Genome-Wide Association and Genomic Prediction of Growth Traits in the European Flat Oyster (Ostrea edulis).
The European flat oyster (Ostrea edulis) is a bivalve mollusc that was once widely distributed across Europe and represented an important food resource for humans for centuries. Populations of O. edulis experienced a severe decline across their biogeographic range mainly due to overexploitation and disease outbreaks. To restore the economic and ecological benefits of European flat oyster populations, extensive protection and restoration efforts are in place within Europe. In line with the increasing interest in supporting restoration and oyster farming through the breeding of stocks with enhanced performance, the present study aimed to evaluate the potential of genomic selection for improving growth traits in a European flat oyster population obtained from successive mass-spawning events. Four growth-related traits were evaluated: total weight (TW), shell height (SH), shell width (SW) and shell length (SL). The heritability of the growth traits was in the low-moderate range, with estimates of 0.45, 0.37, 0.22, and 0.32 for TW, SH, SW and SL, respectively. A genome-wide association analysis revealed a largely polygenic architecture for the four growth traits, with two distinct QTLs detected on chromosome 4. To investigate whether genomic selection can be implemented in flat oyster breeding at a reduced cost, the utility of low-density SNP panels was assessed. Genomic prediction accuracies using the full density panel were high (> 0.83 for all traits). The evaluation of the effect of reducing the number of markers used to predict genomic breeding values revealed that similar selection accuracies could be achieved for all traits with 2K SNPs as for a full panel containing 4,577 SNPs. Only slight reductions in accuracies were observed at the lowest SNP density tested (i.e., 100 SNPs), likely due to a high relatedness between individuals being included in the training and validation sets during cross-validation. Overall, our results suggest that the genetic improvement of growth traits in oysters is feasible. Nevertheless, and although low-density SNP panels appear as a promising strategy for applying GS at a reduced cost, additional populations with different degrees of genetic relatedness should be assessed to derive estimates of prediction accuracies to be expected in practical breeding programmes.


Effects of resistance and all-round, functional training on quality of life, vitality and depression of older adults living in long-term care facilities: a 'randomized' controlled trial [ISRCTN87177281].
Regular physical activity may improve different aspects of wellbeing in older people, such as quality of life, vitality and depression. However, there is little experimental evidence to support this assumption. Therefore, we examined the effect of different training protocols on quality of life, vitality and depression of older adults living in long-term care facilities. Subjects (n = 173, aged 64 to 94 years, living in long-term care facilities), were randomized to six months of three different moderate-intensity group exercise training protocols, or to an 'educational' control condition. Exercise consisted of two 45-60-minute training sessions per week of 1) resistance training; 2) all-round, functional training; or 3) a combination of both. Perceived health, the Geriatric Depression Scale (GDS), the Vitality Plus Scale (VPS) and the Dementia Quality of Life questionnaire (DQoL) were administered at baseline and after six months. In the combined training group a small but significant decline was seen in perceived health, DQoL and VPS score compared to the control group. We conclude that neither strength training nor all-round, functional training of moderate intensity is effective in improving quality of life, vitality or depression of older people living in long-term care facilities.


O-GlcNAcylation Is Essential for Rapid Pomc Expression and Cell Proliferation in Corticotropic Tumor Cells.
Pituitary adenomas have a staggering 16.7% lifetime prevalence and can be devastating in many patients because of profound endocrine and neurologic dysfunction. To date, no clear genomic or epigenomic markers correlate with their onset or severity. Herein, we investigate the impact of the O-GlcNAc posttranslational modification in their etiology. Found in more than 7000 human proteins to date, O-GlcNAcylation dynamically regulates proteins in critical signaling pathways, and its deregulation is involved in cancer progression and endocrine diseases such as diabetes. In this study, we demonstrated that O-GlcNAc enzymes were upregulated, particularly in aggressive adrenocorticotropin (ACTH)-secreting tumors, suggesting a role for O-GlcNAcylation in pituitary adenoma etiology. In addition to the demonstration that O-GlcNAcylation was essential for their proliferation, we showed that the endocrine function of pituitary adenoma is also dependent on O-GlcNAcylation. In corticotropic tumors, hypersecretion of the proopiomelanocortin (POMC)-derived hormone ACTH leads to Cushing disease, materialized by severe endocrine disruption and increased mortality. We demonstrated that Pomc messenger RNA is stabilized in an O-GlcNAc-dependent manner in response to corticotrophin-releasing hormone (CRH). By affecting Pomc mRNA splicing and stability, O-GlcNAcylation contributes to this new mechanism of fast hormonal response in corticotropes. Thus, this study stresses the essential role of O-GlcNAcylation in ACTH-secreting adenomas' pathophysiology, including cellular proliferation and hypersecretion.


Early neuromotor behavior in craniosynostotic rabbits.
Clinical studies have shown both abnormal and normal mental and psychomotor development in patients with craniosynostosis. However, a number of confounding variables make study comparisons difficult. For these reasons, the present study describes early neuromotor development in an homogeneous rabbit model of craniosynostosis. Fifty-three newborn New Zealand white rabbit kits were used: 13 were wild-type, normal control rabbits; 23 had delayed-onset coronal suture synostosis (onset is approximately 57 to 74 days post conception); and 17 had early-onset coronal suture synostosis (onset is approximately 21 to 25 days post conception). All rabbits were observed individually and blindly in an open field, daily for 2 minutes, from birth through the first 14 days of life. The first day of emergence of 10 different mature behaviors and developmental events (in developmental order of appearance: falling, righting, cliff avoidance, first sign of fur, body elevation, head elevation, circling, dragging, eye opening, and hopping) was recorded for each kit. Daily activity levels (grid crossing), and body weights were also recorded. Significant group (p <.05) differences were observed in 9 of 11 measures. Both synostosed groups had significantly (p <.05) accelerated onset of behavior in 8 of 9 measures, compared with wild-type controls. The early-onset synostosis group had significantly (p <.05) accelerated onset in five of eight measures, compared with wild-type controls, and three of eight measures, compared with the delayed-onset synostosis group. Synostotic rabbits showed precocious neuromotor development possibly through frontal lobe constrictions and altered brain activity from increased intracranial pressure, although primary genetic effects cannot be ruled out.


Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions.
Inflammatory pain, such as arthritis pain, is a growing health problem. Inflammatory pain is generally treated with opioids and cyclooxygenase (COX) inhibitors, but both are limited by side effects. Recently, resolvins, a unique family of lipid mediators, including RvE1 and RvD1 derived from omega-3 polyunsaturated fatty acid, have shown marked potency in treating disease conditions associated with inflammation. Here we report that peripheral (intraplantar) or spinal (intrathecal) administration of RvE1 or RvD1 in mice potently reduces inflammatory pain behaviors induced by intraplantar injection of formalin, carrageenan or complete Freund's adjuvant (CFA), without affecting basal pain perception. Intrathecal RvE1 injection also inhibits spontaneous pain and heat and mechanical hypersensitivity evoked by intrathecal capsaicin and tumor necrosis factor-alpha (TNF-alpha). RvE1 has anti-inflammatory activity by reducing neutrophil infiltration, paw edema and proinflammatory cytokine expression. RvE1 also abolishes transient receptor potential vanilloid subtype-1 (TRPV1)- and TNF-alpha-induced excitatory postsynaptic current increases and TNF-alpha-evoked N-methyl-D-aspartic acid (NMDA) receptor hyperactivity in spinal dorsal horn neurons via inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. Thus, we show a previously unknown role for resolvins in normalizing the spinal synaptic plasticity that has been implicated in generating pain hypersensitivity. Given the potency of resolvins and the well-known side effects of opioids and COX inhibitors, resolvins may represent new analgesics for treating inflammatory pain.


Eumelanins and pheomelanins: characterization by electron spin resonance spectroscopy.
Synthetic dopa melanin and cysteinyldopa melanin have different electron spin resonance spectra. Data are reported for mixtures of these melanins and for dopa-cysteinyldopa copolymers, which are spectroscopically similar. A simple parameterization of the spectra allows estimation of the relative amounts of (i) dopa melanin and cysteinyldopa melanin in mixtures and of (ii) dopa and cysteinyldopa incorporated into copolymers. Several natural eumelanins and pheomelanins have been characterized and shown to be copolymers.


Bioinspired Concentric-Cylindrical Multilayered Scaffolds with Controllable Architectures: Facile Preparation and Biological Applications.
Multilayered objects are the most important and interesting structures in nature, exhibiting multiple functionalities. Inspired by the excellent structural-functional characteristics of nature creatures, concentric-cylindrical multilayered scaffolds were prepared by a combination of melt extrusion and leaching, in which well-defined alternating microlayer/gap is assembled. Furthermore, the macroscopic shape, internal structure, and surface topography of such a multilayered scaffold can be elaborately prepared by a simple physical process. The whole process has low cost, is efficient, and is environmentally friendly. Furthermore, such multilayered scaffolds show some interesting applications, e.g., lipophilic/hydrophilic drugs delivery and cell self-seeding. Considering the facile preparation process and versatile applications, this study will open up a new pathway to fabricate scaffolds with controllable architectures and expand their biodegradable polymer applications.


