Microbiological safety of traditional and starter-mediated processes for the manufacture of Italian dry sausage.
Microbiological changes occurring during the commercial manufacture of Italian dry sausages (Genoa and salametti) were studied in two urban Canadian centres over a 5 month period. A comparison was made between 6 plants which used bacterial starter cultures and 4 plants where more traditional processes (without starters) were used. A total of 600 samples of raw, fermented and finished products were tested for the presence of coliforms, salmonellae, staphylococci, streptococci, the rate of pH reduction and final water activity (aW). Numbers of total bacteria peaked earlier and were significantly higher in sausages at the fermentation stage produced with starter cultures than in those traditionally manufactured. This corresponded with a more rapid drop in pH of the starter-inoculated products. Staphylococci and streptococci were significantly higher in starter-fermented Genoa sausages at the fermentation stage, but no significant differences were seen in the microbiological content or aW of mature finished sausages manufactured by the two different techniques. Of 128 randomly chosen isolates of coagulase-positive staphylococci, 34.4% were enterotoxin producers and 80% of these produced type A toxin. Enterotoxigenic staphylococci were found in 2 different samples of finished salametti and one sample of finished Genoa made with starter cultures and in one sample of finished Genoa made without added culture. Total numbers of staphylococci in these samples were not greater than 500/g. No correlation between the method of manufacture and presence of enterotoxigenic staphylococci could be made. Five subsamples from one lot of raw Genoa were the only samples positive for Salmonella during this study. Results indicated that low temperature traditional fermentations can yield products which are as safe as those produced by the higher temperature starter-controlled process. One of the most important elements in the traditional process was believed to be the selection and use of raw materials of the highest possible quality.


Three-Component Integrated Ultrathin Organic Photosensors for Plastic Optoelectronics.
By three-component integration, an integrated organic photosensor is presented using common organic dyes as building blocks. Gray-scale photosensing and signal amplification are achieved in the device within a wide range of light intensities. Moreover, with ultrathin film techniques, 470 nm thick devices are realized and continue to work when harshly bent.


Increase of cervical adenocarcinoma: a report of 520 cases of cervical carcinoma including 112 tumors with glandular elements.
A total of 520 new cases of cervical carcinoma were treated at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, in 1976 through 1980. Of these carcinomas, 95 (18.3%) were pure adenocarcinomas and 17 (3.3%) represented adenosquamous tumors. The mean age was 58.9 years (range 23-88 years). The age distribution was similar in patients with and without malignant glandular elements and the peak incidence was in the age group 60-69 years. In patients with adenocarcinoma, stage I was overrepresented (62.1%) whereas epidermoid carcinomas were more evenly distributed among various stages. The overall 5-year survival rate was 63.1%, with the corresponding corrected rate being 69.1%. The survival rate for patients with adenocarcinoma did not differ significantly from that for patients with squamous cell tumor. It is concluded that in our population the increasing frequency of cervical adenocarcinoma has not influenced the favorable results of the 5-year study. This disease, however, deserves more attention since its etiology, pathogenesis, and biology are still largely unresolved.


Longitudinal changes in uric acid concentration and their relationship with chronic kidney disease progression in children and adolescents.
Elevated serum uric acid concentration is a risk factor for CKD progression. Its change over time and association with CKD etiology and concomitant changes in estimated glomerular filtration rate (eGFR) in children and adolescents are unknown. Longitudinal study of 153 children/adolescents with glomerular (G) and 540 with non-glomerular (NG) etiology from the CKD in Children (CKiD) study. Baseline serum uric acid, change in uric acid and eGFR over time, CKD etiology, and comorbidities were monitored. Adjusted linear mixed-effects regression models quantified the relationship between within-person changes in uric acid and concurrent within-person changes in eGFR. Participants with stable uric acid over follow-up had CKD progression which became worse for increased baseline uric acid (average annual percentage changes in eGFR were - 1.4%, - 7.7%, and - 14.7% in those with G CKD with baseline uric acid < 5.5 mg/dL, 5.5 - 7.5 mg/dL, and > 7.5 mg/dL, respectively; these changes were - 1.4%, - 4.1%, and - 8.6% in NG CKD). Each 1 mg/dL increase in uric acid over follow-up was independently associated with significant concomitant eGFR decreases of - 5.7% (95%CI - 8.4 to - 3.0%) (G) and - 5.1% (95%CI - 6.3 to - 4.0%) (NG) for those with baseline uric acid < 5.5 mg/dL and - 4.3% (95%CI - 6.8 to - 1.6%) (G) and - 3.3% (95%CI - 4.1 to - 2.6%) (NG) with baseline uric acid between 5.5 and 7.5 mg/dL. Higher uric acid levels and increases in uric acid over time are risk factors for more severe progression of CKD in children and adolescents. A higher resolution version of the Graphical abstract is available as Supplementary information.


Illicit drug use and injuries: A review of emergency room studies.
The reviewed emergency room studies (n = 11) show overall prevalence rates of illicit drug use of 35-40% in studies using blood and urine toxicology and 1-5% in self-report studies. Cannabis and cocaine are the substances most prevalent in these studies, with a higher prevalence of cocaine in emergency rooms in the USA than in other countries where cannabis is the most common substance. Illicit drugs and alcohol are often used in combination. No relationship was found between injury severity and illicit drug use. Less clear associations emerged concerning patient and injury characteristics and illicit drug use. However, illicit drug use seems to be more common in men aged 20-40 years and is strongly associated with violence-related injuries. Variations in the prevalence rates and patient characteristics can partly be explained by locale and/or country of research. Moreover, because methodological differences influence the study outcomes, methodological aspects of emergency room studies should be taken into consideration when interpreting the results.


Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.
The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles. The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance. A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework. Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).


MDMA alters emotional processing and facilitates positive social interaction.
±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") produces "prosocial" effects, such as feelings of empathy and closeness, thought to be important to its abuse and its value in psychotherapy. However, it is not fully understood how MDMA alters basic emotional processes to produce these effects, or whether it produces corresponding changes in actual social behavior. Here, we examined how MDMA affects perceptions of and responses to emotional expressions, and tested its effects on behavior during a social interaction. We also examined whether MDMA's prosocial effects related to a measure of abuse liability. Over three sessions, 36 healthy volunteers with previous ecstasy use received MDMA (0.75, 1.5 mg/kg) and placebo under double-blind conditions. We measured (i) mood and cardiovascular effects, (ii) perception of and psychophysiological responses to emotional expressions, (iii) use of positive and negative words in a social interaction, and (iv) perceptions of an interaction partner. We then tested whether these effects predicted desire to take the drug again. MDMA slowed perception of angry expressions, increased psychophysiological responses to happy expressions, and increased positive word use and perceptions of partner empathy and regard in a social interaction. These effects were not strongly related to desire to take the drug again. MDMA alters basic emotional processes by slowing identification of negative emotions and increasing responses to positive emotions in others. Further, it positively affects behavior and perceptions during actual social interaction. These effects may contribute to the efficacy of MDMA in psychotherapy, but appear less closely related to its abuse potential.


Comparison of contrast agents with high molarity and with weak protein binding in cerebral perfusion imaging at 3 T.
To examine and compare properties of high-molarity contrast agent gadobutrol (Gadovist) and weakly protein-binding agent gadobenate-dimeglumine (MultiHance in dynamic susceptibility contrast (DSC) perfusion imaging at 3 T. Sixteen healthy volunteers underwent three separate examinations with contrast agent doses of 0.1 and 0.2 mmol/kg body weight (bw) gadobutrol and 0.1 mmol/kg bw gadobenate-dimeglumine. Maps of relative regional cerebral blood volume (rCBV) and blood flow (rCBF) were calculated using deconvolution based on singular value decomposition. Signal and concentration time curves, the concentration-to-noise ratio (SNR(c)), and gray matter (GM)-to-white matter (WM) rCBV and rCBF contrast and ratios were evaluated in a region of interest (ROI)-based analysis. Image quality of calculated parametric maps was assessed in direct visual comparison and with respect to suitability for diagnostic purposes. The contrast agents displayed very similar results in the 0.1 mmol/kg examinations, both with respect to the quantitative evaluation parameters and in the qualitative assessment of the calculated parametric maps. Maps from 0.2 mmol/kg examinations were rated as being superior in quality, but with respect to diagnostic suitability all contrast agents and doses yielded images of sufficient quality. At 3 T, a gadobutrol or gadobenate-dimeglumine dose of 0.1 mmol/kg is sufficient for DSC magnetic resonance imaging (MRI) perfusion assessment. At the used small injection volumes, the tissue concentration curve was determined only by the gadolinium (Gd) dosage in mmol/kg, and the T2* relaxation effects of the two agents can be considered to be nearly identical in the applied gradient-echo (GRE) sequence.


Effects of methyl bromide concentration, fumigation time, and fumigation temperature on Mediterranean and oriental fruit fly (Diptera: Tephritidae) egg and larval survival.
The effects of methyl bromide (MB) concentration (16, 32,48, or 64 g/m3), fumigation temperature (15, 20, 25, or 30 degrees C), and fumigation time interactions on the survival of Mediterranean fruit fly, Ceratitis capitata (Wiedemann), and oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), eggs and first and third instars were recorded. Increasing the fumigation temperature from 15 to 20 degrees C or from 20 to 25 degrees C resulted in a significant reduction in fumigation time required for equivalent egg and larval mortalities at all studied MB concentrations; no further reductions in fumigation time resulted from increasing the temperature from 25 to 30 degrees C. Conversely, increasing temperature and time allowed for a reduction in MB concentration to obtain equivalent mortality. Thus, the optimum fumigation temperature for Mediterranean and oriental fruit fly eggs and larvae was 25 degrees C. Reducing MB concentrations required for phytosanitary fumigations would save time and expense, and reduce the amount of MB released into the atmosphere during aeration. Mediterranean fruit fly was as or more tolerant to MB than oriental fruit fly in MB tolerance for eggs and first instars. The egg stage was generally more tolerant to MB regardless of concentration. However, Mediterranean fruit fly eggs showed similar tolerance to first instars at 25 degrees C for the three highest concentrations and to third instars at 25 and 30 degrees C for the highest concentration, with no significant difference between them. Therefore, eggs alone can be used to obtain MB fumigation efficacy and quarantine security data at fumigation temperatures between 15 and 30 degrees C for Mediterranean and oriental fruit fly.


