Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome.
This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol-O-methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18 years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1 years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms.


Social Licence to Operate: What Can Equestrian Sports Learn from Other Industries?
The concept of 'social licence to operate' (SLO) is relevant to all animal-use activities. An SLO is an intangible, implicit agreement between the public and an industry/group. Its existence allows that industry/group to pursue its activities with minimal formalised restrictions because such activities have widespread societal approval. In contrast, the imposition of legal restrictions-or even an outright ban-reflect qualified or lack of public support for an activity. This review discusses current threats to equestrianism's SLO and suggests actions that those across the equine sector need to take to justify the continuation of the SLO. The most important of these is earning the trust of all stakeholders, including the public. Trust requires transparency of operations, establishment and communication of shared values, and demonstration of competence. These attributes can only be gained by taking an ethics-based, proactive, progressive, and holistic approach to the protection of equine welfare. Animal-use activities that have faced challenges to their SLO have achieved variable success in re-establishing the approval of society, and equestrianism can learn from the experience of these groups as it maps its future. The associated effort and cost should be regarded as an investment in the future of the sport.


Secretory IgA, IgG, and IgM immunoglobulins isolated simultaneously from colostral whey by selective thiophilic adsorption.
In order to evaluate the collective contribution of immunoglobulins to gastrointestinal and immune system development in newborn infants, it would be advantageous to develop a simple and rapid procedure for the selective and quantitative removal of all immunoglobulin classes from colostrum and milk. Toward this end, the major immunoglobulin classes typically present in colostrum (IgM, sIgA, and IgG) have been isolated simultaneously by selective removal from a porcine colostral whey model system using a single-step, preparative scale procedure termed thiophilic adsorption. At neutral pH, the salt-promoted thiophilic affinity of immunoglobulins for the synthetic sulfone-thioether ligands exploits a common (as yet unknown) structural feature of immunoglobulins. The adsorption and recovery procedures operate efficiently under mild buffer conditions permitting the subsequent comparative biochemical analyses of individual immunoglobulin classes for structural and functional heterogeneity. Thus, 1 liter columns of thiophilic adsorbent (T-gel) were employed to obtain pure, structurally intact immunoglobulins from 1 liter batches of porcine colostral whey. The identity and purity of the isolated immunoglobulins were determined under both structure-stabilizing ('native') conditions and denaturing conditions using high-performance size-exclusion chromatography, sucrose density gradient centrifugation, immunodiffusion techniques, SDS-polyacrylamide gradient gel electrophoresis with immunoblotting identification procedures, and two-dimensional electrophoresis. This is the first procedure known to us that allows for the simultaneous one-step isolation (under homologous conditions) of various immunoglobulins with preserved quaternary structure and apparent biological activity.


Nutraceutical profiling of elite onion germplasm and breeding hybrids with improved nutraceutical quality.
Onion (Allium cepa L) is a major reservoir of important nutraceutical ingredients. Herein, nutraceutical profiling of elite germplasm was assessed and hybrids with improved nutraceutical quality were selected. The nutraceutical components were screened through Fourier Transform Infrared Spectroscopy (FTIR) analysis (scan range 4000-400cm-1) followed by spectrophotometric/colorimetric quantification in oven dried bulb samples. Line × Tester (L×T) analysis was used to identify potential hybrids with better nutraceutical quality. Based on common functional groups obtained from FTIR analysis, as well as bulb color, the onion genotypes were categorized into six groups viz., white, yellowish brown, light brown, dark brown, brown and purplish brown. Results indicated that the purplish brown, yellowish brown and dark brown genotypes had maximum concentration of pyruvic acid, total flavonoids and total phenolic content, while vitamin C content showed weak association with color pigmentation. The onion variety 'Onion Swat' contained the highest level of pyruvic acid (17.18 μM) and 'MKS8823GO' had the highest vitamin C content (13.83mg/100mL). The L×T analysis revealed that out of 35 crosses, 'MKS-77127 × Onion Swat' and 'MKS-77127 × MKS777' were the best hybrids with improved nutraceutical quality. Further, observations for specific combining ability, general combining ability, genetic versus environmental variance, heritability and heterosis indicated that the studied parameters were genetically inherited and could be improved significantly by adopting an appropriate breeding strategy.


Serum IgM/A, IgA and functionally distinct IgM anti-type III pneumococcal polysaccharide (SIII) antibodies in BALB/c and athymic (nude) mice.
The influence of hereditary absence of thymus upon the synthesis of IgA, complement-fixing (CF) hybrid IgM/A, CF-IgM and non-CF-IgM antibodies to pneumococcal type III polysaccharide (SIII) injected into BALB/c and athymic nude mice was studied. Techniques involved the differential absorption of the serum antibodies by protein-A of Staphylococcus aureus (Sa), coprecipitation in gels with 125I-SIII and autoradiography. IgM/A anti-SIII activity was not demonstrable in nude mice but was produced in significant amounts, by day 5, in BALB/c mice injected with SIII. By day 8, nude mice produced more IgA anti-SIII antibodies than BALB/c mice injected with the same antigen. IgA anti-SIII antibodies were not detected in either strain 5 days after SIII administration. The absence of hybrid IgM/A anti-SIII antibodies in athymic mice, prior to the appearance of monotypic IgA anti-SIII antibodies at day 8, suggests that IgM/A and not IgA synthesis is largely T cell-dependent. The evidence also implies that hybrid IgM/A antibody production, maximal on day 5 in BALB/c mice, and absent from nude mice, is not an essential product in the switching from IgM to IgA synthesis. Both strains of mice produced comparable amounts of complement-fixing (CF)-IgM and NCF-IgM anti-SIII antibodies, with the production of non-complement-fixing (NCF)-IgM anti-SIII in athymic mice being delayed. Results indicate that attempts to quantitate the levels of IgA by assays incorporating anti-IgA anti-sera may be complicated by the presence of IgM/A hybrid antibody.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic characterization of human c-rel sequences.
We isolated and sequenced a human genomic-DNA segment that is homologous to a portion of v-rel, the transforming gene of reticuloendotheliosis virus (strain T). We also localized the human rel sequences to human chromosome 2 by screening a panel of rodent X human somatic-cell hybrids with the newly described human rel segment.


Decoupling phenomena in supercooled liquids: signatures in the energy landscape.
A significant deviation from the Debye model of rotational diffusion in the dynamics of orientational degrees of freedom in an equimolar mixture of ellipsoids of revolution and spheres is found to begin at a temperature at which the average inherent structure energy of the system starts falling with drop in temperature. We argue that this onset temperature corresponds to the emergence of the process as a distinct mode of orientational relaxation. Further, we find that the coupling between rotational and translational diffusion breaks down at a still lower temperature where a change occurs in the temperature dependence of the average inherent structure energy.


Caspase-1 inhibits IFN-β production via cleavage of cGAS during M. bovis infection.
Mycobacterium bovis (M. bovis) infection triggers cytokine production via pattern recognition receptors. These cytokines include type I interferons (IFNs) and interleukin-1β (IL-1β). Excessive type I IFN levels impair host resistance to M. bovis infection. Therefore, strict control of type I IFN production is helpful to reduce pathological damage and bacterial burden. Here, we found that a deficiency in caspase-1, which is the critical component of the inflammasome responsible for IL-1β production, resulted in increased IFN-β production upon M. bovis infection. Subsequent experiments demonstrated that caspase-1 activation reduced cyclic GMP-AMP synthase (cGAS) expression, thereby inhibiting downstream TANK-binding kinase 1 (TBK1)- interferon regulatory factor 3 (IRF3) signaling and ultimately reducing IFN production. A deficiency in caspase-1 activation enhanced the bacterial burden during M. bovis infection in vitro and in vivo and aggravated pathological lesion formation. Thus, caspase-1 activation reduced IFN-β production upon M. bovis infection by dampening cGAS-TBK1-IRF3 signaling, suggesting that the inflammasome protects hosts by negatively regulating harmful cytokines.


Tick-borne encephalitis virus (TBEV) infection in pregnancy: Absence of virus transmission to the fetuses despite severe maternal disease - A case study.
Tick-borne encephalitis (TBE) is an emerging infectious disease in large parts of Europe and Asia. Whereas other members of the Flaviviridae family can harm fetal development, there are only very few reports on TBE virus (TBEV) infections during pregnancy. Thus, the implications for fetal health remain largely unknown. In this study, we present detailed pre- and postnatal health assessment of three children in the context of severe maternal TBEV infection during pregnancy. Following acute TBEV infection of the mothers, intrauterine growth and development of all children were assessed by repetitive prenatal ultrasound. Postnatal examinations included clinical and virological analyses over a follow-up period of 18 months. Prenatally, no signs of intrauterine growth restrictions were observed. All neonates were delivered at term. Umbilical cord blood of the newborns tested negative for TBEV RNA. Virus-specific IgG antibodies were positive at birth but negative at 9 and 11 months of age. Importantly, IgM antibodies remained negative throughout the period of observation. Taken together, these clinical and virological data strongly suggest that fetal TBEV infection did not occur, despite severe manifestations in the mothers.


Factors Associated With Delirium in Children: A Systematic Review and Meta-Analysis.
Pediatric delirium (PD) is a neuropsychiatric syndrome caused by a complex interplay between predisposing factors (e.g., age, cognitive impairment), acute illness, and environmental triggers. PD is associated with substantial morbidity and mortality. The objective of this study is to systematically review and evaluate factors associated with PD in hospitalized pediatric patients. A systematic search of PubMed, Embase, Ovid Medline, Web- of-Science, Cochrane, CIHNAL, and Google Scholar databases was conducted for relevant studies (1990-2022). We included studies that compared pediatric patients with and without delirium. Reviews, editorials, congress abstracts, or studies that did not report factors for PD were excluded. No restrictions were imposed on language. Title and abstract were independently screened by two reviewers. Individual characteristics, study design, and outcomes were independently extracted. Categorical dichotomous data were summarized across groups using Mantel-Haenszel odds ratios (ORs) with 95% 95% CIs. Either fixed-effect or random effects models were used as indicated by the results of a heterogeneity test. Of 1,846 abstracts, 24 studies were included. We identified 54 factors studied in univariate analyses, and 27 of these were associated with PD in multivariable analyses. In pooled analyses, greater odds of PD were associated with developmental delay (OR 3.98; 95% CI 1.54-10.26), need for mechanical ventilation (OR 6.02; 95% CI 4.43-8.19), use of physical restraints (OR 4.67; 95% CI 1.82-11.96), and receipt of either benzodiazepines (OR 4.10; 95% CI 2.48-6.80), opiates (OR 2.88; 95% CI 1.89-4.37), steroids (OR 2.02; 95% CI 1.47-2.77), or vasoactive medication (OR 3.68; 95% CI 1.17-11.60). In this meta-analysis, we identified seven factors associated with greater odds of developing delirium during pediatric critical illness.