Involvement of bcl-2 and caspase-3 in apoptosis induced by cigarette smoke extract in the gastric epithelial cell.
Previous studies have shown that short-term passive cigarette smoking can increase apoptosis in rat gastric mucosa. However, the mechanism is not yet defined. Chloroform and ethanol extracts were used to investigate whether cigarette smoke could induce apoptosis in a human gastric epithelial cell line (AGS) as well as the roles of bcl-2, caspase-3, and cytochrome c in this process. AGS cell lines were treated with either chloroform extract (CE) or ethanol extract (EE) for 5 hours, and the level of bcl-2, the activity of caspase-3, and the level of cytosolic cytochrome c in these cells were determined. Time course studies on the effects of cigarette smoke extracts (CSEs) on DNA fragmentation and cytochrome c relocalization were also performed. Data showed that only CE induced apoptosis in a dose- and time-dependent manner in AGS cells, along with a decrease of bcl-2 and an increase of caspase-3 activity. Pretreatment with Z-DEVD-FMK (specific inhibitor of caspase-3) dose-dependently blocked the DNA fragmentation induced by the CE. Moreover, CE could time- and dose-dependently increase the level of cytochrome c in the cytoplasm, which might activate caspase-3. In conclusion, CSE triggers apoptosis in AGS cells through the inhibition of bcl-2 and the activation of a mitochondria-related pathway.


Predicting acute gout in diuretic-treated hypertensive patients.
Factors predisposing to diuretic-induced acute gout were investigated in a case-control study. Seventy hypertensive patients with acute gout occurring during diuretic treatment were identified and matched for age and sex to 140 hypertensive controls who took diuretics but did not develop gout. Gout was related more strongly to the use of loop diuretics than thiazides, with 30% of cases taking a loop diuretic compared to 14% of controls (P less than 0.01). In a sub-group of men who took a thiazide and no other diuretic, gout was significantly associated with obesity (odds ratio 3.7, 95% confidence interval 1.4, 9.1) and high alcohol intake (odds ratio 3.3, 95% confidence interval 1.1, 9.8). In these patients, 23% of gout was attributable to obesity and 16% to high alcohol consumption. Approximately 40% of acute gout might have been prevented by avoiding thiazides in those 20% of men who weighed more than 90 kg and/or consumed more than 56 units of alcohol per week.


Guided imagery, hypnosis and recovery from head and neck cancer surgery: an exploratory study.
The value of a brief, preoperative hypnosis experience was explored with a sample of 36 head and neck cancer surgery patients. 15 patients volunteered for the experimental hypnosis intervention. 21 patients who received usual care (no hypnosis) were followed through their hospital charts and were used as a comparison group. Hypnotic intervention and usual care groups were comparable in terms of relevant demographic variables. Postoperative hospitalizations for the hypnotic intervention group were significantly shorter than for the usual care group. Within the hypnotic intervention group, hypnotizability was negatively correlated with surgical complications and there was a trend toward a negative correlation between hypnotizability and blood loss during surgery. Findings suggest that imagery-hypnosis may be prophylactic, benefitting patients by reducing the probability of postoperative complications and thereby keeping hospital stay within the expected range. Recommendations are presented for a controlled, randomized, clinical trial with a sufficiently large sample to provide the opportunity for statistical analysis with appropriate power.


CT planning studies for robotic total knee arthroplasty.
The aim of this study was to analyze the true costs associated with preoperative CT scans performed for robotic-assisted total knee arthroplasty (RATKA) planning and to determine the value of a formal radiologist's report of these studies. We reviewed 194 CT reports of 176 sequential patients who underwent primary RATKA by a single surgeon at a suburban teaching hospital. CT radiology reports were reviewed for the presence of incidental findings that might change the management of the patient. Payments for the scans, including the technical and professional components, for 330 patients at two hospitals were also recorded and compared. There were 82 incidental findings in 61 CT studies, one of which led to a recommendation for additional testing. Across both institutions, the mean total payment for a preoperative scan was $446 ($8 to $3,870). The mean patient payment was $71 ($0 to $2,690). There was wide variation in payments between the institutions. In Institution A, the mean total payment was $258 ($168 to $264), with a mean patient payment of $57 ($0 to $100). The mean technical payment in this institution was $211 ($8 to $856), while the mean professional payment was $48 ($0 to $66). In Institution B, the mean total payment was $636 ($37 to $3,870), with a mean patient payment of $85 ($0 to $2,690). The total cost of a CT scan is low and a minimal part of the overall cost of the RATKA. No incidental findings identified on imaging led to a change in management, suggesting that the professional component could be eliminated to reduce costs. Further studies need to take into account the patient perspective and the wide variation in total costs and patient payments across institutions and insurances. Cite this article: Bone Joint J 2020;102-B(6 Supple A):79-84.


Drivers of site fidelity in ungulates.
While the tendency to return to previously visited locations-termed 'site fidelity'-is common in animals, the cause of this behaviour is not well understood. One hypothesis is that site fidelity is shaped by an animal's environment, such that animals living in landscapes with predictable resources have stronger site fidelity. Site fidelity may also be conditional on the success of animals' recent visits to that location, and it may become stronger with age as the animal accumulates experience in their landscape. Finally, differences between species, such as the way memory shapes site attractiveness, may interact with environmental drivers to modulate the strength of site fidelity. We compared inter-year site fidelity in 669 individuals across eight ungulate species fitted with GPS collars and occupying a range of environmental conditions in North America and Africa. We used a distance-based index of site fidelity and tested hypothesized drivers of site fidelity using linear mixed effects models, while accounting for variation in annual range size. Mule deer Odocoileus hemionus and moose Alces alces exhibited relatively strong site fidelity, while wildebeest Connochaetes taurinus and barren-ground caribou Rangifer tarandus granti had relatively weak fidelity. Site fidelity was strongest in predictable landscapes where vegetative greening occurred at regular intervals over time (i.e. high temporal contingency). Species differed in their response to spatial heterogeneity in greenness (i.e. spatial constancy). Site fidelity varied seasonally in some species, but remained constant over time in others. Elk employed a 'win-stay, lose-switch' strategy, in which successful resource tracking in the springtime resulted in strong site fidelity the following spring. Site fidelity did not vary with age in any species tested. Our results provide support for the environmental hypothesis, particularly that regularity in vegetative phenology shapes the strength of site fidelity at the inter-annual scale. Large unexplained differences in site fidelity suggest that other factors, possibly species-specific differences in attraction to known sites, contribute to variation in the expression of this behaviour. Understanding drivers of variation in site fidelity across groups of organisms living in different environments provides important behavioural context for predicting how animals will respond to environmental change.


Quantitative autoradiographic characterization of the binding of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine ([3H]MK-801) in rat brain: regional effects of polyamines.
The distribution and properties of N-methyl-D-aspartate (NMDA) receptors, labeled with [3H](+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5 5,10-imine (MK-801), were examined in rat brain. In sections of brain mash, the kinetics of association and dissociation of [3H]MK-801 were monophasic in the presence of 100 microM glutamate and glycine, and Scatchard transformations of saturation isotherms resulted in linear plots. Inhibition of the binding of [3H]MK-801 by other noncompetitive antagonists produced competition curves with Hill coefficients close to 1.0, consistent with a simple bimolecular interaction between the radioligand and the receptor. Scatchard plots based upon densitometric measurements of [3H]MK-801 binding in serial sections of rat brain were also linear, with dissociation constant values ranging from 5.0 to 8.4 nM in different regions at the level of the hippocampus. The distribution of [3H]MK-801 binding sites paralleled the distribution of NMDA displaceable L-[3H]glutamate binding sites. One exception was the cerebellar granule cell layer, where the density of binding sites for [3H]MK-801 was extremely low. The relative density of [3H]MK-801 to NMDA displaceable L-[3H]glutamate binding sites was approximately 1 to 2, consistent with the existence of two transmitter recognition sites per NMDA receptor. The modulatory effects of polyamines on [3H]MK-801 binding were studied in washed brain sections. The polyamine agonists spermine and spermidine enhanced [3H]MK-801 binding in all regions studied, with increases ranging from 18% in the thalamus to 106% in the ventromedial striatum. The effects of spermine and spermidine in these regions were highly correlated. Diethylenetriamine, which blocks the effects of spermidine, by itself produced decreases in the binding of [3H]MK-801 in most regions ranging from 5 to 21% but increased binding in parts of the striatum by 3 to 22%. The decrease in binding produced by diethylenetriamine in different brain regions was negatively correlated with the increase in binding produced by the agonists, suggesting that variability in the residual concentration of endogenous polyamines contributes to the regional variability of agonist effects.(ABSTRACT TRUNCATED AT 250 WORDS)


A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes.
In an accompanying publication we show that a subpopulation of T lymphocytes, which includes allotype suppressor T cells, selectively expresses I-region determinants. In this report, we show that these determinants are controlled by a new locus, Ia-4. Unlike the classically defined Ia antigens, they are not found on B lymphocytes. Antibody against Ia-4 determinants cannot be detected by conventional dye exclusion cytoxicity assays, suggesting that they are present on a small subpopulation (less than 10%) of peripheral T lymphocytes. The Ia-4 locus marks a new I subregion, provisionally designated I-J. This chromosomal segment is defined by the crossover positions in strains B10.A(5R) (K-end boundary) and B10.HTT (D-end boundary), and maps between the I-B and I-C subregions.