Evaluation of O-alkyl and aryl sulfonyl aromatic and heteroaromatic amidoximes as novel potent DNA photo-cleavers.
Several stable O-alkyl and aryl sulfonyl conjugated p-nitro-Ph and o-, m-, p-pyridine N'-hydroxy imidamides, were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA pBluescript KS II. The generated amidinyl and sulfonyloxyl radicals led to effective DNA photo-cleavage. Both alkyl and aryl sulfonyl derivatives were active and the order p-pyridine > p-nitro-Ph > o-pyridine > m-pyridine was schematized for the N'-hydroxy imidamides moiety. Calf thymus-DNA affinity studies which comprised UV interactions, viscosity experiments and competitive studies with ethidium bromide showed good to excellent affinity of the compounds. These properties revealed sulfonyl amidoximes as novel effective DNA-photo-cleavers and may serve in the discovery of new leads for "on demand" biotechnological and medical applications.


Phylogenetic analysis of Ljungan virus and A-2 plaque virus, new members of the Picornaviridae.
In addition to the viruses belonging to the nine proposed genera of the Picornaviridae, Enterovirus, Rhinovirus, Cardiovirus, Aphtovirus, Hepatovirus, Parechovirus, Kobuvirus, Erbovirus and Teschovirus, two new members of this family have recently been discovered. Three strains of Ljungan virus (LV) were isolated from bank voles (Clethrionomys glareolus) and A-2 plaque virus (A-2) was isolated from human sera. To study the genetic relationship between these recently discovered viruses and the members of the family Picornaviridae, an evolutionary analysis has been carried out using the amino acid sequences of the two nonstructural proteins 2C and 3D. Phylogenetic analysis using prime members of the nine genera support the division of picornaviruses into the proposed genera. The study also supports a previous suggestion based on analysis of partial sequences of the structural proteins that LV is more related to the genus of Parechovirus than to other picornaviruses, but also shows that the three LV strains used in the comparison constitute a distinct monophyletic group, clearly separated from the parechoviruses. The analyses using the 2C and 3D sequences clearly showed that A-2 was related to the genera of Rhinovirus and Enterovirus, but it was not possible to group the A-2 with high confidence into one of the genera. Comparison using the VP1 protein sequences of Enterovirus and Rhinovirus showed that although the A-2 virus is positioned between the two genera, the virus is more related to the genus of Enterovirus than to Rhinovirus. Our analysis of the three LV strains based on the phylogenetic analysis of the 2C and 3D proteins suggests that the strains used in this study constitute a monophyletic group clearly related to Parechovirus of Picornaviridae. The taxonomic position of the A-2 virus is presently uncertain but available data indicate that this virus may be classified as a member of the genus of Enterovirus.


A Colorimetric Dermal Tattoo Biosensor Fabricated by Microneedle Patch for Multiplexed Detection of Health-Related Biomarkers.
Detection of biomarkers associated with body conditions provides in-depth healthcare information and benefits to disease management, where the key challenge is to develop a minimally invasive platform with the ability to directly detect multiple biomarkers in body fluid. Dermal tattoo biosensor holds the potential to simultaneously detect multiple health-related biomarkers in skin interstitial fluid because of the features of minimal invasion, easy operation, and equipment-free result reading. Herein, a colorimetric dermal tattoo biosensor fabricated by a four-area segmented microneedle patch is developed for multiplexed detection of health-related biomarkers. The biosensor exhibits color changes in response to the change of biomarker concentration (i.e., pH, glucose, uric acid, and temperature), which can be directly read by naked eyes or captured by a camera for semi-quantitative measurement. It is demonstrated that the colorimetric dermal tattoo biosensor can simultaneously detect multiple biomarkers in vitro, ex vivo, and in vivo, and monitor the changes of the biomarker concentration for at least 4 days, showing its great potential for long-term health monitoring.


Effects of complete and partial lesions of the dopaminergic mesotelencephalic system on skilled forelimb use in the rat.
This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that had received a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. The rats classified Apo(+), that rotated after the administration of apomorphine, had a complete lesion of the nigrostriatal system, whereas those classified Apo(-), that did not rotate after the administration of apomorphine, had a partial lesion of the nigrostriatal system. In the Apo(+) rats, 99.8% of the dopamine in the striatum was depleted, as was 85% of that in the substantia nigra. For the Apo(-) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investigated with the staircase test, the animals with the most severe dopamine depletions were those most impaired in the paw reaching task. Complete and partial unilateral depletions of the dopaminergic mesotelencephalic system impaired the hierarchic phases of paw reaching differently. A complete dopamine depletion, but not a partial one, decreased the number of attempts made with the contralateral paw, and induced a bias towards the ipsilateral paw. A partial dopamine lesion impaired the sensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsilateral paw. The mild paw reaching impairments observed in animals with moderate depletions of dopamine are proposed as a model of the early symptoms of Parkinson's disease that may be useful for the development of protective or restorative therapies.


Annual dynamics of perfluorinated compounds in sediment: A case study in the Morava River in Zlín district, Czech Republic.
Two groups of perfluorined compounds (PFCs), i.e. perfluoroalkyl sulfonates (PFASs) and perfluoroalkyl carboxylates (PFCAs) were analysed during a period of 1 year in monthly collected riverbed sediment samples from five sampling sites in an industrial region in Morava River catchment in Czech Republic. Levels of PFCs determined in sediment samples were up to 6.8 μg kg(-1) of dry weight. Among PFCs analysed, mainly short-chain PFASs (C6 to C8) including PFOS were found in sediment samples and their levels were similar to those found in comparable river basins in other parts of Europe. Concentrations of PFCs were correlated with organic carbon content and their variations were mainly correlated by high flow events on Morava River and its tributaries. The changes in PFC concentrations were induced by displacing of PFCs containing particles to the river sediment during these elevated flow events.


Retinal ultra-wide-field colour imaging versus dilated fundus examination to screen for sickle cell retinopathy.
To compare ultra-wide-field colour fundus imaging (UWFI) to dilated fundus examination (DFE) for the screening of sickle cell retinopathy (SCR). This study is a prospective, blinded, multicentre case series. This study included two groups: an adult group (n=268 eyes) and a paediatric group (n=168 eyes). Sickle cell disease (SCD) types included haemoglobin S homozygous (HbSS), haemoglobin S and C (HbSC) and Hb S with β-thalassaemia (HbSß-Thal). Participants underwent DFE and UWFI. Each eye received three independent grades (1-4), documented by three graders: clinical grader, image grader 1 and image grader 2. Three clinically relevant diagnostic thresholds were determined. Based on these thresholds, the sensitivity, specificity, positive predictive value and negative predictive value for all three graders were calculated relative to each other as reference tests. HbSC was associated with the most advanced SCR grades. When compared to the clinical grader, image grader 1 and image grader 2 consistently detected more SCR and higher SCR grades in both adult and paediatric groups. In both groups, image grader 1 and image grader 2 identified twice as many cases of capillary occlusion/anastomosis than clinical grader. To detect the presence of any proliferative SCR, image grader 1 and image grader 2 had a sensitivity of 82%, 71% in the paediatrics group and 90% and 72% in the adult group. The clinical grader sensitivity was 52% in the paediatrics group and 53% in the adult group. The UWFI is a sensitive tool to screen for SCR. It is superior to DFE in detecting capillary occlusion or anastomosis.


Diesel Aerosols in an Underground Coal Mine.
The case study was conducted in an underground coal mine to characterize submicron aerosols at a continuous miner (CM) section, assess the concentrations of diesel aerosols at the longwall (LW) section, and assess the exposures of selected occupations to elemental carbon (EC) and total carbon (TC). The results show that aerosols at the CM sections were a mixture of aerosols freshly generated at the outby portion of the CM section and those generated in the main drifts that supply "fresh air" to the section. The relatively low ambient concentrations and personal exposures of selected occupations suggest that currently applied control strategies and technologies are relatively effective in curtailing exposures to diesel aerosols. Further reductions in EC and TC concentrations and personal exposures to those would be possible by more effective curtailment of emissions from high-emitting light duty (LD) vehicles.


Hypernatremic hemorrhagic encephalopathy.
A 12-year-old juvenile diabetic was inadvertently given 500 ml of hypertonic saline intravenously. He developed hypernatremia, hyperosmolality, metabolic acidosis, and hyperglycemia. Seizures and stupor ensued, followed by coma and death. Computerized cranial tomography revealed numerous small subcortical hemorrhages that were verified postmortem.


C-reactive protein is linked to lower cognitive performance in overweight and obese women.
Our objective was to ascertain the nature of the associations between C-reactive protein (CRP) and cognition, and to examine how they are affected by gender and obesity. We evaluated 62 females and 63 males between 42 and 82 years of age. There were 20 lean females with a body mass index (BMI) of <25 kg/m2 and 42 overweight or obese females, with BMIs > or =25 kg/m2. There were 14 lean males and 49 with BMIs >/=25 kg/m2. CRP was associated with lower scores on cognitive tests of frontal lobe function among females and these associations were driven by the overweight/obese female group. In these data no associations between CRP and cognition were found among males. Obesity-associated inflammation is much more prominent in females and it appears to be associated with cognitive dysfunction, particularly of frontal lobe tasks.


The development of a new method to detect the adulteration of commercial aloe gel powders.
Simple and accurate methods to detect the adulteration of commercial aloe gel powder were developed. Crude polysaccharide in aloe gel powder was isolated by precipitating with excess ethyl alcohol and total hexose in isolated polysaccharide was determined by Dubois assay. After hydrolysis of non-dialysable polysaccharides, resultant free sugar was determined by gas chromatography for sugar recognition and ash contents was considered simultaneously. In some products, the content of ash was very low while the content of total hexose was very high. And polysaccharides of these products revealed typical dextran pattern, therefore, these products could be identified that adulterated with commercial maltodextrin. The content of maltodextrin in adulterated product was determined by HPLC and TLC analysis which could be adopted as a part of a certification process.