Combined effects of noise, vibration and visual field stimulation on electrical brain activity and optomotor responses.
Eye movements and electroencephalographs (EEG) were recorded in intact rabbits during an optokinetic test. The animals were exposed to pure tone noise (85 dB at 4000 Hz), impulse noise (159 dB), and vibration directed at the abdomen (amplitude 0.9 mm at frequencies of 40, 80, and 120 Hz). The velocity of optokinetic nystagmus (OKN) significantly increased with these stimuli. The increase seen with vibration was greater than the noise-induced increase. The response was strongest when noise and vibration were combined. The increase in OKN induced by vibration was successive and dependent on frequency. The increase was weakest during exposure to vibration at 40 Hz and strongest at 120 Hz. EEGs of the dorsal hippocampus, amygdaloid complex, midbrain reticular formation, and frontal motor cortex were all activated during noise and vibration exposure, but activation of the hippocampal EEG was the most closely related to the increase in OKN. Combination of the different stimuli indicated that their interaction could not be predicted on the basis of responses to single stimuli, and, in most cases, the result was indifference due to the high alerting effect of vibration alone. The findings can be related to the non-specific dizziness found in aerospace workers exposed to excessive noise and vibration.


Biomineralization of hypersaline produced water using microbially induced calcite precipitation.
Reusing produced water (PW) as the subsequent hydraulic fracturing fluid is currently the most economical and dominant practice in the shale oil and gas industry. However, high Ca2+ present in PW needs to be removed prior to reuse to minimize the potential for well clogging and formation damage. In this study, the microbially induced calcite precipitation (MICP), as an emerging biomineralization technique mediated by ureolytic bacteria, was employed to remove Ca2+ and toxic contaminants from hypersaline PW for the first time. Batch and continuous studies demonstrated the feasibility of MICP for Ca2+ removal from hypersaline PW under low urea and nutrient conditions. Throughout the continuous biofiltration operation with biochar as the media, high removal efficiencies of Ca2+ (~96%), organic contaminants (~100%), and heavy metals (~100% for As, Cd, Mn and Ni, 92.2% for Ba, 94.2% for Sr) were achieved when PW co-treated with synthetic domestic wastewater (SDW) under the condition of PW:SDW = 1:1 & urea 4 g/L. Metagenomic sequencing analysis showed that a stable ureolytic bacterial consortium (containing Sporosarcina and Arthrobacter at the genus level) was constructed in the continuous biofiltration system under hypersaline conditions, which may play a crucial role during the biomineralization process. Moreover, the combination of the MICP and ammonium recovery could significantly reduce the acute toxicity of PW towards Vibrio fischeri by 72%. This research provides a novel insight into the biomineralization of Ca2+ and heavy metals from hypersaline PW through the MICP technique. Considering the low cost and excellent treatment performance, the proposed process has the potential to be used for both hydraulic fracturing reuse and desalination pretreatment on a large scale.


SIRT3 prevents angiotensin II-induced renal tubular epithelial-mesenchymal transition by ameliorating oxidative stress and mitochondrial dysfunction.
Silent mating type information regulation 2 homolog 3 (SIRT3) is a major protective mediator that ameliorates oxidative stress and mitochondrial dysfunction, which are associated with the pathogenesis of epithelial-mesenchymal transition (EMT). The present study was aimed to investigate the potential role of SIRT3 in renal tubular EMT both in vitro and in vivo. Firstly, we showed that the expression of SIRT3 was repressed in angiotensin II-induced EMT. SIRT3 deficiency triggered EMT response, while over-expression of SIRT3 attenuated EMT response. In addition, over-expression of SIRT3 repressed AngⅡ-induced excessive production of mitochondrial superoxide, as well as mitochondrial dysfunction evidenced by the maintenance of mitochondrial number and morphology, and the stabilization of mitochondrial membrane potential. In conclusion, these findings identify a protective role of SIRT3 against angiotensin II-induced EMT in the kidney, and suggest SIRT3 upregulation is a potential therapeutic strategy for the treatment of renal tubulointerstitial fibrosis.


Cusp Overlap Technique: Should It Become the Standard Implantation Technique for Self-expanding Valves?
Accurate imaging of the aortic root during valve implantation is crucial for proper prosthesis positioning during TAVR. The purpose of this review was to determine if routine use of the cusp-overlap view should be adopted for self-expanding valves. The use of the cusp-overlap view with the Evolut, Portico, ACURATE neo/neo2, and JenaValve systems is associated with lower post-procedural new permanent pacemaker implantation rates when compared with the standard 3-cusp view, presumably due to more precise valve implantation relative to the conduction system by the non-coronary cusp. By elongating the left ventricular outflow tract and accentuating the right-non commissure in the center of the fluoroscopic view, the cusp-overlap technique allows operators to more precisely control the prosthesis implant depth during self-expanding valve deployment. While the early experience with this approach in Evolut TAVR has been promising, the results of larger studies with longer follow-up across multiple self-expanding systems are warranted.


Correction to: Long-acting bronchodilators improve exercise capacity in COPD patients: a systematic review and meta-analysis.
In the original publication [1] is an incorrect sentence in the abstract under Conclusions.


Isolation and initial characterization of glutathione-deficient mutants of Escherichia coli K 12.
The thiol-oxidizing agent "diamide" (CH3)2NCON equal to NCON(CH3)2 was used to isolate mutants of Escherichia coli K 12 deficient in the biosynthesis of glutathione. A colony-colour technique has been developed for identification of colonies of these mutants. Four glutathione-deficient mutants were isolated. They show normal growth rates in minimal medium without GSH supplementation, indicating that glutathione is not involved in essential metabolic process. In one mutant, glutathione synthetase was entirely inactive. Three mutants were deficient in gamma-glutamylcysteine synthetase; in two of them, this resulted in a complete lack of GSH. These mutants were found to be more susceptible than their parent strains to a wide rang of chemical agents, but did not show a greater sensitivity to X-rays. It must be concluded that the protective role of glutathione is only significant when a chemical challenge is present.


Persistent decrease in spermidine/spermine N1-acetyltransferase activity in 'post-regeneration' rat liver.
The activity of cytosolic spermidine/spermine N1-acetyltransferase and polyamine levels were measured in livers of rats killed at different times after partial hepatectomy. The enzyme activity, which showed an early increase a few hours after the operation, had significantly and persistently decreased by the time the liver mass had been regained (10 days) compared to intact rats or sham-operated rats, and up to 30 days after partial hepatectomy, compared to intact rats of the same age. The early induction of spermidine/spermine N1-acetyltransferase activity was also confirmed by the high level of N1-acetylspermidine, which normally is undetectable, and by a dramatic increase in putrescine content. Spermidine levels were increased during the first 10 days after partial hepatectomy, i.e., when the liver had regained its mass, and progressively decreased after this time until 30 days after the operation. The changes in spermine content were similar but not as marked as the changes in spermidine content at the different observation times.


Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19.
The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45-71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.


DNA Interaction, in vitro Antibacterial and Cytotoxic Activities of Ru(III) Heterochelates.
Ruthenium(III) complexes [Ru(bphtpy)(PPh3)Cl3] (bphfpy = diphenylfuranylpyridine derivatives) were synthesized and characterized by LCMS, IR spectroscopy, elemental analysis and magnetic measurements. All the complexes were screened for their antibacterial activity in terms of minimum inhibitory concentration against two Gram-positive and three Gram-negative bacterial species. DNA binding study by absorption titration and viscosity measurement shows that complexes bind in an intercalating mode, which is also confirmed by molecular docking. All the complexes were also screened for the DNA nuclease property of pUC19 plasmid DNA. The cytotoxicity study of the synthesized complexes was performed to elucidate the LC50 values to find out the toxicity profile of the complexes.


Crossover between magnetism and superconductivity in LaFeAsO with low H-doping level.
By making a systematic study of the hydrogen-doped LaFeAsO system by means of dc resistivity, dc magnetometry, and muon-spin spectroscopy, we addressed the question of universality of the phase diagram of rare-earth-1111 pnictides. In many respects, the behaviour of LaFeAsO(1-x)H(x) resembles that of its widely studied F-doped counterpart, with H(-) realizing a similar (or better) electron doping in the LaO planes. In an x = 0.01 sample we found a long-range spin-density wave (SDW) order with TN = 119 K, while at x = 0.05 the SDW establishes only at 38 K and, below Tc = 10 K, it coexists at a nanoscopic scale with bulk superconductivity. Unlike the abrupt magnetic-superconducting transition found in the La-1111 compound, the presence of a crossover region makes the H-doped system qualitatively similar to other Sm-1111, Ce-1111, and Nd-1111 families.


C3a expressed in the central nervous system protects against LPS-induced shock.
Complement is implicated in the pathogenesis of inflammatory disorders of the central nervous system (CNS), like multiple sclerosis, Alzheimer's disease, and trauma. The anaphylatoxins C3a and C5a are thought to be the major contributors to complement-mediated inflammation in the CNS, likely mediating their effects via their ability to attract and activate leukocytes and common capacity to augment inflammation. For example, in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, CNS-specific expression of C3a in C3a/GFAP transgenic mice renders them prone to massive cellular infiltration of the CNS and increases their mortality. In contrast, other studies have suggested that C3a can function in an anti-inflammatory fashion in the CNS, by inducing neurotrophin production and preventing NMDA-mediated neurotoxicity. To further investigate the seemingly paradoxical role of C3a in acute inflammation of the brain, we studied the pathogenesis of endotoxin shock in C3a/GFAP transgenic, C3a receptor-deficient (C3aR-/-) and C3a/GFAPxC3aR-/- mutant mice. Here we report that C3a/GFAP mice were significantly more resistant to endotoxin-induced lethality than wild-type and C3aR-/- mice. Surprisingly, C3a/GFAPxC3aR-/- hybrids were also significantly protected, indicating that C3a exerts its protective anti-inflammatory effect either directly or via an as yet unidentified non-canonical C3aR.


