Processing of vimentin occurs during the early stages of adenovirus infection.
Evidence is presented that a fraction of vimentin, a component of cytoskeleton recently found to be associated with intracytoplasmic, migrating adenovirus type 2 (Ad2), is processed into smaller polypeptides at early times after infection. The extent of vimentin cleavage appears to depend upon both the multiplicity of infection and the adenovirus serotype. Ad2, Ad5, Ad4, and Ad9 induced similar vimentin cleavage in infected cells, whereas Ad3, Ad7, and Ad12, for which most infecting particles are found sequestered within phagosomes, induced very little, if any, vimentin breakdown. This suggests that vimentin processing is in some way related to the number of virus particles migrating through the cytoplasm. Experiments performed in vitro and in vivo with adenovirus temperature-sensitive mutants H2 ts1 and H2 ts112 and UV-inactivated wild-type Ad2 indicated that vimentin processing is due to a nonvirion, cytoskeleton-associated, proteolytic enzyme activated by adenovirus and sharing characteristics with the protease described by Nelson and Traub (W.J. Nelson and P. Traub, J. Cell Sci. 57:25-49, 1982). The activity of this protease appears to be required for productive infection by adenovirus serotypes 2 and 5 (subgroup C), 4 (subgroup E), and 9 (subgroup D) but not by the oncogenic serotypes 3 and 7 (subgroup B) and 12 (subgroup A).


A double blind, randomised placebo controlled trial of rifampicin with omeprazole in the treatment of human cutaneous leishmaniasis.
This study was conducted on 50 patients of Anthroponotic cutaneous leishmaniasis (oriental sore) to assess the efficacy of rifampicin and omeprazole through a double blind, randomised placebo control study. The diagnosis of Anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica was done by demonstration of Leishmania tropica (LT) bodies from the painless, dry ulcerative lesion. Each patient was assessed clinically in the beginning of the study, at the end of 2,4 and 6 weeks and all observations were compared in both the groups. Twenty-five patients received rifampicin with omeprazole (Group A) whereas other 25 patients received placebo (Group B) for a period of six weeks. Altogether 23 cases in group Aand 21 cases in group B completed the study. About 16 (69.7%) cases in group A and 3 (14.29%) cases in group B had complete healing, whereas 3 patients (13.04%) of group A and 4 patients (19.05%) of group B had partial response and 4 patients (17.93%) of group A and 14 patients (66.67%) of group B had no response at the end of study. The difference of two groups was statistically highly significant (p < 0.00025). All patients tolerated the drug and placebo very well and no side effect was reported. In our opinion rifampicin and omeprazole is a highly effective, less toxic and cheaper alternative for the management of cutaneous leishmaniasis.


Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease.
Little is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited.


Emerging ASL Distinctions in Sign-Speech Bilinguals' Signs and Co-speech Gestures in Placement Descriptions.
Previous work on placement expressions (e.g., "she put the cup on the table") has demonstrated cross-linguistic differences in the specificity of placement expressions in the native language (L1), with some languages preferring more general, widely applicable expressions and others preferring more specific expressions based on more fine-grained distinctions. Research on second language (L2) acquisition of an additional spoken language has shown that learning the appropriate L2 placement distinctions poses a challenge for adult learners whose L2 semantic representations can be non-target like and have fuzzy boundaries. Unknown is whether similar effects apply to learners acquiring a L2 in a different sensory-motor modality, e.g., hearing learners of a sign language. Placement verbs in signed languages tend to be highly iconic and to exhibit transparent semantic boundaries. This may facilitate acquisition of signed placement verbs. In addition, little is known about how exposure to different semantic boundaries in placement events in a typologically different language affects lexical semantic meaning in the L1. In this study, we examined placement event descriptions (in American Sign Language (ASL) and English) in hearing L2 learners of ASL who were native speakers of English. L2 signers' ASL placement descriptions looked similar to those of two Deaf, native ASL signer controls, suggesting that the iconicity and transparency of placement distinctions in the visual modality may facilitate L2 acquisition. Nevertheless, L2 signers used a wider range of handshapes in ASL and used them less appropriately, indicating that fuzzy semantic boundaries occur in cross-modal L2 acquisition as well. In addition, while the L2 signers' English verbal expressions were not different from those of a non-signing control group, placement distinctions expressed in co-speech gesture were marginally more ASL-like for L2 signers, suggesting that exposure to different semantic boundaries can cause changes to how placement is conceptualized in the L1 as well.


[Study of brainstem auditory evoked potentials and its correlation with pontine volume in olivopontocerebellar atrophy].
To investigate the change of latency and interpeak latency of each component of BAEP (brainstem auditory evoked potential, BAEP) and its correlation with PV/PFV (pontine volume/posterior fossa volume, PV/PFV) ratio in OPCA (olivopontocerebellar atrophy, OPCA). We used Keypoint EMG/EP to determine waves I PL (peak latency, PL), III PL, V PL and I - III IPL (interpeak latency, IPL), III - V IPL, I - V IPL and used 1.5TMR 3D volume rendering software to determine PV (pontine volume, PV), CV(cerebellar volume, CV) and PFV (posterior fossa volume,PFV). Then calculated PV/PFV ratio, CV/PFV ratio and PV/ CV ratio in OPCA group and control group. Compared with control group, in OPCA group wave IIII PL, I - III IPL were significantly elongated (P < 0.05), III - V IPL was significantly shorten (P < 0.05), PV/PFV ratio was significantly decreased (P < 0.01); there was a positive correlation between III-V IPL and PV/PFV ratio (r = 0.83, P < 0.01). In patients with OPCA, III PL, I - III IPL of BAEP were elongated and III - V IPL of BAEP was shorten. III - V IPL became shorter when the volume of pontine decreased.


Crystallization and preliminary diffraction data of BaP1, a haemorrhagic metalloproteinase from Bothrops asper snake venom.
BaP1 is a metalloproteinase isolated from the venom of the Central American snake Bothrops asper (terciopelo). It is a 24 kDa protein consisting of a single chain which includes the metalloproteinase domain only, therefore being classified as a class P-I snake-venom metalloproteinase. BaP1 induces prominent local tissue damage, such as haemorrhage, myonecrosis, blistering, dermonecrosis and oedema. In order to elucidate its structure, BaP1 was crystallized by the hanging-drop vapour-diffusion technique in 0.1 M bicine pH 9.0, 10% PEG 20 000 and 2%(v/v) dioxane. Diffraction data were observed to a resolution of 2.7 A. Crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 38.22, b = 60.17, c = 86.09 A.


Comparative evaluation of the efficacy of synthetic nanocrystalline hydroxyapatite bone graft (Ostim®) and synthetic microcrystalline hydroxyapatite bone graft (Osteogen®) in the treatment of human periodontal intrabony defects: A clinical and denta scan study.
To evaluate the relative efficacy of synthetic nanocrystalline hydroxyapatite (HA) (Ostim®) and microcrystalline HA (Osteogen®) bone grafts in the treatment of human periodontal intrabony defects clinically and radiographically through denta scan. Ten chronic periodontitis patients with bilateral intrabony periodontal defects of ≥2 mm radiographic defect depth below 55 years of age were selected randomly and treated with synthetic nanocrystalline HA (Ostim®) or synthetic microcrystalline HA (Osteogen®) bone graft. Clinical parameters including probing depth (PD) and clinical attachment level (CAL) were measured preoperatively and postoperatively at 3 and 6 months for each of the defects using an occlusal acrylic stent. Radiographic parameters were measured with the help of denta scan preoperatively and postoperatively at 6 months. At 6 months following therapy, the Osteogen® group showed a reduction in mean PD from 11.10 ± 1.663 to 8.50 ± 0.850 mm and a change in mean CAL from 6.30 ± 1.160 to 3.40 ± 0.516 mm, whereas in the Ostim® group, the mean PD decreased from 11.20 ± 0.919 to 8.30 ± 0.823 mm and mean CAL decreased from 6.10 ± 0.738 to 3.30 ± 0.483 mm. At 6 months following therapy, denta scan showed a reduction in mean intrabony defect depth in the Osteogen® group from 2.54 ± 0.786 to 1.01 ± 0.448 mm, whereas in the Ostim® group, it was 2.71 ± 0.650 mm to 1.12 ± 0.563 mm. It was concluded that both the HA bone grafts produced statistically significant reduction in pocket depth, in the depth of osseous lesion, and a statistically significant gain in attachment level, irrespective of their physico-chemical properties.


The effect of electrical stimulation of the hypothalamus and other brain areas on urea cycle enzymatic activities in the liver in rabbits--experimental studies on brain and liver interrelationship--.
Changes in urea cycle enzymatic activities in the liver induced by intracerebral electrical stimulation in rabbits with chronically implanted electrodes in the hypothalamus, the thalamus, and the limbic area were studied in comparison with these activities in non-stimulated controls. In stimulating the ventromedial nucleus of the hypothalamus, the two-hour sessions were followed by significantly reduced activity in arginase and the arginine synthetase system in the liver, but the six-hour stimulation sessions were followed by normal range activity in these enzymes. In stimulating the lateral hypothalamic area, the two-hour sessions were followed by only slightly reduced activity in the arginine synthetase system in the liver. Stimulation of the center median nucleus of the thalamus, the medial area of the amygdala and the dorsal hippocampus produced no significant changes in urea cycle enzymatic activities in the liver. The possibility that ammonia metabolism in the liver may be modified through some functional linkage between the brain and the liver was suggested.