Metastatic endometrial carcinoma invading bilateral total knee arthroplasties.
We present a case of a 64-year old female with bilateral knee pain several months after undergoing staged bilateral TKA. Radiolucencies surrounding the keels of bilateral tibial components were found to represent metastatic poorly differentiated endometrial carcinoma. PET scan showed adrenal, pulmonary and tibial foci consistent with metastatic disease. No other cases of bilateral periprosthetic metastasis of endometrial carcinoma have been described in the literature. Metastases around orthopedic implants are a rare occurrence. The possibility of periprosthetic metastasis should remain in the differential diagnosis for any patient with a painful total joint arthroplasty, especially in the setting of a patient with a known diagnosis of cancer elsewhere in their body.


Polymorphisms of interleukin-4--related genes in Japanese children with minimal change nephrotic syndrome.
Minimal change nephrotic syndrome (MCNS) in children frequently is associated with allergy and immunoglobulin E production. T Helper subtype 2 cytokines, such as interleukin-4 (IL-4), may have an important role in the development of atopy. We investigated the associations of gene polymorphisms of IL-4, its receptor (IL-4R), and the signal transducer and activator 6 (STAT6) gene with MCNS. We analyzed these polymorphisms in Japanese children with MCNS (n = 58) and healthy controls with neither allergic nor renal disease (n = 63). The polymerase chain reaction (PCR) and restriction fragment length polymorphism method was used for the IL-4 promoter gene polymorphism (-590C/T), and PCR single-strand conformation polymorphism analysis was used for the IL-4Ralpha chain gene (1902A/G) and STAT6 3' untranslated region (2964G/A) polymorphisms. There was a significant difference between the MCNS group and controls in genotypic distribution of IL-4 promoter gene polymorphism. Frequency of the T allele was significantly lower in the MCNS group than controls. There was no difference between the MCNS group and controls in the IL-4R gene polymorphism. In the STAT6 gene, no significant differences in genotypic and allelic distribution were observed between the 2 groups. However, there were significant differences between patients who did not need cytotoxic agents or who experienced 3 or fewer relapses and controls. These results suggest that genetic variations in the IL-4 and STAT6 genes may be associated with predisposition to MCNS, partially the clinical course of MCNS.


Comprehensive investigation of lactones and furanones in icewines and dry wines using gas chromatography-triple quadrupole mass spectrometry.
A number of lactones and furanones associated with pleasant odorants play a vital role in grape and wine aroma profiles. However, they are usually present at trace levels and are particularly challenging to measure. In this work, an optimized method based on solid-phase extraction (SPE) coupled with gas chromatography-triple quadrupole mass spectrometry (GC-QqQ-MS/MS) was developed for simultaneous determination of 14 lactones and 3 furanones. The validation was carried out using different types of wine as matrices, and satisfactory linearity, sensitivity, trueness and precision were confirmed. Furaneol and sotolon showed significantly lower limits of detection (LODs) in three real wines compared to model wine due to the matrix effect. Furthermore, the method was successfully applied to investigate the concentration range of lactones and furanones in several icewines, dry red and white wines. Icewines contained higher concentrations of most lactones and furanones compared with dry red and white wines. Partial least squares-discriminate analysis (PLS-DA) also indicated that γ-hexa-, γ-octa-, γ-nona-, γ-deca-, δ-hexa-, and δ-decalactone, as well as 5,6-dihydro-6-pentyl-2H-pyran-2-one (C10 massoia lactone), sotolon and homofuraneol contributed greatly to the discrimination between icewines and dry wines. Moreover, the calculation of odor activity value (OAV) suggested that γ-octa-, γ-nona-, and γ-decalactone, as well as furaneol and homofuraneol contributed greatest to the aroma of icewines.


Laryngeal afferents activated by phenyldiguanide and their response to cold air or helium-oxygen.
In anesthetized cats, sensory neurons in the superior laryngeal nerves (SLN) were identified with respect to their response to (1) phenyldiguanide (PDG) i.v., (2) mechanical stimulation and (3) lowering temperature in an isolated tracheolaryngeal segment. The activity originating from 107 SLN afferent units activated by PDG was recorded using glass microelectrodes advanced in the nodose ganglion. All tested afferent units increased their discharge rate during direct touching of the airway mucosa. None showed flow or pressure related activity during abrupt changes in constant laryngeal flow or transmural pressure in the isolated segment. Fifteen units were inhibited by cold air. Sixty-two units significantly increased their firing rate when the temperature approached 18 degrees C, reached a peak discharge near 15 degrees C, then their activity decreased or stopped. The response to cold air was compared to cold heliox (79% He-21% O2), which enhanced the respiratory heat loss by conduction. The peak firing rate was significantly higher with heliox (+356% compared to +246% with air), the temperature threshold higher (25 degrees C +/- 1.0 degree C) and the temperature range broader (25-11.5 degrees C). Present results show that a large proportion (58%) of afferent SLN fibres activated by PDG are likely non-proprioceptive units, which are stimulated by cooling the inspired gas. Thermosensitive units in the upper airways may act as sensors of the thermal flux through the airway wall more than as detectors of the absolute value of temperature in the airway lumen.


The exchange hypothesis for the formation of chromatid aberrations: an experimental test using bleomycin.
The association between bleomycin-induced chromatid aberrations and BUdR-label exchange between sister chromatids was investigated in order to evaluate Revell's exchange hypothesis for the formation of chromatid aberrations. The results of this study indicate that a larger than expected proportion of chromatid breaks can be accounted for by the exchange hypothesis though not all breaks are the result of incomplete exchange.


Evaluation of magnetic resonance imaging characteristics of new nitroxyl radicals on the model of RLS lymphoma.
Toxic and magnetic resonance contrast characteristics of new nitroxyl radicals Fur-135 and Fur-176 were studied in experiments on mice. The test compounds exhibited low toxicity and allowed us to increase contrasting of transplanted RLS lymphoma. Fur-135 differs by the type of contrasting from Gd(3+)-containing preparation omniscan and locates the tumor focus with high precision.


Effectiveness of physician antismoking advice.
The Dartmouth Primary Care Cooperative Information (COOP) Project conducted a controlled trial on the impact of antismoking advice from office-based physicians. Eighteen primary care medical practices were randomly assigned to be intervention or customary care practices. Medical personnel assigned to the intervention practices were to systematically identify cigarette smokers (among patients aged 35 to 59 years making an office visit), advise them to quit smoking, and provide educational materials. A random sample of 258 smokers was identified and followed-up four months later. Intervention-group smokers were more likely to report being advised to quit smoking (77 percent versus 47 percent) and to attempt quitting (39 percent versus 31 percent), but had success rates similar to those of the other group (6 percent versus 7 percent). We conclude that the medical office is an excellent place to identify large numbers of smokers and initiate attempts at quitting, but find that simple antismoking information and advice are not enough to improve cessation rates.


Changes in metabolism and hormone trafficking during exposure of endocrine cells to elevated ammonium.
Endocrine cell cultures have potential in bioprocessing, for the production of biologically active hormones, and in tissue engineering, for the development of implantable artificial tissues for long-term restoration of endocrine function. To optimize such systems, it is necessary to develop a thorough understanding of how inherently present environmental stresses, such as nutrient depletion and metabolite accumulation, affect the cells. This work focuses on the effects of the metabolite ammonium on indicators of endocrine cell metabolism and on the processing, storage and secretion of regulated secretory proteins. Experiments were conducted on recombinant insulin-producing mouse pituitary AtT-20 cells and mouse insulinoma βTC3 cells. Exposure for 24-48 hours to 6 mM of exogenous ammonium resulted in higher rates of glucose consumption by both AtT-20 and βTC3 cells, while the formation of additional ammonium generally decreased relative to ammonium-free controls. When βTC3 cells were discharged of their intracellular insulin stores, the presence of ammonium during a subsequent recharge completely inhibited addition of new insulin-related peptides to the stores, as we had observed previously for both cell lines. There was a correlation between insulin-related peptides stored in βTC3 cells during recharging and the amount that could be released upon secretagogue stimulation. Using a combination of radioimmunoassay and high performance liquid chromatography, we found that intracellular insulin and insulin-related peptides changed in the same fashion. Intracellular mechanisms that may be producing the observed results are discussed.


Small-cell lung carcinoma: survival after combination chemotherapy, radiotherapy or symptomatic treatment.
A retrospective comparison was made of the survival of patients with small-cell lung carcinoma treated by combination cytotoxic chemotherapy (CT), radiotherapy (RT) or symptomatic therapy alone (ST). Forty-three patients received CT and 42 patients of similar age and performance status each received RT or ST at the same group of hospitals. The median survival was 43 weeks with CT, 18 weeks with RT and 6 weeks with ST and 1 year survivals of 36%, 12% and 8% respectively were obtained. Despite the limitations of a retrospective study these results suggest that an improved survival with toxicity acceptable to most patients results from cytotoxic chemotherapy.


Impairment in Functioning and Quality of Life in Patients with Idiopathic Hypersomnia: The Real World Idiopathic Hypersomnia Outcomes Study (ARISE).
Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness, sleep inertia, and prolonged sleep. Its impact on patients' quality of life and daily functioning has not been fully elucidated. The Real World Idiopathic Hypersomnia Outcomes Study (ARISE) evaluated the daily functioning, relationships, cognition, emotional well-being, and productivity/employment of participants with idiopathic hypersomnia. ARISE was a US-based virtual cross-sectional survey comprising multiple patient-reported outcome measures (Functional Outcomes of Sleep Questionnaire, short version [FOSQ-10], Quality of Life in Neurological Disorders [Neuro-QoL] Social Roles and Stigma domains, British Columbia Cognitive Complaints Inventory [BC-CCI], Patient Health Questionnaire [PHQ-9], and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP]). Participants were adults 21-65 years of age with idiopathic hypersomnia. Data were analyzed for all participants and for subgroups with/without long sleep time (LST; self-reported sleep ≥11 hours in 24 hours). Of 75 participants enrolled, most were female (81.3%) and the mean (SD) age was 34.1 (10.7) years. Participants' scores on the FOSQ-10 (mean [SD] score: 10.7 [2.8]) and the Neuro-QoL Social Roles (43.4 [4.2]) and Stigma (57.3 [5.9]) domains reflected impairments in daily functioning and quality of life. More than half of participants reported moderate to severe cognitive complaints (BC-CCI; 62.7%) and moderate to severe depressive symptoms (PHQ-9; 66.7%). Scores on the WPAI:SHP showed substantial impairments in absenteeism, presenteeism, overall work productivity, and overall regular daily activity (mean percent [SD]: 12.3 [23.6], 47.6 [22.7], 51.4 [24.7], and 64.0 [21.9], respectively). These considerable impairments were found in participants with and without LST. ARISE participants with idiopathic hypersomnia demonstrated poor quality of life and impaired functioning across multiple symptom domains.