Early nephrology care provided by the nephrologist alone is not sufficient to mitigate the social and psychological aspects of chronic kidney disease.
Patients with chronic kidney disease who receive early nephrology care have a better prognosis with maintenance dialysis. We aimed to determine whether early referral to a nephrologist can also improve the psychological burden of having chronic kidney disease. Thirty-nine patients with chronic kidney disease that required hemodialysis were studied: 19 had a $ 6-month history of nephrology care (Group1), and 20 had never received any prior nephrology care (Group2). All patients participated in a semi-structured interview that addressed their perceived knowledge and psychological aspects related to CKD and hemodialysis. Demographic and laboratory data as well as socioeconomic status were evaluated. In both groups, most of the patients were of low socioeconomic status. Group 1 had significantly better laboratory parameters (p<0.05). The patients' answers to the questions showed no differences between the groups: 63% of Group 1 and 55% of Group 2 reported that they had no prior knowledge about dialysis; 58% and 40%, respectively, reported that they ''don't completely understand what the doctor says''; and 74% and 85%, respectively, believed that their ''kidneys would work again''. Pre-dialysis nephrology care improves the clinical conditions of the patients with chronic kidney disease but is insufficient for minimizing other aspects of having chronic kidney disease.


Genetic and morphological characterization of Ixodes apronophorus from Western Siberia, Russia.
Genetic variability of I. apronophorus from Western Siberia, Russia was examined using the nuclear internal transcribed spacer 2 (ITS2) and mitochondrial 16S rRNA and cytochrome c oxidase subunit 1 (cox1) genes and compared to those of Ixodes persulcatus and Ixodes trianguliceps from the same site. The I. apronophorus sequences demonstrated the highest nucleotide and haplotype diversity for both mitochondrial genes, whereas I. persulcatus was more variable in the nuclear ITS2. Phylogenetic analysis of the molecular sequence data showed that I. apronophorus differed from other Ixodes species, including Romanian I. apronophorus. The level of identity between 16S rRNA gene sequences of Siberian and Romanian I. apronophorus was only 91%; these sequences did not form a monophyletic group, indicating that I. apronophorus from Siberia and Romania could be different tick species. The analysis of morphological features of the Siberian I. apronophorus confirmed their consistency with those for the previously described I. apronophorus species. Based on the 16S rRNA and ITS2 sequences, Siberian I. apronophorus clustered together with Ixodes kazakstani and Ixodes scapularis, which are the recognized members of the Ixodes ricinus-I. persulcatus species complex within the subgenus Ixodes, and can be assigned to this complex.


Stuck on you: Meninges cellular crosstalk in development.
The spatial and temporal development of the brain, overlying meninges (fibroblasts, vasculature and immune cells) and calvarium are highly coordinated. In particular, the timing of meningeal fibroblasts into molecularly distinct pia, arachnoid and dura subtypes coincides with key developmental events in the brain and calvarium. Further, the meninges are positioned to influence development of adjacent structures and do so via depositing basement membrane and producing molecular cues to regulate brain and calvarial development. Here, we review the current knowledge of how meninges development aligns with events in the brain and calvarium and meningeal fibroblast "crosstalk" with these structures. We summarize outstanding questions and how the use of non-mammalian models to study the meninges will substantially advance the field of meninges biology.


Effects of tributyltin on gonad and brood pouch development of male pregnant lined seahorse (Hippocampus erectus) at environmentally relevant concentrations.
The male pregnancy of seahorses is unique, but their reproductive response to environmental disturbances has not yet been clarified. Tributyltin (TBT) is known to have an endocrine disrupting effect on the reproductive system of coastal marine organisms. This study evaluated the potential effects of exposure to environmentally relevant concentrations of TBT on the development of gonads and brood pouch of the lined seahorse (Hippocampus erectus). Physiological, histological, and transcriptional analyses were conducted, and results showed that high levels of TBT bioaccumulation occurred in male and female seahorses. TBT led to ovarian follicular atresia and apoptosis with the elevation of androgen levels, accompanied by the induction of genes associated with lysosomes and autophagosomes. Comparative transcriptional analyses revealed the likely inhibition of spermatogenesis via the suppression of cyclic AMP and androgen synthesis. Notably, the transcriptional profiles showed that TBT potentially affects the immune system, angiogenesis, and embryo nourishment of the brood pouch, which indicates that it has negative effects on the male reproductive system of seahorses. In summary, this study reveals that environmental levels of TBT potentially affect the reproductive efficiency of seahorses, and may ultimately lead to a reduction in their populations in coastal environments.


Self-Care and Sense of Coherence: A Salutogenic Model for Health and Care in Nursing Education.
Effective advocacy on self-care and the enhancement of a sense of coherence among nurses don't only benefit control over one's health and personal performance, but it may have a direct impact on clinical care and on the entire healing system. In this regard, nursing curricula grounded on a salutogenic model of health (SMH) operate with strategies to engage students in self-care and contribute to improving their mental health and wellbeing. The aim of this study was to explore the relationships between self-care agency and a sense of coherence as dependent variables and the age and self-reported academic performance as independent variables in nursing assistant students. For this cross-sectional study, data were collected from a full sample of 921 Certified Nursing Assistant (CNA) Spanish students. A self-administered questionnaire, including sociodemographic variables, the 'appraisal of self-care agency' (ASA), and the 'sense of coherence' (SOC) constructs, was administered. Older participants presented significantly stronger values of both constructs. Apart from a significant and positive correlation between ASAS and SOC, ANOVA analyses indicate significant differences in terms of academic performance according to different ASAS and SOC degrees. The findings of this study endorse the assumption that there is a consistent relationship between ASA and SOC constructs that might, indeed, have a potential effect on students' academic performance. In practical terms, it seems relevant to try to recognise the students' self-care agency and the sense of coherence as forceful predictive variables of mental health and wellbeing, in addition to academic success as a strength implied in the future career achievement.


Influence of the type of F8 gene mutation on inhibitor development in a single centre cohort of severe haemophilia A patients.
The development of neutralizing antibodies against factor VIII (FVIII) is a major complication of treatment with FVIII in patients with severe haemophilia A. This study was designed to describe the relationship between the type and location of the factor 8 (F8) gene mutation and the development of clinically relevant inhibitors in patients with severe haemophilia A. We conducted a single centre cohort study among 318 consecutive patients (baseline FVIII activity level <0.01 IU mL(-1)) born between 1934 and 2007 who were treated with FVIII on at least 50 exposure days. The primary outcome was clinically relevant inhibitor development, defined as the occurrence of at least two positive inhibitor titres and a decreased recovery. Clinically relevant inhibitors were diagnosed in 14% (43) of patients (30 high-titre). The cumulative incidence of inhibitor development was 18% (35 of 200) in high-risk gene defects (67% in patients with large deletions, 30% in patients with nonsense mutations, 15% in patients with intron 1 or 22 inversions) and 7% (8 of 118) in low-risk gene defects (7% in patients with small deletions and insertions, 6% in patients with missense mutations, 8% in patients with splice site mutations). In patients with point mutations, the cumulative risk of developing inhibitors was highest in patients with mutations in the A3 and C2 domains (13% and 17% respectively). In conclusion, in agreement with earlier observations, the type and location of the F8 gene mutation were important determinants of inhibitor development in patients with severe haemophilia A.


Carboxylesterase inhibitors from clinically available medicines and their impact on drug metabolism.
Mammalian carboxylesterases (CES), the key members of the serine hydrolase superfamily, hydrolyze a wide range of endogenous substances and xenobiotics bearing ester or amide bond(s). In humans, most of identified CES are segregated into the CES1A and CES2A subfamilies. Strong inhibition on human CES (including hCES1A and hCES2A) may modulate pharmacokinetic profiles of CES-substrate drugs, thereby changing the pharmacological and toxicological responses of these drugs. This review covered recent advances in discovery of hCES inhibitors from clinically available medications, as well as their impact on CES-associated drug metabolism. Three comprehensive lists of hCES inhibitors deriving from clinically available medications including therapeutic drugs, pharmaceutical excipients and herbal medicines, alongside with their inhibition potentials and inhibition parameters, are summarized. Furthermore, the potential risks of hCES inhibitors to trigger drug/herb-drug interactions (DDIs/HDIs) and future concerns in this field are highlighted. Potent hCES inhibitors may trigger clinically relevant DDIs/HDIs, especially when these inhibitors are co-administrated with CES substrate-drugs with very narrow therapeutic windows. All data and knowledge presented here provide key information for the clinicians to assess the risks of clinically available hCES inhibitors on drug metabolism. In future, more practical and highly specific substrates for hCES1A/hCES2A should be developed and used for studies on CES-mediated DDIs/HDIs both in vitro and in vivo.


