euthanized and the colon length was measured and the histopathological changes were observed with HE staining. The expression levels of STAT3, NF-κB, and IL-6 in the colon tissues were detected with RT-qPCR and Western blotting. Compared with those in the blank control group, the colon length was significantly shortened and the pathological score of the colon tissue was significantly higher in all the other 5 groups (P < 0.05). Compared with those in the model group, the colon length was significantly longer and the pathological scores were obviously reduced in all the 4 treatment groups (P < 0.05). JWHQ Decoction at the high dose produced significantly better therapeutic effects than the positive drug in terms of the colon length (P < 0.05) and the colon histopathological score (P < 0.05); high-dose JWHQ Decoction also showed better effect than the other two doses (P < 0.05), whose effects were comparable (P > 0.05). The mouse models of UC showed significantly increased expression levels of STAT3, NF-κB, and IL-6 in the colon tissue (P < 0.01), which were obviously lowered by the positive drug and JWHQ Decoction (P < 0.01), especially at the high dose (P < 0.01). JWHQ Decoction at the moderate dose produced similar effects with the positive drug on STAT3, NF-kB and IL-6 levels (P > 0.05), and their effects were stronger than those of low-dose JWHQ Decoction (P < 0.05). JWHQ Decoction can improve UC in mice possibly by down-regulating the expression of STAT3, NF-kB and IL-6 in colonic tissue to affect the STAT3/NF-kB/IL-6 pathway.


Consumer perceptions of dental care in the health services program of an educational institution.
A consumer survey was used to evaluate the University of Massachusetts dental service, a program emphasizing an educational and preventive approach, comprehensive care, and consideration of some prepayment. Attitude and courtesy of staff, explanation of treatment, and the educational approach of the services were favorably assessed by the patients. Those who attended the dental education sessions reported higher levels of satisfaction with the service than those who did not. Mechanisms for financing and the philosophical emphasis on health education seem to have resulted in an extremely successful service.


Mental Distress and Associated Factors Among Hospitalized Medical-Surgical Adult Inpatients in Public Hospitals, Addis Ababa, Ethiopia, 2020: Cross-Sectional Study.
Mental distress is a mental or psychological syndrome which influences the health status, treatment effectiveness, and quality of care of a hospitalized medical-surgical inpatient. It is more common in a hospital setting than in a community setting. Thus, the aim of this study was to assess the prevalence of mental distress and associated factors among hospitalized medical-surgical adult inpatients in public hospitals, Addis Ababa, Ethiopia, 2020. An institutional-based cross-sectional study was conducted among a total of 408 study subjects from March 1 to 30, 2020. The study participants were recruited by systematic random sampling technique and data were collected using an interviewer-administered questionnaire. The collected data were entered into EpiData 3.1 and exported to SPSS version 26 for analysis, and then binary and multiple logistic regressions were performed to check the association between dependent and independent variables. The prevalence of mental distress among hospitalized medical-surgical adult inpatients in public hospitals was 53.1%. Variables of being married [AOR = 2.67; 95% CI (1.065, 6.683)], private employee [AOR = 2.21; 95% CI (1.001, 4.900)], daily laborer [AOR = 4.70; 95% CI (1.218, 18.215)], rural residence [AOR = 1.85; 95% CI (1.047, 3.264)], drinking alcohol [AOR = 1.68; 95% CI (1.025, 2.740)], previous psychiatric illness [AOR = 3.40; 95% CI (1.078, 10.737)] and comorbidity [AOR = 1.93; 95% CI (1.200, 3.094)] were found to be significantly associated with mental distress. The prevalence of mental distress was high and being married, a private employee, daily laborer, living in a rural area, previous history of psychiatric illness, alcohol use, and comorbidity were associated with mental distress among hospitalized adult inpatients. Therefore, healthcare providers should provide special consideration to those groups of patients admitted to the hospital.


[Serum concentration measurements for the monitoring of anti-arrhythmic therapy with lidocaine].
Repeated measurements of lidocaine serum levels during antiarrhythmic treatment were performed by enzyme-immunoassay (EMIT) in 16 patients with acute myocardial infarction. In 12 cases the frequently employed standard dose (100 mg i.v. followed by infusion of 2 mg/min) was not sufficient to reach optimum lidocaine (2-5 mg/l) during the first 2 hours. In this period 6 patients had persistent ectopic beats and required additional bolus injections and increased infusion rates. Lidocaine elimination was delayed in patients with heart failure, which led to potentially toxic drug accumulation in 3 instances. This study indicates the need for individual adaptation of lidocaine dosage in patients with myocardial infarction, especially where left ventricular function is impaired. Monitoring of serum lidocaine levels by a rapid and reliable assay such as the EMIT system may greatly facilitate this task.


The impact of frequent napping and nap practice on sleep-dependent memory in humans.
Napping benefits long-term memory formation and is a tool many individuals use to improve daytime functioning. Despite its potential advantages, approximately 47% of people in the United States eschew napping. The goal of this study was to determine whether people who endorse napping at least once a week (nap+) show differences in nap outcomes, including nap-dependent memory consolidation, compared with people who rarely or never nap (nap-). Additionally, we tested whether four weeks of nap practice or restriction would change sleep and performance profiles. Using a perceptual learning task, we found that napping enhanced performance to a greater degree in nap+ compared with nap- individuals (at baseline). Additionally, performance change was associated with different electrophysiological sleep features in each group. In the nap+ group, spindle density was positively correlated with performance improvement, an effect specific to spindles in the hemisphere contralateral to the trained visual field. In the nap- group, slow oscillatory power (0.5-1 Hz) was correlated with performance. Surprisingly, no changes to performance or brain activity during sleep emerged after four weeks of nap practice or restriction. These results suggest that individual differences may impact the potential benefits of napping on performance and the ability to become a better napper.