Comparative studies of collagens in normal and keratoconus corneas.
In this paper we present strong evidence that the aberrations in keratoconus corneas are not directly related to alterations in collagen composition and distribution. This conclusion is based on comparative studies of collagen types I, III, IV, V and the recently described collagen types VI and VII in keratoconus and normal corneas. The data are derived from biochemical analysis of collagen fractions sequentially extracted with pepsin and sodium-dodecylsulphate, from amino acid analysis of hydrolysates of entire corneal tissues as well as from immunoblotting of the extracted collagens with specific antibodies. These antibodies were also used to examine the distribution of the collagens in immunofluorescence experiments on corneal sections. The yields of the collagen extractions were demonstrated to be age dependent but were not altered in keratoconus samples. Apart from one case associated with osteogenesis imperfecta type I, comparative studies of keratoconus and normal corneas showed no differences in collagen composition of the extracts. This was confirmed by amino acid analysis of tissue-hydrolysates. The distributions of collagen types I, III, IV, V, VI and VII in corneal sections were in general unchanged in keratoconus corneas, the only differences being in scar tissues observed in the Bowman layer of some keratoconus samples.


Colony morphology on agar is a sensitive indicator for growth effectors.
Colonies of Chinese hamster ovary (CHO) cells growing on agar exhibit changes in colony morphology and size in response to extremely low doses of hormones and growth factors. Computer-aided densitometric scanning of photographs of these colonies allows the quantitative measurement of these morphological changes. Correlation of these changes with dosage for a variety of growth effectors is a sensitive assay for the effects of these factors, both alone and in combination, and should be useful in comparing effects of agents with similar biological activities and in the search for variant cell types with altered responsiveness. Cells growing attached to solid substrates are often responsive to these low dosages and do not seem to mimic in vivo growth effector phenomena as well as colonies growing in three dimensions on agar.


Detection and isolation of human disseminated tumor cells in the murine bone marrow stem cell niche.
The presence of disseminated tumor cells (DTCs) in the bone marrow is associated with poor prognosis of cancer patients. However, little is known about the biology of DTCs due to lack of relevant animal models. Here, we describe the methods for detecting and isolating human DTCs from the murine bone marrow niche by PCR using human Alu sequences and by fluorescence-activated cell sorting and immunohistochemistry using anti-HLA antibody. These strategies could be useful for exploring the biology of DTCs.


Existence of inward potassium currents in adult human oligodendrocytes.
We report the first measurements of single channel currents in cultured adult human oligodendrocytes, obtained postmortem. The channels selectively pass potassium inwardly and possess properties which would be suitable for a physiological role for oligodendrocytes in the human brain as part of a regulatory mechanism for maintenance of extracellular potassium concentration near active neurons. These properties include a long mean open time near normal resting potential and a marked dependence of membrane depolarization to increase the channel open time which could be an important factor when the driving force for inward potassium movement was small. Furthermore, the properties of these potassium channels are remarkably similar to those of channels previously observed in adult bovine oligodendrocytes, which supports the use of animal data to describe function in the human brain.


Rapid, scalable, combinatorial genome engineering by marker-less enrichment and recombination of genetically engineered loci in yeast.
A major challenge to rationally building multi-gene processes in yeast arises due to the combinatorics of combining all of the individual edits into the same strain. Here, we present a precise and multi-site genome editing approach that combines all edits without selection markers using CRISPR-Cas9. We demonstrate a highly efficient gene drive that selectively eliminates specific loci by integrating CRISPR-Cas9-mediated double-strand break (DSB) generation and homology-directed recombination with yeast sexual assortment. The method enables marker-less enrichment and recombination of genetically engineered loci (MERGE). We show that MERGE converts single heterologous loci to homozygous loci at ∼100% efficiency, independent of chromosomal location. Furthermore, MERGE is equally efficient at converting and combining multiple loci, thus identifying compatible genotypes. Finally, we establish MERGE proficiency by engineering a fungal carotenoid biosynthesis pathway and most of the human α-proteasome core into yeast. Therefore, MERGE lays the foundation for scalable, combinatorial genome editing in yeast.


Microbial utilisation of biochar-derived carbon.
Whilst largely considered an inert material, biochar has been documented to contain a small yet significant fraction of microbially available labile organic carbon (C). Biochar addition to soil has also been reported to alter soil microbial community structure, and to both stimulate and retard the decomposition of native soil organic matter (SOM). We conducted a short-term incubation experiment using two (13)C-labelled biochars produced from wheat or eucalypt shoots, which were incorporated in an aridic arenosol to examine the fate of the labile fraction of biochar-C through the microbial community. This was achieved using compound specific isotopic analysis (CSIA) of phospholipid fatty acids (PLFAs). A proportion of the biologically-available fraction of both biochars was rapidly (within three days) utilised by gram positive bacteria. There was a sharp peak in CO2 evolution shortly after biochar addition, resulting from rapid turnover of labile C components in biochars and through positive priming of native SOM. Our results demonstrate that this CO2 evolution was at least partially microbially mediated, and that biochar application to soil can cause significant and rapid changes in the soil microbial community; likely due to addition of labile C and increases in soil pH.


The factor structure and validity of a diagnostic interview for avoidant/restrictive food intake disorder in a sample of children, adolescents, and young adults.
There is a paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID) to aid identification and classification of cases for both clinical and research purposes. To evaluate the factor structure, construct validity, and criterion validity of the Pica ARFID and Rumination Disorder Interview (PARDI; ARFID module), we administered the PARDI to 129 children and adolescents ages 9-23 years (M = 16.1) with ARFID (n = 84), subclinical ARFID (n = 11), and healthy controls (n = 34). We used exploratory factor analysis to examine the factor structure of the PARDI in children, adolescents, and young adults with an ARFID diagnosis, the Kruskal-Wallis analysis of variance and Spearman correlations to test the construct validity of the measure, and non-parametric receiver operating characteristic curves to evaluate the criterion validity of the PARDI. Exploratory factor analysis yielded a 3-factor structure: (1) concern about aversive consequences of eating, (2) low appetite/low interest in food, and (3) sensory sensitivity. Participants with ARFID demonstrated significantly higher levels of sensory sensitivity, low appetite/low-food interest, and concern about aversive consequences of eating symptoms relative to control participants. The construct validity for each PARDI subscale was supported and clinical cutoffs for the low appetite/low interest in food (1.1) and sensory sensitivity subscales (0.6) were established. These data present evidence for the factor structure and validity of the PARDI diagnostic interview for diagnosing ARFID in children, adolescents, and young adults, supporting the use of this tool to facilitate ARFID clinical assessment and research. Due to the paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID), we evaluated the factor structure and validity of the Pica ARFID and Rumination Disorder Interview (ARFID module). Findings suggest that the interview assesses 3 components of ARFID: concern about aversive consequences of eating, low-appetite, and sensory sensitivity, and that clinical threshold scores on the latter two subscales can be used to advance ARFID assessment.


Managing femoral head osteonecrosis in patients with sickle cell disease.
With an increasing number of people immigrating between different countries, sickle cell disease (SCD) is spreading all over the world. Due to improved health care, the life span of SCD patients has increased and many of them live to adulthood and middle-age. Osteonecrosis of the femoral head is one of the most common musculo-skeletal problems in SCD patients. Once osteonecrosis starts in the femoral head, it can progress from early to late stages in just a few years. Managing osteonecrosis of the femoral head in young-adults is a challenging problem and, in many situations, it requires major surgical procedures. In the early stages of the disease it is advisable to treat it by femoral head preserving procedures. In advanced stages, hip replacement arthroplasty (HPA) is indicated. In SCD patients, the incidence of operative complications and failure rates are higher than that for osteonecrosis due to other causes. Understanding the problems of SCD patients; appropriate diagnosis, prognosis, implications of the procedure performed and taking the necessary precautions, can reduce the complications and delay the failure of surgical procedures.


Targeting Disease Persistence in Gastrointestinal Stromal Tumors.
SummaryGastrointestinal stromal tumors (GISTs) represent 20%-40% of human sarcomas. Although approximately half of GISTs are cured by surgery, prognosis of advanced disease used to be poor due to the high resistance of these tumors to conventional chemo- and radiotherapy. The introduction of molecularly targeted therapy (e.g., with imatinib mesylate) following the discovery of the role of oncogenic mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor α (PDGFRA) significantly increased patient survival. However, GIST cells persist in 95%-97% of imatinib-treated patients who eventually progress and die of the disease because of the emergence of clones with drug-resistant mutations. Because these secondary mutations are highly heterogeneous, even second- and third-line drugs that are effective against certain genotypes have only moderately increased progression-free survival. Consequently, alternative strategies such as targeting molecular mechanisms underlying disease persistence should be considered. We reviewed recently discovered cell-autonomous and microenvironmental mechanisms that could promote the survival of GIST cells in the presence of tyrosine kinase inhibitor therapy. We particularly focused on the potential role of adult precursors for interstitial cells of Cajal (ICCs), the normal counterpart of GISTs. ICC precursors share phenotypic characteristics with cells that emerge in a subset of patients treated with imatinib and in young patients with GIST characterized by loss of succinate dehydrogenase complex proteins and lack of KIT or PDGFRA mutations. Eradication of residual GIST cells and cure of GIST will likely require individualized combinations of several approaches tailored to tumor genotype and phenotype. Gastrointestinal stromal tumors (GISTs) are one of the most common connective tissue cancers. Most GISTs that cannot be cured by surgery respond to molecularly targeted therapy (e.g., with imatinib); however, tumor cells persist in almost all patients and eventually acquire drug-resistant mutations. Several mechanisms contribute to the survival of GIST cells in the presence of imatinib, including the activation of "escape" mechanisms and the selection of stem-like cells that are not dependent on the expression of the drug targets for survival. Eradication of residual GIST cells and cure of GIST will likely require individualized combinations of several approaches tailored to the genetic makeup and other characteristics of the tumors.