A symptomatological assessment of organophosphate-induced lethality in mice: comparison of atropine and clonidine protection.
A comprehensive symptomatological observational battery in conjunction with acute toxicity testing, evaluated with the method of a hyperbolic curve relating survival time (T) to dose (D), was used to characterize quantitatively the lethal toxicities of the organophosphorus (OP) compound, sarin, in mice. The experimental data observed with sarin (0.4-4.0 mg/kg s.c.), alone or in combination with atropine (ATR) (20 mg/kg i.p.), were plotted as a graph of D/T against D, a linearizing transformation of the hyperbolic function. This linearized plot gave two straight lines, deflecting at 1.2 mg/kg, in terms of latency to whole body tremor (BT) and loss of the righting reflex (LR). At lower lethal doses of sarin (0.4-1.2 mg/kg) with ATR pretreatment, the D/T vs. D curves of BT and LR were shifted in parallel to the left, while at high lethal doses (1.6-4.0 mg/kg) these curves interpolatedly converged. The sequelae and/or severity of symptoms were also comparatively different between the range of lower and high lethal doses as noted above. It has been claimed that the protective actions of ATR and clonidine (CLD) against the lethal effects of cholinesterase inhibitors are associated with different underlying mechanisms, i.e. presynaptic versus post-synaptic cholinergic inhibition. The protective effects of a single dose of ATR (20 mg/kg) and CLD (1.0 mg/kg), after 38 and 15 min of intraperitoneal pretreatment, respectively, alone or in combination, challenged with 2 x, 4x and 8x LD50's of sarin were also comparatively evaluated. ATR resulted in a nonsignificant increase in latency to onset of BT and LR. CLD significantly delayed the onset of these symptoms against all 3 dose levels of sarin intoxication, whereas ATR plus CLD additively increased the latency to the onset of these symptoms. The present results indicate that at lower dosages of sarin (less than or equal to 4 x LD50's) its mode of action appears to be mediated mainly by a/muscarinic mechanism, whereas at high doses it is mediated by some other non-specific actions superimposed on the cholinergic actions of sarin. The present study also lends support to the hypothesis of the existence of different forms of OP intoxication on the strength of lethal exposure. The possible mechanisms of both sarin lethality and ATR- and CLD-mediated protection are briefly discussed.


A novel Cdk2 interactor is phosphorylated by Cdc7 and associates with components of the replication complexes.
Initiation of DNA replication in eukaryotic cells depends on the assembly of the prereplication complexes containing two hexamers, the Origin Recognition Complex (ORC) and the Minichromosome maintenance/DNA Replication Licensing complex (MCM); and on the subsequent conformational changes in the MCM complex leading to the formation of a competent DNA replication complex, firing of the DNA polymerase and disassembly of the MCM. The dynamics of the MCM complex is under the control of two Ser/Thr kinases, the Cell cycle-dependent kinase 2 (Cdk2) and Cell division cycle gene 7 (Cdc7). The precise substrates of the kinases at the origins and the sequence of events leading to the origins firing are not well understood. Using the two hybrid selection in yeast, we have identified a novel gene, the Cdk2 interacting protein, CINP. We show that CINP is a component of the active cyclin E /Cdk2 and cyclin A /Cdk2 complexes. CINP also interacts with Cdc7 and is phopshorylated by Cdc7, but not by Cdk2. We further show that CINP binds to chromatin in a replication-dependent manner, and associates with ORC2-containing complexes and MCM. We propose that CINP is part of the Cdc7-dependent mechanism of origin firing and a functional and physical link between Cdk2 and Cdc7 complexes at the origins.


Precautionary risk assessment of Bt maize: what uncertainties?
GM crops have become a test case for the conflicting slogans of 'the precautionary principle' versus 'sound science.' The issues can be illustrated by developments in regulatory science for Bt maize in the European Union. As this case study suggests, risk assessment is always framed by some account of the relevant uncertainties. These in turn depend upon how the environment is valued and how scientific questions are posed about cause-effect pathways of potential harm. The slogan of 'sound science' hides such judgements, by representing ignorance or value-judgements as 'science.' By contrast, precaution can challenge such judgements, identify new unknowns, generate different criteria for evidence, open up new scientific questions, and make these judgements more transparent. It is doubtful whether these complexities have been fully acknowledged by specialists, and thus whether the continued risk debate is due solely to a public misunderstanding of science.


The functional role of UBA1 cysteine-278 in ubiquitination.
Although total UBA1 levels were unchanged, after oxidation for 60 min, we observed dramatic changes in the levels of BIAM-labeled UBA1 in both the membrane and cytosol fractions that suggested oxidative stress induces translocation of UBA1 from the cytosol to the membrane. Notably, in PrdxII(-/-) oxRBCs, ubiquitination levels were reduced about 75% in the membrane fraction after 90 min, even though UBA1 levels were increased. These results suggest ubiquitination levels are determined by UBA1 activity, not the level of UBA1 protein. Levels of ubiquitin conjugate (denoted ∼Ub) in HEK293T and CMT93 cells transfected with UBA1(C278S) or UBA1(C632S) were lower than in cells expressing UBA1(WT) or another cysteine mutant. During the reaction, UBA1(WT)∼Ub was nearly completely eliminated within 30 min, whereas UBA1(C278S)∼Ub and UBA1(C632S)∼Ub persisted. Within UBA1(C278S)∼Ub, the catalytic cysteine (Cys-632) remained intact; nonetheless, migration of UBA1(C278S)∼Ub and UBA1(C632S)∼Ub were similar. These data suggest that Cys-278 can affect Ub charging through a change in the structural conformation of UBA1, not through direct interaction at the UBA1-Ub interface.


CHRONIC PEDIATRIC RETINAL DETACHMENT WITH MULTIPLE MACROCYSTS.
To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature. Case report with fundus photography and optical coherence tomography. We describe a case of an asymptomatic, 11-year-old boy with a chronic rhegmatogenous retinal detachment with multiple peripheral macrocysts. The patient had counting fingers visual acuity on presentation. The detachment was successfully surgically repaired with scleral buckling, subretinal fluid drainage, cryotherapy, and a SF6 tamponade. At the 12-month follow-up, the retina remained attached with improvement of visual acuity to 20/100 with resolution of the cysts. Optical coherence tomography revealed loss of macular ellipsoid zone. Genetic testing revealed a heterozygous dominant COL11A1 mutation. To the authors' knowledge, this is the first reported case of chronic retinal detachment presenting with multiple peripheral macrocysts in a pediatric patient with Stickler syndrome. More research is needed into the cause and significance of retinal macrocysts, particularly in the pediatric population.


Use of horseradish peroxidase-labelled antiglobulin for the colorimetric quantitation of erythrocyte antibodies.
Horseradish peroxidase (HRP)-labelled antiglobulin has been used extensively as a histochemical marker. In the method described the stable reaction product formed by using 3,3'-diaminobenzidine (DAB) as the hydrogen donor in the peroxidase reaction was dissolved in a fluoro alcohol, 1,1,1,3,3,3-hexafluoroisopropanol (HPF). Reproducible standardisation curves resulted with HRP. Based on these observations a colorimetric assay procedure was developed to quantitate the amount of antibody coating red cells. This was achieved by treating the coated red blood cells with HRP-labelled rabbit antihuman IgG followed by hypotonic lysis separating the ghosts for colour development with the DAB reagent, solubilisation in HFP, and reading at 450 nm. Preliminary estimates of the number of anti-D molecules on Rhesus positive red cells were found to approximate the results reported using radioiodinated antibodies. The smallest number of anti-D molecules detected was 350 per red cell. Qualitative studies indicate that this procedure can be applied to other blood group systems.


Regulation of IgA responses in cattle, humans and mice.
Secretory IgA (SIgA) constitutes the largest component of the humoral immune system of the body with gram quantities of this isotype produced by mammals on a daily basis. Secretory IgA (SIgA) antibodies function by both blocking pathogen/commensal entry at mucosal surfaces and virus neutralization. Several pathways of induction of IgA responses have been described which depend on T cells (T cell dependent or TD) pathways or are independent of T cells (T-independent or TI) and are mediated by dendritic cells (DCs) and/or epithelial cells. Many elements of IgA regulation readily cross species barriers (adjuvants, soluble and cognate factors) and are highly conserved whereas other pathways may be more specific to any given species and must be evaluated. Regulation of IgA production in cattle is not completely understood and thus we have focused in part on highly conserved factors such as transforming growth factor beta, Type I and Type 2 interferons, neuropeptides which interdigitate mucosal tissues (vasoactive intestinal peptide or VIP), and a small peptide (IgA inducing peptide or IGIP) which can serve as targets for modulation and increasing SIgA virus-specific antibodies. We have evaluated the potential utility of modulating these factors in vitro in regulation of qualitative aspects of antibodies of the IgM, IgG and IgA isotypes at mucosal surfaces and in secretions of the upper and lower respiratory tract to a virus of economic and public health importance, foot and mouth disease virus (FMDV). IgA responses in cattle are essential for host defense in response to various infectious agents. In cattle, IgA is not released into the colostrum, as is the case for other mammals but only IgG1 is selectively transported. In previous studies in cattle, IgA has been shown to be regulated by several cytokines including IFN-gamma, Type I interferons such as IFN-alpha and IFN-tau, transforming growth factor beta, IgA inducing peptide and other potential factors such as APRIL and BlyS which have not yet been fully evaluated in cattle. Many of these factors, namely TGF-beta and Type I interferons block cell cycle progression which is an essential component of Ig class switching and thus these factors require additional regulatory factors such as IL-2 to drive cells through cell cycle resulting in class switch recombination. Among these factors, IgA inducing peptide was originally identified from a bovine gut associated lymphoid tissue expression library and is highly conserved in pigs and humans at >90% at the amino acid level. The factor is regulated differently in various species but is consistently produced by dendritic cells.


Fabrication and performance of a 40-MHz linear array based on a 1-3 composite with geometric elevation focusing.
The fabrication and performance of a 256-element high-frequency (40-MHz) linear array is described. The array was fabricated using a high-frequency 1-3 PZT-polymer composite material developed in our laboratory. The spacing of the pillars in the composite was chosen to match the 40-microm center-to-center element spacing of the array electrodes. The element electrodes were created using photolithography, and connections to the electrodes were made using ultrasonic wire bonding. The array was focused in the elevation direction by geometrically shaping the composite material using a cylindrical die with a 6-mm radius of curvature. The resulting transducer produced pulses with a -6 dB two-way bandwidth of 50% and a peak-to-peak pressure of 503 kPa when excited with a +/-30 V monocycle pulse. The measured one-way (-6 dB) directivity for a single array element was 24 degrees and the -3 dB one-way elevation beamwidth was measured to be 130 microm. The radiation pattern for a focused 64-element subaperture was measured by mechanically translating the aperture above a needle hydrophone. A -3 dB one-way beamwidth of 97 microm was found at a depth of 6 mm. The one-way radiation pattern decreased smoothly to less than -30 dB at a lateral distance of 640 microm.