Controllable Synthesis of Highly Symmetrical Streamlined Structure for Wideband Microwave Absorption.
Highly symmetrical and streamlined nanostructures possessing unique electron scattering, electron-phonon coupling, and electron confinement characteristics have attracted a lot of attention. However, the controllable synthesis of such a nanostructure with regulated shapes and sizes remains a huge challenge. In this work, a peanut-like MnO@C structure, assembled by two core-shell nanosphere is developed via a facile hydrogen ion concentration regulation strategy. Off-axis electron holography technique, charge reconstruction, and COMSOL Multiphysics simulation jointly reveal the unique electronic distribution and confirm its higher dielectric sensitive ability, which can be used as microwave absorption to deal with currently electromagnetic pollution. The results reveal that the peanut-like core-shell MnO@C exhibits great wideband properties with effective absorption bandwidth of 6.6 GHz, covering 10.8-17.2 GHz band. Inspired by this structure-induced sensitively dielectric behavior, promoting the development of symmetrical and streamlined nanostructure would be attractive for many other promising applications in the future, such as piezoelectric material and supercapacitor and electromagnetic shielding.


An exploratory wastewater analysis study of drug use in Auckland, New Zealand.
New Zealand is considered to have unusual drug use patterns by international standards. However, this understanding has largely been obtained from social surveys where respondents self-report use. The aim of this paper is to conduct the first wastewater study of drug use in Auckland. Wastewater sampling was completed from 2 May to 18 July 2014 at 2 Auckland wastewater treatment plants which service 1.3 million people. Samples were analysed for 17 drug residues by using liquid chromatography-tandem mass spectrometry. Consumption of methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cocaine, codeine and methadone (mg/day/1000 people) was estimated by using a back-calculation formula. Methamphetamine, codeine, morphine and methadone were detected with high frequency (80-100%), followed by amphetamine (~60%), MDMA (~7%, i.e. 8 occasions) and methylone (3 occasions). An overall mean of 360 mg of methamphetamine and 60 mg of MDMA was estimated to have been consumed per day per 1000 people. Methamphetamine consumption was found at similar levels in both catchments (377 and 351 mg/day/1000 people). Cocaine was only detected in 1 catchment and on only 8 occasions. JWH-018 was detected in 1 catchment and only on 1 occasion. Methamphetamine, codeine and other opioids were detected at a consistent level throughout the week. 3,4-Methylenedioxymethamphetamine and methylone were detected only during the weekends. Wastewater analysis confirms that methamphetamine was one of the most commonly detected illegal drugs in Auckland and was detected consistently throughout the week. In contrast, cocaine and MDMA were rarely detected, with detection limited to weekends. [Lai FY, Wilkins C, Thai P, Mueller JF. An exploratory wastewater analysis study of drug use in Auckland, New Zealand. Drug Alcohol Rev 2017;00:000-000].


Effect of dimecron on the blood parameters of Heteropneustes fossilis.
The effects of an organophosphate insecticide. dimecron. has been studied on certain haematological parameters, viz., haemoglobin concentration, RBC number, haematocrit, O2 carrying capacity of blood, etc. of Heteropneustes fossilis following exposures to the LC50 for 24 h and 96 h and 1/10 and 1/50 parts of 96 h LC50 for 90 days. There was a significant decrease in the Hb%, RBC number, HCt% and O2 carrying capcity of blood. But, there was significant increase in the MCH and MCV values following both acute and chronic exposures. The results indicate possible induction of anaemia in the exposed fish.


Factors Associated With Hyperphagic Behavior in Patients With Dementia Living at Home.
To investigate the prevalence and patterns of and factors associated with hyperphagic behavior in Taiwanese patients with dementia living at home. A cross-sectional and correlational design was used. A total of 104 patients with dementia and their primary caregivers were recruited from the geriatric, neurology, and memory clinics of a regional hospital, a medical center and two day-care centers in central Taiwan. The data related to hyperphagic behavior, functional abilities, medical conditions, body weight, and demographic characteristics of patients as well as the demographic characteristics of their primary caregivers were collected between January and May 2013. Based on a strict criterion (a median score of 3 for the hyperphagic subscale), the prevalence of hyperphagia in patients with dementia was 53.8%. Specific hyperphagic patterns exhibited included increased food intake (49% of patients with dementia), hoarding (8.7%), oral exploration (6.8%), and pica (3.9%). Years of education of the patient, the use of antipsychotics in patients, and the age of primary caregivers explained 16.3% of the variance in hyperphagic behavior subscale scores (F = 6.47, p < .001). For the early identification and treatment of hyperphagic behavior in patients with dementia in home care or in clinic services provided by health professionals, specific attention should be paid to the usual eating behaviors of patients with lower levels of education or who are taking antipsychotic medication or those who have a female primary caregiver.