Salicylic acid: A key regulator of redox signalling and plant immunity.
In plants, the reactive oxygen species (ROS) formed during normal conditions are essential in regulating several processes, like stomatal physiology, pathogen immunity and developmental signaling. However, biotic and abiotic stresses can cause ROS over-accumulation leading to oxidative stress. Therefore, a suitable equilibrium is vital for redox homeostasis in plants, and there have been major advances in this research arena. Salicylic acid (SA) is known as a chief regulator of ROS; however, the underlying mechanisms remain largely unexplored. SA plays an important role in establishing the hypersensitive response (HR) and systemic acquired resistance (SAR). This is underpinned by a robust and complex network of SA with Non-Expressor of Pathogenesis Related protein-1 (NPR1), ROS, calcium ions (Ca2+), nitric oxide (NO) and mitogen-activated protein kinase (MAPK) cascades. In this review, we summarize the recent advances in the regulation of ROS and antioxidant defense system signalling by SA at the physiological and molecular levels. Understanding the molecular mechanisms of how SA controls redox homeostasis would provide a fundamental framework to develop approaches that will improve plant growth and fitness, in order to meet the increasing global demand for food and bioenergy.


MOF-derived nanocrystalline ZnO with controlled orientation and photocatalytic activity.
We show here that MOF-5, a sample Zn-based MOF, can uniquely transform into distinct zinc oxide nanostructures. Inspired by the interconversion synthesis of zeolites, we converted MOF-5 into nanocrystalline ZnO. We found the conversion of MOF-5 into ZnO to be tunable and straightforward simply by controlling the treatment temperature and choosing an appropriate structure-directing agent (SDA). Refined X-ray diffraction (XRD) patterns showed that a synthesis temperature of 180 °C (sample ZnO-180) was optimal for achieving high crystallinity. We examined ZnO-180 with high-resolution transmission electron microscopy (HRTEM), which confirmed that the samples were made of individual crystallites grown along the c-axis, or the (001) direction, thus exposing lower energy surfaces and corroborating the XRD pattern and the molecular dynamics calculations. Further investigations revealed that the obtained ZnO at 180 °C has a superior photocatalytic activity in degrading methylene blue to other ZnO nanostructures obtained at lower temperatures.


Subtype-selective antagonists of lysophosphatidic Acid receptors inhibit platelet activation triggered by the lipid core of atherosclerotic plaques.
Lysophosphatidic acid (LPA) is a platelet-activating component of mildly oxidized LDL (mox-LDL) and lipids isolated from human atherosclerotic plaques. Specific antagonists of platelet LPA receptors could be useful inhibitors of thrombus formation in patients with cardiovascular disease. Short-chain analogs of phosphatidic acid (PA) were examined for their effect on two initial platelet responses, platelet shape change and Ca2+ mobilization. Dioctylglycerol pyrophosphate [DGPP(8:0)] and dioctylphosphatidic acid [PA(8:0)], recently described selective antagonists of the LPA1 and LPA3 receptors, inhibited platelet activation evoked by LPA but not by other platelet stimuli. DGPP(8:0) was more potent than PA(8:0). DGPP(8:0) also inhibited platelet shape change induced by mox-LDL and lipid extracts from human atherosclerotic plaques. Notably, we demonstrate for the first time that the lipid-rich core isolated from soft plaques was able to directly induce shape change. This effect was completely abrogated by prior incubation of platelets with DGPP(8:0). Moreover, coapplication of the lipid-rich core or LPA together with subthreshold concentrations of ADP or epinephrine synergistically induced platelet aggregation; this effect was inhibited by DGPP(8:0). Analysis by liquid chromatography-mass spectrometry revealed the presence of LPA alkyl- and acyl-molecular species with high platelet-activating potency (16:0-alkyl-LPA, 20:4-acyl-LPA). LPA molecules present in the core region of atherosclerotic plaques trigger rapid platelet activation through the stimulation of LPA1 and LPA3 receptors. Antagonists of platelet LPA receptors might provide a new strategy to prevent thrombus formation in patients with cardiovascular diseases.


Isolated renal artery and combined aortic and renal artery reconstruction for renovascular hypertension. Late results of surgical treatment.
Fifty consecutive patients with renal artery occlusive disease underwent surgery for renovascular hypertension. The etiology was arteriosclerosis; only three patients had fibromuscular hyperplasia. Isolated renal artery stenosis was operated on in 22 patients while 28 patients underwent combined renal and aortoiliac/femoral procedures. Four of the patients required re-operation because of unsuccessful primary results. There was no operative mortality. Renin was determined in 29 patients and postoperative angiography was carried out in 22 cases. The patency rate of the aorto-renal grafts was 94%; 2 aneurysmal vein graft dilatations occurred. Preoperative renin assays were positive in 90% of the patients with isolated renal artery stenosis but in only 45% of those having renal and aortoiliac/femoral arteriosclerosis. Postoperatively, the renin values had returned to normal limits in 95% of the patients. Long-term (2-11 years) successful treatment of hypertension was achieved in 79% of the cases with isolated stenosis and in 59% of the cases with aorto-iliac/femoral arteriosclerosis. The patients having a preoperative ipsilateral/contralateral renin ratio greater than or equal to 1.5 showed a success rate of 69%. Normal levels of renin were found in 85% of the successful cases.


A sensitive and robust method for the simultaneous determination of thirty-three legacy and emerging per- and polyfluoroalkyl substances in human plasma and serum.
Legacy and emerging per- and polyfluoroalkyl substances (PFAS) have attracted growing attention due to their potential adverse effects on humans. We developed a method to simultaneously determine thirty-three PFAS (legacy PFAS, precursors, and alternatives) in human plasma and serum using solid phase extraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The method yielded good linearity (>0.995) and excellent limits of detection (LODs) (0.0005~0.012 ng mL-1 in plasma and 0.002~0.016 ng mL-1 in serum). The relative recoveries ranged from 80.1 to 116%, with intra- and inter-day precision less than 14.3%. The robustness of this method has been tested continuously for 10 months (coefficients of variation <14.9%). Our method was successfully applied to the PFAS analysis of 42 real human plasma and serum samples collected from women. The proposed method is attractive for the biomonitoring of multi-class PFAS in human health risk assessment and epidemiological studies.


Growth of 'Candidatus Liberibacter asiaticus' in a host-free microbial culture is associated with microbial community composition.
'Candidatus Liberibacter asiaticus' ('Ca. L. asiaticus'), the suspected causative agent of citrus greening disease, is one of many phloem-restricted plant pathogens that have not been isolated and grown in an axenic culture. In this study, infected Asian citrus psyllids were used to prepare a host-free source of 'Ca. L. asiaticus'. Host-free mixed microbial cultures of 'Ca. L. asiaticus' were grown in the presence of various antibiotic treatments to alter the composition of the microbial communities. Our hypothesis was that the presence of selected antibiotics would enhance or reduce the presence of 'Ca. L. asiaticus' in a host-free culture composed of a mixed bacterial population through changes in the microbial community structure. We determined how 'Ca. L. asiaticus' growth changed with the various treatments. Treatment with vancomycin (50 μg/mL), streptomycin (0.02 μg/mL), or polymyxin B (4 μg/mL) was associated with an increased abundance of 'Ca. L. asiaticus' of 7.35 ± 0.27, 5.56 ± 0.15, or 4.54 ± 0.83 fold, respectively, compared to untreated mixed microbial cultures, while treatment with 100 μg/mL vancomycin; 0.5, 1, or 2 μg/mL streptomycin; or 0.5 μg/mL of polymyxin B was associated with reduced growth. In addition, the growth of 'Ca. L. asiaticus' was associated with the microbial community composition of the mixed microbial cultures. A positive relationship between the presence of the Pseudomonadaceae family and 'Ca. L. asiaticus' growth was observed, while the presence of 'Ca. L. asiaticus' was below the detection limit in cultures that displayed high abundances of Bacillus cereus. Our findings offer strategies for developing effective axenic culture conditions and suggest that enrichment of the Bacillaceae family could serve as a paratransgenic approach to controlling citrus greening disease.


Atrial Fibrillation in Indigenous Australians: A Multisite Screening Study Using a Single-Lead ECG Device in Aboriginal Primary Health Settings.
Circulatory diseases continue to be the greatest cause of mortality for Australian Aboriginal and Torres Strait Islander people, and a major cause of persistently lower life expectancy compared with non-Aboriginal Australians. The limited information that exists on atrial fibrillation (AF) prevalence in Aboriginal and Torres Strait Islander communities is mostly based on hospital admission data. This shows AF as principal or additional admission diagnosis was 1.4 times higher compared to non-Aboriginal Australians, a higher incidence of AF across the adult life span after age 20 years and a significantly higher prevalence among younger patients. Our study estimates the first national community prevalence and age distribution of AF (including paroxysmal) in Australian Aboriginal people. A handheld single-lead electrocardiograph (ECG) device (iECG), known to be acceptable in this population, was used to record participant ECGs. This co-designed, descriptive cross-sectional study was conducted in partnership with 16 Aboriginal Community Controlled Health organisations at their facilities and/or with their services delivered elsewhere. The study was also conducted at one state community event. Three (3) Australian jurisdictions were involved: New South Wales, Western Australia and the Northern Territory. Study sites were located in remote, regional and urban areas. Opportunistic recruitment occurred between June 2016 and December 2017. People <45 years of age were excluded. Thirty (30) of 619 Aboriginal people received a 'Possible AF' and 81 an 'Unclassified' result from a hand-held smartphone ECG device. A final diagnosis of AF was made in 29 participants (4.7%; 95%CI 3.0-6.4%), 25 with known AF (five paroxysmal), and four with previously unknown AF. Three (3) of the four with unknown AF were aged between 55-64 years, consistent with a younger age of AF onset in Aboriginal people. Estimated AF prevalence increased with age and was higher in those aged >55 years than the general population (7.2% compared with 5.4%). Slightly more men than women were diagnosed with AF. This study is a significant contribution to the evidence which supports screening for AF in Aboriginal and Torres Strait Islander people commencing at a younger age than as recommended in the Australian guidelines (>65 years). We recommend the age of 55 years. Consideration should be given to the inclusion of AF screening in the Australian Government Department of Health annual 'Aboriginal and Torres Strait Islander Health Assessment'. ACTRN12616000459426.


Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.
Notch1 signalling plays a multifaceted role in tissue development and homeostasis. Currently, due to the pivotal role of Notch1 signalling, the relationship between NOTCH1 expression and the development of health disorders is being intensively studied. Nevertheless, Notch1 signalling is not only controlled at the transcriptional level but also by a variety of post-translational events. First is the ligand-dependent mechanical activation of NOTCH receptors and then the intracellular crosstalk with other signalling molecules-among those are long non-coding RNAs (lncRNAs). In this review, we provide a detailed overview of the specific role of lncRNAs in the modulation of Notch1 signalling, from expression to activity, and their connection with the development of health disorders, especially cancers.


Influence of hemoglobin and albumin on the NO donation effect of tetranitrosyl iron complex with thiosulfate.
The effects of deoxyhemoglobin (Hb) and albumin on the NO-donor activity of the anionic tetranitrosyl iron complex with thiosulfate ligands (1) were studied for the first time. It was shown that Hb significantly stabilizes complex 1; in its presence, NO generation from the complex proceeds at a noticeably slower rate. A similar effect is observed when complex 1 is bound to albumin, in which case complex 1 decomposes 27 times slower than in the absence of albumin in the solution. The observed effects provide a prolonged action of complex 1 as NO-donor, which may enhance its potential pharmacological efficacy.


Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis.
Caspase-8 is the initiator caspase of extrinsic apoptosis1,2 and inhibits necroptosis mediated by RIPK3 and MLKL. Accordingly, caspase-8 deficiency in mice causes embryonic lethality3, which can be rescued by deletion of either Ripk3 or Mlkl4-6. Here we show that the expression of enzymatically inactive CASP8(C362S) causes embryonic lethality in mice by inducing necroptosis and pyroptosis. Similar to Casp8-/- mice3,7, Casp8C362S/C362S mouse embryos died after endothelial cell necroptosis leading to cardiovascular defects. MLKL deficiency rescued the cardiovascular phenotype but unexpectedly caused perinatal lethality in Casp8C362S/C362S mice, indicating that CASP8(C362S) causes necroptosis-independent death at later stages of embryonic development. Specific loss of the catalytic activity of caspase-8 in intestinal epithelial cells induced intestinal inflammation similar to intestinal epithelial cell-specific Casp8 knockout mice8. Inhibition of necroptosis by additional deletion of Mlkl severely aggravated intestinal inflammation and caused premature lethality in Mlkl knockout mice with specific loss of caspase-8 catalytic activity in intestinal epithelial cells. Expression of CASP8(C362S) triggered the formation of ASC specks, activation of caspase-1 and secretion of IL-1β. Both embryonic lethality and premature death were completely rescued in Casp8C362S/C362SMlkl-/-Asc-/- or Casp8C362S/C362SMlkl-/-Casp1-/- mice, indicating that the activation of the inflammasome promotes CASP8(C362S)-mediated tissue pathology when necroptosis is blocked. Therefore, caspase-8 represents the molecular switch that controls apoptosis, necroptosis and pyroptosis, and prevents tissue damage during embryonic development and adulthood.


[How to deal with the different serum AMH kits in France in 2017?]
Serum AMH measurement became a key element in clinical practice, especially before using Assisted reproductive techniques (ART). However, many AMH kits exist giving different AMH results, leading to a confusion in their interpretation. Until recently, only manual ELISA kits existed (mainly Gen II Beckman, EIA/AMH Immunotech and two Anshlab kits) reporting non-interchangeable results. High and low AMH cut-off values, mainly useful to adapt therapeutics in ART, were different between kits. Since the end of 2014, the arrival of two automatic assays (Access Dxi Beckman and AMH Elecsys Roche) seems to improve the sensitivity and the reproducibility of AMH measurement. It could simplify the interpretation of AMH values and improve our clinical choices. This review synthetizes the main comparisons between the different AMH kits available in 2017 to help clinicians in their daily clinical practice.


Further enhanced production of heterologous proteins by double-gene disruption (ΔAosedD ΔAovps10) in a hyper-producing mutant of Aspergillus oryzae.
The filamentous fungus Aspergillus oryzae is used as one of the most favored hosts for heterologous protein production due to its ability to secrete large amounts of proteins into the culture medium. We previously generated a hyper-producing mutant strain of A. oryzae, AUT1, which produced 3.2- and 2.6-fold higher levels of bovine chymosin (CHY) and human lysozyme (HLY), respectively, compared with the wild-type strain. However, further enhancement of heterologous protein production by multiple gene disruption is difficult because of the low gene-targeting efficiency in strain AUT1. Here, we disrupted the ligD gene, which is involved in nonhomologous recombination, and the pyrG gene to create uridine/uracil auxotrophy in strain AUT1, to generate a hyper-producing mutant applicable to pyrG marker recycling with highly efficient gene targeting. We generated single and double disruptants of the tripeptidyl peptidase gene AosedD and vacuolar sorting receptor gene Aovps10 in the hyper-producing mutant background, and found that all disruptants showed significant increases in heterologous protein production. Particularly, double disruption of the Aovps10 and AosedD genes increased the production levels of CHY and HLY by 1.6- and 2.1-fold, respectively, compared with the parental strain. Thus, we successfully generated a fungal host for further enhancing the heterologous protein production ability by combining mutational and molecular breeding techniques.


Assessing the deformation of pulmonary capillaries produced by ventilation.
We used a Fourier transform method to compute from the density fluctuation of aortic blood the changes in the blood volume of pulmonary capillaries and the transit time from the capillaries to the aorta. First the time constants of a lagged normal density function capable of simulating the saline dilution through the central circulation were established. Then we decomposed the Fourier transform of the lagged normal density function to determine an attenuation for the estimation of the density fluctuation in blood leaving the capillaries. Regarding the low hematocrit blood in the capillaries as a density indicator, we deduced from the density fluctuation the percentage change of capillary volume for dogs ventilated mechanically. This change was found to range from 3.8 to 5.8% for frequencies within 6 to 20 cycles per minute. Based on this simulation and the delay time of the density fluctuation from the tracheal pressure, we estimated that the transit time for the density indicator being released from the pulmonary capillaries to the aorta was 45% of the mean transit time of the central circulation, suggesting that the releasing sites are midway of the pulmonary capillaries.


Inhibition of low density lipoprotein receptor expression by long-term exposure to phorbol ester via p38 mitogen-activated protein kinase pathway.
The proximal region -234 to (+58 bp) of low-density lipoprotein receptor (LDLR) is responsible for its up-regulation by sterol regulatory element binding protein (SREBP). However, the mechanism of sterol-independent repression of LDLR has not been determined yet. In this study, we observed that there was an early induction and a later repression of LDLR by phorbol ester (PMA) in SK-Hep1 hepatocarcinoma cells and investigated the mechanisms through which PMA repressed LDLR transcription. SK-Hep1 cells were exposed to PMA and LDLR mRNA was evaluated by RT-PCR and Northern blot analysis. The effect of phorbol ester on LDLR transcriptional activity was studied using transient transfection of LDLR promoter-luciferase constructs. Overexpression of N-SREBP-2, a dominant positive SREBP2, did not reverse the PMA-repressed LDLR promoter activity. Serial deletion of LDLR promoter revealed that the region between -1,563 and -1,326 was responsible for the repression. The pretreatment with SB202190, an inhibitor for p38 mitogen-activated protein kinase pathway (p38-MAPK), but not other signaling inhibitors, reversed the PMA-induced repression. The 24 h-treatment with PMA efficiently arrested the SK-Hep1 cell cycle at G0/G1 as demonstrated by FACS analysis and decreased the 3H-thymidine incorporation. The PMA-induced repression of LDLR transcription may be exerted by the factor(s), not SREBP2, induced or modified by p38-MAPK-mediated signaling pathway and associated with cell cycle blockage.


Using a Time Timer to increase appropriate waiting behavior in a child with developmental disabilities.
This study aimed to examine the use of a predictive stimulus (Time Timer) and delayed reinforcement to increase appropriate waiting behavior in a child with developmental disabilities and problem behavior maintained by access to tangible items and activities. The study employed a changing criterion design across settings to gradually increase reinforcement delay from 1s to 10 min. Firstly a baseline phase was conducted to measure the duration of appropriate waiting behavior to access tangible reinforcers/activities. Phase 2 involved the use of a red cue card and the verbal instruction "wait". Phase 3 involved the introduction of the Time Timer with the cue card attached, and the verbal instruction "wait". Finally, Phase 4 utilised the Time Timer without the cue card. This method was an effective strategy for increasing appropriate waiting behavior with this participant in a school setting. The role of adding a concurrent activity during the reinforcement delay, using cues to predict reinforcement, future generalization, maintenance and the teaching of functionally equivalent skills are discussed.


Totally extraperitoneal repair for the 'sportsman's groin' via 'the Manchester Groin Repair': a comparison of elite versus amateur athletes.
Surgery has a recognised role in the treatment of 'sportsman's groin'. This study hypothesises that elite athletes have a superior advantage in both pre- and post-op rehabilitation and therefore will present and resume sporting activities quicker. A retrospective analysis on a secure database of athletes presenting with groin pain that underwent surgery for 'inguinal disruption'. All data were explored via appropriate descriptive statistics and comparisons made between elite and amateur athletes. All patients were male (n = 144). The median age 33 years (range 14-72). The median return to sporting activity was 4.5 weeks (range 2.0-16.0) with one amateur athlete being unable to return to sporting activity. Using the mean of both sides, a comparison of VAS pain scores at pre-operative and 1 month post-operative time points showed a significant reduction (p < 0.001). Comparing 'elite' versus 'amateur' athletes, significant differences were seen in patient age (median 26 vs 40 years; p < 0.001), lead time to clinic presentation (median 62.0 vs 111.5 days; p = 0.004), and time to return to sporting activity (4 vs 5 weeks; p = 0.019). Additional MRI findings within the groin girdle were found in 89 patients (66.4%) and 34 patients (23.6%) had an MRI finding within the adductor tendon. The Manchester Groin Rrepair is an effective surgical management for 'inguinal disruption'. Elite athletes present quicker and return to sport sooner. Given the prevalence of other findings, a multidisciplinary approach to the 'sportsman's groin' is required.