Investigating the contribution of the upper and lower lumbar spine, relative to hip motion, in everyday tasks.
It is commonplace for clinicians to measure range of motion (ROM) in the assessment of the lumbar spine. Traditional single 'joint' models afford measuring only a limited number of regions along the spine and may, therefore, over-simplify the description of movement. It remains to be determined if additional, useful information can be gleaned by considering the traditional 'lumbar region' as two regions. The aim of this study was to determine whether modelling the lumbar spine as two separate regions (i.e. upper and lower), yields a different understanding of spinal movement relative to hip motion, than a traditional single-joint model. This study is unique in adopting this approach to evaluate a range of everyday tasks. Lumbar spine motion was measured both by being considered as a whole region (S1 to T12), and where the lumbar spine was modelled as two regions (the upper (L3-T12) and lower (S1-L3)). A significant difference was evident between the relative contribution from the lower and upper spine across all movements, with the lower lumbar spine consistently contributing on average 63% of the total ROM. A significant difference was also evident between the whole lumbar spine-hip ratio, and the lower lumbar spine-hip ratio, for the movement of lifting only. The lower lumbar spine achieved greater velocity for all tasks, when compared to the upper lumbar spine. This study has consistently demonstrated differences in the contribution of the upper and lower spinal regions across a range of everyday tasks; hence, it would appear that greater focus should be given to performing more detailed assessments to fully appreciate spinal movement.


Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene-Long-Term Follow-Up of a Sibling.
Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic variant in ACO2 gene (NM_001098.3) was found to be causative of this disease. To date, approximately 44 variants displaying various clinical features have been reported. Here, we report a case of two siblings with compound heterozygous variants in the ACO2 gene. Two siblings without perinatal problems were born to healthy non-consanguineous Korean parents. They showed GDD and seizures since infancy. Their first brain magnetic resonance imaging (MRI), electroencephalography, and metabolic workup revealed no abnormal findings. As they grew, they developed symptoms including ataxia, dysmetria, poor sitting balance, and myopia. Follow-up brain MRI findings revealed atrophy of the cerebellum and optic nerve. Through exome sequencing of both siblings and their parents, we identified the following compound heterozygous variants in the ACO2: c.85C > T (p.Arg29Trp) and c.2303C > A (p.Ala768Asp). These two variants were categorized as likely pathogenic based on ACMG/AMP guidelines. In conclusion, this case help to broaden the genetic and clinical spectrum of the ACO2 variants associated with ICRD. We have also documented the long-term clinical course and serial brain MRI findings for two patients with this extremely rare disease.


[Study of mumps immunity after administrating measles-mumps-rubella vaccine among children aged 2-7 years old in Jiangsu Province in 2015].
Objective: To investigate the immunity to mumps after administrating measles-mumps-rubella vaccine (MMR) among children aged 2-7 years old in Jiangsu province in 2015. Methods: A total of 4 190 healthy children aged 2-7 years old, living in local places for at least 3 months, and having been vaccinated at least 1 dose MMR were recruited to the study from Wujin district of Changzhou city, Gaogang district of Taizhou city and Ganyu district of Lianyungang city by using stratified cluster random sampling method between September and November, 2015. Those who did not accept MMR vaccination, who refused venous blood collection, who had affected mumps according to the memory of parents or teachers and who were diagnosed serious disease by clinical doctors were excluded from study. The self-designed questionnaire was used to collect the general information of the subjects and their MMR immunization history; and 0.5-2.0 ml of venous blood was collected from each subject. ELISA was used to detect the mumps antibody level in the serum of patients. Positive was defined as the antibody level ≥108 mU/ml, and negative as <108 mU/ml. χ(2) test was used to compare the difference in positive rates among subjects; and analysis of variance was used to compare the GMC changes in different time points after MMR vaccination. Results: Among 4 190 children, 2 280 were males (54.42%) and 1 910 were females(45.58%), and the positive rate of IgG antibody was 81.38% (3 344). There were 3 156 (95.18%) children vaccinated with one dose MMR, 187 (4.80%) children with two dose MMR, and 1 (0.02%) child with three dose MMR. The difference in positive rate of IgG antibody among different aged subjects showed statistical significance (χ(2)=58.61, P<0.001), the highest positive rate was in group of subjects aged 4-5 years old, at 89.43% (406/454), while the lowest positive rate was found among subjects aged 6-7 years old, at 75.63% (1 648/2 179). The positive rate after one dose of MMR vaccination was 79.14% (3 156/3 988), significantly less than it after two doses (93.03%, 187/201) (χ(2)=22.93, P<0.001). The GMC level at years<1, 1-<2, 2-<3, 3-<4, ≥4 following one dose MMR in the 3 988 children was 152.47, 227.78, 167.08, 126.91, 79.43 mU/ml, whose difference was statistically significant (F=51.29, P<0.001). Conclusion: The sero-prevalence of IgG antibody in the children aged 2-7 years old in Jiangsu province was high. The positive rate among who received two doses MMR was significantly higher than it among who received just one dose, and the GMC level waned with times.


Emergency attendances and hospitalisations for complications after transrectal ultrasound-guided prostate biopsies: a five-year retrospective multicentre study.
Transrectal ultrasound-guided (TRUS) prostate biopsy is an established procedure for diagnosis of prostate cancer. Complications after TRUS biopsy are not well reported in Hong Kong. This study evaluated the 5-year incidences of TRUS biopsy complications and potential risk factors for those complications. This was a retrospective review of biopsies performed from 2013 to 2017 in two local hospitals, using data retrieved from electronic medical records. The primary outcome was the occurrence of complications requiring either emergency attendances or hospitalisations within 30 days after biopsy. Potential risk factors were examined using multiple logistic regression analysis. In total, 1699 men were included (mean age ± standard deviation: 67 ± 7 years; median prostate-specific antigen level: 7.9 μg/L [interquartile range, 5.5-12.6 μg/L]); 4.3% had pre-biopsy bacteriuria. Overall, 5.7% and 3.8% of post-biopsy complications required emergency attendances and hospitalisations, respectively. Gross haematuria and rectal bleeding requiring emergency attendances developed in 2.1% and 0.4% of men; 0.8% and 0.4% required hospitalisations. Furthermore, 1.5% of men developed acute urinary retention requiring hospitalisations; 1.9% and 1.2% had post-biopsy infections requiring emergency attendances and hospitalisations, respectively, and 0.9% had urosepsis requiring hospitalisations. Prostate volume >48 cc was associated with an increased risk of post-biopsy retention (odds ratio 2.75, 95% confidence interval: 1.23-4.17). The rate of overall complications after TRUS biopsy was low. The most common complications requiring emergency attendances and hospitalisations were gross haematuria and acute urinary retention, respectively. Prostate volume >48 cc increased the risk of post-biopsy urinary retention.


Scanning the intracellular S6 activation gate in the shaker K+ channel.
In Kv channels, an activation gate is thought to be located near the intracellular entrance to the ion conduction pore. Although the COOH terminus of the S6 segment has been implicated in forming the gate structure, the residues positioned at the occluding part of the gate remain undetermined. We use a mutagenic scanning approach in the Shaker Kv channel, mutating each residue in the S6 gate region (T469-Y485) to alanine, tryptophan, and aspartate to identify positions that are insensitive to mutation and to find mutants that disrupt the gate. Most mutants open in a steeply voltage-dependent manner and close effectively at negative voltages, indicating that the gate structure can both support ion flux when open and prevent it when closed. We find several mutant channels where macroscopic ionic currents are either very small or undetectable, and one mutant that displays constitutive currents at negative voltages. Collective examination of the three types of substitutions support the notion that the intracellular portion of S6 forms an activation gate and identifies V478 and F481 as candidates for occlusion of the pore in the closed state.


Is There a Bidirectional Association between Polycystic Ovarian Syndrome and Periodontitis? A Systematic Review and Meta-analysis.
Polycystic ovary syndrome (PCOS) has reproductive and metabolic properties that may be linked to periodontitis (PD). This study aimed to update and render a robust critical assessment on all evidence linking PCOS and PD, and appraising a hypothetical bidirectional association. Five databases (PubMed, Scholar, EMBASE, Web of Science and CENTRAL) were searched up to May 2020. Case-control and cohort studies on the association of PCOS and PD were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses of standardized mean difference (SMD) and risk ratio (RR) were performed. We followed Strength of Recommendation Taxonomy (SORT) to appraise the strength and quality of the evidence. Twelve case-controls fulfilled the inclusion criteria (876 with PCOS and 48170 healthy controls), all scored as having a low risk of bias. Meta-analysis revealed that PCOS females have 28% more risk towards PD, and PD females have 46% more risk to have PCOS. PCOS females with PD had higher gum bleeding, periodontal pocket depth and clinical attachment loss than non-PCOS females with PD. Populations with undefined periodontal status contribute to underestimated results. On the basis of the available evidence, it is possible to assume a bidirectional link between PCOS and PD. That is, PCOS increases by 28% the risk of having PD and in the same fashion, PD increases by 46% the risk of having PCOS. Furthermore, women with PCOS were associated with worsening clinical characteristics and inflammation of PD. These findings suggest that PCOS and PD may be linked. Hence, further prospective and clinical trial studies with nonsurgical periodontal therapy are necessary to clarify the existence of an increased risk of PCOS in women with PD and vice-versa.