Psychiatric disorder in a rural and an urban population: 3. Social integration and the morphology of affective disorder.
This paper focuses on the morphology of affective disorder. We set out to confirm on the island of Lewis a cross-over result originally found on the island of North Uist, whereby in those sections of the population where the rates of depression were lowest the rates of anxiety were highest. These sections of the population varied in the degree to which their members were integrated into the traditional way of life. 'Integration' was characterized in terms of churchgoing and crofting (the word for farming in the Hebrides). It is predicted here that the churchgoing rather than the crofting component of the integration measure would account for any cross-over result found concerning the morphology of symptoms. This hypothesis, derived from a theoretical concern with links between repression and anxiety, is not confirmed. Instead, crofting is found to be the component of the integration index which predicts anxiety/phobia without depression. In seeking to explain this unexpected finding further significant associations between crofting, pure anxiety/phobia and the style of personal relationships are revealed. It is also confirmed that types of severe events among women are also found to vary with the degree of integration into traditional society. A perspective is then developed which might explain how the interaction between style of personal attachments and types of provoking event could produce variations in the morphology of affective disorder.


Prospectively gated cardiac computed tomography.
A fourth-generation scanner has been modified to perform prospectively gated cardiac computed tomography (CT). A computer program monitors the electrocardiogram (ECG) and predicts when to initiate the next scan in a gated series in order to acquire all projection data for a desired phase of the heart cycle. The system has been tested with dogs and has produced cross-sectional images of all phases of the cardiac cycle. Eight to ten scans per series were sufficient to obtain reproducible images of each transverse section in the end-diastolic and end-systolic phases. The radiation dose to the skin was approximately 1.4 cGy per scan. The prospectively gated system is more than twice as efficient as a retrospectively gated system in obtaining complete angular projection data for a 10% heart cycle window. A temporal smoothing technique to suppress reconstruction artifacts due to sorting inconsistent projection data was developed and evaluated. Image noise was reduced by averaging together any overlapping projection data. Prospectively gated cardiac CT has also been used to demonstrate that the error in attenuation measured with a single nongated CT scan through the heart can be as large as 50-60 CT numbers outside the heart in the lung field.


[A Case of Amusia Following Right Temporal Subcortical Hemorrhage].
A woman in her 60s presented with amusia due to a localized subcortical hemorrhage of the right temporal lobe. No other symptoms of higher brain dysfunction or body paralysis were observed. One characteristic symptom in this case was rhythm impairment. Few cases of this impairment have been previously reported, and the responsible lesion and underlying mechanisms are still a matter of speculation. However, in this case, a relationship with the right temporal lobe was indicated.


Recurrent outbreaks of mumps in Lothian and the impact of waning immunity.
Another large outbreak of mumps occurred in Lothian from October 2017, which coincided with the commencement of the higher education term. During this period 324 cases were notified, most of whom were aged 18-22 years old. Although previous outbreaks had a focus in student populations, 43% of current cases reported that they were not a student. There has been increases in private student housing where students from all universities live, which may have contributed to the wide spread of the outbreak and complicated outbreak control. Information on vaccination status was available for 244 cases (75%), of whom the majority (75.8%) reported having two MMR doses. To investigate potential waning vaccine immunity the mean length of time since last mumps containing vaccine was calculated as 14.3 years. The outbreak was declared over in May 2018 after case numbers returned to background levels. This outbreak highlighted that mumps outbreaks occur cyclically coinciding with new cohorts of susceptible students entering the Lothian population. The lessons from this outbreak are to encourage students to have two MMR doses and also be prepared for mumps outbreaks in the near future. In future outbreaks the utility of a third MMR for outbreak control could be examined.


Retrograde amnesia for facts and events: findings from four new cases.
Two patients with presumed hippocampal formation lesions and two patients with more extensive temporal lobe damage, all of whom became amnesic in a known year, were given tests of anterograde and retrograde memory function. The two patients with hippocampal formation lesions had moderately severe anterograde amnesia and limited retrograde amnesia for facts and events that affected, at most, the decade preceding the onset of amnesia. Content analysis could not distinguish the autobiographical recollections of the patients from the recollections of control subjects. The two patients with more extensive temporal lobe damage had severe anterograde amnesia and extensive retrograde memory loss for both facts and events. The results suggest that whether retrograde amnesia is temporally limited or very extensive depends on whether the damage is restricted to the hippocampal formation or also involves additional temporal cortex.


Challenges of autism in the inpatient setting.
Julie is a 4-year-old girl with autism spectrum disorder (ASD) who presented to the emergency room with severe unilateral hip pain and limping. Initial evaluation indicated increased inflammatory markers and blasts on a blood smear. A bone marrow biopsy revealed acute lymphoblastic leukemia (ALL), and Julie was admitted for induction chemotherapy. Julie was diagnosed with ASD 1 year before this presentation. Her parents, who had immigrated to the United States from China before her birth, indicated that it took them some time to accept the diagnosis of ASD but they were feeling more confident in addressing her behavior challenges and comfortable with the progress she had been making. They now expressed concerns about the possible loss of services in the setting of her hospitalization. At the time of diagnosis, Julie had been receiving in-home behavioral therapy (applied behavioral analysis), speech therapy, and occupational therapy at a hospital-based center. In addition, she had an individualized education plan and was enrolled in a specialized preschool classroom for children with ASD.As Julie's hospital stay became more prolonged, her medical care team started reporting more challenges communicating with Julie without the presence of 1 of her parents, difficulty conducting routine care (e.g., obtaining vitals), sleep disruption, and safety concerns (e.g., Julie would frequently climb on the window sill increasing her fall risk). As her primary care clinician, you are called by the hospital team to help bridge the communication and behavioral divide that has widened--what would you do next?