Family values, religiosity, and emotional reactions to schizophrenia in Mexican and Anglo-American cultures.
This study was designed to test whether two sociocultural variables, family cohesion and religiosity, related to affective reactions toward schizophrenia. It was hypothesized that increasing perceptions of one's family as cohesive and religious would be associated with the expression of more favorable and less unfavorable emotions toward patients with the disorder. Eight-eight Anglo-American undergraduates from Los Angeles and 88 Mexican undergraduates from Guadalajara read vignettes of a hypothetical family member described as meeting DSM-IV criteria for schizophrenia. Results of this study suggest that perceptions of family unity may be one important factor underlying emotional reactions toward schizophrenia. As expected, increasing perceptions of family cohesion were associated with greater reports of favorable emotion and decreased reports of unfavorable emotion toward the patient. However, after controlling for social desirability, family cohesion no longer significantly predicted unfavorable affect. Contrary to expectations, religiosity was not found to predict unfavorable or favorable emotions. However, religiosity was found to covary with nationality. Mexicans, compared to Anglos, reported greater moral-religious values in their families. No national differences were found with respect to family cohesion. Implications of this study are discussed along with suggested directions for future research.


A case of tracheal obstruction during oesophageal removal of a foreign body.
A patient was admitted with an impacted foreign body in the oesophagus. Repeated attempts to remove it during oesophagoscopy proved difficult and caused obstruction of the trachea during manipulation of the foreign body. A smaller endotracheal tube was subsequently placed in the trachea relieving the obstruction.


Erythrodermic Psoriasis Causing Uric Acid Crystal Nephropathy.
Erythrodermic psoriasis is a rare and severe variant of psoriasis. It is characterized by widespread skin erythema, scaling, pustules, or exfoliation of more than 75% of the body's surface area. This condition has life-threatening complications to include hemodynamic, metabolic, immunologic, and thermoregulatory disturbances. One metabolic complication, hyperuricemia, occurs from rapid keratinocyte differentiation and infiltration of inflammatory cells into psoriatic lesions. Although renal injury caused by shunting of blood to the skin has been reported, there are no reports of erythrodermic psoriasis causing crystal-induced nephropathy. We present a case of erythrodermic psoriasis and hyperuricemia complicated by uric acid crystal nephropathy. A 57-year-old male with long-standing psoriatic arthritis presented with diffuse scaling of his skin. He was being treated with adalimumab, leflunomide, and topical clobetasol, but had recently stopped taking his medications. Physical exam revealed yellow scaling covering his entire body with underlying erythema and tenderness without mucosal involvement. Labs were notable for a creatinine of 3.3 mg/dL, with no prior history of renal disease, and uric acid of 12.7 mg/dL. He was admitted to the intensive care unit given >80% of body surface area involvement and acute renal failure. Despite aggressive fluid resuscitation, renal function did not improve, and creatinine peaked at 4.61 mg/dL. Urine microscopy showed diffuse polymorphic uric acid crystals, consistent with uric acid crystal-induced nephropathy. He was started on rasburicase, urinary alkalinization, and fluids. His renal function improved dramatically; urine output, uric acid, and electrolytes normalized. He was discharged on topical clobetasol and leflunomide and started on secukinumab with little to no skin involvement. This case presents the rare complication of crystal-induced nephropathy in a patient with erythrodermic psoriasis. Uric acid crystal nephropathy is well described in diseases with rapid cell turnover such as tumor lysis syndrome. It is thought that rapid keratinocyte differentiation and inflammatory infiltration of psoriatic lesions produced life-threatening electrolyte abnormalities similar to tumor lysis syndrome. Early recognition of this rare complication is critical, and aggressive fluid resuscitation, urine alkalinization, and uric acid lowering agents should be administered immediately.


[The reverse turn of actin].
A model of actin sliding is proposed, which is based on the occurrence of actin-myosin interactions and the generation in actin filaments of elastic deformations of torsion, compression, and tension. Previously in experiments in vitro, an unusually stable right-handed axial rotation of actin filaments sliding relative to myosin with a rotation pitch of 1 microm was observed. However, the reported value of the rotation pitch is significantly greater (14 times) than the pitch of actin right-handed double helix (72 nm), which supposedly determines the rotation pitch of actin. This result is explained in terms of the model by the presence of the reverse turn of actin at each elementary step.


Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon.
HeLa DNA polymerase epsilon (pol epsilon), possibly involved in both DNA replication and DNA repair, was previously isolated as a complex of a 261-kDa catalytic subunit and a tightly bound 59-kDa accessory protein. Saccharomyces cerevisiae pol epsilon, however, consists of four subunits: a 256-kDa catalytic subunit with 39% identity to HeLa pol epsilon p261, a 80-kDa subunit (DPB2) with 26% identity to HeLa pol epsilon p59, a 23-kDa subunit (DPB3), and a 22-kDa subunit (DPB4). We report here the identification and the cloning of two additional subunits of HeLa pol epsilon, p17, and p12. Both proteins contain histone fold motifs which are present also in S. cerevisiae DPB4 and DPB3. The histone fold motifs of p17 and DPB4 are related to that of subunit A of the CCAAT binding factor, whereas the histone fold motifs found in p12 and DPB3 are homologous to that in subunit C of CCAAT binding factor. p17 together with p12, but not p17 or p12 alone, interact with both p261 and p59 subunits of HeLa pol epsilon. The genes for p17 and p12 can be assigned to chromosome locations 9q33 and 2p12, respectively.


Multilineage Differentiation for Formation of Innervated Skeletal Muscle Fibers from Healthy and Diseased Human Pluripotent Stem Cells.
Induced pluripotent stem cells (iPSCs) obtained by reprogramming primary somatic cells have revolutionized the fields of cell biology and disease modeling. However, the number protocols for generating mature muscle fibers with sarcolemmal organization using iPSCs remain limited, and partly mimic the complexity of mature skeletal muscle. Methods: We used a novel combination of small molecules added in a precise sequence for the simultaneous codifferentiation of human iPSCs into skeletal muscle cells and motor neurons. Results: We show that the presence of both cell types reduces the production time for millimeter-long multinucleated muscle fibers with sarcolemmal organization. Muscle fiber contractions are visible in 19-21 days, and can be maintained over long period thanks to the production of innervated multinucleated mature skeletal muscle fibers with autonomous cell regeneration of PAX7-positive cells and extracellular matrix synthesis. The sequential addition of specific molecules recapitulates key steps of human peripheral neurogenesis and myogenesis. Furthermore, this organoid-like culture can be used for functional evaluation and drug screening. Conclusion: Our protocol, which is applicable to hiPSCs from healthy individuals, was validated in Duchenne Muscular Dystrophy, Myotonic Dystrophy, Facio-Scapulo-Humeral Dystrophy and type 2A Limb-Girdle Muscular Dystrophy, opening new paths for the exploration of muscle differentiation, disease modeling and drug discovery.


Schizophrenia and violent crime: a population-based study.
Previous studies have found that patients with schizophrenia are more likely to be violent than the general population. The aim of this study was to investigate the association between schizophrenia and violent crime in the Israeli population. Using the Israeli Psychiatric Hospitalization Case Registry we identified 3187 patients with a discharge diagnosis of schizophrenia. For each proband we identified parents and siblings, and gender- and age-matched controls for patients, parents and siblings. Information on violent crimes was obtained from police records. Patients with schizophrenia were at increased risk for violent crimes compared with controls [odds ratio (OR) 4.3, 95% confidence interval (CI) 3.8-4.9], especially women (OR 9.9, 95% CI 6.2-15.7). Risk for violent crimes was higher among patients with co-morbid substance misuse than in patients without such co-morbidity (OR 5.1, 95% CI 4.2-6.3). The results of this study suggest that increased risk of violence is part of the clinical picture of schizophrenia and needs to be recognized as a legitimate, essential, aspect of clinical management.


NCBI's Virus Discovery Hackathon: Engaging Research Communities to Identify Cloud Infrastructure Requirements.
A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create a crowd-sourced set of analysis and processing pipelines for a complex biological data set in a three-day event on the San Diego State University campus starting 9 January 2019. Prior to the hackathon, 141,676 metagenomic data sets from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) were pre-assembled into contiguous assemblies (contigs) by NCBI staff. During the hackathon, a subset consisting of 2953 SRA data sets (approximately 55 million contigs) was selected, which were further filtered for a minimal length of 1 kb. This resulted in 4.2 million (Mio) contigs, which were aligned using BLAST against all known virus genomes, phylogenetically clustered and assigned metadata. Out of the 4.2 Mio contigs, 360,000 contigs were labeled with domains and an additional subset containing 4400 contigs was screened for virus or virus-like genes. The work yielded valuable insights into both SRA data and the cloud infrastructure required to support such efforts, revealing analysis bottlenecks and possible workarounds thereof. Mainly: (i) Conservative assemblies of SRA data improves initial analysis steps; (ii) existing bioinformatic software with weak multithreading/multicore support can be elevated by wrapper scripts to use all cores within a computing node; (iii) redesigning existing bioinformatic algorithms for a cloud infrastructure to facilitate its use for a wider audience; and (iv) a cloud infrastructure allows a diverse group of researchers to collaborate effectively. The scientific findings will be extended during a follow-up event. Here, we present the applied workflows, initial results, and lessons learned from the hackathon.