Immune-related signature of periodontitis and Alzheimer's disease linkage.
Background: Periodontits (PD) and Alzheimer's disease (AD) are both associated with ageing and clinical studies increasingly evidence their association. However, specific mechanisms underlying this association remain undeciphered, and immune-related processes are purported to play a signifcant role. The accrual of publicly available transcriptomic datasets permits secondary analysis and the application of data-mining and bioinformatic tools for biological discovery. Aim: The present study aimed to leverage publicly available transcriptomic datasets and databases, and apply a series of bioinformatic analysis to identify a robust signature of immune-related signature of PD and AD linkage. Methods: We downloaded gene-expresssion data pertaining PD and AD and identified crosstalk genes. We constructed a protein-protein network analysis, applied immune cell enrichment analysis, and predicted crosstalk immune-related genes and infiltrating immune cells. Next, we applied consisent cluster analysis and performed immune cell bias analysis, followed by LASSO regression to select biomarker immune-related genes. Results: The results showed a 3 gene set comprising of DUSP14, F13A1 and SELE as a robust immune-related signature. Macrophages M2 and NKT, B-cells, CD4+ memory T-cells and CD8+ naive T-cells emerged as key immune cells linking PD with AD. Conclusion: Candidate immune-related biomarker genes and immune cells central to the assocation of PD with AD were identified, and merit investigation in experimental and clinical research.


Short communication: economics of sex-biased milk production.
In a recent data study using 2.4 million lactations of 1.5 million cows, it was reported that gestation of a female calf in the first parity increases cumulative milk production by approximately 445kg over the first 2 lactations. The reported effect in this study is large and remarkable because it has not been found before. To our knowledge, the economic implications of this or any other sex bias have not been studied. The objective of the current study was to quantify the reported influence of fetal sex across lactations by using a simulation model of a dairy herd including youngstock. Two scenarios were evaluated and compared with a scenario in which cows and heifers were exclusively bred with conventional (nonsexed) semen. In the first scenario, sexed semen was used moderately-on 30% of all heifers and 30% of the first parity cows. A second scenario was studied in which sexed semen was used intensively-on all heifers and 50% of the first-parity cows. The simulated proportion of cows giving birth to 2 consecutive heifers increased from 23% when using exclusively conventional semen up to 31 and 48% when using sexed semen moderately and intensively, respectively. The proportion of cows having 2 consecutive bulls decreased from 27% (conventional semen only) to 20 and 8% when using sexed semen moderately and intensively, respectively. When incorporating the sex bias in the simulation model, the simulated milk yield in the scenario in which sexed semen was used moderately increased by 48kg of energy-corrected milk (ECM) per cow/yr, compared with only 36kg of ECM when not incorporating the sex bias in the model. For the scenario in which sexed semen was used intensively, milk yield increased by 66 and 99kg of ECM when excluding and including the sex bias, respectively. The economic implications of the assumed sex bias were €4.0 and €9.9 per cow/yr, in the scenarios in which sexed semen was used moderately and intensively, respectively.


Lactation performance of mid-lactation dairy cows fed ruminally degradable protein at concentrations lower than national research council recommendations.
The aim of this study was to test whether feeding of diets containing lower proportions of ruminally degradable protein (RDP) but with a constant proportion of ruminally undegradable protein (RUP) alters feed intake, milk production and yield, and the apparent efficiency of N utilization by mid-lactation dairy cows. During the covariate period (d 1 to 28), 40 mid-lactation cows (36 Holstein and 4 Jersey x Holstein cross-breds) were fed a common diet formulated to contain 11.3% of diet dry matter (DM) as RDP. During the treatment period (d 29 to 47), cows were randomly assigned to 1 of 4 diets formulated to contain 11.3, 10.1, 8.8, or 7.6% RDP, whereas ruminally undegradable protein remained constant at 7.1% of DM. All diets contained 47.5% forage and 52.5% concentrate on a DM basis. Dry matter intake was significantly reduced for the 7.6% RDP diet. The lowest RDP content was associated with a trend for reduced milk yield. Dietary RDP had no effect on body weight or milk fat, protein, and lactose contents. Milk protein yield was not affected by RDP level; however, milk fat yield decreased linearly as dietary RDP was reduced. Concentrations of plasma essential amino acids were unaffected, whereas milk urea-N concentrations decreased linearly as dietary RDP content was reduced. The apparent efficiency of N utilization for milk N production increased from 27.7% on the 11.3% RDP diet to 38.6% on the 7.6% RDP diet. The dietary RDP requirement of cows in this study was apparently met between 15.9 and 14.7% dietary crude protein. Milk production was not significantly affected by the 8.8% RDP (15.9% crude protein) diet even though the NRC (2001) model predicted that RDP supply was 87% of that required, suggesting the current NRC recommendations for RDP may be overestimated for mid-lactation dairy cows in this study.


[The association of beta zero-thalassemia and Hb D Punjab in a family of Indian origin. The second case reported in Spain].
The present report described the hematologic and molecular study of the second case of Hb D-Punjab associated with a beta zero-thalassemia found in Spain and the first case in which the mutations have been identified at molecular level. A family from India is studied, which is constituted by mother (I2) and 3 children (II1, II2 and II3). The molecular characterization of the hemoglobinopathy was made by electrophoretic and chromatographic techniques and confirmed by sequencing of the beta-globin gene. The mutation causer of the beta-thalassemia was studied by PCR-ARMS. The mother (I2) and one of her child (II2) are carriers of the gene for beta zero-thalassemia owing to the frameshift CD 8/9 mutation (+ G). Other of them (II1) is heterozygous for Hb D-Punjab without beta-thalassemia association. The third child (II3) knows a double heterozygote state for Hb D-Punjab/beta zero-thalassemia (hemoglobin D-thalassemia). In spite of the patient with hemoglobin D-thalassemia has 94.5% of Hb D, without Hb A, the hematologic picture belongs to thalassemia trait with moderate haemolytic anemia, intense microcytosis and hypochromia and numerous target cells. This hematologic picture discloses the mildness of the Hb D-Punjab, but the reliable responsible for the phenotype is the disbalance in the synthesis of globin chains, because of frameshift CD 8/9 mutation (+ G) beta zero-thalassemia mutation.


Outcome assessment of breast distortion following submuscular breast augmentation.
Animation deformity or breast distortion during pectoralis muscle contraction following subpectoral breast augmentation is a known entity, but its prevalence and significance remain unclear. The purpose of this study was to identify the incidence and severity of animation deformity as well as its effect on patient satisfaction and interference with certain activities. All procedures were performed by the senior author using a variation of a previously described dual-plane technique. The first part of this study was an evaluation of breast distortion by a group of independent observers in a series of 40 consecutive patients who underwent primary subpectoral breast augmentation. The second part of the study was a questionnaire sent to 195 consecutive patients asking about overall satisfaction, degree of animation deformity, and whether there was interference with any activities. Of the 40 patients' photographs that were evaluated, 9 (22.5%) had no distortion, 25 (62.5%) had minimal distortion, 4 (10%) had moderate distortion, and 2 (5%) had severe distortion. Of the 195 questionnaires, there were 69 responses, a 35% response rate. Fifty-six (82%) described mild to no distortion, 7 (10%) were moderate, and 5 (7%) were severe. According to the survey, the most common activities that were problematic were lifting weights and exercising (24 and 19%, respectively). Only one (1%) patient stated that she would not recommend subpectoral positioning. Although animation deformities do exist, nearly all patients in this study would still choose subpectoral positioning. Patients who may be better candidates for subglandular placement are those for whom exercise is central to their daily living. As a result of this study, surgeons and patients should have more accurate and reliable information regarding the significance of animation deformity after subpectoral breast augmentation.


Optical systems for controlled specular depolarization.
Optical coatings are known to be highly polarizing at oblique incidence. On the other hand, they cannot reduce the degree of polarization of light. We show how to overcome this difficulty and reach spatial depolarization with significant efficiency. Applications concern space optical systems.


Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines.
Interleukin (IL)-36 cytokines belong to the IL-1 family and include three agonists, IL-36 α, β and γ and one inhibitor, IL-36 receptor antagonist (IL-36Ra). IL-36 and IL-1 (α and β) activate similar intracellular pathways via their related heterodimeric receptors, IL-36R/IL-1RAcP and IL-1R1/IL-1RAcP, respectively. However, excessive IL-36 versus IL-1 signaling induces different phenotypes in humans, which may be related to differential expression of their respective receptors. We examined the expression of IL-36R, IL-1R1 and IL-1RAcP mRNA in human peripheral blood, tonsil and skin immune cells by RT-qPCR. Monocyte-derived dendritic cells (MDDC), M0, M1 or M2-polarized macrophages, primary keratinocytes, dermal macrophages and Langerhans cells (LC) were stimulated with IL-1β or IL-36β. Cytokine production was assessed by RT-qPCR and immunoassays. The highest levels of IL-36R mRNA were found in skin-derived keratinocytes, LC, dermal macrophages and dermal CD1a(+) DC. In the blood and in tonsils, IL-36R mRNA was predominantly found in myeloid cells. By contrast, IL-1R1 mRNA was detected in almost all cell types with higher levels in tonsil and skin compared to peripheral blood immune cells. IL-36β was as potent as IL-1β in stimulating M2 macrophages, keratinocytes and LC, less potent than IL-1β in stimulating M0 macrophages and MDDC, and exerted no effects in M1 and dermal macrophages. Levels of IL-1Ra diminished the ability of M2 macrophages to respond to IL-1. Taken together, these data are consistent with the association of excessive IL-36 signaling with an inflammatory skin phenotype and identify human LC and M2 macrophages as new IL-36 target cells.