Temperature sensing using junctions between mobile ions and mobile electrons.
Sensing technology is under intense development to enable the Internet of everything and everyone in new and useful ways. Here we demonstrate a method of stretchable and self-powered temperature sensing. The basic sensing element consists of three layers: an electrolyte, a dielectric, and an electrode. The electrolyte/dielectric interface accumulates ions, and the dielectric/electrode interface accumulates electrons (in either excess or deficiency). The ions and electrons at the two interfaces are usually not charge-neutral, and this charge imbalance sets up an ionic cloud in the electrolyte. The design functions as a charged temperature-sensitive capacitor. When temperature changes, the ionic cloud changes thickness, and the electrode changes open-circuit voltage. We demonstrate high sensitivity (∼1 mV/K) and fast response (∼10 ms). Such temperature sensors can be made small, stable, and transparent. Depending on the arrangement of the electrolyte, dielectric, and electrode, we develop four designs for the temperature sensor. In addition, the temperature sensor has good linearity in the range of tens of Kelvin. We further show that the temperature sensors can be integrated into stretchable electronics and soft robots.


Corrigendum: Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.
[This corrects the article DOI: 10.3389/fpsyg.2020.568073.].


Effect of contact vector direction on achieving cavotricuspid isthmus block.
Cavotricuspid isthmus (CTI) ablation is an important treatment strategy for CTI-dependent atrial flutter (AFL). The location of the catheter contact area is confirmed by the contact vector direction (CVD) through three-dimensional mapping during the procedure. However, the relationship between CVD during radiofrequency ablation and its efficacy in achieving CTI block has not been clarified. This study aimed to investigate the relationship between CVD and efficacy in achieving CTI block. CVDs during radiofrequency ablation were divided into proximal vectors against the distal tip (P-vector) and other vectors (normal-vector). In 39 patients who underwent CTI linear ablation, the CTIs were divided into two segments: the tricuspid valve area (anterior) and inferior vena cava area (posterior). The frequency of the residual conduction gap was compared between segments in which the P- and normal-vectors were observed. P-vectors were observed in 13 of the 78 segments. The median ablation index was not significantly different between segments in which the P-vector and normal-vector were observed (398.2 [384.2-402.2] vs. 393.3 [378.3-400.1], p = 0.15). However, residual conduction gaps were significantly more frequently observed in the segment in which the P-vector was observed than those in which only the normal-vector was observed (6/13, 46.2% vs. 3/65, 4.6%; p < 0.01). During a 6-month follow-up, two patients required a second session of ablation due to AFL recurrence. A residual conduction gap was observed in one patient at the site where the P-vector was observed in the first session. Avoiding the P-vector might be an important factor in improving CTI block and reducing AFL recurrence.


Intranasal Salvinorin A Improves Long-term Neurological Function via Immunomodulation in a Mouse Ischemic Stroke Model.
Salvinorin A (SA), a highly selective kappa opioid receptor agonist, has been shown to reduce brain infarct volume and improve neurological function after ischemic stroke. However, the underlying mechanisms have not been fully understood yet. Therefore, we explored whether SA provides neuroprotective effects by regulating the immune response after ischemic stroke both in the central nervous system (CNS) and peripheral circulation. In this study, adult male mice were subjected to transient Middle Cerebral Artery Occlusion (tMCAO) and then were treated intranasally with SA (50 μg/kg) or with the vehicle dimethyl sulfoxide (DMSO). Multiple behavioral tests were used to evaluate neurofunction. Flow cytometry and immunofluorescence staining were used to evaluate the infiltration of peripheral immune cells into the brain. The tracer cadaverine and endogenous immunoglobulin G (IgG) extravasation were used to detect blood brain barrier leakage. We observed that SA intranasal administration after ischemic stroke decreased the expression of pro-inflammatory factors in the brain. SA promoted the polarization of microglia/macrophages into a transitional phenotype and decreased the pro-inflammatory phenotype in the brain after tMCAO. Interestingly, SA treatment scarcely altered the number of peripheral immune cells but decreased the macrophage and neutrophil infiltration into the brain at 24 h after tMCAO. Furthermore, SA treatment also preserved BBB integrity, reduced long-term brain atrophy and white matter injury, as well as improved the long-term neurofunctional outcome in mice. In this study, intranasal administration of SA improved long-term neurological function via immuno-modulation and by preserving blood-brain barrier integrity in a mouse ischemic stroke model, suggesting that SA could potentially serve as an alternative treatment strategy for ischemic stroke.


Presurgical accuracy of dipole clustering in MRI-negative pediatric patients with epilepsy: Validation against intracranial EEG and resection.
To assess the utility of interictal magnetic and electric source imaging (MSI and ESI) using dipole clustering in magnetic resonance imaging (MRI)-negative patients with drug resistant epilepsy (DRE). We localized spikes in low-density (LD-EEG) and high-density (HD-EEG) electroencephalography as well as magnetoencephalography (MEG) recordings using dipoles from 11 pediatric patients. We computed each dipole's level of clustering and used it to discriminate between clustered and scattered dipoles. For each dipole, we computed the distance from seizure onset zone (SOZ) and irritative zone (IZ) defined by intracranial EEG. Finally, we assessed whether dipoles proximity to resection was predictive of outcome. LD-EEG had lower clusterness compared to HD-EEG and MEG (p < 0.05). For all modalities, clustered dipoles showed higher proximity to SOZ and IZ than scattered (p < 0.001). Resection percentage was higher in optimal vs. suboptimal outcome patients (p < 0.001); their proximity to resection was correlated to outcome (p < 0.001). No difference in resection percentage was seen for scattered dipoles between groups. MSI and ESI dipole clustering helps to localize the SOZ and IZ and facilitate the prognostic assessment of MRI-negative patients with DRE. Assessing the MSI and ESI clustering allows recognizing epileptogenic areas whose removal is associated with optimal outcome.


Release and characterization of cholecystokinin from isolated canine jejunal cells.
We have developed an isolated intestinal cell system to study the regulation of cholecystokinin release. Enzymatically dispersed canine jejunal mucosal cells were separated by counterflow elutriation to enrich cholecystokinin content 20-fold. Release of cholecystokinin from freshly isolated cells was determined by radioimmunoassay. Elevated extracellular potassium, dibutyryl cyclic adenosine monophosphate, and the diterpene derivative forskolin each stimulated an increase in cholecystokinin release over a 60-min period compared to basal secretion. L-Tryptophan stimulated a dose-dependent and stereospecific increase in cholecystokinin. D-Tryptophan did not significantly alter basal cholecystokinin secretion. Carbachol inhibited L-tryptophan-stimulated cholecystokinin release in a dose-dependent manner. Analysis of extracts from intact jejunal mucosa by high-pressure liquid chromatography revealed three components with cholecystokinin immunoreactivity eluting in positions with cholecystokinin 8, with cholecystokinin 33/39, and after cholecystokinin 33/39. Only the two molecular forms coeluting, respectively, with cholecystokinin 8 and cholecystokinin 33/39 were present in the elutriator-enriched jejunal cells, and these two forms of cholecystokinin immunoreactivity were released from cells upon stimulation. These data suggest that L-tryptophan directly regulates the release of cholecystokinin and that membrane depolarization and intracellular generation of cyclic adenosine monophosphate may play a role in activating cholecystokinin cells. Stimulated cholecystokinin release is inhibited by the muscarinic agonist carbachol. The molecular profile of released cholecystokinin corresponded to the two molecular components, cholecystokinin 8 and cholecystokinin 33/39, contained in dispersed cells.


Sirex noctilio infestation led to inevitable pine death despite activating pathways involved in tolerance.
Defense-related metabolome traits in pine species after infestation by Sirex noctilio are largely unknown, despite, in most cases, trees being overwhelmed. Using LC-MS-based untargeted metabolomics, we revealed the systemic metabolic changes induced by this insect in 14-year-old Pinus radiata trees, the most affected species worldwide. An immediate metabolome alteration was expressed in needles after infestation, including the up-regulation of flavonols, flavan-3-ols, oxyneolignans, auxins, proline, and tryptophan, among others. The flavan-3-ols (catechin and procyanidin B1) suggested a rapidly induced photoprotection mechanism aided by diverting proline as an alternative substrate for respiration to compensate for the progressive chlorosis that degrades photosystems. Meanwhile, glutathione, glutamate, and ascorbate levels significantly dropped in needles, which may indicate the critical oxidative stress that trees had to face since the onset of the infestation. They were not fully replenished after long-term infestation, and redox homeostasis was probably not achieved, compromising tree survival. Nevertheless, a huge auxins overexpression detected in needles throughout the infestation may reflect tolerance against the premature senescence caused by the woodwasp venom. In contrast, the metabolome of wood tissues remained initially unchanged, although it seems to collapse after three months. Overall, the metabolomics strategy adopted in this work evidenced its usefulness in uncovering the fundamental roles of plants' chemical defense that govern interactions with specific stressors.


Consumption of cannabis and cocaine: correct mix for arterial occlusions.
We present a case of a young Afro-Caribbean man who presented with sudden unilateral loss of vision due to central retinal artery occlusion. He was a cocaine and cannabis abuser for 6 years. Acute central retinal artery occlusion at such a young age is unusual. We discuss the possible pathogenesis and treatment options for acute retinal artery occlusion, due to suspected cocaine and cannabis abuse, and present our experience of its management.


Lesion locations associated with persistent proprioceptive impairment in the upper limbs after stroke.
Proprioceptive deficits are common after stroke and have been associated with poorer recovery. Relatively little is known about the brain regions beyond primary somatosensory cortex that contribute to the percept of proprioception in humans. We examined a large sample (n = 153) of stroke survivors longitudinally to determine which brain regions were associated with persistent post-stroke proprioceptive deficits. A robotic exoskeleton quantified two components of proprioception, position sense and kinesthesia (movement sense), at 2 weeks and again at 6 months post-stroke. A statistical region of interest (sROI) analysis compared the lesion-behaviour relationships of those subjects with cortical and subcortical stroke (n = 136). The impact of damage to brainstem and cerebellum (n = 17) was examined separately. Results indicate that damage to the supramarginal gyrus, the arcuate fasciculus, and Heschl's gyrus are associated with deficits in position sense and kinesthesia at 6 months post-stroke. These results suggest that regions beyond the primary somatosensory cortex contribute to our sense of limb position and movement. This information extends our understanding of proprioceptive processing and may inform personalized interventions such as non-invasive brain stimulation where specific brain regions can be targeted to potentially improve stroke recovery.