Early detection of hepatitis C allograft reinfection after orthotopic liver transplantation: a molecular and histologic study.
After orthotopic liver transplantation (OLT), patients with chronic hepatitis C virus (HCV) infection show nearly universal persistence of viremia and reinfection of the liver, but identifying the point at which the liver is reinfected morphologically can be difficult. One tool that may potentially be useful to detect reinfection is reverse transcriptase-polymerase chain reaction (RT-PCR), which has proven to be highly sensitive for detecting HCV RNA in formalin-fixed paraffin-embedded liver tissue. Our purpose was to gain insight into the time frame of HCV reinfection by assaying for HCV RNA in serial posttransplant liver biopsy specimens. Our study population consisted of 14 patients who underwent liver transplantation for hepatitis C and had confirmed HCV RNA in pretransplant serum, absence of HCV RNA in donor livers, and available consecutive posttransplant liver allograft specimens. We performed RT-PCR for HCV RNA in serial posttransplant liver biopsy specimens, beginning at 1 week until at least one biopsy from each tested positive. HCV RNA was detected in liver tissue by RT-PCR in 1-week post-OLT liver samples in 6 of 14 (42.8%) patients, the earliest being 5 days post-OLT. Eventually, each of the remaining eight samples became RT-PCR positive as well; the first detections occurred in these at 3 weeks (three cases), 4 weeks (three cases), 48 weeks (one case), and 144 weeks (one case). Histologic identification of hepatitis C recurrence was relatively insensitive in relation to these molecular data. These data suggest that (1) HCV RNA reinfection is nearly universal after liver transplantation in patients with chronic hepatitis C infection, (2) molecular reinfection by HCV occurs at a variable interval post-OLT, with the majority of allograft livers reinfected as early as 1 week, and (3) morphologic features of hepatitis C are usually appreciable at the time of "molecular" recurrence.


Study of gastrointestinal tract viability and motility via modulation of serotonin in a zebrafish model by probiotics.
The relationship between bacterial strains and serotonin regulation was studied via the in vitro screening of the strains. Using the transparent visibility of zebrafish, the strains for intestinal peristalsis were quickly screened. The methods and results were as follows: (1) 18 strains with outstanding gastrointestinal viability via their surface hydrophobicity, self-aggregation ability, acid tolerance, bile tolerance, simulated gastric digestion and intestinal fluid tolerance were determined from 54 unpublished strains. (2) 5dpf zebrafish were randomly selected and divided into 22 groups with 12 tails in each group. The intestinal peristalsis frequency of each group within 1 min was calculated after immersing the model zebrafish in a 108 CFU mL-1 strain solution, with 5 effective strains obtained. (3) The serotonin in zebrafish was measured by Elisa and fluorescence immunization. The regulation mechanism of serotonin by Bifidobacterium animalis F1-7 was revealed by RT-PCR and the results show that this most effective strain promotes intestinal peristalsis in zebrafish via the modulation of serotonin release and key genes for serotonin synthesis in zebrafish.


Unfolding and Targeting Thermodynamics of a DNA Intramolecular Complex with Joined Triplex-Duplex Domains.
Our laboratory is interested in developing methods that can be used for the control of gene expression. In this work, we are investigating the reaction of an intramolecular complex containing a triplex-duplex junction with partially complementary strands. We used a combination of isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and spectroscopy techniques to determine standard thermodynamic profiles for these targeting reactions. Specifically, we have designed single strands to target one loop (CTTTC) or two loops (CTTTC and GCAA) of this complex. Both reactions yielded exothermic enthalpies of -66.3 and -82.8 kcal/mol by ITC, in excellent agreement with the reaction enthalpies of -72.7 and -88.7 kcal/mol, respectively, obtained from DSC Hess cycles. The favorable heat contributions result from the formation of base-pair stacks involving mainly the unpaired bases of the loops. This shows that each complementary strand is able to invade and disrupt the secondary structure. The simultaneous targeting of two loops yielded a more favorable reaction free energy, by approximately -8 kcal/mol, which corresponds to the formation of roughly four base-pair stacks involving the unpaired bases of the 5'-GCAA loop. The main conclusion is that the targeting of loops with a large number of unpaired bases results in a more favorable reaction free energy.


Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Cross-specificity among TMEV substrains and related picornaviruses, but not myelin proteins.
Following intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV), susceptible mouse strains develop a chronic demyelinating disease characterized by mononuclear cell-rich infiltrates in the central nervous system. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility class II-restricted delayed-type hypersensitivity, which temporally correlates with disease onset and remains chronically elevated in susceptible mice. This study examined the fine specificity of class II-restricted T cell responses in TMEV-infected mice to better define the relevant virus-encoded T cell determinant(s) responsible for triggering the demyelinating process, and to determine if class II-restricted neuroantigen-specific autoimmune responses could be detected in mice with TMEV-induced demyelination. The data clearly show that T cell responses in TMEV-infected mice are directed against determinants shared by closely related TMEV strains and are cross-reactive with related picornaviruses, such as encephalomyocarditis virus. In contrast, class II-restricted autoimmune responses against syngeneic mouse spinal cord homogenate and the two major protein components of myelin, myelin basic protein and proteolipid protein, are not demonstrable in susceptible SJL/J mice undergoing chronic TMEV-induced demyelinating disease, but are readily seen in SJL/J mice displaying chronic, relapsing experimental allergic encephalomyelitis. Cross-reactivity (or lack thereof), as determined by functional T cell analyses, was found to correlate with the extent of exact amino acid homology between the TMEV capsid proteins, the two neuroantigens, and related picornaviruses. The data thus do not support a major role for autoimmune responses against myelin proteins in TMEV-induced demyelinating disease, but are consistent with our previously proposed hypothesis that TMEV-specific T cell responses constitute a major effector mechanism of myelin breakdown.


Morphological relationship between the cranial and supraorbital regions in Homo sapiens.
Although some hypotheses that attempt to explain the variation in supraorbital region morphology in modern humans have been proposed, this issue is still not well understood. In this study, the craniofacial size and spatial models were tested using a sample of modern human crania from geographically diverse populations, and the co-occurrence of the degrees of glabella (GL) and superciliary arch (ST) expression were analyzed. The two supraorbital structures were examined by visual assessment, and eight quantitative variables were included in the three-way ANOVA, canonical variates analysis and partial rank correlation. The influences of sex and the region of origin of the cranial samples on the relationships between the examined variables and the degrees of supraorbital structures expression were also considered. The results only partially supported the craniofacial size and spatial models and suggested that GL and ST experienced separate influences during development. In the sample of all crania, the neurocranial size more strongly influenced the morphological variation of the ST than of the GL, and sex influenced both of these structures the most. The results suggest that sex may be the main factor (having an influence independent of the other traits) on the morphological variation of the GL and ST.


Selection, application, and validation of a set of molecular descriptors for nuclear receptor ligands.
A methodology for the selection and validation of nuclear receptor ligand chemical descriptors is described. After descriptors for a targeted chemical space were selected, a virtual screening methodology utilizing this space was formulated for the identification of potential NR ligands from our corporate collection. Using simple descriptors and our virtual screening method, we are able to quickly identify potential NR ligands from a large collection of compounds. As validation of the virtual screening procedure, an 8, 000-membered NR targeted set and a 24, 000-membered diverse control set of compounds were selected from our in-house general screening collection and screened in parallel across a number of orphan NR FRET assays. For the two assays that provided at least one hit per set by the established minimum pEC(50) for activity, the results showed a 2-fold increase in the hit-rate of the targeted compound set over the diverse set.


Advancements in Positron Emission Tomography/Magnetic Resonance Imaging and Applications to Diagnostic Challenges in Neuroradiology.
Since the clinical adoption of magnetic resonance (MR) in medical imaging, MR has proven to be a workhorse in diagnostic neuroradiology, with the ability to provide superb anatomic detail as well as additional functional and physiologic data, depending on the techniques utilized. Positron emission tomography/computed tomography has also shown irreplaceable diagnostic value in certain disease processes of the central nervous system by providing molecular and metabolic information through the development of numerous disease-specific PET tracers, many of which can be utilized as a diagnostic technique in and of themselves or can provide a valuable adjunct to information derived from MR. Despite these advances, many challenges still remain in neuroradiology, particularly in malignancy, neurodegenerative disease, epilepsy, and cerebrovascular disease. Through improvements in attenuation correction, motion correction, and PET detectors, combining the 2 modalities of PET and MR through simultaneous imaging has proven feasible and allows for improved spatial and temporal resolution without compromising either of the 2 individual modalities. The complementary information offered by both technologies has provided increased diagnostic accuracy in both research and many clinical applications in neuroradiology.