Functional Vegetable Guar (Cyamopsis tetragonoloba L. Taub.) Accessions for Improving Flavonoid Concentrations in Immature Pods.
Dry guar (Cyamopsis tetragonoloba L. Taub) seeds are primarily used to extract galactomannan gum for oil fracking, however, the immature pods are used as a vegetable in India and sold in ethnic grocery stores in the Atlanta, Georgia area. Nineteen guar genotypes were grown in the field at Griffin, GA, USA for two years (2010-2011). Since the determination of flavonoid concentration would add value to the guar accessions for use as a functional food vegetable, immature guar pods were evaluated for flavonoid concentration. In this study, the immature pods from these 19 guar accessions were analyzed for flavonoid concentration using high-performance liquid chromatography. Several accessions including PI 253182, PI 262152, PI 263698, and PI 288357 showed significantly greater daidzein concentration than all three controls based on seed production in 2010. However, PI 179926, PI 180434, PI 182969, PI 183400, PI 253182, PI 262152, PI 263882, and PI 263897 exhibited significantly greater genistein concentration than the second and third best controls in 2011. Both PI 180434 and PI 288359 produced significantly higher kaempferol concentration than the third best control. Daidzein concentration was significantly correlated with genistein concentration (r2 = 0.47*) for both years. Luteolin concentration showed a significant negative correlation with genistein (r2 = -0.45*). Quercetin concentration significantly correlated with kaempferol (r2 = 0.854***) and genistein (r2 = 0.455*) concentrations. The accession, PI 542608 was observed to contain high concentrations of kaempferol and quercetin in the cluster analyses. These results will help plant breeders develop guar cultivars with superior flavonoid concentrations.


Self-trephination of the skull with an electric power drill.
There is extensive archaeological evidence of the practice of trephination of the skull in many ancient cultures in different parts of the world. We report a case of self-trephination of the skull by a patient using an electrical power drill subsequently requiring neurosurgical intervention.


Blunted Pain Modulation Response to Induced Stress in Women with Fibromyalgia with and without Posttraumatic Stress Disorder Comorbidity: New Evidence of Hypo-Reactivity to Stress in Fibromyalgia?
There is evidence regarding the presence of alterations in both the stress response and the endogenous pain modulation systems of people with fibromyalgia (FM). However, research on pain modulation under induced stress on FM patients is scarce and contradictory. The present study analyzes stress-induced changes in pain and intolerance thresholds among FM patients, examining the possible existence of differences linked to PTSD comorbidity and gaining insights into the role of cardiovascular reactivity. Eighteen women diagnosed with FM and comorbid PTSD (FM + PTSD), 18 women diagnosed with FM and no PTSD (FM-PTSD), and 38 healthy women (HC) were exposed to the Social Stress Test task. Pressure pain thresholds and intolerance thresholds were measured before and during stress induction, and after a recovery period, while systolic blood pressure and heart rate were simultaneously recorded. Overall, while pain thresholds decreased during stress and recovery for HC, no significant changes were observed for women with FM. The intolerance threshold decreased for HC during stress, but was maintained at basal level during recovery. FM-PTSD women exhibited a delayed response, with a drop at recovery. For FM + PTSD, tolerance levels remained unchanged. In addition, cardiovascular reactivity did not seem to explain these results. This performance of the pain modulation system seems to follow the same pattern of hypoactive responsiveness under stressors that has previously been observed in FM patients on the autonomic and neuroendocrine axes. Such a hypoactive pattern may involve a non-adaptive response that may contribute to the development and maintenance of chronic pain.


Positron emission tomography imaging as a cancer biomarker.
The practice of oncology is changing, with novel biologic agents broadening our therapeutic armamentarium. Along with excitement and promise, multiple new challenges arise. The concept of 'individualized cancer care,' where therapies are selected based on the unique characteristics of a patient's tumor, is gaining favor as an approach to address the heterogeneity of cancer. As a result, we must strive to discover biomarkers with prognostic and predictive value to improve drug selection, alteration and development. Metabolic and molecular imaging with PET appears at the forefront of this critical field. In this review, we discuss cancer biomarker development, opportunities for PET to elucidate tumor biology and the potential role of PET in clinical research and practice.


Efficacy of antiseptics for rubber dam sterilization prior to endodontic treatment.
This study investigated the efficacy of various antiseptics for disinfection of rubber dams used during endodontic treatment, the duration of disinfection effectiveness, and the disinfection protocol employed by dental schools in Thailand. The efficacy of 10% povidone-iodine, 1.5% tincture iodine and 70% ethyl alcohol in eliminating Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans) on the rubber dam was investigated. Time duration of disinfection was evaluated at 0, 30, 60, and 120 min. The two-step disinfection method adopted at Thai dental school was examined. Independent t-test or Kruskal-Wallis followed by a Dunnett's test was used for statistical analysis. Among the three antiseptics, 10% povidone and 1.5% tincture iodine eradicated the microorganisms completely, whereas 70% ethyl alcohol did not achieve a statistically significant decrease. The duration of sterilization effectiveness was 120 min for 10% povidone-iodine, but bacteria were eliminated only at 0 min by 1.5% tincture iodine. The results also indicated that the two-step protocol scarcely eliminated the microorganisms. The best antiseptic for rubber dam disinfection is 10% povidone-iodine, which remains effective for 120 min. The two-step protocol typically practiced in Thai dental schools needs to be updated. The use of 10% povidone-iodine alone is adequate for complete eradication of E. faecalis and C. albicans.