Unusual exchange bias in Sr2FeIrO6/La0.67Sr0.33MnO3 multilayer.
Here, we study interface induced magnetic properties in a 3d-5d based multilayer made of La0.67Sr0.33MnO3 and double perovskite Sr2FeIrO6, respectively. Bulk La0.67Sr0.33MnO3 is metallic and shows ferromagnetic (FM) ordering above room temperature. In contrast, bulk Sr2FeIrO6, is an antiferromagnet (AFM) with a Néel temperature around 45 K ([Formula: see text]) and exhibits an insulating behavior. Two set of multilayers have been grown on SrTiO3 (1 0 0) crystal with varying thickness of FM layer. A multilayer with equal thickness of La0.67Sr0.33MnO3 and Sr2FeIrO6 (∼10 nm) shows exchange bias (EB) effect both in conventionally field cooled (FC) as well as in zero field cooled (ZFC) magnetic hysteresis measurements which is rather unusual. The ZFC EB effect is weakened both with increasing maximum field during initial magnetization process at low temperature and with increasing temperature. Interestingly, a multilayer with reduced thickness of La0.67Sr0.33MnO3 (∼5 nm) does not exhibit ZFC EB phenomenon, however, the FC EB effect is strengthened showing much higher value. We believe that an AFM type exchange coupling at the interface and its evolution during initial application of magnetic field causes this unusual EB in present multilayers.


The rational use of 201Tl scintigraphy in the evaluation of differentiated thyroid cancer.
Fifteen patients with differentiated thyroid cancer were examined following 131I thyroid ablation, of these seven were examined after radio-iodine therapy to disseminated neck cancer. They had no further radio-iodine uptake and were evaluated using a 201Tl scan. In thirteen patients there was a good correlation between the results and the clinical diagnosis, showing no uptake in seven subjects with negative clinical findings, and positive delineation of tumour tissue in the neck region in six patients. The remaining two patients with lymph node metastases after previous radio-iodine irradiation showed marked clinical regression of the metastases with absent uptake of both 131I and 201Tl, probably due to radiation-induced changes. The comparison of thallium scans with plasma thyroglobulin levels showed certain differences (high plasma thyroglobulin without any proof of remaining thyroid tissue in one patient and normal/low plasma thyroglobulin in the presence of a tumour in two patients) but both measurements could give additional information. It is believed that while in the differential diagnosis of a thyroid nodule no important information could be expected of scanning (compared with the high value of aspiration biopsy), the evaluation of patients without 131I uptake by 201Tl scans could provide important information for further therapy.


Extraction of pure cellular fluorescence by cell scanning in a single-cell microchip.
A 3-dimensional liquid flow control method has been developed to manipulate and retain a single yeast cell freely in a microchip. This method allows us to carry out single-cell experiments by selecting any desired single cell from a group, retaining the cell for cellular signal detection, and delivering reagents to the cell during continual detection and observation without any negative impact from the liquid flow on the live cell. The cell was scanned back and forth across an observation window in order to extract pure cellular fluorescent signals. Different scanning methods were discussed for effective collection of the cellular fluorescent signal. The cell scanning technique results in many advantages, such as distinguishing a small part of a cell, allowing for background correction and monitoring the switch of reagents. In addition, it is possible to evaluate the photobleaching effects on both the background and cellular fluorescence, with the latter found to be less significant in a restricted cellular environment.


The cytoprotective effect of iloprost against carbon tetrachloride induced necrosis in rat liver.
The aim of this study was to investigate the cytoprotective effect of Iloprost on the liver against carbon tetrachloride induced necrosis. The serum histamine-like activity was found to be increased when compared with that of controls after treatment with carbon tetrachloride for 18 weeks while prostaglandin E2- and leukotriene C4-like activities were unchanged. After pretreatment with Iloprost for 18 weeks the increased activity of histamine was found to be unchanged while prostaglandin E2-like activity was increased. It is concluded that Iloprost protects the liver against carbon tetrachloride-induced damage and reduces the level of histamine that has a role in the pathogenesis of portal hypertension.


HRET patient safety leadership fellowship: the role of "community" in patient safety.
Community engagement is widely endorsed but poorly defined as a strategy to improve patient safety. With strong evidence that engaging patients can positively influence health outcomes, it is presumed that community engagement could improve patient safety. Leaning on the models from other disciplines such as public health, the adequate knowledge and application of the principles of community engagement are critical for this approach to be effective. This article provides a description of the theories supporting patient partnership and community engagement, reviews critical elements of successful community-based programs, and identifies the potential for empowering communities to improve patient safety.


Scout anteroposterior and lateral CT scans as a screening test for thoracolumbar spine injury in blunt trauma.
Anteroposterior and lateral radiographs have traditionally been required to clear the thoracolumbar spine (TLS) after blunt trauma. The routine use of CT scans led to a pilot trial to determine if CT scout images can accurately evaluate the TLS after blunt trauma. The purpose of the study was to determine the sensitivity, specificity, positive and negative predictive values of CT scout images for the evaluation of the TLS. Patients admitted to our level II trauma center requiring CT evaluation of the chest, abdomen, and pelvis were considered for this study. Patients with blunt trauma, without neurologic deficits, or other evidence of spinal trauma on physical examination were included. Charts were reviewed for demographics, scout CT image findings, and full CT scan findings. Scout CT images were compared with reconstructed spine CT scans from chest, abdomen, and pelvis CT scans. Injuries to the TLS were defined as compression fractures, burst fractures, and subluxation. One hundred seventeen patients were included. Average Injury Severity Score was 25.1 (+/-9.4) and average age was 42.5 years. Twenty-three patients had diffuse back tenderness, three had ecchymosis, and 64 had distracting injuries. Twelve injuries to the TLS were present; 11 were seen on scout images. Sensitivity was 92 per cent, specificity 100 per cent, positive predictive value 100 per cent, and negative predictive value 99 per cent. Scout CT images provide an accurate assessment of the TLS after blunt trauma. We are encouraged by the results and will continue to investigate to identify the criteria that allow scout CT images to safely replace anteroposterior and lateral radiographs in the evaluation of the TLS in blunt trauma.


NLR proteins: integral members of innate immunity and mediators of inflammatory diseases.
The innate immune system is the first line of defense against microorganisms and is conserved in plants and animals. The nucleotide-binding domain, leucine rich containing (NLR) protein family is a recent addition to the members of innate immunity effector molecules. These proteins are characterized by a central oligomerization domain, termed nucleotide-binding domain (NBD) and a protein interaction domain, leucine-rich repeats (LRRs) at the C terminus. It has been shown that NLR proteins are localized to the cytoplasm and recognize microbial products. To date, it is known that Nod1 and Nod2 detect bacterial cell wall components, whereas Ipaf and Naip detect bacterial flagellin, and NACHT/LRR/Pyrin 1 has been shown to detect anthrax lethal toxin. NLR proteins comprise a diverse protein family (over 20 in humans), indicating that NLRs have evolved to acquire specificity to various pathogenic microorganisms, thereby controlling host-pathogen interactions. Activation of NLR proteins results in inflammatory responses mediated by NF-kappaB, MAPK, or Caspase-1 activation, accompanied by subsequent secretion of proinflammatory cytokines. Mutations in several members of the NLR protein family have been linked to inflammatory diseases, suggesting these molecules play important roles in maintaining host-pathogen interactions and inflammatory responses. Therefore, understanding NLR signaling is important for the therapeutic intervention of various infectious and inflammatory diseases.


Dental hygienists in the United States: results of an ADA survey.
The Survey Center of the American Dental Association conducts an annual survey of approximately 5 percent of all private practitioners in the United States. This survey is sent to a randomly selected group of dentists in private practice, including general practitioners and specialists and ADA members and nonmembers. It attempts to collect information on various practice characteristics such as work schedules, patient visits, non-dentist staff employment, expenses and wages. Using information from the 1991 to 1995 Survey of Dental Practice reports, this article examines the employment of dental hygienists.


Characterization of a de novo unbalanced chromosome rearrangement by comparative genomic hybridization and fluorescence in situ hybridization.
Fluorescence in situ hybridization (FISH) has proven useful for the identification of chromosomal material of unknown origin. More recently, comparative genomic hybridization (CGH) has been used to identify deletions and amplifications, particularly in neoplastic samples. Here, we describe the combined use of CGH and FISH to identify the origin of a de novo unbalanced translocation in a newborn with multiple congenital anomalies. GTG banding of metaphases from cultured lymphocytes showed an unbalanced karyotype, with extra material on a chromosome 5: 46,XX,add(5)(q35). Parental karyotypes were both normal. CGH revealed the additional material was from distal 11q (11q23-->'qter). This finding was confirmed by FISH with a whole chromosome paint for chromosome 11. Based on the CGH and FISH analyses, the proband's karyotype was therefore 46,XX,der(5)t(5;11)(q35.2; q23.2).ish der(5)(wcp11+). This case demonstrates the efficient use of CGH and confirmatory FISH for the identification of chromosomal material of unknown origin.