Histopathological evaluation of nail lichen planus: A cross-sectional study.
Up to 10% of patients with lichen planus (LP) have nail involvement; still there is a paucity of studies on histopathological features. Nevertheless, nail biopsy is the diagnostic standard, especially for isolated nail LP. Nails of 45 patients with nail LP were evaluated clinically and biopsies taken from most involved nail (25 nail bed and 20 matrix biopsies). Correlation of clinical and histopathological features was also done. The mean age of the study group participants was 36.91 ± 18.27 years with a M:F ratio of 1.81:1. The most common clinical variant of LP seen was oral LP (51%), with isolated nail involvement in 29%. Clinically, major features were onychorrhexis (92.3%), longitudinal melanonychia (74.3%), and nail bed erythema (54%). Histopathologically, hypergranulosis of nail matrix and bed epithelium (51.1%), followed by sawtooth acanthosis (44.4%) and lichenoid band (24.4%) were most common. A diagnosis using prevalent diagnostic criteria was confirmed in 51.1% biopsies. Distinctive "fraying of nail plate," a change not previously described, was noted in 33.3% cases. Histopathology of nail LP has been attributed a diagnostic role; however, existing diagnostic criteria are not sensitive enough and need refinement. Not hitherto described features like fraying of nail plate are seen in a significant number of cases.


Density functional theory study on characterization of 3-chloro-1,2-benzisothiazole.
The FT-IR and FT-Raman spectra of 3-chloro-1,2-benzisothiazole (CBT) have been recorded and analyzed. Theoretical information on the optimized geometry, harmonic vibrational frequencies, infrared and Raman intensities were obtained by means of density functional theory (DFT) gradient calculations, using 6-311++G(d,p) basis set. Mulliken population analysis shows charge distribution on the molecule. Thermodynamic properties like entropy, heat capacity, zero point energy have been calculated for the molecule. The calculated HOMO and LUMO energies show the charge transfer occurs within the molecule. Stability of the molecule has been analyzed using Natural Bond Orbital (NBO) and Natural Localized Molecular Orbital (NLMO) analysis. The results of the calculations were applied to simulated spectra of the title compound, which show the excellent agreement with the observed spectra.


In vitro performance investigation of bioresorbable scaffolds - Standard tests for vascular stents and beyond.
Biodegradable polymers are the main materials for coronary scaffolds. Magnesium has been investigated as a potential alternative and was successfully tested in human clinical trials. However, it is still challenging to achieve mechanical parameters comparative to permanent bare metal (BMS) and drug-eluting stents (DES). As such, in vitro tests are required to assess mechanical parameters correlated to the safety and efficacy of the device. In vitro bench tests evaluate scaffold profiles, length, deliverability, expansion behavior including acute elastic and time-dependent recoil, bending stiffness and radial strength. The Absorb GT1 (Abbott Vascular, Temecula, CA), DESolve (Elixir Medical Corporation, Sunnyvale, CA) and the Magmaris (BIOTRONIK AG, Bülach, Switzerland) that was previously tested in the BIOSOLVE II study, were tested. Crimped profiles were 1.38±0.01mm (Absorb GT1), 1.39±0.01mm (DESolve) and 1.44±0.00mm (Magmaris) enabling 6F compatibility. Trackability was measured depending on stiffness and force transmission (pushability). Acute elastic recoil was measured at free expansion and within a mock vessel, respectively, yielding results of 5.86±0.76 and 5.22±0.38% (Absorb), 7.85±3.45 and 9.42±0.21% (DESolve) and 5.57±0.72 and 4.94±0.31% (Magmaris). Time-dependent recoil (after 1h) was observed for the Absorb and DESolve scaffolds but not for the Magmaris. The self-correcting wall apposition behavior of the DESolve did not prevent time-dependent recoil under vessel loading. The results of the suggested test methods allow assessment of technical feasibility based on objective mechanical data and highlight the main differences between polymeric and metallic bioresorbable scaffolds.


Pancreatic acinar cells: effects of micro-ionophoretic polypeptide application on membrane potential and resistance.
1. Acinar cell membrane potential and resistance were measured from superfused segments of mouse pancreas, in vitro, using intracellular glass micro-electrodes. One or two extracellular micropipettes containing caerulein, bombesin nonapeptide (Bn) or acetylcholine (ACh) were placed near to the surface of the impaled acinus. The secretagogues were ejected rapidly from the micropipettes by ionophoresis.2. Each secretagogue evoked a similar electrical response from the impaled acinar cell: membrane depolarization and a simultaneous reduction in input resistance. The duration of cell activation from caerulein ionophoresis was longer than that observed for ACh and Bn. The cell response to the peptide hormone applications could be repeated in the presence of atropine.3. The minimum interval before the onset of cell depolarization after caerulein ionophoresis was determined. Values ranged between 500 and 1000 msec. The minimum latencies after Bn ionophoresis were 500-1400 msec.4. With two electrodes inserted into electrically coupled acinar cells, direct measurements of the caerulein and Bn null potentials were made. At high negative membrane potentials an enhanced depolarization was evoked by caerulein ionophoresis. At low negative membrane potentials the caerulein stimulation produced a diminished depolarization, and at membrane potentials less than - 10 mV acinar cell hyperpolarizations were observed. A similar series of responses was obtained in experiments where Bn ionophoresis was used. The caerulein and the Bn null potentials were always contained within - 10 to - 15 mV.5. The results describe the almost identical electrical response of acinar cells to stimulation by ACh, caerulein and bombesin. All three secretagogues have similar null potentials and latencies of activation on acinar cells. The bombesin latency responses appear as short as those measured for caerulein and provide electro-physiological evidence that Bn acts directly on acinar cells. The findings support the hypothesis that ACh, caerulein and Bn, though acting on different receptors, evoke the observed changes in electrical properties of acinar cell membranes, through a common pathway.


Detection of an IgM antiidiotype directed against anti-HBs in hepatitis B patients.
An IgM-specific anti-[anti-HBs] antibody was detected by radioimmunoassay using anti-IgM-coated beads and 125I-labeled anti-HBs. This antiidiotype was found only in the sera of hepatitis B virus-infected patients, both acute and chronic. However, not all HBsAg-positive patients exhibited this reaction, and activity was correlated with the presence of HBeAg. Approximately 93% of sera that contained antiidiotype activity also contained HBeAg. Conversely, 70% of the sera positive for HBeAg reacted in the IgM assay. No correlation was observed between the presence of antiidiotype and rheumatoid factor or elevated SGPT levels. Two approaches were used to determine whether the reactive moiety was an IgM anti-[anti-HBs] as postulated or an IgM anti-HBs/HBsAg complex. It was shown that chicken anti-HBs sera, which does not share the common idiotype of human and other mammalian anti-HBs, did not block a positive reaction in this radioimmunoassay even though it specifically bound HBsAg. It was also demonstrated that treatment with polyethylene glycol, which will precipitate IgM anti-HBs/HBsAg activity, did not precipitate the reactive moiety in 6 of 7 sera tested, lending further evidence to the existence of an IgM antiidiotype in these patients. It is suggested that this antiidiotype directed against anti-HBs may be involved in a defective feedback mechanism resulting in the suppression of production of anti-HBs and maintenance of the carrier state.


Cell-size space effects on phase separation of binary polymer blends.
Within living cells, a diverse array of biomolecules is present at high concentrations. To better understand how molecular behavior differs under such conditions (collectively described as macromolecular crowding), the crowding environment has been reproduced inside artificial cells. We have previously shown that the combination of macromolecular crowding and microscale geometries imposed by the artificial cells can alter the molecular behaviors induced by macromolecular crowding in bulk solutions. We have named the effect that makes such a difference the cell-size space effect (CSE). Here, we review the underlying biophysics of CSE for phase separation of binary polymer blends. We discuss how the cell-size space can initiate phase separation, unlike nano-sized spaces, which are known to hinder nucleation and phase separation. Additionally, we discuss how the dimensions of the artificial cell and its membrane characteristics can significantly impact phase separation dynamics and equilibrium composition. Although these findings are, of themselves, very interesting, their real significance may lie in helping to clarify the functions of the cell membrane and space size in the regulation of intracellular phase separation.


Designated nurse for children role must not be watered down.
RISING WORKLOADS are causing designated nurses for safeguarding children to struggle, new research suggests.


The impact of environmental regulations on the location choice of newly built polluting firms: based on the perspective of new economic geography.
Based on the unique micro-data of newly built polluting firms for the period of 2009-2018, this paper adopts the conditional logit model to empirically evaluate the impact of environmental regulations on the location choice of polluting firms. Moreover, we extend the theoretical model by considering that the environment regulations not only influence the pollution cost but also the level of technological innovation and labor cost. The empirical results show that polluting firms tend to flow into areas with stringent environmental regulations, which supports the Porter hypothesis, but the effect of environmental regulations have a divergent impact on heavily polluting firms. Heterogeneous analysis indicates that environmental regulations have shown a positive impact on the location choice of private and foreign-funded firms but no significant impact on that of state-owned firms; the impact of environmental regulation is consistent with pollution haven hypothesis for firms in the central region but is in line with Porter hypothesis for firms in other regions. Meanwhile, the probability of air polluting firms entering areas with stricter environmental regulations is higher than that of water-polluting ones. Finally, this paper further empirically tests the conduction mechanism, that is, environmental regulations can affect the location choice of polluting firms by affecting the regional technological innovation capabilities and labor cost.