Opposite alterations of 5-HT2A receptor brain density in subjects with schizophrenia: relevance of radiotracers pharmacological profile.
The status of serotonin 5-HT2A receptors (5-HT2ARs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5-HT2AR density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist properties. This study investigates 5-HT2AR density in the post-mortem prefrontal cortex from subjects with schizophrenia and controls using three radiotracers with a different pharmacological profile. The specific binding parameters of the inverse agonist [18F]altanserin, the agonist [3H]lysergic acid diethylamide (LSD) and the antagonist [3H]MDL100907 to brain cortex membranes from 20 subjects with schizophrenia and 20 individually matched controls were evaluated under similar methodological conditions. Ten schizophrenia subjects were antipsychotic-free at death. Saturation curve analyses were performed by non-linear regression to obtain a maximal density of binding sites (Bmax) and the affinity of the respective radiotracers (Kd). In schizophrenia subjects, 5-HT2AR density was decreased when quantified by [18F]altanserin binding, whereas increased when evaluated by [3H]LSD binding. However, [3H]MDL100907 binding was unaltered. A slight loss of affinity (higher Kd) was observed exclusively in [3H]LSD binding. The findings were more evident in antipsychotic-free subjects than in antipsychotic-treated subjects. In conclusion, a higher proportion of the 5-HT2AR-active functional conformation, which is rather identified by agonist radiotracers, was observed in schizophrenia patients. A consequent reduction of the inactive 5-HT2AR conformation, which is preferentially identified by inverse agonist radiotracers, was also obtained. Antagonist radiotracers do not distinguish between molecular conformations of the receptor, and accordingly, the absence of changes was shown. These results are compatible with the proposed increased functional activity of brain cortical 5-HT2ARs in schizophrenia.


In utero fetal left ventricular rupture and pseudoaneurysm formation: a case report.
Cardiac ventricular aneurysms affect 1 in 200,000 live births. To the best of our knowledge, no reported cases of a left ventricular pseudoaneurym and in utero rupture exist to guide optimal management. We present a case of fetal left ventricular rupture with a large pericardial effusion, cardiac tamponade and subsequent pseudoaneurysm formation with concerns for a poor prognosis. Interventional drainage of the pericardial effusion led to resolution of tamponade and significant improvement in fetal condition. A multidisciplinary team was utilised to plan birth to minimise risk of pseudoaneurysmal rupture and a catastrophic bleed at birth. For similar cases we recommend consideration of birth by caesarean section, delayed cord clamping and a prostaglandin E1 infusion, to reduce the systemic pressures on the left ventricle during transition from fetal to neonatal circulations, until definitive surgical repair. In this case, this resulted in a successful outcome.


False Activations for ST-Segment Elevation Myocardial Infarction.
First-medical-contact-to-device (FMC2D) times have improved over the past decade, as have clinical outcomes for patients presenting with ST-elevation myocardial infarction (STEMI). However, with improvements in FMC2D times, false activation of the cardiac catheterization laboratory (CCL) has become a challenging problem. The authors define false activation as any patient who does not warrant emergent coronary angiography for STEMI. In addition to clinical outcome measures for these patients, STEMI systems should collect data regarding the total number of CCL activations, the total number of emergency coronary angiograms, and the number revascularization procedures performed.


Topographic differences in mean computational sleep depth between healthy controls and obstructive sleep apnoea patients.
In this work, topographic differences in computational sleep depth between healthy controls and obstructive sleep apnoea syndrome (OSAS) patients have been examined. Sleep depth estimation was based on continuous monitoring of the mean frequency of the EEG. During the experiments, all-night sleep EEG recordings of carefully age and gender matched sets of 16 healthy controls and 16 OSAS patients were compared on six electrode locations (Fp1-M2, Fp2-M1, C3-M2, C4-M1, O1-M2, and O2-M1). To optimise the diagnostic ability of the method, we examined the influence of 45 sets of adjustable analysis parameters on the ability of the method to show differences in computational sleep depth between the diagnostic groups. The results show clearly that although the visual scores for a set of epochs are the same for both clinical groups, computational sleep depth measure still shows deeper local sleep for healthy controls, both during NREM and REM sleep. Although the best achievable performance in different sleep stages is reached in different EEG derivations and with different parameter values, computation of sleep depth with 1-s output resolution in non-overlapping segments of 2s (400 samples) with maximum analysis band frequency of 20.5 Hz and 51-point moving median smoothing on Fp2-M1 or O1-M2 leads to near-optimal performance in deep sleep or wakefulness/light sleep, respectively.


Interpretation of HBV Serologies.
Hepatitis B was discovered by researchers who were investigating jaundice associated with blood transfusions as well as parenterally administered medications. Through trial and error, the HBV was identified. There are specific tests that detect HBV infection, whether it is a previous exposure or active infection. The various HBV serologies are reviewed in this work as well. Hepatitis B surface antigen has emerged as a tool in defining treatment endpoint and its significance is reviewed. HBV genotypes are distributed uniquely throughout the world, in particular, genotype C is associated with higher rates of hepatocellular carcinoma. Various HBV genotypes and their impact on the clinical course are discussed. The relationship of HBV serologies and HBV DNA to disease progression is outlined. There are specific recommendations on monitoring those infected with HBV and this is reviewed here. HBV mutations have an impact on the disease course and those of significance are also discussed.


Alternating unbalanced SSFP for 3D R2' mapping of the human brain.
Measuring the transverse-relaxation rate R2' provides valuable information in quantitative evaluation of tissue microstructure, for example, in terms of oxygenation levels. Here, we propose an alternating unbalanced SSFP pulse sequence for rapid whole-brain 3D R2' mapping. Unlike currently practiced, spin echo-based R2' measurement techniques, the proposed method alternates between SSFP-FID and SSFP-ECHO modes for rapid 3D encoding of transverse relaxation rates expressed as R2 + R2' and R2-R2' . Z-shimming gradients embedded into multi-echo trains of each SSFP module are designed to achieve relative immunity to large-scale magnetic-field variations (ΔB0 ). Appropriate models for the temporal evolution of the two groups of SSFP signals were constructed with ΔB0 -induced modulations accounted for, leading to ΔB0 -corrected estimation of R2 , R2' , and R2∗ (= R2 + R2' ). Additionally, relative magnetic susceptibility (Δχ) maps were obtained by quantitative susceptibility mapping of the phase data. Numerical simulations were performed to optimize scan parameters, followed by in vivo studies at 3 T in 7 healthy subjects. Measured parameters were evaluated in six brain regions, and subjected to interparameter correlation analysis. The resultant maps of R2' and additionally derived R2 , R2∗ , and Δχ all demonstrated the expected contrast across brain territories (eg, deep brain structures versus cortex), with the measured values in good agreement with previous reports. Furthermore, regression analyses yielded strong linear relationships for the transverse relaxation parameters ( R2' , R2 , and R2∗ ) against Δχ. Results suggest feasibility of the proposed method as a practical and reliable means for measuring R2' , R2 , R2∗ , and Δχ across the entire brain.


Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.
Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD50 was greater than 3000 mg/kg in both mice and rats. The drug was stable in plasma from several different species during an 8 h in vitro incubation at 37 degrees C. Following a single intravenous (iv) bolus injection (1000 mg/kg) to rats, HMBA was removed from the plasma with a half time of 2.2 +/- 0.5 h, and 65 +/- 8% of the dose was excreted unchanged in the urine during the first 24 h after dosing. During an 8 h iv infusion, plasma concentrations of 4 mM were easily maintained with no apparent adverse effects. Drug was uniformly distributed, with highest concentrations found in thymus, kidney, liver, and lymph node throughout the first 24 h after a single iv bolus dose. In vivo metabolism was very small, and the presence of apparent metabolites was undetectable until 48 h after iv administration. Oral bioavailability was good (32%), with peak plasma concentrations of 2 mM achieved one hour after oral administration. After oral dosing urinary excretion and plasma decay were comparable to similar data obtained after iv dosing.


Unusual η1 -Coordinated Alkyne and Alkene Complexes.
This mechanistic study demonstrates that an unusual η1 -coordinated alkyne complex is critical for the 1-pentyne 1,1-diboration reaction. The comparative studies suggest the "pull-push" antagonistic effect arising from Lewis acidity and steric congestion as the reason for the existence of η1 -coordinated alkyne complexes. Analogous η1 -coordinated alkene complexes are also predicted and seem to be promising for their application to the important olefin polymerization reaction.


Who is best at predicting children's anxiety in response to a social evaluative task? A comparison of child, parent, and teacher reports.
The purpose of this preliminary study was to examine the validity of child, parent, and teacher reports of child social anxiety in predicting the child's responses to a social evaluative task. Children, parents, and teachers each completed a measure of social anxiety, as well as a measure that asked them to predict the child's anxiety during a behavioral approach task (BAT) of reading aloud in front of a video camera. Consistent with previous literature, analyses revealed poor agreement across informants. Importantly, children's reports predicted their own anxious feelings and, to some degree, their behaviors during the task, whereas other informants' reports did not. We recommend that further research examine the relative validity of multiple informants' reports in predicting children's real-life behavior.


Chest radiography in the ICU.
Proper positioning and assessment of abnormalities and complications of the above-mentioned devices have a significant impact on the management of critically ill patients in the intensive care unit (ICU). The timely assessment of new or rapidly evolving findings is critical. Optimal radiographic technique, availability of images to the clinicians, and rapid reporting by the radiologist all serve to maximize the efficacy of bedside chest radiography in the ICU. Sometimes, changes in cardiopulmonary status may only be appreciated on chest radiographs (CXRs). Complications from ventilatory assistance, such as barotrauma, occur frequently and must be detected promptly. The position of monitoring devices, an important component of critical care management, is best checked radiographically. Indications for CXRs and the recommended frequency for repeat follow-up CXRs are based on the existing literature and the consensus of an expert panel formed by the American College of Radiology.