Comparison of the Analgesic Efficacy of a Single Dose of Epidural Dexmedetomidine versus Fentanyl as an Adjuvant to Bupivacaine in Abdominal Surgery.
Fentanyl as an epidural additive act on spinal opioid receptors, while dexmedetomidine has selective alpha-2 receptor agonist action enhancing analgesic effects. We aimed to compare the postoperative analgesic efficacy of single doses of dexmedetomidine against fentanyl as epidural adjuvant to 0.125% bupivacaine. A prospective, randomized, controlled, double-blind trial was conducted in a tertiary care teaching institute. Forty-six patients undergoing abdominal surgery under general anesthesia with epidural analgesia were allocated into two groups to receive postoperative analgesia with single doses of 10 mL 0.125% bupivacaine with the addition of dexmedetomidine 0.5 μg.kg-1 (Group D) or fentanyl 0.5 μg.kg-1 (Group F). The primary outcome was the duration of postoperative analgesia between the two groups. The secondary outcomes were hemodynamic variations, vasopressor need, and motor blockade. Chi-square test for static parameters and Student's t-test or Mann-Whitney test for continuous variables were used for analysis. The duration of analgesia was longer in Group D (5.0 ± 2.0 h) versus Group F (2.9 ± 1.4 h), Sixteen patients in Group D versus seven patients in Group F needed vasopressors after the bolus to maintain the blood pressure (BP) within 20% of prebolus value (P = 0.018). Heart rate and mean and systolic BP were lower in Group D at various time points following bolus administration. A single dose of dexmedetomidine as an additive to epidural local anesthetic postoperatively prolongs the duration of analgesia in comparison to fentanyl but is associated with changes in hemodynamics, including the need for the administration of vasoactive drugs.


Dilemmas surrounding passive euthanasia--a Malaysian perspective.
In western societies where the principle of autonomy is jealously guarded, perhaps active euthanasia is more often the focus of public concern and debates rather than any other forms of euthanasia. However due to the advance in technology and its corresponding ability in prolonging life, in Malaysia passive euthanasia presents more of a dilemma. For those concerned and involved with end of life decision-making, it is generally agreed that this is an area fraught with not only medical but legal and ethical issues. In Malaysia where the society is not homogenous but is multi-cultural and multi-religious, in addition to medical, legal and ethical issues, religious principles and cultural norms further impact and play significant roles in end of life decision-making. This paper seeks to identify the issues surrounding the practice of passive euthanasia in Malaysia. It will be shown that despite applicable legal provisions, current practice of the medical profession combined with religious and cultural values together affect decision-making which involves the withholding and/or withdrawing of life-saving treatment.


The Pittsburgh Poison Center profile of an American poison information center.
The Pittsburgh Poison Center (PPC), a department of Children's Hospital of Pittsburgh, was established in 1971 to provide emergency poison information to the residents of western Pennsylvania, especially the children. The PPC provides comprehensive poison information center services to the lay public and to medical professionals, poison prevention education, professional education and specialized services to the business and industry sector and governmental agencies.


Early Poultry Vaccine Company Development: the Era of Entrepreneurs.
Early events leading to the establishment of various branches of the U.S. poultry industry and the animal health industry in the United States are reviewed. Entrepreneurs see needs in a developing market and take action to meet these needs. Their skills are suited to organize people and processes to supply these needs. As the early poultry industry consolidated, this was followed by technical education as a marketing tool to expand access to the customer base. Focus will be on two entrepreneurial individuals not well covered by prior history articles, namely Hiram Lasher and Kenneth Eskelund. A discussion of how industries pass from an entrepreneurial phase to a corporate phase will follow, thus explaining the corporate- and biotechnology-oriented vaccine companies we see today.


Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte differentiation from a novel V-96 plate aggregation system highlights interline variability.
Although all human ESC (hESC) lines have similar morphology, express key pluripotency markers, and can differentiate toward primitive germ layers in vitro, the lineage-specific developmental potential may vary between individual lines. In the current study, four hESC lines were cultured in the same feeder-free conditions to provide a standardized platform for interline analysis. A high-throughput, forced-aggregation system involving centrifugation of defined numbers of hESCs in V-96 plates (V-96FA) was developed to examine formation, growth, and subsequent cardiomyocyte differentiation from >22,000 EBs. Homogeneity of EBs formed by V-96FA in mouse embryo fibroblast-conditioned medium was significantly improved compared with formation in mass culture (p < .02; Levene's test). V-96FA EB formation was successful in all four lines, although significant differences in EB growth were observed during the first 6 days of differentiation (p = .044 to .001; one-way analysis of variance [ANOVA]). Cardiomyocyte differentiation potential also varied; 9.5% +/- 0.9%, 6.6% +/- 2.4%, 5.2% +/- 3.1%, and 1.6% +/- 1.0% beating EBs were identified for HUES-7, NOTT2, NOTT1, and BG01, respectively (p = .008; one-way ANOVA). Formation of HUES-7 V-96FA EBs in defined medium containing activin A and basic fibroblast growth factor resulted in 23.6% +/- 3.6% beating EBs, representing a 13.1-fold increase relative to mass culture (1.8% +/- 0.7%), consistent with an observed 14.8-fold increase in MYH6 (alphaMHC) expression by real-time polymerase chain reaction. In contrast, no beating areas were derived from NOTT1-EBs and BG01-EBs formed in defined medium. Thus, the V-96FA system highlighted interline variability in EB growth and cardiomyocyte differentiation but, under the test conditions described, identified HUES-7 as a line that can respond to cardiomyogenic stimulation.