Laser printing of microbial systems: effect of absorbing metal film.
Recently, it was shown that laser-induced forward transfer (LIFT) technology and the laser engineering of microbial systems (LEMS) technique (based on LIFT method) are effective for isolation of micro-organisms from different complex substrates. These techniques frequently utilize Au as an absorbing layer material. The purpose of this study was to investigate the influence of absorbing film materials (Au, Ti and Cr) on the effectiveness of laser printing of micro-organisms to improve LEMS and LIFT techniques. It was shown that application of Ti and Cr absorbing layers activates bacterial growth after laser printing and is significantly more effective in comparison to Au films, which actually show a suppressing effect on bacterial cells. Results of this study can be applied for LEMS and LIFT protocols for improving bacterial isolation and microbial growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Laser-induced forward transfer technique (LIFT) is currently used for printing of micro-organisms and in biosensor techniques, for single-cell isolation, and for culturing of micro-organisms from complex substrates. We have studied the influence of absorbing film materials (Au, Ti and Cr) on the effectiveness laser printing of micro-organisms. It was shown that application of Ti and Cr absorbing layers activates bacterial growth and is more effective in LIFT compared to Au films, which actually have a suppressive effect on bacteria cells. The results can improve LIFT protocols for bacteria isolation and culturing of microbial systems.


Emotion Dysregulation and Workplace Satisfaction in Direct Care Worker Burnout and Abuse Risk.
Direct care workers frequently encounter difficult interactions with the patients they serve and experience frustration and burnout. The current study tested a hypothesized model in which predictors of caregiver abuse risk (emotional dysregulation, difficulty managing patient behavior, and workplace satisfaction) were mediated by symptoms of burnout. The study used an online cross-sectional survey design. The study was implemented online via Qualtrics. Participants were 206 direct care workers (eg, certified nursing assistants, patient care technicians, home health aides, and medical assistants). All respondents completed the Caregiver Abuse Screen (CASE), Difficulty with Emotional Regulation Scale (DERS-SF), and the Abbreviated Maslach Burnout Inventory. Demographic data and employment history were also collected. Correlational methods, including path analysis, were used to assess associations between study variables. More than half of this heterogenous sample endorsed significant risk for engaging in patient abuse. Path analysis suggested emotional dysregulation and low workplace satisfaction were associated with greater risk of patient abuse, and these associations were partially and simultaneously mediated by burnout facets of depersonalization and emotional exhaustion. This study provided preliminary support for a model of caregiver abuse in which underlying difficulties regulating emotions convey risk for caregiver abuse via burnout facets including emotional exhaustion and depersonalization. Enhancing basic emotion regulation skills and reducing burnout in direct care staff may reduce the risk of abuse for older adults. Thus, providing training necessary to help direct care workers manage their own emotions in order to better recognize, understand, and respond effectively to the needs of older adults may reduce staff burnout and, consequently, lower the risk of abuse for older adults.


Wright hang-back recession with fibrin glue compared with standard fixed suture recession for the treatment of horizontal strabismus.
To evaluate the clinical safety and efficacy of the novel Wright hang-back recession with fibrin glue for the treatment of horizontal strabismus. Retrospective, case-controlled clinical study comparing surgical outcomes of the Wright hang-back rectus recession with fibrin glue (WHBG) versus standard fixed suture rectus recession (SFR). Medical records of all patients who underwent strabismus surgery by one strabismus surgeon between 2016 and 2018 for horizontal deviations only, including cases of WHBG (group 1) or SFR (group 2), were reviewed. Good surgical outcome was defined as a postoperative deviation ≤10 prism diopters (PD) at a minimum 2 months of follow-up. 32 eyes of 17 patients underwent WHBG and 32 eyes of 17 patients underwent SFR; in each group, 35% had esotropia and 65% had exotropia. Mean preoperative deviations between groups were similar: esotropia 25.5 PD and exotropia 26.6 PD in WHBG; esotropia 28.3 PD and exotropia 23.8 PD in SFR. The mean postoperative deviation was <7 PD for both groups. Good surgical outcomes were similar between groups, 16/17 (94%) in WHBG and 15/17 (88%) in SFR, with no complications. WHBG was safe and effective with postoperative results similar to SFR. WHBG has an important advantage, eliminating the complication of retinal perforation that can occur with SFR while avoiding under- or overcorrection that can occur with traditional hang-back recession. This technique increases patient safety without sacrificing surgical outcomes and is especially useful in patients with thin sclera such as patients with high myopia or with difficult posterior exposure.


Taste and chirality: l-glucose sweetness is mediated by TAS1R2/TAS2R3 receptor.
Naturally occurring sugars usually have d-chirality. While a change in chirality typically affects ligand-receptor interaction, non-caloric l-glucose was reported as sweet for humans. Here we show that l- and d-glucose have similar sensory detection thresholds (0.041 ± 0.006 M for d-glucose, and 0.032 ± 0.007 M for l-glucose) and similar sweetness intensities at suprathreshold concentrations. We demonstrate that l-glucose acts via the sweet taste receptor TAS1R2/TAS1R3, eliciting a dose-dependent activation in cell-based functional assays. Computational docking of glucose to the VFT domain of TAS1R2 suggests two sub-pockets, each compatible with each of the enantiomers. While some polar residues (Y103, D142, N143, S144, Y215) are unique for sub-pocket A and others (D307, T326, E382, R383) for sub-pocket B, no interaction is unique for only one enantiomer. The many options for creating hydrogen bonds with the hydroxyl moieties of glucose explain how both enantiomers can fit each one of the sub-pockets.


Influence of the ultrasound cavitation intensity on reduced graphene oxide functionalization.
Graphene is a valuable and useful nanomaterial due to its exceptionally high tensile strength, electrical conductivity and transparency, as well as the ability to tune its materials properties via functionalization. One of the most important features needed to integrate functionalized graphene into products via scalable processing is the effectiveness of graphene dispersion in aqueous and organic solvents. In this study, we aimed to achieve the functionalization of reduced graphene oxide (rGO) by sonication in a one-step process using polyvinyl alcohol (PVA) as a model molecule to be bound to the rGO surface. We investigated the influence of the sonication energy on the efficacy of rGO functionalization. The correlation between the performance of the high-intensity ultrasonic horn and the synthesis of the PVA functionalized rGO was thoroughly investigated by TGA coupled with MS, and IR, Raman, XPS, Laser diffraction, and SEM analysis. The results show that the most soluble PVA-functionalized rGO is achieved at 50% of the ultrasonic horn amplitude. Analysis of cavitation dynamics revealed that in the near vicinity of the horn it is most aggressive at the highest amplitude (60%). This causes rGO flakes to break into smaller domains, which negatively affects the functionalization process. On the other hand, the maximum of the pressure pulsations far away from the horn is reached at 40% amplitude, as the pressure oscillations are attenuated significantly in the 2-phase flow region at higher amplitudes. These observations corelate well with the measured degree of functionalization, where the optimum functionalized rGO dispersion is reached at 50% horn amplitude, and generally imply that cavitation intensity must be carefully adjusted to achieve optimal rGO functionalization.


The effect of penicillin administration in early life on murine gut microbiota and blood lymphocyte subsets.
Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4+ cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii.


Comparison between the areas of scarred and active toxoplasmic retinochoroiditis.
To assess the ratio of scarred/active areas of fundus lesions in patients with presumed ocular toxoplasmosis. Retrospective monocentric study of patients with presumed ocular toxoplasmosis seen between May 2004 and February 2018. Patients with a positive anti-Toxoplasma serology presenting characteristic fundus lesions. Cases with images of both baseline active and scarred lesions of the fundus were included. The borders of each active or scarred lesion were delineated on colour photographs by two independent observers and the area of the lesions was calculated using Digimizer 4.2.2 (MedCalc Software, Ostend, Belgium). The interobserver variability of the measures was recorded and their means were used for further calculations. To study the ratio of the area of scarred retinochoroiditis over the area of the baseline active lesion (R). A total of 171 cases (83 males, 88 females) with a mean age of 31.6 ± 13.8 years were included. The average areas of active and scarred retinochoroiditis were, respectively, 1.32 ± 1.59 and 1.79 ± 2.36 optic disc area. The average ratio between scarred and active areas of retinochoroiditis was 1.36 [range 0.54-2.18]. The administration of a systemic treatment [R = 1.25, p = 0.003], the absence of a pre-existing scar [R = 1.05, p < 0.001] and a peripapillary location of the lesion [R = 0.85, p < 0.001] were each significantly associated with smaller scarred/active area ratios. We assessed in a standardized manner the ratio of scarred/active areas of toxoplasmic lesions and showed that the area of scarred lesions was on average slightly larger than the area of active retinochoroiditis.


The effect of genotyping error in sib-pair genomewide linkage scans depends crucially upon the method of analysis.
In genomewide linkage scans for complex diseases involving many loci with small genetic effects, it may be the case that no loci reach conventional statistical significance. A complementary method of evaluating linkage results, locus counting, may provide evidence for the existence of a number of genetic loci in these cases. Sib-pair study designs are often used in genomewide linkage scans, but because all genotype configurations are consistent with Mendelian inheritance, genotyping error will go largely undetected. Previous work on the effect of genotyping error has focused on a single disease locus. We considered the effect of two levels of genotyping error on genomewide evidence for linkage by using the simulated GAW 13 data. For affected sib-pair and non-parametric quantitative trait study designs, a 0.5% genotyping error rate reduced the number of independent linkage regions towards that expected under the null hypothesis of no linkage. A 2% genotyping error rate yielded less independent linkage regions than expected under the null hypothesis of no linkage. For a quantitative trait analysed using a parametric regression-based method, there was very little erosion of the linkage signal, even for error rates as high as 2%.


Relative afferent pupillary defect in optic tract hemianopias.
We saw four patients with optic tract lesions and complete homonymous hemianopia. In each patient, the visual acuity was good in both eyes. All four patients had a relative afferent pupillary defect in the eye with the temporal field loss. This pupillary sign is to be expected in all such cases and may serve to differentiate acute optic tract lesions from acute geniculostriate lesions when the characteristic midnasal pallor of the nerve head has not had time to develop.