Mechanisms of CNS myelin inhibition: evidence for distinct and neuronal cell type specific receptor systems.
Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack of neuronal repair is often associated with significant functional deficits, and depending on the severity of injury, may result in permanent paralysis distal to the site of injury. A detailed understanding of the molecular mechanisms that limit neuronal growth in the injured spinal cord is an important step toward the development of specific strategies aimed at restoring functional connectivity lost as a consequence of injury. While rapid progress is being made in defining the molecular identity of CNS growth inhibitory constituents, comparatively little is known about their receptors and downstream signaling mechanisms. Emerging new evidence suggests that the mechanisms for myelin inhibition are likely to be complex, involving multiple and distinct receptor systems that may operate in a redundant manner. Furthermore, the relative contribution of a specific ligand-receptor system to bring about growth inhibition may greatly vary among different neuronal cell types. Myelin-associated glycoprotein (MAG), for example, employs different mechanisms to inhibit neurite outgrowth of cerebellar, sensory, and retinal ganglion neurons in vitro. Nogo-A harbors distinct growth inhibitory regions, which employ different signaling mechanisms. The Nogo-66 receptor 1 (NgR1), a shared ligand binding component in a receptor complex for Nogo-66, MAG, and OMgp, participates in neuronal growth cone collapse to acutely presented myelin inhibitors, but is dispensable for longitudinal neurite outgrowth inhibition on substrate-bound Nogo-66, MAG, OMgp, or crude CNS myelin in vitro. Consistent with the idea of cell-type specific mechanisms for myelin inhibition, different types of CNS neurons possess very different regenerative capacities and respond differently to experimental treatment strategies in vivo. We speculate that differences in regenerative axonal growth among different fiber systems are a reflection of their intrinsic ability to elongate axons and their distinct cell surface receptor profiles to respond to the growth inhibitory extracellular milieu. The existence of cell type specific mechanisms to impair regenerative axonal growth in the CNS may have important implications for the development of treatment strategies. Depending on the fiber tract injured, different ligand-receptor systems may need to be targeted in order to elicit robust and long-distance regenerative axonal growth.


Ischemic stroke and depression.
Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 +/- 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 +/- 6.7 years). We required a SIGH-D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH-D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke.


Nociceptor activation and pain.
This paper reviews advances in our knowledge on the physiological properties of human nociceptors and their capacity to signal pain. Conventional microneurography was used in combination with intraneural microstimulation in subjects who estimated the magnitude of pain from nociceptor stimulation. The experimental evidence favours the notion that C polymodal nociceptors can provide a peripheral neuronal basis for determination of heat pain threshold and also an essential peripheral code for suprathreshold magnitude judgments of heat pain. Furthermore, sensitized C polymodal nociceptors can contribute to hyperalgesia after a mild heat injury to hairy skin. Temporal summation is documented for dull, delayed C fibre pain, which is different in quality and less accurately projected than the fast, sharp pain from high-threshold A delta nociceptors. A segmental organization is shown for projected and referred pain from deep structures. Examples are given of central inhibition of pain by a prostaglandin synthetase inhibitor, and by physical manoeuvres such as vibration and cooling. Recent reports on microneurographic findings after nerve injury indicate that the technique may be useful for future studies on pathophysiological pain mechanisms.


Osmolarity determines the solubility of anesthetics in aqueous solutions at 37 degrees C.
The authors determined whether they could predict accurately the solubility of anesthetics in aqueous solutions at 37 degrees C, knowing the osmolarity and the pH of the solution and the solute composition. The partition coefficients of the four volatile anesthetics, isoflurane, enflurane, halothane, and methoxyflurane, were determined concurrently at 37 degrees C between air and aqueous solutions containing sodium chloride, dextrose, mannitol, or heparin. The osmolarities of these solutions ranged from 0 to 7,000 mOsm/l. The partition coefficients decreased linearly with increasing osmolarity when plotted on a semilogarithmic scale. The effect of osmolarity on the partition coefficient of the alkane anesthetic, halothane, was 20% less (P less than 0.001) than the effect of osmolarity on the partition coefficients of the three methyl-ethyl ether anesthetics, isoflurane, enflurane, and methoxyflurane. The solubility of anesthetics in aqueous solutions did not depend on either the molecular structure of the solute or the pH of the solution. The solubility of volatile anesthetics in aqueous solutions at 37 degrees C is inversely and predictably dependent on the osmolarity of the solutions.


Trichomonas vaginalis and Giardia lamblia Growth Alterations by Low-Frequency Electromagnetic Fields.
There is an increasing interest in using physical factors such as magnetic fields as antimicrobial strategy, with variable results. The current study was aimed to evaluate the influence of extremely low-frequency electromagnetic fields (ELF-EMFs) on the axenically-cultured parasite protozoans Trichomonas vaginalis and Giardia lamblia growth. Bioassays were developed using T. vaginalis, GT-13 and G. lamblia IMSS-0989 strains cultured at 37 ºC in TYI-S-33 medium. The following treatment regimens and controls were considered: (a) cells exposed to ELF-EMFs, (b) untreated cells, (c) cells treated with Metronidazole, used as positive controls, and (d) cells co-exposed to ELF-EMFs and Metronidazole. When cultures reached the end of logarithmic phase, they were exposed to ELF-EMFs for 72 h, in a standardized magnetic field exposure facility. For determining cytotoxic effects, trophozoite density was blindly evaluated in a Neubauer chamber. A significant decrease in trophozoite growth was observed for T. vaginalis, in magnetic field-treated cultures. On the other hand, cultures co-exposed to ELF-EMFs and Metronidazole showed no significant differences when compared with cultures treated with Metronidazole alone. On the contrary, an increased trophozoite density was observed in G. lamblia cultures after exposure to magnetic fields. An absence of a synergistic or antagonistic effect was observed. ELF-EMFs induced T. vaginalis and G. lamblia growth alterations, indicating a potential effect in cell cycle progression.


METABOLIC SYNDROME AND ASSOCIATED RISK FACTORS AMONG SECONDARY SCHOOL ADOLESCENTS IN NORTHEAST NIGERIA.
Metabolic syndrome (MetS) is a cluster of risk factors that may predispose to cardiovascular diseases and type 2 diabetes mellitus. These risk factors include hypertension, central obesity, hyperglycaemia, hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). The presence of at least three of these risks factors defines MetS. Globally, MetS now affects children and adolescents with increasing obesity prevalence. This study determined the prevalence of MetS and associated risk factors among secondary school adolescents in Gombe Local Government Area(LGA), Northeast Nigeria. A cross-sectional study; 688 participants from 12 secondary schools in Gombe LGA, Northeast Nigeria. Data were obtained using structured questionnaire. Anthropometry and blood pressure were measured. Fasting plasma glucose, serum triglyceride and HDL-C were determined. Data were analysed using SPSS version 21. The prevalence of MetS was 1.3%. Low serum HDL-C was the commonest risk factor. MetS was significantly higher in upper socio-economic class and private school participants. Lifestyle and family medical history were not significantly associated with MetS. This study showed that the prevalence of metabolic syndrome was low in the overall study population but high among centrally obese adolescents. Metabolic syndrome occurred in normal weight and underweight participants. Low HDL-C was the commonest risk factor for metabolic syndrome and lifestyle and family medical history were not associated with metabolic syndrome.


Cold Atmospheric Pressure Plasma Comb-A Physical Approach for Pediculosis Treatment.
Pediculosis, that is the infestation of humans with Pediculus humanus capitis (head lice), poses a worldwide problem that is as old as mankind itself. Over the centuries, man has developed a variety of remedies, all of which have ultimately culminated in the use of chemical agents. Some of these remedies are known to produce successful results. A large portion of the effective remedies used to kill lice and their eggs contain insecticides, but there is an increasing number of reports of head lice populations revealing an increased resistance. This study presents an alternative treatment approach, the efficacy of which is based on physical effects. Cold atmospheric pressure plasmas have successfully shown their formidably wide application range within the field of plasma medicine. This study presents a plasma device in its current stage of development that is engineered as a consumer product to enable an alternative physical and insecticide-free option for the treatment of pediculosis. An efficacy study concerning different developmental stages of P. humanus humanus is presented. P. humanus humanus was chosen as a substitute test organism for P. humanus capitis due to possible laboratory rearing and high anatomic similarity. The study shows how a single stroke of the plasma device over a hair strand (approximately 22 cm in length with a weight of 1.5 g) led to mortality rates of 68.3% (50.0; 79.7) (95% CI) in the juvenile test group, a mortality rate of approx. 67.7% (54.9; 78.8) (95% CI) in the female test group, and approx. 46.7% (28.3; 65.7) (95% CI) in the male test group. When single eggs were introduced directly into the plasma for approx. 1 s, younger eggs (0⁻2 d) showed a higher mortality of 66.7% (42.7; 82.7) than the older (4⁻6 d) eggs, with 16.7% (5.6; 34.7) (CI). Furthermore, the results of a risk assessment of the device are described. The article concludes with necessary handling instructions as well as further developmental steps, derived from the results of the efficacy and the risk assessment study.


Aliskiren: a novel renin inhibitor for hypertension.
Hypertension is one of the major causes of cardiovascular morbidity. Most patients who are on treatment for hypertension fail to achieve adequate control with the existing therapy and rates of cardiovascular morbidity remain high. As the renin-angiotensin-aldosterone system is strongly implicated in the development of hypertension-related target organ damage, intensive efforts have been devoted towards the development of drugs targeting this system. In addition to angiotensin converting enzyme inhibitors and angiotensin receptor blockers, inhibition of renin has also become a clinical reality. Aliskiren, a novel renin inhibitor, has overcome a number of shortcomings of existing drugs and is now available to address angiotensin production directly at its rate-limiting step.