Factors Associated with Substance Use Disorder Treatment Completion, Rhode Island, USA, 2018.
The successful retention of individuals with substance use disorders in treatment remains a challenge but is an important indicator of positive post-treatment outcomes. The aim of this study is to advance understanding of pre-admission factors associated with substance use treatment completion in Rhode Island. Data for this longitudinal analysis are from the RI Behavioral Health On-Line Database (RI-BHOLD). The primary outcome of interest was substance use treatment completion defined as any planned discharge from treatment, including transfers to other facilities. Associations were assessed using generalized estimating equations (GEE) to account for the potential of repeated measures for the same individuals. Among the 7,351 clients discharged from a substance use treatment program in RI in 2018, the treatment completion rate was 58.1%. There was a positive relationship between the frequency of attendance of voluntary self-help groups and odds of treatment completion. Treatment completion rates were lower among those who reported use of opioids (AOR: 0.59; 95% CI: 0.52-0.66) and other drugs (AOR: 0.52; 95% CI: 0.44-0.62), compared to alcohol and for those with co-occurring mental health conditions (AOR: 0.85; 95% CI: 0.76-0.94). This study highlights the importance of social connectedness in substance use disorder treatment completion. Future research is needed to identify the characteristics of persons who are most likely to benefit from self-help groups and the optimal combination of treatment participation and attendance of self-help groups across a spectrum of disorder severity and community resources.


The effect of pre- and after-treatment of sevoflurane on central ischemia tolerance and the underlying mechanisms.
In recent years, with continuous research efforts targeted at studying the effects of pre- and after-treatment of inhaled anesthetics, significant progress has been made regarding the common clinical use of low concentrations of inhaled sevoflurane and its effect on induced central ischemia tolerance by pre- and post-treatment. In this study, we collected, analyzed, classified, and summarized recent literature regarding the effect of sevoflurane on central ischemia tolerance and its related mechanisms. In addition, we provide a theoretical basis for the clinical application of sevoflurane to protect the central nervous system and other important organs against ischemic injury.


De Novo Assembly of the Liver Transcriptome of the European Starling, Sturnus vulgaris.
The European starling, Sturnus vulgaris, is a prolific and worldwide invasive species that also has served as an important model for avian ecological and invasion research. Although the genome sequence recently has become available, no transcriptome data have been published for this species. Here, we have sequenced and assembled the S. vulgaris liver transcriptome, which will provide a foundational resource for further annotation and validation of the draft genome. Moreover, it will be important for ecological and evolutionary studies investigating the genetic factors underlying rapid evolution and invasion success in this global invader.


Echography: a new approach to the diagnosis of adrenal hemorrhage of the newborn.
A case of adrenal hemorrhage of the newborn, diagnosed by ultrasound, is presented. All other diagnostic modalities were found to be non-specific. Ultrasonic evaluation is recommended in the evaluation of pediatric abdominal masses. This is a safe, non-invasive, rapid and easily performed study. It is felt that the use of diagnostic ultrasound in evaluating neonates for adrenal hemorrhage wil obviate the necessity of more invasive procedures, such as exploratory laparotomy.


Intellectual functioning and executive functions in children and adolescents with attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD).
Several studies have shown neuropsychological deficits across multiple domains in attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD), but differences and similarities between these disorders have been little considered. We were interested in analyzing the intellectual and executive profiles in a sample of children and adolescents, divided according to the diagnosis into the ADHD group and the SLD group, and in identifying the differences and similarities between these disorders. The sample included two clinical groups: the first included 36 children and adolescents with a diagnosis of ADHD (5-15 years; mean = 9.42; SD = 2.22) while the second included 36 children and adolescents with a diagnosis of SLD (7-15 years; mean = 9.43; SD = 2.25). The WISC-IV was used to measure intellectual ability and the NEPSY-II was employed to measure executive functions. The results showed that the SLD group had significantly higher scores than the ADHD group on the NEPSY-II in the inhibition, cognitive flexibility, short-term verbal memory and verbal working memory domains. The ANCOVA showed differences regarding the FSIQ of WISC-IV, in that the SLD group obtaining higher scores than ADHD group. Findings showed that ADHD children are more impaired than SLD children, in particular in cognitive inhibition, cognitive flexibility, verbal memory, working memory and intellectual functioning. The recognition of the strengths and weaknesses of children and adolescents with ADHD and SLD allows to outline an educational and clinical intervention focused on their specific executive and intellectual functioning.


Rapid assessment methods of resilience for natural and agricultural systems.
The resilience, ecological function and quality of both agricultural and natural systems were evaluated in the mountainous region of the Atlantic Rain Forest of Rio de Janeiro through Rapid Assessment Methods. For this goal new indicators were proposed, such as eco-volume, eco-height, bio-volume, volume efficiency, and resilience index. The following agricultural and natural systems have been compared according: (i) vegetables (leaf, fruit and mixed); (ii) citrus; (iii) ecological system; (iv) cattle, (v) silvo-pastoral system, (vi) forest fragment and (vii) forest in regeneration stage (1, 2 and 3 years old). An alternative measure (index) of resilience was proposed by considering the actual bio-volume as a function of the potential eco-volume. The objectives and hypotheses were fulfilled; it is shown that there does exist a high positive correlation between resilience index, biomass, energy efficiency and biodiversity. Cattle and vegetable systems have lowest resilience, whilst ecological and silvo-pastoral systems have greatest resilience. This new approach offers a rapid, though valuable assessment tool for ecological studies, agricultural development and landscape planning, particularly in tropical countries.


Extended-Release Guanfacine Does Not Show a Large Effect on Tic Severity in Children with Chronic Tic Disorders.
To evaluate the tolerability, safety, and preliminary efficacy of extended-release guanfacine in children with chronic tic disorders, including Tourette's disorder (collectively referred to as CTD). This was a multisite, 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS) total score. Key secondary outcomes included the Improvement item of Clinical Global Impressions-Improvement (CGI-I) scale and the Tic Symptom Self-report (TSSR). Adverse events were monitored at each visit. Thirty-four subjects (23 boys and 11 girls) of ages 6 to 17 years (mean = 11.1 ± 3.1) with CTD were randomly assigned to extended-release guanfacine (n = 16) or placebo (n = 18). At baseline, the mean YGTSS total score was 26.3 ± 6.6 for the guanfacine group versus 27.7 ± 8.7 for the placebo group. Within the guanfacine group (mean final daily dose of 2.6 ± 1.1 mg, n = 14), the mean YGTSS total score declined to 23.6 ± 6.42 [t(15) = 1.84, p = 0.08; effect size = 0.35]. The results were similar in the placebo group with a score of 24.7 ± 10.54 at week 8 [t(17) = 1.83, p = 0.08; effect size = 0.38]. There was no significant difference in the rate of positive response on the CGI-I between the guanfacine group and placebo (19% [3/16] vs. 22% [4/18], p = 1.0). The most common adverse events were fatigue, drowsiness, dry mouth, headache, and irritability. Two subjects in the guanfacine group discontinued early-one because of an adverse event (depressed mood) and one because of lack of efficacy; two subjects in the placebo group discontinued because of lack of efficacy. This pilot study did not confirm a clinically meaningful effect size within the guanfacine group. These results do not support the launch of a larger efficacy trial for tics in children and adolescents with CTD.


Dynamic behaviours of a rationally prepared flexible MOF by postsynthetic modification of ligand struts.
Through postsynthetic modification of ligand struts, controllable conversion of a Zr MOF between rigidity and flexibility is realized. The rationally prepared flexible MOF exhibits interesting dynamic behaviours, such as reversible structural deformation, vapour sorption hysteresis and unexpected adsorption of bulky guest molecules.


Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria.
Curcumin, the principal curcuminoid of tumeric, has potent anticancer activity. To determine the mechanism of curcumin-induced cytotoxicity in prostate cancer cells, we exposed PC3 prostate carcinoma cells to 25 to 100 microM curcumin for 24 to 72 h. Curcumin treatment of PC3 cells caused time- and dose-dependent induction of apoptosis and depletion of cellular reduced glutathione (GSH). Exogenous GSH and its precursor N-acetyl-cysteine, but not ascorbic acid (AA) or ebselen, decreased curcumin accumulation in PC3 cells and also prevented curcumin-induced DNA fragmentation. The failure of AA and ebselen to protect PC3 cells from curcumin-induced apoptosis argued against the involvement of reactive oxygen species; rather, GSH-mediated inhibition of curcumin-induced cytotoxicity was due to reduced curcumin accumulation in PC3 cells. Curcumin-treated PC3 cells showed apoptosis-inducing cellular ceramide accumulation and activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK). Caspase-3, caspase-8, and caspase-9 were activated, and cytochrome c and apoptosis-inducing factor (AIF) were released from mitochondria following curcumin treatment. Interestingly, curcumin-induced apoptosis was not prevented by p38 MAPK, JNK, or caspase inhibition. We conclude that curcumin-induced cytotoxicity was due to cellular ceramide accumulation and damage to mitochondria that resulted in apoptosis mediated by AIF and other caspase-independent processes.


Reconstructing nonlinearities with intermodulation spectroscopy.
We describe a method of analysis which allows for reconstructing the nonlinear disturbance of a high Q harmonic oscillator. When the oscillator is driven with two or more frequencies, the nonlinearity causes intermodulation of the drives, resulting in a complicated spectral response. Analysis of this spectrum allows one to approximate the nonlinearity. The method, which is generally applicable to measurements based on resonant detection, increases the information content of the measurement without requiring a large detection bandwidth, and optimally uses the enhanced sensitivity near resonance to extract information and minimize error due to detector noise.