Micro-optical vibrometer/accelerometer using dielectric microspheres.
In this paper, an optical vibrometer/accelerometer is designed using micro-optical dielectric sensors based on whispering gallery modes (WGM) phenomena. The proposed design is created as a sphere made from polydimethylsiloxane (PDMS). The dielectric sensor would be laid between a piezo stack and a proof mass of 10-4 kg (implemented as body force to the sensor) in the vertical position. Once the piezo stack starts to impose a vibration in the vertical direction, the proof mass starts to vibrate, leading to a change in the morphology of the sensor. In turn, the WGM shifts would be seen on the transmission spectrum and would be related to the vibration/acceleration of the piezo stack. An analysis based on the force transmissibility from the piezo stack to the optical sensor and calibrations are carried out along with preliminary designs and experiments. Results showed that the proposed sensor could reach a very high resolution up to 8 nano-g with sensitivity dλ/da≈2.33 pm/μg.


The prevalence and consequences of burnout on a group of preclinical dental students.
The aim of this study is to investigate the prevalence of burnout among a group of Turkish preclinical dental students, to compare the level of burnout and to determine the consequences in structural equation model. Preclinical dental students (n = 329, 50.5% of females and 49.5% of males) aged between 18 and 24 took part in the study. Maslach burnout inventory student version, academic satisfaction scale, and personal information sheet were used to gather data. Pearson correlation analyses, t-test, and one-way ANOVA were used for statistical analysis. The proposed theoretical model was tested via observed variable path analysis using maximum likelihood parameter estimation with AMOS 7.0. About 22.3% of students had high level of emotional exhaustion, 16.7% of students had high level of cynicism, and 17.9% of students suffered from high level of reduced academic efficacy. While the students attending the first grade reported higher level of reduced academic efficacy, the students in the third grade reported higher level of emotional exhaustion. Academic workload played an important role in the development of burnout. As consequences of burnout, students with high levels of burnout intended to change their current major and did not to plan to continue to postgraduate education. Students with high level of burnout reported less level of academic satisfaction and academic achievement. Creating awareness on the burnout of dental students from the preclinical period may be useful for prevention and more compatible dental education environment.


Transposon mutagenesis of group B streptococcus beta-hemolysin biosynthesis.
Beta-hemolysin production by group B streptococci (GBS) is speculated to be a major virulence factor of the organism. A virulent, beta-hemolytic group B streptococcus strain was mutagenized with the self-conjugative transposon Tn916 to derive isogenic strains with mutations only in the gene(s) responsible for beta-hemolysin biosynthesis. There was no significant difference between the virulence of the parent strain and that of the mutant strains in a neonatal rat sepsis model.


What residents do after graduation.
This article reports the results of an investigation of the professional activities of graduates of National Institute of Mental Health-supported residency programs, spanning the five-year period 1968 to 1972. The results explode the mythical notion that the majority of such trainees enter straightway into the private practice careers. In fact, the majority devote at least half-time to some type of public-service psychiatry, with no less than 43% in full-time public service.


Tools for visualizing multidimensional images from living specimens.
Over the last 50 years modern cell biology has been driven by the development of powerful imaging techniques. In particular, new developments in light microscopy that provide the potential to image the dynamics of biological events have had significant impact. Optical sectioning techniques allow three-dimensional information to be obtained from living specimens noninvasively. When used with multimodal fluorescence microscopy, advanced optical sectioning techniques provide multidimensional image data that can reveal information not only about the changing cytoarchitecture of a cell but also about its physiology. These additional dimensions of information, although providing powerful tools, also pose significant visualization challenges to the investigator. Particularly in the current postgenomic era there is a greater need than ever for the development of effective tools for image visualization and management. In this review we discuss the visualization challenges presented by multidimensional imaging and describe three open-source software programs being developed to help address these challenges: ImageJ, the Open Microscopy Environment, and VisBio.


Metschnikowia pulcherrima Influences the Expression of Genes Involved in PDH Bypass and Glyceropyruvic Fermentation in Saccharomyces cerevisiae.
Previous studies reported that the use of Metschnikowia pulcherrima in sequential culture fermentation with Saccharomyces cerevisiae mainly induced a reduction of volatile acidity in wine. The impact of the presence of this yeast on the metabolic pathway involved in pyruvate dehydrogenase (PDH) bypass and glycerol production in S. cerevisiae has never been investigated. In this work, we compared acetic acid and glycerol production kinetics between pure S. cerevisiae culture and its sequential culture with M. pulcherrima during alcoholic fermentation. In parallel, the expression levels of the principal genes involved in PDH bypass and glyceropyruvic fermentation in S. cerevisiae were investigated. A sequential culture of M. pulcherrima/S. cerevisiae at an inoculation ratio of 10:1 produced 40% less acetic acid than pure S. cerevisiae culture and led to the enhancement of glycerol content (12% higher). High expression levels of pyruvate decarboxylase PDC1 and PDC5, acetaldehyde dehydrogenase ALD6, alcohol dehydrogenase ADH1 and glycerol-3-phosphate dehydrogenase PDC1 genes during the first 3 days of fermentation in sequential culture conditions are highlighted. Despite the complexity of correlating gene expression levels to acetic acid formation kinetics, we demonstrate that the acetic acid production pathway is altered by sequential culture conditions. Moreover, we show for the first time that the entire acetic acid and glycerol metabolic pathway can be modulated in S. cerevisiae by the presence of M. pulcherrima at the beginning of fermentation.


[Origin and nature of the neutralizing immune response against therapeutic factor VIII].
The use of therapeutic proteins induces in some patients the appearance of neutralizing antibodies. This is the case of pro-coagulant factor VIII (FVIII) used in patients with hemophilia A. Several parameters related to the protein itself, to the type of pathology or to the patients, condition the immunogenicity of a therapeutic protein. Understanding these parameters would help to anticipate or prevent the development of neutralizing antibodies. In the case of FVIII, we propose that the development of neutralizing antibodies does not result from an unpredicted immune response but rather from the inability of the patient's organism to develop an anti-inflammatory or regulatory response.