Cannabinoids and cardiovascular disease: the outlook for clinical treatments.
Cannabinoid drugs exert their effects primarily through activation of cannabinoid CB1 and CB2 receptors. Both CB1 and CB2 receptors have been implicated in a number of cardiovascular processes, including vasodilation, cardiac protection, modulation of the baroreceptor reflex in the control of systolic blood pressure, and inhibition of endothelial inflammation and the progress of atherosclerosis in a murine model. These effects are mainly mediated through central and peripheral nervous system CB1 receptors, vascular CB1 receptors and immune cell CB2 receptors. Relevant cellular effects include: the inhibition of neurotransmitter release in the nucleus tractus solitarius and in peripheral adrenergic neurons; regulation of NOS activity in vascular beds; inhibition of vascular smooth muscle cell excitability; regulation of endothelial cell migration and proliferation; and effects on immune cell proliferation, activation, and inflammatory functions. We review the pre-clinical evidence for beneficial effects of cannabinoid drugs in a range of vascular and cardiovascular pathologies. We also discuss the clinically relevant potential of cannabinoids.


Beta 2-adrenoceptor stimulation increases the number of antigen-specific precursor B lymphocytes that differentiate into IgM-secreting cells without affecting burst size.
Previous studies have shown that early addition of a beta 2-adrenergic agonist to whole splenocyte cultures immunized with SRBC induced an increase in the number of cells secreting Ag-specific antibody. Because of the low frequency of Ag-specific B lymphocytes in these cultures, it has been difficult to determine the cellular mechanism by which this increase is produced. To gain insight into this cellular mechanism, the present study was designed to evaluate the responsiveness of TNP-specific B lymphocytes cultured at both high density and limiting dilution with keyhole limpet hemocyanin (KLH)-specific, IL-4-producing Th lymphocytes, TNP-KLH, and the beta 2-adrenergic agonist, terbutaline. The results showed that a maximal twofold increase in both the number of anti-TNP IgM-secreting cells and the amount of anti-TNP IgM secretion occurred in terbutaline-exposed lymphocytes after 5 days of bulk culture. This response occurred in a concentration-dependent manner and was inhibited by concomitant culture with beta-adrenoceptor antagonists. No appreciable change was measured in the level of either IgG1 secretion in terbutaline plus Ag-exposed bulk cultures or MHC class II expression on terbutaline plus Ag-exposed TNP-specific B lymphocytes as compared with Ag alone. These data raised the possibility that beta 2-adrenoceptor stimulation induced either the differentiation of a larger proportion of TNP-specific B lymphocyte precursors into anti-TNP IgM-secreting cells, or the extensive proliferation of a constant number of TNP-specific B lymphocyte precursors, or both. Limiting dilution results showed that beta 2-adrenoceptor stimulation induced a twofold increase in the number of TNP-specific B lymphocyte precursors that differentiated into anti-TNP IgM-secreting cells, without affecting the number of anti-TNP IgM-secreting cells produced by each precursor clone.


[Neonatal screening of G6PD deficiency in Tunisia].
The Glucose-6-phosphate dehydrogenase (G6PI) deficiency is the most common enzymopathy worldwide. WHO had classified Tunisia among countries that are moderately affected by this affection. However, no mass-screening reflecting the real incidence was realized. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis in Tunisia. A total of 1102 neonates, born in CMNT center of Maternity and of Neonatology of Tunis during the going periods from April, 2005 till May, 2005 and from June, 2006 till September, 2006, have been enclosed in the study. The samplings included 953peripheral venous blood and 149 blood cordon. Among 1102 samplings, only 976 were of use to the screening. In our mass-screening, we consider all newborns that were born in the CMNT during the period of study and were included in the screening. A dosage of the enzymatic activity was realized using spectrophotometric method. G6PD electrophoresis and molecular study by PCR/RFLP were realized for the overdrawn newborn children. Among 976 screening neonates, 43 individuals (4.4%) were found to be G6PD deficient by quantitative enzyme assay. Newborn affected were distributed in 23 boys and 20 girls (sex ratio of 1.15). The electrophoretic mobility and the molecular biology were realized for the affected newborn. Molecular characterization of 30 G6PD deficient neonates revealed that the G6PD A- was the most common and was detected in 20 of 43 individuals (66.7%), followed by G6PD Mediterranean that was detected in 6 (13.3%). At least, 4 other unknown mutations were not able to be determined by PCR/RFLP (n=4). In conclusion G6PD deficiency is frequent in our country, justifying a systematic neonatal screening, to avoid the arisen of grave consequences of this affection. The African variant is the most frequent in our country followed by the Mediterranean one.


Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner.
As the primary active substance in tobacco, nicotine affects the activity of the central nervous system, and its effects are sex-dependent. There are complex interactions between the gut and brain, and the gut microbiome can influence neuronal activity and host behavior, with diverse chemical signaling being involved. However, it is unclear whether nicotine can affect the normal gut microbiome and associated chemical signaling of the gut-brain axis. Sex is an important factor that shapes the gut microbiome, but the role of sex in the interaction among nicotine, gut bacteria, and related metabolites remains unknown. In this study, we applied high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) to explore how nicotine exposure affects the gut microbiome and its metabolism in female and male C57BL/6J mice, with a focus on the chemical signaling involved in gut-brain interactions. 16S sequencing results indicated that the community composition of the gut microbiome was differentially perturbed by nicotine in females and males. Differential alterations of bacterial carbohydrate metabolic pathways are consistent with lower body weight gain in nicotine-treated males. Oxidative stress response and DNA repair genes were also specifically enriched in the nicotine-treated male gut microbiome. The fecal metabolome indicated that multiple neurotransmitters, such as glutamate, gamma-aminobutyric acid (GABA), and glycine, were differentially altered in female and male mice. Some neuroactive metabolites, including leucine and uric acid, were also changed. This study demonstrates a sex-dependent effect of nicotine on gut microbiome community composition, functional bacterial genes, and the fecal metabolome.


Semantic, executive, and visuospatial abilities in mathematical reasoning of referred college students.
Semantic retrieval (SR) and executive-procedural (EP), but not visuospatial (VS) skills, have been found to be uniquely predictive of mathematical calculation skills in a sample of clinically referred college students. This study set out to cross-validate these results in an independent sample of clinically referred college students (N = 337) as well as extend them by examination of the contributions of these cognitive domains to math reasoning skills. Results indicate that these cognitive domains were able to predict 30% of the variance in calculation skills and 50% of the variance in math reasoning; however, in both cases, only the domains of semantic retrieval and visuospatial skill contributed uniquely. Differences between studies, and the lack of unique contribution of the EP domain to either type of math skill, may be due to measurement and sampling differences, the degree of shared relations among domains, and the choice of measures that represent the EP domain. Implications and future directions are explored.


Urticaria is a frequent skin condition presenting with wheals, angioedema or both due to the activation of mast cells. Acute urticaria (less-than 6 weeks duration) is associated with infections and allergies, whereas chronic urticaria (≥ 6 weeks) is either spontaneous (chronic spontaneous urticaria (CSU)), inducible or both. Quality of life (QoL) is frequently impaired. The pathogenesis of CSU is often of an autoimmune nature. As argued in this review, the treatment aims to restore QoL with a stepwise approach, most often using second-generation H1-antihistamines, omalizumab and cyclosporine.


How state-funded home care programs respond to changes in Medicare home health care: resource allocation decisions on the front line.
To examine how case managers in a state-funded home care program allocate home care services in response to information about a client's Medicare home health care status, with particular attention to the influence of work environment. Primary data collected on 355 case managers and 26 agency directors employed in June 1999 by 26 of the 27 regional agencies administering the Massachusetts Home Care Program for low-income elders. Data were collected in a cross-sectional survey study design. A case manager survey included measures of work environment, demographics, and factorial survey vignette clients (N = 2,054), for which case managers assessed service eligibility levels. An agency director survey included measures of management practices. Hierarchical linear models estimated the effects of work environment on the relationship between client receipt of Medicare home health care and care plan levels while controlling for case-mix differences in agencies' clients. Case managers did not supplement extant Medicare home health services, but did allocate more generous service plans to clients who have had Medicare home health care services recently terminated. This finding persisted when controlling for case mix and did not vary by work environment. Work environment affected overall care plan levels. Study findings indicate systematic patterns of frontline resource allocation shaping the relationships among community-based long-term care payment sources. Further, results illustrate how nonuniform implementation of upper-level initiatives may be partially attributed to work environment characteristics.


Is benzyl alcohol a significant contact sensitizer?
Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet. Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019. Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol-positive patients, compared to benzyl alcohol-negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases. Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful.


Step by step: cells with multiple functions in cortical circuit assembly.
It is often thought that the construction of cortical circuits occurs as the result of an elegantly designed process that unfolds sequentially as an animal develops until adult functional networks emerge. In reality, cortical circuits are shaped by evolutionary mechanisms, changes in developmental programmes driven by neuronal activity or epigenetic mechanisms and the need to adapt to the external world, and must pass through several important phases and timely checkpoints as they form. Some cortical cell types serve multiple functions during this developmental journey and are then reused (or 'recycled') to perform different functions in the adult cortex. Understanding the different stages of the cortical construction process and taking into account the ways in which cellular functions change across time and space is therefore essential if we are to build a comprehensive framework of cortical wiring in both health and disease.