Early detection of anthracycline cardiotoxicity in a rabbit model: left ventricle filling pattern versus troponin T determination.
Anthracycline cardiotoxicity represents a serious risk of anticancer chemotherapy. The aim of the present pilot study was to compare the potential of both the left ventricular (LV) filling pattern evaluation and cardiac troponin T (cTnT) plasma levels determination for the early detection of daunorubicin-induced cardiotoxicity in rabbits. The echocardiographic measurements of transmitral LV inflow as well as cTnT determinations were performed weekly for 10 weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each). Surprisingly, no significant changes in LV-filling pattern were observed through the study, most likely due to the xylazine-containing anesthesia, necessary for appropriate resolving of the E and A waves. In contrast to the echographic measurement, the dP/dt(min) index obtained invasively at the end of the study revealed a significant impairment in LV relaxation, which was further supported by observed disturbances in myocardial collagen content and calcium homeostasis. However, at the same time cTnT plasma levels were progressively rising in the daunorubicin-treated animals from the fifth week (0.024+/-0.008 microg/l) until the end of the experiment (0.186+/-0.055 microg/l). Therefore, in contrast to complicated non-invasive evaluation of diastolic function, cTnT is shown to be an early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit model.


Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma.
Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences. At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04-6.56; p = 0.04). This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.


Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene.
Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the alpha(4) and beta(2) subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucleotide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.


Colonic diverticulosis is not a risk factor for colonic adenoma.
Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.


Dysregulation of immune response in otitis media.
Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM. A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review. Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites. Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.


Hepatic glutamine transport and metabolism.
Although the liver was long known to play a major role in the uptake, synthesis, and disposition of glutamine, metabolite balance studies across the whole liver yielded apparently contradictory findings suggesting that little or no net turnover of glutamine occurred in this organ. Efforts to understand the unique regulatory properties of hepatic glutaminase culminated in the conceptual reformulation of the pathway for glutamine synthesis and turnover, especially as regards the role of sub-acinar distribution of glutamine synthetase and glutaminase. This chapter describes these processes as well as the role of glutamine in hepatocellular hydration, a process that is the consequence of cumulative, osmotically active uptake of glutamine into cells. This topic is also examined in terms of the effects of cell swelling on the selective stimulation or inhibition of other far-ranging cellular processes. The pathophysiology of the intercellular glutamine cycle in cirrhosis is also considered.


Cell Polarity Regulates Biased Myosin Activity and Dynamics during Asymmetric Cell Division via Drosophila Rho Kinase and Protein Kinase N.
Cell and tissue morphogenesis depends on the correct regulation of non-muscle Myosin II, but how this motor protein is spatiotemporally controlled is incompletely understood. Here, we show that in asymmetrically dividing Drosophila neural stem cells, cell intrinsic polarity cues provide spatial and temporal information to regulate biased Myosin activity. Using live cell imaging and a genetically encoded Myosin activity sensor, we found that Drosophila Rho kinase (Rok) enriches for activated Myosin on the neuroblast cortex prior to nuclear envelope breakdown (NEB). After NEB, the conserved polarity protein Partner of Inscuteable (Pins) sequentially enriches Rok and Protein Kinase N (Pkn) on the apical neuroblast cortex. Our data suggest that apical Rok first increases phospho-Myosin, followed by Pkn-mediated Myosin downregulation, possibly through Rok inhibition. We propose that polarity-induced spatiotemporal control of Rok and Pkn is important for unequal cortical expansion, ensuring correct cleavage furrow positioning and the establishment of physical asymmetry.


A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3.
Body-size constancy and symmetry are signs of developmental stability. Yet, it is unclear exactly how developing animals buffer size variation. Drosophila insulin-like peptide Dilp8 is responsive to growth perturbations and controls homeostatic mechanisms that coordinately adjust growth and maturation to maintain size within the normal range. Here we show that Lgr3 is a Dilp8 receptor. Through the use of functional and adenosine 3',5'-monophosphate assays, we defined a pair of Lgr3 neurons that mediate homeostatic regulation. These neurons have extensive axonal arborizations, and genetic and green fluorescent protein reconstitution across synaptic partners show that these neurons connect with the insulin-producing cells and prothoracicotropic hormone-producing neurons to attenuate growth and maturation. This previously unrecognized circuit suggests how growth and maturation rate are matched and co-regulated according to Dilp8 signals to stabilize organismal size.


Socioenvironmental adversity and risk of prostate cancer in non-Hispanic black and white men.
Non-Hispanic black (NHB) men experience higher risk of prostate cancer than other racial/ethnic groups, and it is possible that socioenvironmental (SE) adversity and resulting stress may contribute to this disparity. Data from the Southern Community Cohort Study were used to evaluate associations between SE adversity and perceived stress in relation to prostate cancer risk, overall and by race/ethnicity and grade. Between 2002 and 2009, 26,741 men completed a questionnaire, from which an 8-item SE adversity composite was created (covering socioeconomic status, residential environment, and social support/buffers). Two items from the Perceived Stress Scale were assessed. With follow-up through 2011, 527 prostate cancer cases were diagnosed. In multivariable models, each one-unit increase in the SE adversity composite was associated with increased prostate cancer risk among non-Hispanic white (NHW) men (HR 1.23; 95% CI 1.02-1.48) and reduced risk among NHB men (HR 0.89; 95% CI 0.82-0.95) (p interaction: 0.001). This pattern held for low grade, but not high grade, cancers although power was limited for the latter. Perceived stress variables were associated with increased risk of prostate cancer among NHW men, but not among NHB men. Results do not support the hypothesis that SE adversity my underlay the racial disparity in prostate cancer, over and above that of covariates, including healthcare utilization.


Embryo and Developmental Toxicity of Cefazolin Sodium Impurities in Zebrafish.
Cefazolin sodium is an essential drug that is widely used in clinical therapy for certain infective diseases caused by bacteria. As drug impurities are considered to be one of the most important causes of drug safety issues, we studied embryotoxicity, cardiotoxicity, and neurotoxicity of nine cefazolin sodium impurities in zebrafish embryo and larvae for the objective control of impurity profiling. LC-MS/MS was employed to analyze the compound absorbance in vivo, and the structure-toxicity relationship was approached. Our results suggested that the structure of MMTD (2-mercapto-5-methyl-1, 3, 4-thiadiazole) is the main toxic functional group for embryo deformities; the 7-ACA (7-aminocephalosporanic acid) structure mainly affects motor nerve function; and both the MMTD and 7-ACA structures are responsible for cardiac effects. Impurity G (7-ACA) presented with the strongest toxicity; impurity A was most extensively absorbed to embryo and larvae; and impurity F (MMTD) exhibited the strongest apparent toxic effect; Therefore, impurities F and G should be monitored from the cefazolin sodium preparations.


Clarifying the Controversial Catalytic Performance of Co(OH)2 and Co3O4 for Oxygen Reduction/Evolution Reactions toward Efficient Zn-Air Batteries.
Cobalt-based nanomaterials have been widely studied as catalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) due to their remarkable bifunctional catalytic activity, low cost, and easy availability. However, controversial results concerning OER/ORR performance exist between different types of cobalt-based catalysts, especially for Co(OH)2 and Co3O4. To address this issue, we develop a facile electrochemical deposition method to grow Co(OH)2 directly on the skeleton of carbon cloth, and further Co3O4 was obtained by post thermal treatment. The entire synthesis strategy removes the use of any binders and also avoids the additional preparation process (e.g., transfer and slurry coating) of final electrodes. This leads to a true comparison of the ORR/OER catalytic performance between Co(OH)2 and Co3O4, eliminating uncertainties arising from the electrode preparation procedures. The surface morphologies, microstructures, and electrochemical behaviors of prepared Co(OH)2 and Co3O4 catalysts were systemically investigated by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and electrochemical characterization methods. The results revealed that the electrochemically deposited Co(OH)2 was in the form of vertically aligned nanosheets with average thickness of about 4.5 nm. After the thermal treatment in an air atmosphere, Co(OH)2 nanosheets were converted into mesoporous Co3O4 nanosheets with remarkably increased electrochemical active surface area (ECSA). Although the ORR/OER activity normalized by the geometric surface area of mesoporous Co3O4 nanosheets is higher than that of Co(OH)2 nanosheets, the performance normalized by the ECSA of the former is lower than that of the latter. Considering the superior apparent overall activity and durability, the Co3O4 catalyst has been further evaluated by integrating it into a Zn-air battery prototype. The Co3O4 nanosheets in situ supported on carbon cloth cathode enable the assembled Zn-air cells with large peak power density of 106.6 mW cm-2, low charge and discharge overpotentials (0.67 V), high discharge rate capability (1.18 V at 20 mA cm-2), and long cycling stability (400 cycles), which are comparable or even superior to the mixture of state-of-the-art Pt/C and RuO2 cathode.


Dynamic Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer.
Plasma circulating tumor DNA (ctDNA) is a valuable resource for tumor characterization and for monitoring of residual disease during treatment; however, it is not yet introduced in metastatic colorectal cancer (mCRC) routine clinical practice. In this retrospective exploratory study, we evaluated the role of ctDNA in patients with mCRC treated with chemotherapy plus bevacizumab. Fifty-three patients were characterized for RAS and BRAF status on tumor tissue before the start of treatment. Plasma was collected at baseline, at first clinical evaluation, and at disease progression. ctDNA analysis was performed using Oncomine Colon cfDNA Assay on the Ion S5 XL instrument. At baseline, from a plasma sample, RAS, BRAF, or PIK3CA mutations were detected in 44 patients. A high correspondence was observed between ctDNA and tumor tissue mutations (KRAS 100%, NRAS 97.9%, BRAF 97.9%, PIK3CA 90%). Low baseline variant allele frequency (VAF) was found to be associated with longer median progression-free survival (PFS) compared with those with high VAF (15.9 v 12.2 months, P = .02). A higher PFS {12.29 months (95% CI, 9.03 to 17.9) v 8.15 months (95% CI, 2.76 to not available [NA]), P = .04} and overall survival (34.1 months [95% CI, 21.68 to NA] v 11.1 months [95% CI, 3.71 to NA], P = .003) were observed in patients with large decline in VAF at first evaluation. ctDNA analysis is useful for molecular characterization and tumor response monitoring in patients with mCRC. Quantitative variations of released ctDNA are associated with clinical outcomes.


High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas.
Molecular target therapy against L-type amino acid transporter 1 (LAT1) is unique and expected to be developed soon. LAT1 expression was investigated in pancreatic cancer as a prognostic predictor. Surgically resected pancreatic ductal adenocarcinomas (PDAC, n=66) were investigated using immunohistochemistry. For reference, intraductal papillary mucinous carcinomas (IPMC, including intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia or with an associated invasive carcinoma, n=13) and adenomas (IPMA, including IPMN with low- and intermediate-grade dysplasia, n=5) were also examined. LAT1 expression scores increased from PDAC to IPMA to IPMC. Kaplan-Meier analysis showed significant differences between LAT1-high and -low scores in PDAC. Even in each Ki-67-labelling index (LI) low and high PDAC group (cut off 40%), high LAT1 expression could also predict poor prognosis. Multivariable analysis showed that LAT1 expression, Ki-67 LI, tumour differentiation and size were individual prognostic factors. LAT1 aberrant overexpression in PDAC predicts poor prognosis, independent of Ki-67 LI, and offers a potential target for future anticancer therapy with its inhibitors.


Steroid users and the unique challenge they pose to needle and syringe program workers.
Needle and syringe programs (NSP), which provide sterile injecting equipment, are a cornerstone of Australia's drug harm reduction strategy and assist in reducing the spread of blood-borne virus infections, such as HIV and hepatitis C, among people who inject drugs. Some reports suggest that steroid users are an increasing proportion of clientele at NSPs. In this research, we investigate the experience of NSP workers who come into contact with people who use steroids and other performance- and image-enhancing drugs (PIED). Thirteen NSP workers were recruited using purposive sampling strategies. Participants were interviewed using a semi-structured interview guide. Interviews were recorded, transcribed and coded for themes. There are three key findings of this study. Firstly, NSP workers do not feel well informed about the substances that PIED users are injecting. Secondly, they were unsure what equipment PIED users required. Thirdly, PIED users were perceived to differ from other client groups, and these differences impacted upon the level of rapport staff could build with this group. PIED users pose unique challenges for NSP workers compared with other NSP client groups. The PIEDs used and the way in which they are used are substantially different compared with other NSP clients, and there appears to be a lack of knowledge within the workforce about these substances. This study highlights the need to engage in workforce training, but also the need to more effectively engage with PIED users in relation to effective harm reduction strategies.


Proportional vascularization along the fallopian tubes and ovarian fimbria: assessment by confocal microtomography.
To evaluate and reconstruct three-dimensional images of vascularization along the fallopian tube (FT), as well as to determine its relationship with the ovary and ovarian fimbria, and to quantify the blood vessels along the FT according to its anatomical segments, using confocal microtomography (micro-CT). Nine specimens (six FTs and three FTs with ovaries) were fixed in a solution of 10% formalin for > 24 h at room temperature. Iodine staining was performed by soaking the specimens in 10% Lugol's solution for 24 h. All specimens were evaluated using micro-CT. A morphometric analysis was performed on the reconstructed images to quantify the vascular distribution along the FT. In the FTs evaluated, the density of blood vessels was significantly greater in the fimbrial segments than in the isthmic segments (p < 0.05). The ovarian fimbria was clearly identified, demonstrating the important relationship between these vessels and the FT fimbriae. We believe that the vascularization in the fimbriae is greater than and disproportional that in the other segments of FT, and that the ovarian fimbria plays an important role in the development of that difference.


Body weight status, dietary habits, and physical activity levels of middle school-aged children in rural Mississippi.
Obesity and cardiovascular diseases are more prevalent in the Southeast as compared with other geographic regions of the United States. However, few investigations have addressed health disparities among children in rural Southeastern areas. The purpose of this investigation was to determine the risk of overweight and obesity in middle school-aged children residing in a racially diverse rural community, and to characterize their dietary and physical activity habits. Two hundred and five middle school children from Scott County, Mississippi were enrolled in this investigation. Measurements included height, weight, body mass index, dietary intake using a 24-hour recall, and physical activity level using pedometers. Of the 205 children studied, 54% were "overweight" or "at risk for overweight" according to a body mass index-for-age sex-specific percentile. Intake of saturated fat and sodium exceeded recommended levels, whereas intake of calcium, fruits, and vegetables was inadequate. One third of the sample consumed 12 fluid ounces or more of soda on the day of the recall. Physical activity level was below that previously reported for children in this age range, and knowledge of the importance of diet and physical activity in the prevention of cardiovascular disease was poor, particularly among African-American children. The children in our sample are at increased risk for overweight and obesity. Factors that may be targeted for intervention include a reduction in dietary intake of fat, saturated fat, sodium, and soft drinks, and an increased intake of fruits and vegetables. Physical activity should be encouraged. Many of these factors could be improved through changes within the school environment.


Cervical lymphadenitis caused by Mycobacterium lentiflavum.
We report a case of human infection caused by Mycobacterium lentiflavum and review the literature for infections caused by this bacterium. The patient was a 19-month-old boy with involvement of a cervical lymph node. Surgical removal of the lymphadenopathy was both diagnostic and curative.


The Sustained Impact of a Medical School-Based Physical Activity Module on Interns' Perceived Competence in Advising Older Adults about Exercise.
The study aimed to examine the sustained impact of a 1.5-hour medical school-based physical activity (PA) module on interns' perceived competence and importance in advising older adults about exercise. The modified Exercise and Physical Activity Competence Questionnaire (EPACQ) was administered in 2017 (CG: control group) and 2018 (IG: intervention group) two years post-course. The perceived competence of both, CG (n=23) and IG (n=18), decreased significantly over two years (p≤0.05) with no difference between the groups (p>0.05). However, 72.2% (n=13) of the interns who attended the PA module still felt competent in advising older adults about exercise (4.21±0.66) compared to 47.8% (n=11) of the CG (3.89±0.67). The perceived importance decreased significantly in both groups (p≤0.05) with no difference between the groups (p>0.05). However, both groups still perceived exercise for older people as important (CG:4.55±0.61; IG:4.83±0.47). Subsequently, continued professional development is likely to be a key requirement for ensuring sustainability over time.


Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia.
Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli including touch, temperature, and pain to the central nervous system. Recent advances in single-cell RNA-sequencing (scRNA-seq) have provided new insights into the diversity of sensory ganglia cell types in rodents, non-human primates, and humans, but it remains difficult to compare transcriptomically defined cell types across studies and species. Here, we built cross-species harmonized atlases of DRG and TG cell types that describe 18 neuronal and 11 non-neuronal cell types across 6 species and 19 studies. We then demonstrate the utility of this harmonized reference atlas by using it to annotate newly profiled DRG nuclei/cells from both human and the highly regenerative axolotl. We observe that the transcriptomic profiles of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The new resources and data presented here can guide future studies in comparative transcriptomics, simplify cell type nomenclature differences across studies, and help prioritize targets for future pain therapy development.


Therapeutic Error Calls Among Older Adults Reported to a Regional Poison Control Center in Alabama.
Although Americans aged 65 years and older account for only 13.0% of the population, they consume one-third of all prescription medications each year. Increased life expectancy, age-related deterioration in health, and polypharmacy lead to a significant risk of potential medication errors. National Poison Data System studies have evaluated the older adult population and their interaction with poison centers; however, descriptive studies using regional poison center data to evaluate older adult-related medication errors, specifically in Alabama, have not been conducted. Our study assessed therapeutic errors in patients aged 65 years and older to evaluate the need for potential interventions by pharmacists and preventive education to reduce errors reported to the Regional Poison Control Center (RPCC) at Children's of Alabama. A four-year retrospective analysis was conducted by gathering call-specific data from the RPCC toxiCALL database. Calls were included if they were made to the RPCC between January 1, 2010 and December 31, 2013, involved patients aged 65 years and older, and were coded as unintentional therapeutic errors. Analysis of call data was conducted using the Centers for Disease Control and Prevention's EpiInfo version 184.108.40.206. A total of 1699 calls were evaluated for patient demographics (sex, age), call data (month, year, shift, caller site), reason for therapeutic error, clinical effects, medical outcome, management site, and reported substance details. Nearly 40.0% of the therapeutic errors were caused by patients taking or being given the same medication twice. Five of the 15 reasons for therapeutic errors accounted for nearly 82.0% of all calls reported. The reasons included taking or being given the same medication twice (37.3%), taking or being given the wrong medication (14.6%), using an incorrect dosing route (13.1%), other incorrect dosing errors (9.9%), and taking doses too close together (7.5%). The top individual substance involved in a therapeutic error was reported verbatim by callers as Spiriva inhalation capsules (10.5%). Therapeutic error calls represent a significant and increasing proportion of calls made by older adults to the RPCC. The frequent interactions between healthcare providers and patients create opportunities to prospectively prevent medication problems in older adult patients. Healthcare providers, specifically pharmacists, should encourage clients to always read the label on medications and should counsel patients carefully when dispensing a product that is not an oral preparation. In addition, although national drug take-back days are conducted biennially, patients should be encouraged to dispose of old medications and expired over-the-counter medications. The RPCC toll-free telephone number (800-222-1222) may be displayed to educate patients on its 24-hour/day availability. Current data will be used to implement programs for pharmacist interventions and to create appropriate educational material.


Personality prototypes and ego development: conceptual similarities and relations in adult women.
Three studies investigated how three personality prototypes (K. York & O.P. John, 1992) relate to J. Loevinger's (1976) stages of ego development (ED). Study 1 examined their conceptual similarities, and Study 2 their relations in a sample of adult women. In both studies, the personality prototypes mapped onto regions defined by multiple ED stages: The Individuated prototype was most likely to reach the high region of ED (Individualistic, Autonomous, and Integrated); the Traditional prototype was most likely to function in the middle region (Conformist, Self-aware, and Conscientious); and the Conflicted prototype was more likely to remain in the low region (Impulsive and Self-protective). In addition to these between-prototype differences, Study 3 explored whether differences in life outcomes within the prototypes are also related to ED; findings suggest that personality prototype and ego development may interact in shaping the life course.


An appraisal of moulting on post-moult egg production and egg weight distribution in white layer hens; meta-analysis.
1. The aim of this study was to establish how different moulting methods and body weight losses influenced post-moult performance and USDA egg weight distribution. 2. Data on 5 laying flocks (#34-38) of the North Carolina Layer Performance and Management Test were used in this meta-analysis. 3. The moulting methods were non-fasted moulted (NF), short feed restricted (SF), 13-d feed restricted (FR), non-anorexic moult programme (NA), non-anorexic moult programme with low sodium (NALS) as well as non-moulting programme as control treatment. The percentages of targeted body weight loss during the moulting period were 20, 24, 25 and 30% of body weight at the end of the first egg production cycle. 4. Post-moult egg production and egg mass were influenced by all moulting methods. Maximum increase in post-moult egg production rate and egg mass occurred with FR and NF programmes, respectively, at 30% of body weight loss, compared to non-moulted hens. Non-fasting methods reduced mortality rate more effectively than fasting methods. 5. Moulting resulted in increases in percentage of grade A and decreases in percentage of grade B eggs. Non-fasting methods increased percentage of grade A eggs more effectively than fasting methods. Percentage of cracked eggs decreased in moulted rather than non-moulted hens and the lowest rate was associated with the NA programme. 6. Post-moult egg weight was not significantly influenced by moulting methods. However, percentage of body weight reduction affected egg weight. The optimum increment in egg weight was achieved by 24% body weight reduction. 7. Overall, non-fasting methods resulted in similar egg production compared with fasting methods. Considering post-moult mortality and USDA egg weight distribution, non-fasting methods, especially NF and NA programmes, performed much better than fasting methods, indicating that non-fasting moulting methods, which are better for animal welfare, are effective alternatives to fasting methods.


FindPeaks 3.1: a tool for identifying areas of enrichment from massively parallel short-read sequencing technology.
Next-generation sequencing can provide insight into protein-DNA association events on a genome-wide scale, and is being applied in an increasing number of applications in genomics and meta-genomics research. However, few software applications are available for interpreting these experiments. We present here an efficient application for use with chromatin-immunoprecipitation (ChIP-Seq) experimental data that includes novel functionality for identifying areas of gene enrichment and transcription factor binding site locations, as well as for estimating DNA fragment size distributions in enriched areas. The FindPeaks application can generate UCSC compatible custom 'WIG' track files from aligned-read files for short-read sequencing technology. The software application can be executed on any platform capable of running a Java Runtime Environment. Memory requirements are proportional to the number of sequencing reads analyzed; typically 4 GB permits processing of up to 40 million reads. The FindPeaks 3.1 package and manual, containing algorithm descriptions, usage instructions and examples, are available at http://www.bcgsc.ca/platform/bioinfo/software/findpeaks Source files for FindPeaks 3.1 are available for academic use.


Protective role of rhapontin in experimental pulmonary fibrosis in vitro and in vivo.
Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated. The effect of rhapontin on TGF-β1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-β1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo. Fibrotic mice were induced by intratracheal instillation of bleomycin, and then treated with rhapontin (25, 50, or 100mg/kg/day) or prednisone (6.5mg/kg/day, positive drug) for 2weeks. In TGF-β1 stimulated PLFs, treatment with rhapontin resulted in a reduction of ECM with a decrease in Lox2 and p-Smad2/3. In LPS activated macrophages, treatment with rhapontin reduced TGF-β1 production. However, in vitro the attenuated ECM deposition and inflammatory response by rhapontin were closely associated with AMPK activation, and these suppression of rhapontin were significantly abolished by the AMPK inhibitor. Treatment with rhapontin for 2weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower Lox2, whereas a higher AMPK expression, with reductions of the pathological score, collagen deposition, TGF-β1, α-SMA, Lox2, and HIF-1α expressions in lung tissues at fibrotic stage at 100mg/kg. In summary, rhapontin reversed ECM, as well as Lox2 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating AMPK activation and suppressing the TGF-β/Smad pathway.


An enhanced block matching algorithm for fast elastic registration in adaptive radiotherapy.
Image registration has many medical applications in diagnosis, therapy planning and therapy. Especially for time-adaptive radiotherapy, an efficient and accurate elastic registration of images acquired for treatment planning, and at the time of the actual treatment, is highly desirable. Therefore, we developed a fully automatic and fast block matching algorithm which identifies a set of anatomical landmarks in a 3D CT dataset and relocates them in another CT dataset by maximization of local correlation coefficients in the frequency domain. To transform the complete dataset, a smooth interpolation between the landmarks is calculated by modified thin-plate splines with local impact. The concept of the algorithm allows separate processing of image discontinuities like temporally changing air cavities in the intestinal track or rectum. The result is a fully transformed 3D planning dataset (planning CT as well as delineations of tumour and organs at risk) to a verification CT, allowing evaluation and, if necessary, changes of the treatment plan based on the current patient anatomy without time-consuming manual re-contouring. Typically the total calculation time is less than 5 min, which allows the use of the registration tool between acquiring the verification images and delivering the dose fraction for online corrections. We present verifications of the algorithm for five different patient datasets with different tumour locations (prostate, paraspinal and head-and-neck) by comparing the results with manually selected landmarks, visual assessment and consistency testing. It turns out that the mean error of the registration is better than the voxel resolution (2 x 2 x 3 mm(3)). In conclusion, we present an algorithm for fully automatic elastic image registration that is precise and fast enough for online corrections in an adaptive fractionated radiation treatment course.


Thermal regimes of Rocky Mountain lakes warm with climate change.
Anthropogenic climate change is causing a wide range of stresses in aquatic ecosystems, primarily through warming thermal conditions. Lakes, in response to these changes, are experiencing increases in both summer temperatures and ice-free days. We used continuous records of lake surface temperature and air temperature to create statistical models of daily mean lake surface temperature to assess thermal changes in mountain lakes. These models were combined with downscaled climate projections to predict future thermal conditions for 27 high-elevation lakes in the southern Rocky Mountains. The models predict a 0.25°C·decade-1 increase in mean annual lake surface temperature through the 2080s, which is greater than warming rates of streams in this region. Most striking is that on average, ice-free days are predicted to increase by 5.9 days ·decade-1, and summer mean lake surface temperature is predicted to increase by 0.47°C·decade-1. Both could profoundly alter the length of the growing season and potentially change the structure and function of mountain lake ecosystems. These results highlight the changes expected of mountain lakes and stress the importance of incorporating climate-related adaptive strategies in the development of resource management plans.


Prefabricated silicone subdermal mandibular implants: observations and problems related to their application.
Success in the use of custom-fabricated Silastic implants in patients with facial contour defects led us to utilize this method in reconstructing mandibular defects. However, mandibular reconstruction with alloplastic material is quite difficult because of the presence of continous stress and motion in that region. The evolution in the use in the use of the mandibular implant from the commercially available one to the K-wire reinforced, prefabricated, silicone implant was largely dependent on the availability of silicone and the ultimate result obtained. In the past few years, about 30 subdermal implants were inserted. Some of those implants were placed immediately into patients undergoing resection for tumor. The implant was prefabricated prior to surgery from x-ray measurements of the anticipated segment to be resected; it was then used to reconstruct the defect prior to the final closure of the operative wound. Other implants were manufactured 6-18 months after resection for tumor or for deformity as a result of trauma. The implants were used to reconstruct the facial defects and to correct the funtional abnormality, such as drooling or deviation of the affected side by the unstable mandibular segment. Patients with severe congenital malformation have soft tissue deficiency in association with their bony malformation. Therefore, implants in such conditions were doomed to failure. Patient selection is the key to successful implantation.