Estimating the distribution and productivity characters of Larix kaempferi in response to climate change.
Understanding the distribution, net primary productivity (NPP) and environmental constraints of Larix kaempferi is crucial to predict how global climate change will affect its growth and future dynamics. We simulated future changes in the globally suitable distribution patterns and the NPP dynamics under different representative concentration pathways (RCPs) using MaxEnt and Physiological Principles in Predicting Growth (3-PG) models. The results showed that suitable distribution areas for Larix kaempferi were concentrated in Europe and Asia, followed by North America, under current climate conditions. Globally, about 33.75% of the suitable area was in China. Suitable areas decreased and shifted northward in Asia, Europe and China in the RCP scenarios. Larix kaempferi could adapt or move to higher latitudes/altitudes to mitigate the negative impacts of climate change. The NPP of Larix kaempferi in China was 241.85-863.57 g m-2 a-1 simulated by the 3-PG model after local parameterization, which was consistent with the measured NPP. Changes in NPP were predicted in future climates. When the correlations between climate factors and NPP were examined, under the more optimistic scenarios, NPP would increase significantly. The key parameters of the 3-PG model were the optimal temperature for growth, forest age, and the number of days of lost productivity in each frost period. Therefore, climate change has a quantitative and significant impact on the distribution and productivity of L. kaempferi, which was estimated successfully with the two modeling approaches. Our results will contribute to the improved cultivation, environment and management of L. kaempferi and potentially of other deciduous gymnosperms.


Developmental changes in the subcellular localization of R-cadherin in chick retinal pigment epithelium.
It has been reported that in the chick embryonic retina, N-cadherin first appears at the very early stages and is subsequently substituted by R-cadherin at the middle to late stages of development. To examine the role of R-cadherin in the morphogenesis of chick retinal pigment epithelium (RPE), the distribution of this adhesion molecule was studied by immunofluorescence cytochemistry and immunoelectron microscopy from embryonic day (E) 6 to hatching. R-cadherin immunoreactivity was detected at E6, and was strongest at E12-13. During these stages, R-cadherin was expressed uniformly on the lateral plasma membranes of RPE cells in contact with each other. Thereafter, R-cadherin immunoreactivity was markedly decreased, with intense immunoreactivity restricted to zonulae adherentes in latero-apical regions at E16. R-cadherin immunoreactivity was no longer detectable in the newly hatched chick RPE, even though morphologically well developed zonulae adherentes were present in latero-apical regions. No immunoreactivity was detected on the apical side facing the neural retina or on the basal side facing the basal lamina at any stage of development. These findings indicate that R-cadherin plays an important role as a major cadherin subtype in the morphogenesis of chick embryo RPE, and is involved initially in non-specific cell-cell adhesions, and subsequently in the formation and maintenance of developing zonulae adherentes.


Bias-controlled multi-functional transport properties of InSe/BP van der Waals heterostructures.
Van der Waals (vdW) heterostructures, consisting of a variety of low-dimensional materials, have great potential use in the design of a wide range of functional devices thanks to their atomically thin body and strong electrostatic tunability. Here, we demonstrate multi-functional indium selenide (InSe)/black phosphorous (BP) heterostructures encapsulated by hexagonal boron nitride. At a positive drain bias (VD), applied on the BP while the InSe is grounded, our heterostructures show an intermediate gate voltage (VBG) regime where the current hardly changes, working as a ternary transistor. By contrast, at a negative VD, the device shows strong negative differential transconductance characteristics; the peak current increases up to ~5 μA and the peak-to-valley current ratio reaches 1600 at VD = -2 V. Four-terminal measurements were performed on each layer, allowing us to separate the contributions of contact resistances and channel resistance. Moreover, multiple devices with different device structures and contacts were investigated, providing insight into the operation principle and performance optimization. We systematically investigated the influence of contact resistances, heterojunction resistance, channel resistance, and the thickness of BP on the detailed operational characteristics at different VD and VBG regimes.


Social-ecological predictors of school functioning in Hispanic children treated for cancer with central nervous system-directed therapies.
Children with brain tumor or acute leukemia are at risk for neurotoxic side effects associated with their cancer therapies. These long-term deficits include poor health-related quality of life (HRQOL) in school and lower educational achievement. Although social-ecological factors may impact these outcomes, it is not known which factors play a role. Our objective was to evaluate the factors affecting school HRQOL in Hispanic childhood cancer survivors, an important at-risk group. Multivariable regression analyses examined whether selected social-ecological factors contribute toward suboptimal school HRQOL in 73 Hispanic children treated with central nervous system (CNS)-directed cancer therapies after accounting for effects associated with established cancer-related risk factors. Consistent with expectations from prior research, in our multivariate analysis, the cancer-related factors of having a brain tumor diagnosis and being younger at cancer diagnosis were significant predictors of reduced parent-reported school HRQOL (F(2,65) = 5.46, P < .01) and accounted for 14% of the variance. Adding the social-ecological variables of parent education, child motivation, and parental knowledge accounted for an additional 25% of the variance in school HRQOL, where higher levels were associated with better child school HRQOL. Parenting knowledge was a contributor even after controlling for effects associated with the other variables in the model (F(1,62) = 4.88, P < .05). Cancer survivorship care should incorporate parent education interventions to enhance the child's school functioning, particularly for Hispanic childhood cancer survivors from predominantly Spanish-speaking families. Future research should consider other at-risk groups and incorporate social-ecological indicators to predict HRQOL outcomes.


Effects of acoustic complexity on processing sound intensity in 10- to 11-year-old children: evidence from cortical auditory evoked potentials.
The environmental complexity that sounds are presented in, as well as the stimulus presentation rate, influences how sound intensity is centrally encoded with differences between children and adults. Cortical auditory evoked potential (CAEP) comparison study in children and adults examining two stimulus rates and three different stimulus contexts. Twelve 10 and 11 year olds and 11 adults were studied in two experiments examining the CAEP to a 1-KHz, 50-ms tone. A Slow-Rate experiment at 750-ms stimulus onset asynchrony (SOA) compared the CAEPs of 78 dB to 86 dB SPL in 2 complexity conditions. A Fast-Rate experiment was performed at 125 ms SOA with the same conditions plus an additional complexity condition. Repeated measures and mixed-model analysis of variance (ANOVA) was used to examine the latency and amplitude of the CAEP components. CAEP amplitudes and latencies were significantly affected by rate, intensity, and age with complexity interacting in multiple mixed-mode ANOVAs. P1 was the only CAEP component present at the Fast Rate. There were main effects of rate, age, and stimulus intensity level on the CAEP amplitudes and latencies. Maturational differences were seen in the interactions of intensity with complexity for the different CAEP components. Complexity of the sound environment was reflected in the relative amplitude of the CAEPs evoked by sound intensity. The effect of stimulus intensity depended on the complexity of the surrounding environment. Effects of the surrounding sounds were different in children than in adults.


Ecotoxicity of marine sediments: Sampling and laboratory artifacts and their impacts on risk classification.
Assessing the ecotoxicological risk of marine sediments is now a critical factor in deciding how to treat dredged material in harbor and coastal areas. Although ecotoxicological analyses are routinely required by some regulatory agencies in Europe, laboratory skills necessary to perform them are often underestimated. According to the Italian Ministerial decree No. 173/2016, ecotoxicological tests are performed on the solid phase and elutriates, and the classification of sediment quality is defined using the "Weight of Evidence" (WOE) approach. However, the decree does not provide adequate information regarding the preparation techniques and laboratory skills. As result, a wide variability among laboratories occurs. An error in the classification of ecotoxicological risk has a negative impact on the whole environmental quality and/or the economy and management of the interested area. Thus, the main aim of this study was to determine if such variability can affect the ecotoxicological outcomes of tested species and WOE associated classification, producing different options for the management of dredged sediments. Four different sediment types were selected to assess the ecotoxicological responses and their changes as a function of variability of the following factors: a) the storage time laps (STL) for both the solid phase and the elutriates; b) the methods used to prepare the elutriates (centrifugation vs. filtration), and the conservation method used for the elutriates (freshly prepared vs. freezing). Results suggest a wide variability of ecotoxicological responses among the four sediment samples here considered, differentiated according to chemical pollution, grain-size texture, and macronutrient contents. The storage time laps significantly affect the physicochemical parameters and the ecotoxicity of both the solid phase test and elutriates. For the elutriates preparation, centrifugation is preferred to filtration to preserve a better representation of sediment heterogeneity. Freezing of elutriates does not seem to show any significant effects on the toxicity. Findings allow to define a weighted schedule of the storage time of sediments and elutriates useful for laboratories to scale analytical priority and strategies related to different sediment types.


Advances in research of biological functions of Isthmin-1.
Isthmin-1 (ISM1) was initially thought to be a brain secretory factor, but with the development of technical means of research and the refinement of animal models, numerous studies have shown that this molecule is expressed in multiple tissues, suggesting that it may have multiple biological functions. As a factor that regulates growth and development, ISM1 is expressed in different animals with spatial and temporal variability and can coordinate the normal development of multiple organs. Recent studies have found that under the dependence of a non-insulin pathway, ISM1 can lower blood glucose, inhibit insulin-regulated lipid synthesis, promote protein synthesis, and affect the body's glucolipid and protein metabolism. In addition, ISM1 plays an important role in cancer development by promoting apoptosis and anti-angiogenesis, and by regulating multiple inflammatory pathways to influence the body's immune response. The purpose of this paper is to summarize relevant research results from recent years and to describe the key features of the biological functions of ISM1. We aimed to provide a theoretical basis for the study of ISM1 related diseases, and potential therapeutic strategies. The main biological functions of ISM1. Current studies on the biological functions of ISM1 focus on growth and development, metabolism, and anticancer treatment. During embryonic development, ISM1 is dynamically expressed in the zebrafish, African clawed frog, chick, mouse, and human, is associated with craniofacial malformations, abnormal heart localization, and hematopoietic dysfunction. ISM1 plays an important role in regulating glucose metabolism, lipid metabolism, and protein metabolism in the body. ISM1 affects cancer development by regulating cellular autophagy, angiogenesis, and the immune microenvironment.


Rats with partial striatal dopamine depletions exhibit robust and long-lasting behavioral deficits in a simple fixed-ratio bar-pressing task.
It is widely accepted that enduring parkinsonian symptoms are only evident if there are few remaining dopaminergic neurons in the substantia nigra and dopamine levels in the basal ganglia are very low [26,41]. In the present study, partial dopamine depletions were produced by infusing 6-OHDA bilaterally into the ventrolateral striatum as previously described [11,12,44]. Consistent with previous studies, behavioral deficits were detectable in rats with partial lesions with a simple fixed-ratio bar-pressing task. The present study demonstrated that these behavioral deficits were long-lasting, and that the sensitivity of this bar-pressing task could be increased by manipulating the level of difficulty of the task-higher fixed ratios were more sensitive to partial dopamine depletions. Deficits in rats with partial dopamine depletions could also be detected using non-automated neurological tests of parkinsonian symptoms developed for rats with severe unilateral dopamine depletions, but these deficits were transient and not as robust as those detected with the bar-pressing task. Oral Sinemet (L-DOPA:carbidopa) did not attenuate behavioral deficits related to partial dopamine depletions in this simple fixed-ratio bar-pressing task, but the present results suggest that Parkinson's patients might be identifiable earlier in the disease process, at a time when they could benefit from treatment with neuroprotective/neurotrophic agents. In addition, the results of the present study demonstrate that robust behavioral deficits may emerge with age. Mild dopamine depletions that were not detectable behaviorally at the time of the insult became clearly evident 10 months after the lesion with this bar-pressing task, and this may represent a more clinically relevant rodent model of Parkinson's disease.


LsrR, the effector of AI-2 quorum sensing, is vital for the H2O2 stress response in mammary pathogenic Escherichia coli.
Mammary pathogenic Escherichia coli (MPEC) is an important causative agent of mastitis in dairy cows that results in reduced milk quality and production, and is responsible for severe economic losses in the dairy industry worldwide. Oxidative stress, as an imbalance between reactive oxygen species (ROS) and antioxidants, is a stress factor that is common in most bacterial habitats. The presence of ROS can damage cellular sites, including iron-sulfur clusters, cysteine and methionine protein residues, and DNA, and may cause bacterial cell death. Previous studies have reported that Autoinducer 2 (AI-2) can regulate E. coli antibiotic resistance and pathogenicity by mediating the intracellular receptor protein LsrR. This study explored the regulatory mechanism of LsrR on the H2O2 stress response in MPEC, showing that the transcript levels of lsrR significantly decreased under H2O2 stress conditions. The survival cell count of lsrR mutant XW10/pSTV28 was increased about 3080-fold when compared with that of the wild-type WT/pSTV28 in the presence of H2O2 and overexpression of lsrR (XW10/pUClsrR) resulted in a decrease in bacterial survival rates under these conditions. The β-galactosidase reporter assays showed that mutation of lsrR led to a remarkable increase in expression of the promoters of ahpCF, katG and oxyR, while lsrR-overexpressing significantly reduced the expression of ahpCF and katG. The electrophoretic mobility shift assays confirmed that LsrR could directly bind to the promoter regions of ahpCF and katG. These results revealed the important role played by LsrR in the oxidative stress response of MPEC.


A new vaccine against tick-borne encephalitis: initial trial in man including a dose-response study.
A new vaccine against tick-borne encephalitis was investigated in 56 healthy volunteers randomized for five different doses of antigen in a comparative group trial. Good tolerability and high immunogenicity were found using three different antibody test systems. The dose response study revealed that there was a strong relationship between the amount of antigen administered and the antibody response over the range of 0.03-3.0 micrograms antigen per dose.


Subgingival odontoclastic resorptive lesions. Classification, treatment, and results in 58 cats.
A commonly recognized dental problem in cats is the resorption of tooth structure and subsequent loss of the tooth. These tooth defects are often very painful, because the sensitive dentin layer is exposed. The destruction of the tooth through odontoclastic resorption is considered a consequence of inflammatory resorption, probably secondary to periodontal inflammation. Because these resorptive lesions are progressive in nature, it is best to stage this progression of resorption in order to address treatment planning. The purpose of this study was to evaluate a group of 58 cats with resorptive lesions to determine the outcome of treatment 6 months or longer after restoration. In 81% of the cats, there was loss of the tooth, evidence of further resorption, or loss of the restoration at one or more resorption sites. Of the 154 teeth restored, only 33% showed no further evidence of loss of tooth structure.


Aerial medical evacuation of health workers with suspected Ebola virus disease in Guinea Conakry-interest of a negative pressure isolation pod-a case series.
We report 4 cases of Health Workers (HW) suspected of having contracted Ebola Virus Disease (EVD), transported from the Alliance for International Medical Action (ALIMA) Ebola Treatment Centre (ETC) in N'Zerekore, Guinea to the Treatment Centre for Carers run by the medical corps of the French army in Conakry, the capital of Guinea, which was established on 17 January 2015 and closed on 7 July 2015. In total more than 500 HWs have died from EVD since the epidemic began. This mortality has had significant effects on the ability of local services to respond appropriately to the disaster. The HWs were transported by air in the "Human Stretcher Transit Isolator-Total Containment (Oxford) Limited" (HSTI-TCOL) negative pressure isolation pod. Medical evacuation of patients with suspected, potentially fatal, infectious diseases is feasible with the use of a light isolator for patients without critical dysfunctions.


Diagnostic Validity of the Sleep Condition Indicator to Screen for Diagnostic and Statistical Manual-5 Insomnia Disorder in Patients with Parkinson's Disease.
Insomnia is a highly common sleep disorder in patients with Parkinson's disease (PD). Yet, no screening questionnaires following the Diagnostic and Statistical Manual-5 (DSM-5) criteria have been validated in PD patients. We assessed the validity and reliability of the French version of the sleep condition indicator (SCI), in patients with PD. In a sample of 65 patients (46% women, mean age 63.8 ± 7.9 years) with PD, but without dementia, insomnia was assessed with a clinical interview and the SCI. Statistical analyses were performed to determine the reliability, construct validity, and divergent validity of the SCI. In addition, an explanatory factor analysis was performed to assess the underlying structure of the SCI. Of the 65 patients (mean duration PD 9.7 ± 6.9 years), 51% met the criteria for insomnia disorder when measured with a clinical interview. The mean SCI score was 18.05 ± 8.3. The internal consistency (α = 0.89) of the SCI was high. Using the previously defined cutoff value of ≤16, the area under the receiver operating characteristic curve was 0.86 with a sensitivity of 86% and a specificity of 87%. Exploratory factor analysis showed a 2-factor structure with a focus on sleep and daytime effects. Additionally, good construct and divergent validity were demonstrated. The SCI can be used as a valid and reliable screener for DSM-5 insomnia disorder in PD patients. Due to its short length, it is useful in both clinical practice and scientific research.


Can fluconazole be used for inpatient re-treatment of coccidioidomycosis among patients with past fluconazole exposures?
Coccidioides spp. may cause significant disease requiring hospitalisation, but optimal antifungal therapy among inpatients following outpatient fluconazole exposures is unknown. The objective of this study is to describe the effectiveness of fluconazole among patients hospitalised for coccidioidomycosis despite recent outpatient fluconazole treatment. Patients were admitted to an academic medical center in Phoenix, Arizona from 1 January 2013 through 31 December 2020 for coccidioidomycosis following at least 30 days of outpatient treatment and re-initiation of fluconazole upon admission. The primary outcome was the proportion of patients with an improved response per the change in the modified Mycosis Study Group (MSG) score (a composite of symptoms, serology and radiographic findings) and clinician impressions. Sixty-seven patients were included, with most (54%) admitted to the intensive care unit. Meningitis was the most common infectious presentation (55%), 17 patients (25%) had multiple infection sites, and 23 (34%) were culture-positive for Coccidioides. Upon admission, the median (IQR) MSG score was 11 (9-14), which dropped to 4 (1-7) at end of therapy or last follow-up. Overall, after initiation of fluconazole therapy at a median daily dose of 800 mg, 48 patients (72%) improved in overall status, 10 (15%) showed stable disease and 9 (13%) were unresponsive. Improved response rates were high across all infection sites, including meningitis (68%) and bone infection (71%). There was no significant difference in response rates between patients with and without reported outpatient fluconazole nonadherence. The majority of patients admitted to the hospital for coccidioidomycosis appeared responsive to fluconazole therapy despite past outpatient exposures.


Trends in prematurity: what do changes at an urban institution suggest about the public health impact of 17-alpha hydroxyprogesterone caproate?
Despite the introduction of 17-alpha-hydroxyprogesterone caproate (17P), the national preterm birth (PTB) rate remains unchanged. Our objectives were to determine whether the overall rate of PTB has decreased and whether there has been a shift in the trends of prematurity at our institution since the initiation of 17P use. We performed a cross sectional study of the PTB rate and gestational age distribution at delivery (GA-del) at our institution over two, 2-year time periods: TP1 (pre 17P, 1 Jan 2004-31 Dec 2005) and TP2 (post 17P, 1 Jan 2008-31 Dec 2009). Statistical analyses included χ(2) tests for categorical data, t-tests for continuous data, and multivariable logistic regression to control for confounders. Overall (n = 15,421), there was no difference in the rate of PTB from TP1 to TP2 (16.65 vs 16.95%, p = 0.62). Among those with a history of prior PTB (n = 2,141), the mean preterm GA-del was 10 days later in TP2 than in TP1 (33.13 vs 31.64 weeks, p < 0.01) and significantly more preterm infants in TP2 delivered between 34-36 6/7 weeks than in TP1 (65.00 vs 45.63%, p < 0.01). The odds of a preterm infant delivering in the late preterm period was 2.3-fold higher in TP2 than TP1 (95% CI 1.49-3.54) after controlling for confounders. The significant shift in GA-del towards the late preterm period in TP2 may be due to the introduction of 17P use at our institution. Additional studies are needed to determine whether these trends persist on a nationwide level.