The diagnosis of thoracic malignant mesothelioma: practical considerations and recent developments.
Pleural biopsies for the evaluation of malignant mesothelioma can be some of the most challenging cases faced by the practicing surgical pathologist. We review the epidemiology, clinical presentation, and imaging studies in patients with malignant mesothelioma, and then present a practical approach to the diagnosis using the cytologic features for malignancy and whether there is an epithelioid or spindled morphology; four main scenarios are discussed. The pertinent immunohistochemical work-up is reviewed for each scenario. Following this general overview, more unusual histologic patterns are compared and unusual presentations are discussed. Brief mention of grading systems for malignant mesothelioma and the use of electron microscopy and molecular studies is made. Practical considerations in the diagnosis of malignant mesothelioma are made throughout.


Quit attempts and smoking cessation in Italian adults (25-64 years): factors associated with attempts and successes.
Over the past 50 years there was a substantial decrease in the prevalence of smoking in Italy. The objective of this work is to describe attempts to quit and cessation success in Italian smokers. A surveillance on health-related behaviors (PASSI) was conducted in 2007-13 on a sample of 203 610 Italian adults 25-64 years of age. An analysis of smokers' characteristics and behaviors was performed, focusing on attempts to quit and quit success. Data from national surveys (ISTAT) from 1983 to 2013 (Italian adults, 25-64 years of age, 1983: 46 634; 1987: 40 915; 1990: 36 622; 2000: 77 531; 2005: 71 032; 2013: 64 205) were used to explore if a cessation trend in Italy exists. Smokers who quit in the previous year and were still abstinent when interviewed increased from 1990 to 2013. In the years 2011-13, 38% of people who had smoked in the last 12 months reported at least a quit attempt during the same period and 7% were still abstinent when interviewed. An association of successful recent quit attempts with higher educational level, absence of economic difficulties and younger age was found. In the years 2007-13, the great majority tried to stop unaided. Having received assistance from a cessation program did not increase the probability of enduring abstinence. In Italy interventions to drive more smokers to quit should be focused in particular on disadvantaged groups. Initiatives have to be studied not only to incentive more smokers to try to quit, but also to maintain abstinence over time.


Activation of latent rheumatoid synovial collagenase by human mast cell tryptase.
The functional role of mast cells in rheumatoid synovium was investigated by assessing the ability of mast cell tryptase to activate latent collagenase derived from rheumatoid synoviocytes. Tryptase, a mast cell neutral protease, was demonstrated in situ to reside in rheumatoid synovial mast cells, by an immunoperoxidase technique using a mouse mAb against tryptase, and in vitro to be released by dispersed synovial mast cells after both immunologic and nonimmunologic challenge. Each rheumatoid synovial mast cell contains an average of 6.2 pg of immunoreactive tryptase and the percent release values of this protease correlated with those of histamine (r = 0.58, p less than 0.01). The ability of purified tryptase to promote collagenolysis was demonstrated in a dose-dependent fashion using latent collagenase derived from rheumatoid synovium, synovial fluid, IL-1-stimulated cultured synoviocytes, and partially purified latent collagenase derived from conditioned media, with between 10 and 92% of the collagen substrate degraded. [3H] Collagen, treated with tryptase-activated latent collagenase, was subjected to electrophoresis on SDS polyacrylamide gels and autoradiography showed the collagen degradation pattern (A, B) characteristically produced by collagenase. Mast cell lysates also activated synovial latent collagenase yielding 24% digestion of collagen substrate. This activator in mast cell lysates could be inhibited by diisopropylflurophosphate or by immunoadsorption of tryptase. Thus, mast cells may activate metalloproteinases and play a role in the catabolism of collagen that occurs in rheumatoid synovium.


Single mothers: their health and health service use.
The aim of the study was to investigate differences in reported health and health service use in single mothers. The study was a survey of data derived from the General Household Surveys conducted by the Office of Population Censuses and Surveys (OPCS). The OPCS data are derived from samples of households throughout Great Britain. OPCS data for 1983 and 1984 were used, comprising approximately 60,000 individuals, of whom 793 were single mothers. Five different health outcomes were examined, two on perceived morbidity and three on the use of health services. The chief determinants of health and health services use among single mothers were housing tenure, employment status and the age of the youngest child. Single mother status did not consistently contribute to self reported morbidity and uptake of care when adjusted for other social variables, but there was a difference between categories of single mother, with those who were separated/divorced and those who were widowed reporting more acute illness than those who were married. The findings suggest that single mothers do not form a homogeneous group and that, if special consideration is to be given to them when planning and allocating health service resources, this needs to be taken into account in the context of other socioeconomic factors.


Neutral Chromium Complex with a Cr≡Si Triple Bond: Synthesis and Photoinduced H-H and Benzene C-H Bond Activation.
A neutral silylyne complex with a Cr≡Si triple bond was prepared by dehydrogenation of a chromium silylene complex with Cr-H and Si-H bonds, and was isolated as monomeric crystals, unlike dimeric forms of its tungsten and molybdenum congeners. The strong Cr(δ-)-Si(δ +) bond polarity was revealed by the reaction with MeOH and DFT calculations. The chromium silylyne complex reacted with H2 under LED (365 nm) irradiation to reproduce the precursor silylene complex with a (H)Cr=Si(H) moiety, as a result of 1,2-H-H addition across the Cr≡Si triple bond. Similarly, the chromium silylyne complex reacted with benzene under irradiation to afford an 1,2-addition product with a (H)Cr=Si(Ph) moiety, via benzene C-H bond activation accompanied by Si-C bond forming.


Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.
Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored. For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations. For prevention, oral sCT reduced body weight by ∼16% to 19% (P < 0.001), reduced plasma insulin and leptin by ∼50%, and improved impaired fasting glycemia (P < 0.05) concomitantly with amelioration of IR (HOMA-IR; P < 0.01) in HFD- and OVX-induced obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P < 0.001). Finally, oral sCT alleviated glucose intolerance predominantly in the portal circulation. Oral sCT treatment displays weight-regulatory and glucoregulatory efficacy in HFD- and OVX-induced obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.


Does risk perception motivate preventive behavior during a pandemic? A longitudinal study in the United States and China.
Controlling the spread of an infectious disease depends critically on the general public's adoption of preventive measures. Theories of health behavior suggest that risk perceptions motivate preventive behavior. The supporting evidence for this causal link is, however, of questionable validity. The COVID-19 pandemic provides a rare opportunity to examine how risk perceptions, preventive behavior, and the link between them develop in a fast-changing risky environment. In a 4-wave longitudinal study conducted in the United States and China, we found that for Chinese participants, there was little relationship between risk perceptions and preventive behavior. This may be a result of the Chinese government's strict control and containment policies and a collectivistic culture that encourages conforming to norms-both of which limit individuals' nonconformist behavior. For U.S. participants, risk perceptions did motivate preventive behavior in the early stage of the pandemic; however, as time went by and the risk of COVID-19 persisted, preventive behavior also led to perception of higher infection risk, which in turn further motivated preventive behavior. Thus, instead of the presumed unidirectional influence from perception to behavior, our results indicate that the two could mutually reinforce each other. Overall, our findings suggest that risk perceptions-at least in the context of a dynamic health hazard-may only motivate preventive behavior at specific stages and under specific conditions. They also highlight the importance of early interventions in promoting preventive behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Inflammatory conditions distinctively alter immunological functions of Langerhans-like cells and dendritic cells in vitro.
The specific function of human skin-resident dendritic cell (DC) subsets in the regulation of immunity or tolerance is still a matter of debate. Langerhans cells (LC) induce anti-viral immune responses but, conversely to dermal DC, maintain tolerance to bacteria. However, the definite function of epidermal LC and cutaneous DC appears even more complex under inflammatory conditions. Here we investigated the immune responses of human immature monocyte-derived DC (MoDC) and LC-like cells (MoLC) upon stimulation with different Toll-like receptor ligands in the presence or absence of pro-inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In MoDC, bacterial antigens selectively up-regulated CD83 and CD86 expression and induced the release of T helper type 1 (Th1) and Th17 cytokines and led to a higher CCR7-dependent migratory capacity compared with a low responsiveness of MoLC. Importantly, MoLC activation with lipopolysaccharide under inflammatory conditions strongly enhanced a phenotypically mature state, increased IL-12p70, IL-23 and IL-6 production and Th1 cytokine secretion by CD4(+) T cells. Treatment with poly(I:C) specifically up-regulated surface expression of co-stimulatory molecules and increased release of IL-12p70 in MoLC and co-stimulation with TNF-α and IL-1β further elevated Th1 and Th17 cytokine production. Poly(I:C)-induced up-regulation of type I interferon mRNA levels in MoLC and MoDC was Toll-like receptor 3-dependent but not, or only weakly, modulated by pro-inflammatory cytokines. Our results indicate that inflammatory conditions greatly facilitate recognition of bacteria by MoLC. Furthermore, we suggest a critical involvement of both subsets in innate defence against viruses, whereas inflammatory skin environments additionally favour MoLC as potent inducers of Th1 and Th17 cytokines.