Comparison of the properties of implantable matrices prepared from degradable and non-degradable polymers for bisphosphonate delivery.
The aim of the present study was the development of directly compressed tablets for implantable delivery of risedronate sodium for osteoporosis treatment and the comparison of the mechanism and kinetics of drug release from biogradable (chitosan) and non-degradable (PVC) polymer matrices. The compositions and process parameters were optimized in accordance to a mixed 2 and 3 level full factorial design. Critical Quality Attributes (CQA), such as diametral breaking hardness, porosity and speed of drug dissolution were investigated. The results revealed significant differences between the behaviours of the two polymers. Chitosan exhibited poor compressibility, which resulted in poor mechanical properties and the fast disintegration of chitosan based tablets. Nevertheless, despite the fast disintegration, the chitosan based matrices exhibited one-week-long continuous drug release, which can be due to a strong drug-carrier interaction. The presence of intermolecular hydrogen bonds was confirmed with FT-IR and NIR measurements. In contrast, PVC based compositions exhibited excellent compressibility, good tablet hardness and low porosity. The tablets remained intact during the dissolution and exhibited a slower release rate than what was measured in the case of chitosan based matrices. There was no sign of intermolecular association on NIR spectra, suggesting that the dissolution rate is basically determined by the porosity of tablets, but FT-IR measurements revealed some details of the molecular background of drug release mechanism.


Food Advertising to Children in New Zealand: A Critical Review of the Performance of a Self-Regulatory Complaints System Using a Public Health Law Framework.
New Zealand has the second highest overweight and obese child population in the Organisation for Economic Co-operation and Development (OECD). This paper evaluates whether New Zealand's self-regulatory controls on the advertising of unhealthy food and beverages to children and young people adequately protects children from the exposure to, and power of, such marketing in order to limit its impact on children's food and beverage preferences. First, an analysis of the relevant New Zealand Advertising Standards Authority (ASA) Codes was conducted, including the ASA Complaints Board and Appeals Board decisions from 2017-2019 to determine the application of the Codes in practice. Second, a public health law framework was applied to the self-regulatory system. Of the 16 complaints assessed, 12 were not upheld, and only one was upheld under the Children and Young People's Advertising Code (CYPA Code). Three complaints were upheld under the Advertising Standards Code (ASC) but not the CYPA Code. An analysis of the Codes and their interpretation by the Complaints Board found that many facets of the public health law framework were not met. The self-regulatory system does not adequately protect children from the exposure to, and power of, unhealthy food and beverage marketing, and government-led, comprehensive, and enforceable marketing restrictions are required.


Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: rationale for the active-comparator CAROLINA trial.
Sulphonylureas (SUs) are widely used glucose-lowering agents in type 2 diabetes mellitus (T2DM) with apparent declining efficacy over time. Concerns have been raised from observational retrospective studies on the cardiovascular (CV) safety of SUs but there are few long-term data on CV outcomes from randomized controlled trials (RCTs) involving the use of this class of agents. Most of the observational studies and registry data are conflicting and vary with study population and methodology used for analyses. To address the SU controversy, we reviewed the recently published literature (until end of the year 2011) to evaluate the impact of SUs on CV outcomes in modern, longer-term (≥72 weeks) RCTs where they were compared in a head-to-head fashion versus an active comparator or were used as part of a treatment strategy. We identified 15 trials and found no report of an increase in the incidence of CV events with the use of SUs. However, the available data are limited, and, most importantly, there was no adequately powered formal head-to-head CV outcome trial designed to address CV safety. Since SUs are still being advocated as second-line therapy added-on to metformin, as one of several classes, and in certain circumstances first-line therapy in T2DM management, definitive data from a dedicated RCT addressing the CV safety question with SUs would be informative. Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) is such a trial, ongoing since November 2010, and is currently the largest head-to-head CV outcome trial that involves a comparison of a SU (glimepiride) with a dipeptidyl peptidase-4 (DPP-4) inhibitor (linagliptin) and will provide a unique perspective with respect to CV outcomes with these two commonly used agents.


MCP-1 derived from stromal keratocyte induces corneal infiltration of CD4+ T cells in herpetic stromal keratitis.
Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers CD4(+) T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in CD4(+) T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed CD4(+) T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed CD4(+) T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of CD4(+) T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts CD4(+) T cells into the cornea.


Upconversion luminescence and blackbody radiation in tetragonal YSZ co-doped with Tm(3+) and Yb(3+).
Lanthanide doped inorganic nanoparticles with upconversion luminescence are of utmost importance for biomedical applications, solid state lighting and photovoltaics. In this work we studied the downshifted luminescence, upconversion luminescence (UCL) and blackbody radiation of tetragonal yttrium stabilized zirconia co-doped with Tm(3+) and Yb(3+) single crystals and nanoparticles produced by laser floating zone and laser ablation in liquids, respectively. The photoluminescence (PL) and PL excitation (PLE) were investigated at room temperature (RT). PL spectra exhibit the characteristic lines in UV, blue/green, red and NIR regions of the Tm(3+) (4f(12)) under resonant excitation into the high energy (2S+1)LJ multiplets. Under NIR excitation (980 nm), the samples placed in air display an intense NIR at ∼800 nm due to the (1)G4→(3)H5/(3)H4→(3)H6 transitions. Additionally, red, blue/green and ultraviolet UCL is observed arising from higher excited (1)G4 and (1)D2 multiplets. The power excitation dependence of the UCL intensity indicated that 2-3 low energy absorbed photons are involved in the UCL for low power levels, while for high powers, the identified saturation is dependent on the material size with a enhanced effect on the NPs. The temperature dependence of the UCL was investigated for single crystals and targets used in the ablation. An overall increase of the integrated intensity was found to occur between 12 K and the RT. The thermally activated process is described by activation energies of 10 meV and 30 meV for single crystals and targets, respectively. For the NPs, the UCL was found to be strongly sensitive to pressure conditions. Under vacuum conditions, instead of the narrow lines of the Tm(3+), a wide blackbody radiation was detected, responsible for the change in the emission colour from blue to orange. This phenomenon is totally reversible when the NPs are placed at ambient pressure. The UCL/blackbody radiation in the nanosized material exhibits non-contact pressure colour-based sensor characteristics. Moreover, tuning the color of the blackbody radiation in the nanoparticles by harvesting the low energy photons into the visible spectral region was found to be possible by adjusting the excitation power, paving the way for further developments of these nanoparticles for lighting and photovoltaic applications.


Electroneurography in the evaluation of oxaliplatin-induced neuropathy in colorectal cancer patients.
Cold-induced neuropathy is the most observed side effect of oxaliplatin. Presence of neuropathy is routinely assessed by electroneurographical examination. The use of electroneurography has not been a part of typical oncological monitoring and treatment protocols, leading to untreated, irreversible damage to patients' peripheral nerves, undiagnosed for long periods of time. 36 colorectal cancer patients followed FOLFOX4 with/without bevacizumab or XELOX were enrolled between February 2013 and January 2015 in the study at the University Hospital Oncological Department, Krakow, Poland. Electroneurography was performed prior to the first cycle of chemotherapy and after the 4th cycle. 32 out of 36 enrolled patients completed neurological evaluation. Pre-treatment neurographic examination revealed presence of peripheral neuropathy in 10 (31.25%) patients; 6 (18.75%) had sensory neuropathy and 4 (12.5%) had mixed, sensorimotor neuropathy. After treatment examination revealed significant increase in the number of neuropathic patients; presence of peripheral neuropathy was observed in 19 patients (59%), sensory polyneuropathy was diagnosed in10 patients (31.25%) and mixed neuropathy was diagnosed in 9 patients (28.13%). Early electrophysiological monitoring followed by a symptom dependent oxaliplatin regimen would be highly beneficial for patients undergoing oxaliplatin treatment, improving their well-being and positively affecting their life quality.


The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis.
Reduced mental health (MH) is prevalent in rheumatoid arthritis (RA). Although longitudinal studies are limited, there is evidence that depression is associated with worse disease outcomes. We evaluated reciprocal relationships between MH, RA severity, and genetic risks for depression for 2 years in a well-characterized cohort of RA patients. We evaluated 520 early RA patients previously enrolled to two clinical trials. MH was measured using the short form-36 MH domain and mental component summary scores (MCS). MCS/MH associations over 2 years with disease activity (disease activity score on a 28-joint count), disability (health assessment questionnaire), pain visual analog scale scores, and a weighted genetic risk score for depression were tested using linear mixed-effects and regression models. Poorer MH was associated with worse RA outcomes. Lower MCS scores (indicating worse MH) were seen in patients with a greater genetic risk for depression (weighted genetic risk score: coefficient = -1.21, p = .013). Lower baseline MCS was associated with lower 2-year improvements in disease activity score on a 28-joint count (coefficient = -0.02, p < .001), pain (coefficient = -0.33, p < .001), and health assessment questionnaire (coefficient = -0.01, p = .006). Baseline MCS was associated with changes in the swollen joint count (coefficient = -0.09, p < .001) and patient global assessment (coefficient = -0.28, p < .001) but not the tender joint count (p = .983) and erythrocyte sedimentation rate (p = .973). Only baseline pain visual analog scale (coefficient = -0.07, p = .002) was associated with 2-year changes in MCS. Reduced baseline MH was associated with lower improvements in disease activity, disability, and pain for 2 years, supporting current national guidelines recommending screening for depression in RA. Pain had a bidirectional relationship with MH. Depression genetic risk had a significant association with MH.


Association of antimicrobial resistance in Campylobacter isolated from food-producing animals with antimicrobial use on farms.
On 1,374 food-producing animal farms in 2001-2004, we investigated the influence of antimicrobial usage within 6 months before a survey conducted on antimicrobial resistance in Campylobacter. Tetracyclines and fluoroquinolones were used for therapeutic purposes on 107 and 21 farms, respectively. Oxytetracycline-resistant C. jejuni and C. coli were found in 57.1% (8/14) and 92.5% (37/40) of the farms, respectively, when the animals were treated with tetracyclines. However, they were found in 43.2% (112/259) and 74.3% (122/164) of the farms, respectively, when the animals were not treated with tetracyclines. Enrofloxacin-resistant C. jejuni and C. coli were found in 66.7% (2/3) and 16.7% (1/6) of the farms, respectively, when the animals were treated with fluoroquinolones. However, they were found in 15.5% (42/270) and 28.8% (57/198) of the farms, respectively, when the animals were not treated with fluoroquinolones. The percentage of oxytetracycline resistance in C. coli was significantly elevated when the animals were treated with tetracyclines (P < 0.05). The farms on which antimicrobials included by their resistance pattern were used accounted for 9.1% (4/44) and 24.1% (14/58) of the farms where enrofloxacin-resistant C. jejuni and C. coli were isolated, respectively. It is likely that several factors account for the presence of fluoroquinolone-resistant Campylobacter.