Recent advances in X-ray microanalysis in dermatology.
Electron microprobe and proton microprobe X-ray analysis can be used in several areas of dermatological research. With a proton probe, the distribution of trace elements in human hair can be determined. In contrast to sulfur, which is homogeneously distributed, calcium, iron, and zinc appear to be non-homogeneously distributed over the hair cross-section. Electron microprobe analysis on freeze-dried cryosections of guinea-pig and human epidermis shows a marked gradient of Na, P and K over the stratum granulosum. In sections of freeze-substituted human skin this gradient is less steep. This difference is likely to be due to a decrease in water content of the epidermis towards the stratum corneum. Electron microprobe analysis of the epidermis can, for analysis of trace elements, be complemented by the proton microprobe. Quantitative agreement between the two techniques can be obtained by the use of a standard. Proton microprobe analysis was used to determine the distribution of Ni or Cr in human epidermis exposed to nickel or chromate ions. Possible differences in water content between the stratum corneum of patients with atopic eczema and normal stratum corneum was investigated in skin freeze-substituted with Br-doped resin. No significant differences were observed. Proliferative reactions in the epidermis appear to be associated with increased levels of the elements P and K. Such changes were found in guinea-pig skin after exposure to sodium lauryl sulfate, and in plaques of skin from patients with psoriasis.


Effect of nebulized salbutamol in preterm infants during the first year of life.
The acute effect on lung function of nebulized salbutamol and saline (placebo) has been investigated in preterm infants at follow-up. Twenty two premature infants, median gestational age 29 weeks (range 26-32 weeks) and birthweight 1,264 g (720-1,800 g), were studied at a median postnatal age of 7 months (range 6-9 months). Nine of the infants had recurrent respiratory symptoms; they coughed and/or wheezed at least 3 days per week for the previous 4 weeks. The remaining 13 infants were free from recurrent or persistent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured and specific airway conductance sGaw calculated before and 10 min after salbutamol and normal saline given via a nebulizer. Amongst the symptomatic infants administration of nebulized salbutamol was associated with a median reduction in Raw of 25% (p less than 0.01) and also a significant improvement in sGaw (p less than 0.01). In the asymptomatic infants neither Raw nor sGaw changed significantly. Nebulized saline caused no significant change in lung mechanics in either the symptomatic or asymptomatic infants. We conclude that nebulized salbutamol is an effective bronchodilator for symptomatic preterm infants less than one year of age.


An Activity-Mediated Transition in Transcription in Early Postnatal Neurons.
The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers that appear to be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.


Pilot study of a utilities-based treatment decision intervention for prostate cancer patients.
This pilot study evaluates a shared decision-making approach to individual decision making in localized prostate cancer care. The approach is based on a decision analytic model that incorporates patient utilities, ie, patient preferences among possible health states that might occur with prostate cancer treatments. Data on comorbidities, histologic grade of the biopsy, and age were obtained for 13 patients with newly diagnosed localized prostate cancer who received care in a Veterans Administration medical center. Using a standard gamble technique, interviewers obtained patient utilities for 5 distinct health states related to prostate cancer treatment. Utilities and patient clinical and pathologic characteristics were incorporated into the decision analytic model, and the derived quality-adjusted life expectancies were shared with the treating urologist before the first patient-physician discussion about treatment options. The results of the pilot study raised 2 major concerns. First, 4 patients had utility scores of 1.0 for all of the possible health states, and 7 patients had inconsistent utilities in which they rated both impotence and incontinence as a better health state than having just one of these problems. Second, the model recommended radiation therapy to individuals with a broad range of clinical characteristics, pathologic findings, and utility scores. Many of the patients who were recommended radiation therapy by the model received discordant recommendations from the treating urologist. Future refinements of both the utility assessment exercise and decision analytic model may be needed before the feasibility of the model in the clinical setting can be determined.


Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features.
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.


Dietary variety and its effect on food intake of elderly adults.
Older people frequently have poor food intake. This present study investigated the effect of dietary variety on food intake in younger and older people. Eighteen young adults (mean age = 26 years) and 18 older adults (mean age = 70 years) consumed four consecutive courses of sandwiches on two occasions. In the plain treatment, each course of sandwiches was of the same type, while in the variety treatment four courses, each of a different type of sandwich, were served. Each time the participants were presented with a serving of sandwiches and asked to eat as much as they liked. In the plain condition, the older adult group consumed more than their young counterparts. This situation was reversed for the variety condition when the young group ate more than the older adults. Interestingly, the older adult group ate more when a variety of sandwiches was presented. This may be contrary to what is predicted by the sensory-specific satiety model of eating behaviour. This study suggests that presenting the older people with a varied meal may be a valid strategy to improve food intake in this group.


Comparative pharmacokinetics of the main active components in normal and ulcerative colitis rats after oral administration of Zingiberis Rhizoma-Ginseng Radix et Rhizoma herb pair and its single herb extracts by LC-MS/MS.
Zingiberis Rhizoma and Ginseng Radix et Rhizoma are usually used together for the treatment of ulcerative colitis in clinical practices. However, their compatibility mechanism remains unclear. In this study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6-gingerol in rat plasma after oral administration of Zingiberis Rhizoma-Ginseng Radix et Rhizoma herb pair and its single herb extracts. The calibration curves exhibited good linearity, with correlation coefficients of more than 0.993. The precision deviations of intra- and interday analysis were within 10.66%, and accuracy error ranged from -12.74 to 11.56%. The average recoveries of analytes were higher than 76.60% and the matrix effects were minimal. Thus, the validated method was successfully applied to a pharmacokinetic study of four ingredients in normal and ulcerative colitis rat plasma. The results indicated that the pharmacokinetic parameters of four analytes in normal and model groups showed significant differences. The larger exposure (the mean AUC0-t of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6-gingerol were increased by 50.93, 141.90, 3.68, and 37.25%, respectively) and slower elimination (the CLz/F of ginsenoside Re, ginsenoside Rg1, and 6-gingerol were decreased by 52.94, 83.64, and 32.18%, respectively) were observed in ulcerative colitis rats. Furthermore, compared with single herbs, the analytes in rat plasma after oral administration of combined extracts presented relatively high systemic exposure levels with AUC0-t > 2000 h·ng/mL and Cmax > 200 ng/mL. Collectively, the differences of pharmacokinetic characteristics revealed the synergistic effect of Zingiberis Rhizoma-Ginseng Radix et Rhizoma herb pair, which provided a valuable and reliable basis for its clinical application in the treatment of ulcerative colitis.


Safety of hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol.
Herein we assess the safety of an inhaled formulation of beclomethasone dipropionate (BDP) which uses the propellant hydrofluoroalkane-134a (HFA) for the treatment of asthma. Acute local tolerability (as assessed by the incidence of cough and mean forced expiratory volume after 1 s inhalation) was similar for both BDP and placebo formulated in either chlorofluorocarbon (CFC) or HFA propellants. A total of 43 patients were treated with HFA-BDP (0, 200, 400 or 800 micrograms day-1) or CFC-BDP (800 micrograms day-1) for 14 days and their 24 h urinary free cortisol (UFC) excretion and response to cosyntropin stimulation were measured. There was no difference in UFC between any of the doses of HFA-BDP and CFC-BDP. Adrenal responsiveness to cosyntropin stimulation was normal in all but one patient. Two large 12 week phase III trials compared HFA-placebo, HFA-BDP 400 micrograms day-1 and CFC-BDP 800 micrograms day-1 (n = 347), and HFA-BDP 800 micrograms day-1 and CFC-BDP 1500 micrograms day-1 (n = 233). For HFA-BDP at either dose, CFC-BDP 800 micrograms day-1 and HFA-placebo, the number of patients with morning plasma cortisol concentrations below normal was less than 4.4% but was 14.6% for CFC-BDP 1500 micrograms day-1. The incidence of adverse events was lower in the HFA-BDP groups than in the CFC-BDP groups (P = 0.012). The data indicate that, at doses of up to 800 micrograms day-1, HFA-BDP is at least as well tolerated as CFC-BDP. Other studies have found that equivalent efficacy is reached at lower doses of HFA-BDP than CFC-BDP. Equivalent efficacy at a lower dose and equivalent safety at the same dose imply that HFA-BDP may have a more favourable risk: benefit ratio than CFC-BDP when used at the recommended lower doses.


Modeling and calibration of a precise optical positioning system based on four linear cameras.
This study is intended for modeling and calibration of a precise optical positioning system for tracking 3D positions of remote targets in a large space. This system is made up of four linear cameras, which are equipped with cylindrical lenses. The four cameras are paired up as two identical groups. Each camera group is composed of two linear cameras that are packaged together with their imaging orientations normal to each other. The specially designed structure makes the system superior to existing three-linear-CCD-camera systems used for position tracking, in the efficiency of eliminating distortion of cylindrical lenses, a long-standing problem in precise calibration of linear cameras with cylindrical lenses. During the modeling and calibration process, each camera group is treated as an integrated 2D image sensor. A complete imaging model is established for each camera group, and the object-space error is used in calibration for obtaining optimal camera parameters. Simulative and real experiments have verified that, when the two cameras in each group have a good distortion consistency, the proposed calibration approach can effectively fit the model of linear cameras and correct the distortion of cylindrical lenses, thus leading to a significant improvement of positioning accuracy.


Global changes in Staphylococcus aureus gene expression in human blood.
Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LACΔhlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LACΔhlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LACΔhlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence.