Clinical, aesthetic, and patient-related outcome of immediately loaded single implants in the anterior maxilla: a prospective study in extraction sockets, healed ridges, and grafted sites.
The objective of this prospective clinical study was to document the overall treatment outcome of immediately loaded single Astra Tech Osseospeed™ (Astra Tech AB, Mölndal, Sweden) implants placed in extraction sockets, healed ridges, and grafted sites. Forty-eight patients in need of a single implant in the anterior maxilla (15-25) were recruited. Patients were allocated to a conventional implant treatment (CIT) or immediate implant treatment (IIT) group on the basis of specific criteria. If the buccal bone plate was damaged or missing upon tooth removal, patients were allocated to a grafted implant treatment (GIT) group. Irrespective of the treatment concept, implants were immediately provisionalized. Hard and soft tissue alterations, aesthetic parameters (pink and white esthetic scores, [PES and WES]) and patient's opinion (Oral Health Impact Profile [OHIP-14] questionnaires) were registered at different time points. After 1 year of function, the overall implant survival rate was 98% with one failure following IIT. The mean bone level to the implant-abutment interface was 0.65 (SD 0.79), 0.85 (SD 0.64), and 0.56 mm (SD 0.44) for CIT, IIT, and GIT. Complete papilla loss was rare following either strategy. Mean midfacial recession amounted to 1.00 (SD 1.15), 0.12 (SD 0.78), and 0.49 mm (SD 0.82) for CIT, IIT, and GIT, respectively. The aesthetic outcome showed a mean PES of 10.30 (SD 1.89) and mean WES of 7.11 (SD 2.14), all patients considered. Patient's satisfaction showed a significant improvement after 1 year of function on all seven domains (p < .001). This prospective study showed that single implants clinically and aesthetically perform well under immediate non-occlusal loading conditions in the premaxilla. In this context, it is of pivotal importance to stress that patients were carefully selected for IIT and GIT.


Micro-scale investigation of intestinal schistosomiasis transmission on Ngamba and Kimi islands, Lake Victoria, Uganda.
A study to investigate the effect of environmental predictors on abundance of Biomphalaria, the intermediate host snails of Schistosoma mansoni, was carried out on two small islands in Lake Victoria, Uganda. Malacological surveys were performed at 40 shoreline sites on Kimi and Ngamba islands documenting occurrence of Biomphalaria; other environmental and limnological conditions were also recorded, including gastropod community diversity. Snails were examined for shedding of schistosomes and emerging cercariae were DNA 'barcoded'. For population genetics analysis of Biomphalaria, snails from four populations from each island were also sequenced. Aquatic phosphate concentrations were higher on Kimi island, confirming greater anthropogenic influence, although, snail species diversity and community assemblages were not significantly different between islands. Bayesian geostatistical models were fitted to assess the effect of environmental factors on Biomphalaria abundance and snails' risk of shedding schistosome or non-schistosome cercariae. No factors were found to be significant in the spatial model. The local population genetics of S. mansoni and Biomphalaria on each island followed similar patterns as that seen in previous studies on a lake-wide basis. These findings suggest that smaller scale studies may prove useful as proxies for regional level investigations, with reduced logistical and resource output required. However, further research should also include surveys of terminal host parasite burden, as these will affect even micro-scale dynamics of parasite-intermediate host interactions, as well as be important from a public health perspective in their own right.


Giant High-Grade Immature Teratoma of the Central Nervous System (CNS) in an Infant: A Case Report.
BACKGROUND The central nervous system (CNS) is a rare point of origin for mature or immature teratomas. However, immature teratomas are extremely rare. CNS teratomas have been known for poor patient prognosis and recovery and also reduce survival. However, chemoradiotherapy has been reported to increase patient survival. CASE REPORT This study presents a rare giant immature teratoma invading a newborn infant's brain tissue and CNS. The tumor was surgically removed, and in a further 1-year follow-up, it did not need chemotherapy or radiotherapy according to alpha-fetoprotein (aFP) level and other serum markers. The teratoma had affected multiple loci of his brain's left hemisphere, including parietal, frontal, temporal, and occipital lobes. A teratoma was diagnosed lateral to the midline, which is not common in CNS teratomas, as they mainly occur in or near the midline. The tumor was excised completely. The patient was followed up for 1 year, and no further recurrence was observed. CONCLUSIONS Early diagnosis and treatment of immature teratomas are essential in patient prognosis. Chemotherapy is not always needed, but complete surgical removal and patient follow-up are always a necessity. In addition, adequate follow-up of these patients is critical to evaluate their further treatment plan and recurrence risk.


Remission from insulin dependence induced by continuous subcutaneous insulin infusion (CSII) in type I, newly diagnosed diabetics: role of some hormonal and immunologic factors.
Optimal and early control of recent onset, type I diabetes by intensive insulin therapy has been reported to allow insulin withdrawal in about two thirds of subjects treated. We used continuous s.c. insulin infusion (CSII) in the attempt to induce a temporary remission of insulin dependence in 18 newly diagnosed young adult diabetics. After 10 days of optimized glycometabolic control, insulin infusion was stopped and patients were switched to glibenclamide (15 mg/die) plus metformin (1 g/die). Diabetics were considered in remission of insulin dependence when their metabolic control fulfilled the following criteria for at least 3 months: absence of glycosuria, pre- and post-prandial blood glucose less than or equal to 120 and 180 mg/dl, respectively, HbA1c less than or equal to 7%. Insulin therapy could be discontinued for periods of over three months in 11 subjects (61%) and for as long as 18 months in one case. Insulin requirement during CSII was slightly higher in nonremitters (NR) than in remitters (R): 0.36-0.64 vs 0.26-0.41 U/kg/die. After 24 months from CSII, R still showed lower insulin requirement (0.35-0.42 U/kg/die) than NR (0.55-0.75 U/kg/die). Further, the role of some hormonal and immunologic factors was investigated. Plasma C-peptide and glucagon were measured, fasting and 2h after each meal, both on admission and immediately after CSII, when patients were switched to oral therapy. No difference in hormone levels could be detected on admission, whereas, after CSII, mean post-prandial increase of C-peptide over basal was significantly higher in R than in NR (1.18 +/- 0.37 vs 0.22 +/- 0.16 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Exploring the prevalence and impact of hip and knee pain in pulmonary rehabilitation: a propensity-matched cohort study.
Musculoskeletal pain is more common in individuals with chronic respiratory diseases than the aged-matched general population. This investigation aimed to understand the prevalence and impact of hip and knee pain on pulmonary rehabilitation outcomes and completion rates. Participants who experienced hip/knee pain in the 4 weeks prior to pulmonary rehabilitation completed an Oxford Hip and/or Knee Score alongside a routine pulmonary rehabilitation assessment. Participants engaged in a twice-weekly, 6-week outpatient pulmonary rehabilitation programme. A 1:1 propensity score match for age, sex, BMI, sessions attended and MRC score was completed prior to group comparison for a pulmonary rehabilitation cohort without hip/knee pain. 6.5% (n = 97) of pulmonary rehabilitation participants reported pain: hip (n = 27), knee (n = 40) or hip and knee pain (n = 30). 75 participants with hip/knee pain provided sufficient data for pre pulmonary rehabilitation matching and were propensity matched with a pulmonary rehabilitation group without hip/knee pain. The average Oxford Score across all reported joints was 28.7 (8.5) indicating moderate/severe pain at baseline. Statistically significant improvements were made in Oxford Scores for the left hip, left knee and right knee (P < 0.01) but not the right hip following pulmonary rehabilitation. There was no statistically significant difference between groups for improvements in quadriceps strength, walking tests or depression scores, both groups achieved within group significance. There were no significant differences in pulmonary rehabilitation completion rates between groups. Prevalence of hip/knee pain in individuals presenting to pulmonary rehabilitation is 6.5%. Pain improved in the majority of joints following pulmonary rehabilitation and pain did not impact the effectiveness or completion of the programme. This trial was an evaluation of a clinical service and has not been registered in a public domain.


Discrete systems, cell-cell interactions and color pattern of animals. II. Clonal theory and cellular automata.
The morphogenesis of the color pattern of animals is modeled with cellular automata. The cell-cell near neighbor interactions are taken into account and impose restrictions on the model. The allowed patterns are observed in reptiles, felines and fishes.


Construct validity of the walk ratio as a measure of gait control in people with multiple sclerosis without mobility aids.
Ambulatory limitations are a key component of disability in people with multiple sclerosis (PwMS). Various tools are employed to assess walking performance in PwMS; however, no ideal measure has as yet been attained. In this situation, a walk ratio might be more advantageous compared with other gait measures. The walk ratio, a simple index for describing temporal and spatial co-ordination, denotes the relationship between step length and cadence during walking. Hence, the primary objective of this study was to determine the relationship between the walk ratio and measures of other theoretically related constructs. The walk ratio was studied using the GAITRite™ system (CIR Systems, Inc. Havertown, USA). The study group included 229 PwMS (143 women) and a mean disease duration of 5.8 (SD=7.1) years. The walk ratio score of the total sample was 5.3 (SD=0.8). Significant differences based on the expanded disability status scale (EDSS) scores (F=11.616, P<0.001) were observed between the neurological disability subgroups. Scores of the very mild (EDSS 0-2.0), mild (EDSS 2.5-4.0) and moderate (EDSS 4.5-5.5) groups were 5.5 (SD=0.7), 5.2 (SD=0.7), 4.9 (SD=0.9), respectively. In terms of fall status, the MS fallers demonstrated a significant lower walk ratio compared to the MS non-fallers; 5.1 (SD=0.8) vs. 5.5 (SD=0.7); P<0.001. Modest significant correlation scores were found between walk ratio and ambulation tests. Scores were slightly higher in the short walking tests, timed 25-foot walk and timed up and go tests (Pearson's rho=0.369, 0.364) compared to the 6 and 2-min walk time tests (Pearson's rho=0.344, 0.308). Collectively, the current study supports the construct validity of the walk ratio index in PwMS without mobility aids.


Ubiquitin-dependent down-regulation of the neurokinin-1 receptor.
Transient stimulation with substance P (SP) induces endocytosis and recycling of the neurokinin-1 receptor (NK(1)R). The effects of sustained stimulation by high concentrations of SP on NK(1)R trafficking and Ca(2+) signaling, as may occur during chronic inflammation and pain, are unknown. Chronic exposure to SP (100 nm, 3 h) completely desensitized Ca(2+) signaling by wild-type NK(1)R (NK(1)Rwt). Resensitization occurred after 16 h, and cycloheximide prevented resensitization, implicating new receptor synthesis. Lysine ubiquitination of G-protein-coupled receptors is a signal for their trafficking and degradation. Lysine-deficient mutant receptors (NK(1)RDelta5K/R, C-terminal tail lysines; and NK(1)RDelta10K/R, all intracellular lysines) were expressed at the plasma membrane and were functional because they responded to SP by endocytosis and by mobilization of Ca(2+) ions. SP desensitized NK(1)Rwt, NK(1)RDelta5K/R, and NK(1)RDelta10K/R. However, NK(1)RDelta5K/R and NK(1)RDelta10K/R resensitized 4-8-fold faster than NK(1)Rwt by cycloheximide-independent mechanisms. NK(1)RDelta325 (a naturally occurring truncated variant) showed incomplete desensitization, followed by a marked sensitization of signaling. Upon labeling receptors in living cells using antibodies to extracellular epitopes, we observed that SP induced endocytosis of NK(1)Rwt, NK(1)RDelta5K/R, and NK(1)RDelta10K/R. After 4 h in SP-free medium, NK(1)RDelta5K/R and NK(1)RDelta10K/R recycled to the plasma membrane, whereas NK(1)Rwt remained internalized. SP induced ubiquitination of NK(1)Rwt and NK(1)RDelta5K/R as determined by immunoprecipitation under nondenaturing and denaturing conditions and detected with antibodies for mono- and polyubiquitin. NK(1)RDelta10K/R was not ubiquitinated. Whereas SP induced degradation of NK(1)Rwt, NK(1)RDelta5K/R and NK(1)RDelta10K/R showed approximately 50% diminished degradation. Thus, chronic stimulation with SP induces ubiquitination of the NK(1)R, which mediates its degradation and down-regulation.


Soil and cultivar type shape the bacterial community in the potato rhizosphere.
The rhizospheres of five different potato cultivars (including a genetically modified cultivar) obtained from a loamy sand soil and two from a sandy peat soil, next to corresponding bulk soils, were studied with respect to their community structures and potential function. For the former analyses, we performed bacterial 16S ribosomal RNA gene-based PCR denaturing gradient gel electrophoresis (PCR-DGGE) on the basis of soil DNA; for the latter, we extracted microbial communities and subjected these to analyses in phenotype arrays (PM1, PM2, and PM4, Biolog), with a focus on the use of different carbon, sulfur and phosphorus sources. In addition, we performed bacterial PCR-DGGE on selected wells to assess the structures of these substrate-responsive communities. Effects of soil type, the rhizosphere, and cultivar on the microbial community structures were clearly observed. Soil type was the most determinative parameter shaping the functional communities, whereas the rhizosphere and cultivar type also exerted an influence. However, no genetically modified plant effect was observed. The effects were imminent based on general community analysis and also single-compound analysis. Utilization of some of the carbon and sulfur sources was specific per cultivar, and different microbial communities were found as defined by cultivar. Thus, both soil and cultivar type shaped the potato root-associated bacterial communities that were responsive to some of the substrates in phenotype arrays.


Hydrogen at symmetric tilt grain boundaries in aluminum: segregation energies and structural features.
Aluminum is envisioned to be an important material in future hydrogen-based energy systems. Here we report an ab initio investigation on the interactions between H-atoms and common grain boundaries (GBs) of fcc Al: Σ9, Σ5, Σ11 and Σ3. We found that upon segregation to the GBs, single H-atoms can cause displacement of Al-atoms. Increasing their concentration revealed large cooperative effects between H-atoms that favor the segregation when other H-atoms are bound at neighboring sites. This makes these GBs able to accommodate high concentrations of H-atoms with considerable segregation energies per atom. Structural analyses derived from Laguerre-Voronoi tessellations show that these GBs have many interstitial sites with higher symmetry than the bulk tetrahedral interstitial site. Many of those sites have also large volumes and higher coordination numbers than the bulk sites. These factors are the increased driving force for H-atom segregation at the studied GBs in Al when compared to other metals. These GBs can accommodate a higher concentration of H-atoms which indicates a likely uniform distribution of H-atoms at GBs in the real material. This suggests that attempting to mitigate hydrogen uptake solely by controlling the occurrence of certain GBs may not be the most efficient strategy for Al.


Distribution and frequency of G119S mutation in ace-1 gene within Anopheles sinensis populations from Guangxi, China.
Malaria is one of the most serious vector-borne diseases in the world. Vector control is an important measure for malaria prevention and elimination. However, this strategy is under threat as disease vectors are developing resistance to insecticides. Therefore, it is important to monitor mechanisms responsible for insecticide resistance. In this study, the presence of G119S mutation in the acetyl cholinesterase-encoding gene (ace-1) was investigated in nine Anopheles sinensis populations sampled across Guangxi Zhuang Autonomous Region China. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method was used to genotype each individual adult of An. sinensis. Direct sequencing of PCR products was performed to verify the accuracy of PCR-RFLP genotyping result. Population genetics analysis was conducted using Genepop programme. The frequencies of susceptible homozygotes, heterozygotes and resistant homozygotes in the nine populations ranged between 0-0.296, 0.143-0.500 and 0.333-0.857, respectively. Overall, a high frequency (0.519-0.929) of mutant 119S allele was observed and the genotype frequency of the ace-1 gene of An. sinensis was at Hardy-Weinberg equilibrium in each of the nine examined populations. The G119S mutation has become fixed and is widespread in An. sinensis field populations in Guangxi, China. These findings are useful in helping design strategies for An. sinensis control.


WITHDRAWN: LncRNA DSCAM-AS1 Promotes Proliferation, Migration and Invasion of Colorectal Cancer Cells via Modulating miR-144-5p/CDKL1.
This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Specificity of elevated intercostal space ECG recording for the type 1 Brugada ECG pattern.
Right precordial (V1-3) elevated electrode placement ECG (EEP-ECG) is often used in the diagnosis of Brugada syndrome (BrS). However, the specificity of this has only been studied in smaller studies in Asian populations. We aimed to study this in a larger European population. Two different populations consisting of healthy subjects were used. A total of 340 subjects were included, 80% were men, the median age was 43 year (interquartile range: 31-51) and all were of European ethnicity. No type 1 ECG patterns were identified but 16 (4.7%) subjects with a type 2 ECG and 32 (9.4%) subjects with a type 3 ECG were identified in any lead placement. In total 43 (13%) subjects had any BrS ECG pattern in any lead placement. The specificity was 100% (one-sided 97.5% CI: 99%) for the use of EEP-ECG to uncover type 1 pattern. For type 2 pattern the specificity was 95% (95% CI: 92-97%) and for type 3 pattern 91% (95% CI: 88-94%). Elevated electrode placement ECG in the diagnosis of BrS seems to have a very high specificity with regards to the finding of a type 1 ECG pattern in a European population; conversely a finding of a type 2 or 3 pattern is of a significantly lower specificity and should perhaps be disregarded.


Assembly and immunogenicity of baculovirus-derived infectious bronchitis virus-like particles carrying membrane, envelope and the recombinant spike proteins.
To assemble infectious bronchitis virus (IBV)-like particles bearing the recombinant spike protein and investigate the humoral immune responses in chickens. IBV virus-like particles (VLPs) were generated through the co-infection with three recombinant baculoviruses separately encoding M, E or the recombinant S genes. The recombinant S protein was sufficiently flexible to retain the ability to self-assemble into VLPs. The size and morphology of the VLPs were similar to authentic IBV particles. In addition, the immunogenicity of IBV VLPs had been investigated. The results demonstrated that the efficiency of the newly generated VLPs was comparable to that of the inactivated M41 viruses in eliciting IBV-specific antibodies and neutralizing antibodies in chickens via subcutaneous inoculation. This work provides basic information for the mechanism of IBV VLP formation and develops a platform for further designing IBV VLP-based vaccines against IBV or other viruses.


Magnetic particle targeting for diagnosis and therapy of lung cancers.
Over the past decade, the growing interest in targeted lung cancer therapy has guided researchers toward the cutting edge of controlled drug delivery, particularly magnetic particle targeting. Targeting of tissues by magnetic particles has tackled several limitations of traditional drug delivery methods for both cancer detection (e.g., using magnetic resonance imaging) and therapy. Delivery of magnetic particles offers the key advantage of high efficiency in the local deposition of drugs in the target tissue with the least harmful effect on other healthy tissues. This review first overviews clinical aspects of lung morphology and pathogenesis as well as clinical features of lung cancer. It is followed by reviewing the advances in using magnetic particles for diagnosis and therapy of lung cancers: (i) a combination of magnetic particle targeting with MRI imaging for diagnosis and screening of lung cancers, (ii) magnetic drug targeting (MDT) through either intravenous injection and pulmonary delivery for lung cancer therapy, and (iii) computational simulations that models new and effective approaches for magnetic particle drug delivery to the lung, all supporting improved lung cancer treatment. The review further discusses future opportunities to improve the clinical performance of MDT for diagnosis and treatment of lung cancer and highlights clinical therapy application of the MDT as a new horizon to cure with minimal side effects a wide variety of lung diseases and possibly other acute respiratory syndromes (COVID-19, MERS, and SARS).


Comparison of Digital Self-Assessment Systems and Faculty Feedback for Tooth Preparation in a Preclinical Simulation.
Regarding the new dental licensing regulations in Germany (AOZ), this study evaluated the effectiveness of two different digital tooth preparation validation systems in comparison to traditional faculty feedback. Participants were randomly divided into groups: Faculty Feedback (FF: n = 33), PrepCheck® (PC: n = 32) and Dental Teacher™ (n = 32). Students had the task to prepare tooth 16 for a retentive full-cast crown. Preparations could be repeated as often as desired. Feedback was provided either by faculty staff or by digital validation systems only. Exams were conducted and graded by two independent and experienced examiners. A survey was performed to evaluate the assessment concepts. No statistical difference in examination performance between groups could be observed. Nevertheless, the survey showed participants preferred consulting the faculty staff rather than the digital validation systems. Students preferred practising with DT rather than with PC. Although both classical and digital methods showed comparable results regarding the preparation examination performance, direct feedback by the faculty staff is still appreciated by the students. A combination of both methods is mandatory since demonstration and advice by the teacher is needed. However, digital tooth preparation validation systems are predestined for free practice sessions, providing self-assessment.


Impact of anomalous origin of the ophthalmic artery from the middle meningeal artery on selection of surgical approach to skull base meningioma.
Ectopic sites of origin of the ophthalmic artery from the MMA are associated with visual complications of surgery directed along the sphenoidal wing or embolization of the MMA. Three cases of skull base meningioma in which retinal blood supply originated from the MMA are presented. In one case, the patient experienced transient blindness during selective angiography of the external carotid artery. Because surgical obliteration of the MMA might have caused visual impairment due to sacrifice of the collateral branches from the MMA to the retina during a skull base approach, we selected an approach not involving the MMA. In a case in which retinal blush is observed from the MMA on selective angiography of the ECA, we should select an appropriate surgical approach to avoid visual complications in cranial base surgery, taking into account a retinal blood supply.


In vivo viability of extended 4°C-stored autologous apheresis platelets.
The current 5-day storage time of room temperature (22°C)-stored platelets (RSPs) severely limits platelet (PLT) availability. Extended cold (4°C)-stored PLTs (CSPs) are currently being investigated for actively bleeding patients. However, we currently do not know how to best store PLTs in the cold for extended periods of time. In this study, we investigate how storage in plasma and PLT additive solutions (PASs) affects PLT viability in vivo. Twenty normal subjects had a 2-unit hyperconcentrated apheresis PLT collection. One unit was stored at 4°C in plasma for 3 days ("control unit"), and the CSP "test" unit was stored for 10 or 15 days in plasma or 10 days in 35% plasma with either 65% Intersol or Isoplate. After storage, all units were radiolabeled and transfused into their donors. For 10-day storage, both the plasma and the Intersol units had significantly better PLT recoveries than the Isoplate units (24% ± 8% vs. 11% ± 3% [55% ± 11% vs. 21% ± 8% as percentage of control data], p = 0.002; and 18% ± 4% vs. 11% ± 3% [43% ± 6% vs. 21% ± 8% as percentage of control data], p = 0.004, respectively). There was a trend for lower PLT recoveries with Intersol compared to plasma (p = 0.056). PLT survivals and most in vitro measurements did not differ significantly among the units. While the in vitro variables suggest largely comparable results between plasma and PASs, in vivo recoveries were higher with plasma compared with both Intersol and Isoplate (p = 0.057 and p = 0.002, respectively). Whether this difference leads to clinically relevant differences in hemostatic efficacy remains to be determined.


Vitamin D metabolism and calcium absorption.
Vitamin D along with parathyroid hormone (PTH) and calcitonin (CT) are the three principal effectors of calcium and phosphorus homeostasis. The secosteroid, vitamin D3, is subject to metabolic conversion to its biologically active form(s) 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] prior to initiation of its physiologic responses in the intestine and skeletal system. The production of 1,25(OH)2D3 is stringently regulated by a variety of endocrine signals including PTH as well as the "calcium needs" of the organism. At the target intestine, 1,25-(OH)2D3 stimulates the intestinal absorption of calcium via a mechanism analogous to that of other steroid hormones. Definitive biochemical evidence exists supporting the existence in the intestine of a highly specific protein receptor for 1,25(OH)2D3. After formation of the steroid-receptor complex, it migrates to the nucleus of the cell and stimulates messenger-RNA synthesis for proteins (including a calcium-binding protein) which are necessary for the generation of the biologic response. Current efforts to biochemically characterize vitamin D-mediated intestinal calcium transport include efforts to understand the role of calcium-binding protein in this process, as well as to identify other protein components present either in the brush border or basal lateral membranes.


Follicular mucinosis developing into cutaneous lymphoma. Report of two cases and review of literature and 64 cases in Japan.
Two cases of follicular mucinosis which developed into lymphoma are reported. The infiltrative atypical lymphocytes proved to be T cells, which were identified by monoclonal antibodies. The association of follicular mucinosis and lymphoma in Japan is estimated to be 9.4%.


Taste in chimpanzees. III: Labeled-line coding in sweet taste.
In peripheral taste the coding mechanism remains an enigma. Among coding theories the "across-fiber pattern" argues that activity across fibers codes for taste, whereas the "labeled line" claims that activity in a particular set of fibers underlies a taste quality. We showed previously that chimpanzee chorda tympani taste fibers grouped according to human taste qualities into an S-cluster, responding predominantly to sweet stimuli, a Q-cluster, sensitive to bitter tastants, and an N-cluster, stimulated by salts. The analysis showed that information in the S-line suffices to distinguish stimuli of one taste quality from the others. However, one condition for the labeled line remained: that blockage of activity in a particular line must cause blockage of one taste quality, but of no other, or its onset give rise to the sensation of a taste quality. Here we studied this requirement with gymnemic acids and miraculin. In humans and chimpanzees, gymnemic acids suppress the sweet taste of all sweeteners whereas miraculin adds a sweet taste quality to sour stimuli. Gymnemic acids also abolish miraculin-induced sweet taste. We found that gymnemic acids practically abolished the response to every sweetener in the chimpanzee S-cluster. Equally important, they had no effect on the responses of the Q- and N-clusters. After miraculin, the S-cluster fibers responded to acids as well as to sweeteners, although they had not responded to acids before miraculin. Gymnemic acids abolished this miraculin-induced response to acids and responses to sweeteners in the S-fibers. These results link the sweet taste quality to activity in fibers of the S-cluster. Thus the S-cluster fibers satisfy the definition of the labeled-line theory: "that activity in a particular fiber type represents a specific taste quality."


The effect of the mode of sampling on BHV-1 detection in infected cattle by dot-blot hybridization.
The BHV-1 genome in nasal swabs and washings was detected by dot-blot hybridization using the 32P-pUR-1 probe (1.8 kb EcoRI-HindIII random fragment of BHV-1 DNA ligated into the pUC-9 plasmid) as early as on day 1 after the experimental infection of cattle. In dependence on the sampling method, differences were observed in the maximum of hybridization signals. During nasal swab analyses maximum amounts of BHV-1 differed in the individual samples (day 1-3). Hybridization signals obtained at the analysis of BHV-1 DNA nasal washings did not vary but showed a continuous maximum on day 2 after infection. Nasal washings proved to be more advantageous for detection of the BHV-1 genome by the hybridization technique.


Telehealth adaptation of perinatal mental health mother-infant group programming for the COVID-19 pandemic.
The COVID-19 pandemic and ensuing isolation stressed pregnant and postpartum women and their families pervasively. This necessitated addressing young families' mental health needs while protecting both patients and providers from COVID-19 exposure. Our experience of rapidly adapting Pregnancy, Maternal Postpartum Peer Support, and Mother-Infant Postpartum Group interventions to high-quality telehealth modalities elucidates benefits and challenges of mother-infant dyadic treatment amidst the pandemic. This study compares 2019 in-person and 2020 telehealth services during the period from mid-March through mid-December in each year. Initial program Warmline contacts were similar across years despite pandemic-related restrictions, with 2020 program contacts surpassing the 147 unique patient outreaches during the commensurate 2019 period. Pregnancy Group enrollment remained consistent. Maternal Postpartum Peer Support Group participation increased with transition to telehealth with 27 individuals with over 100 group-based visits in 2020. Twenty-five mother-infant Postpartum pairs initially enrolled in the 12-week multicomponent Mother-Infant Therapy Group (M-ITG) during 2019 in-person services, and 16 completed the program (36% non-completion rate). During 2020 telehealth, 15 of 18 mother-infant pairs completed the program (17% non-completion rate); a greater than 50% reduction in non-completion. We further compare pre-/post-pandemic onset M-ITG participant demographics, enrollment, and Edinburgh Postnatal Depression Scale (EPDS) scores.


Synthesis of novel derivatives of bispodophyllotoxin as potential antineoplastic agents--part XVI.
Podophyllotoxin and related analogs present numerous challenges associated with optimal antitumor activity and severe unpredictable toxicity. In an attempt to find biorational podophyllotoxin-related drug, two moieties of podophyllotoxin have been linked at C4-position by a simple modification of the carbodiimide procedure to provide novel bispodophyllotoxin analogs (4a-4e) and their structural information was extensively characterized by using 1H-NMR, IR, and HRMS.


Fatty Liver Disease and Non-Alcoholic Fatty Liver Disease Worsen the Outcome in Acute Pancreatitis: A Systematic Review and Meta-Analysis.
The prevalence of fatty liver disease (FLD) and that of non-alcoholic fatty liver disease (NAFLD) share some risk factors known to exacerbate the course of acute pancreatitis (AP). This meta-analysis aimed to investigate whether FLD or NAFLD carry a higher risk of untoward outcomes in AP. In accordance with PRISMA guidelines, we performed a systematic search in seven medical databases for cohort studies that compared the outcomes of AP for the presence of FLD or NAFLD, and we calculated pooled odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI). We included 13 articles in our meta-analysis. AP patients with FLD were more likely to die (5.09% vs 1.89%, OR = 3.56, CI = 1.75-7.22), develop severe AP (16.33% vs 7.87%, OR = 2.67, CI = 2.01-3.56), necrotizing pancreatitis (34.83% vs 15.75%, OR = 3.08, CI = 2.44-3.90) and had longer in-hospital stay (10.8 vs 9.2 days, WMD = 1.46, OR = 0.54-2.39). Patients with NAFLD were more likely to have severe AP and longer hospital stay. Both FLD and NAFLD proved to be independent risk factors of a more severe disease course (OR = 3.68, CI = 2.16-6.29 and OR = 3.39, CI = 1.52-7.56 for moderate/ severe vs. mild AP, respectively). FLD and NAFLD worsen the outcomes of AP, which suggests that incorporating FLD or NAFLD into prognostic scoring systems of AP outcomes might improve the prediction of severity and contribute to a more individualized patient care.


Reconstitution of nucleosome demethylation and catalytic properties of a Jumonji histone demethylase.
Jumonji histone demethylases catalyze removal of methyl marks from lysine residues in histone proteins within nucleosomes. Here, we show that the catalytic domain of demethylase JMJD2A (cJMJD2A) utilizes a distributive mechanism to remove the histone H3 lysine 9 trimethyl mark. By developing a method to assess demethylation of homogeneous, site-specifically methylated nucleosomes, we determined that the kinetic parameters for demethylation of nucleosomes by cJMJD2A are comparable to those of peptide substrates. These findings imply that other domains of the demethylase or its protein partners may contribute to nucleosome recognition in vivo and, in this way, may further regulate demethylation activity and processivity. The quantitative assays of nucleosome demethylation developed in our work provide a platform for future work with complex chromatin substrates and full-length demethylases.


Pesticide residues in Nile tilapia (Oreochromis niloticus) and Nile perch (Lates niloticus) from Southern Lake Victoria, Tanzania.
Nile tilapia (Oreochromis niloticus) and Nile perch (Lates niloticus) samples were collected from fish landing stations in nine riparian districts on the Tanzanian side of Lake Victoria and screened for residues of 64 organochlorine, organophosphorus, carbamate, and pyrethroid pesticides. The residue levels in the fish fillet were up to 0.003, 0.03 and 0.2 mg/kg fresh weight (0.7, 3.8 and 42 mg/kg lipid weight) of fenitrothion, DDT and endosulfan, respectively. Mean levels within sites were up to 0.002, 0.02 and 0.1 mg/kg fresh weight (0.5, 0.5 and 16 mg/kg lipid weight), respectively. The detection of higher levels of p,p'-DDT than the degradation products (p,p'-DDD and p,p'-DDE), and higher levels of endosulfan isomers (alpha and beta) than the sulphate, in fish samples, implied recent exposure of fish to DDT and endosulfan, respectively. Generally, most of the fish samples had residue levels above the average method detection limits (MDLs), but were within the calculated ADI.


Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302.
The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear. To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR. COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test. In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48-0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47-0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62-0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62-0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68-0.88). Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP.


Simplified plasma essential amino acid-based profiling provides metabolic information and prognostic value additive to traditional risk factors in heart failure.
In heart failure (HF), metabolic disturbances represent functional perturbations in peripheral tissues and also predict patient outcomes. This study developed a simplified essential amino acid-based profile and tested whether it could improve prognostication. Plasma essential amino acids and lipidomics were measured on 1084 participants. The initial cohort included 94 normal controls and 599 patients hospitalized due to acute/decompensated HF. The validation cohort included 391 HF patients. Patients were followed for composite events (death/HF related re-hospitalization) and were categorized into three groups: high risk type 1 (leucine ≥145 μM and phenylalanine ≥ 88.9 μM), high risk type 2 (leucine < 81.2 μM), and low risk (other). Types 1 and 2 were associated with higher event rates [hazard ratio (95% confidence intervals) = 1.88 (1.27-2.79) and 7.71 (4.97-11.9), respectively, p < 0.001]. Compared to the low-risk group, both types of high-risk patients were older and had lower blood pressure and estimated glomerular filtration rates, but higher B-type natriuretic peptides (BNP). In addition, type 1 was associated with more incompletely metabolized lipids in the blood; type 2 patients had lower body mass indexes, rates of using guideline-based medications, and levels of cholesterol, hemoglobin, and albumin. The prognostic value of types 1 and 2 remained significant after adjusting for age, BNP and other risk factors. The value of using high-risk types for prognosis was confirmed in the validation cohort. In conclusion, simplified essential amino acid-based profiling identified two high-risk populations and provided metabolic information and prognostic value additive to traditional risk factors.


Calcium dynamics and endoplasmic reticular function in the regulation of protein synthesis: implications for cell growth and adaptability.
The endoplasmic reticulum (ER) possesses the structural and functional features expected of an organelle that supports the integration and coordination of major cellular processes. Ca(2+) sequestered within the ER sustains lumenal protein processing while providing a reservoir of the cation to support stimulus-response coupling in the cytosol. Release of ER Ca(2+) sufficient to impair protein processing promotes ER stress and signals the "unfolded protein response" (UPR). The association of the UPR with an acute suppression of mRNA translational initiation and a longer term up-regulation of ER chaperones and partial translational recovery is discussed. Regulatory sites in mRNA translation and the mechanisms responsible for the early and later phases of the UPR are reviewed. The regulatory significance of GRP78/BiP, a multifunctional, broad-specificity ER chaperone, in the coordination of ER protein processing with mRNA translation during acute and chronic ER stress is addressed. The relationship of ER stress to protein misfolding in the cytoplasm is examined. Translational alterations in embryonic cardiomyocytes during treatments with various Ca(2+)-mobilizing, growth-promoting stimuli are described. The importance of ER Ca(2+) stores, ER chaperones, and cytosolic-free Ca(2+) in translational control and growth promotion by these stimuli is assessed. Some perspectives are provided regarding Ca(2+) as an integrating factor in the generation or diversion of metabolic energy. Circumstances impacting upon cellular adaptability during exposure to growth stimuli or during stressful conditions that require rapid adjustments in ATP for continued viability are considered.


Morphological and histochemical observations on the intestinal epithelium of Ascardia galli (Nematoda: Ascaridida).
The intestinal epithelium of Ascardia galli has been studied with various cytological and cytochemical techniques. It consists of large epithelial cells resting on a thick collagenous basal lamina. Their luminal surface is provided with microvilli. The intestinal cells store considerable amounts of glycogen and neutral lipids. Some intracellular granular inclusions, which stain for proteins, phospholipids and lipoproteins, are distributed throughout the cytoplasm. The brush border is composed of microvilli whereas the outer surface coat consists of saliva resistant PAS-positive material. The detailed histochemical analysis of surface material has revealed that it is composed of nonacetylated acid mucopolysaccharides rich in hyaluronic acid with carboxylate polyanions. The brush border shows intense activities of acid phosphatase and glucose-6-phosphatase, moderate of ATPase, and lipase, weak of 5'-nucleotidase. Acid phosphatase-positive intracellular structures are seen in the intestinal epithelium which form distinct aggregations.


Advanced glycation end products inhibit the osteogenic differentiation potential of adipose-derived stem cells in mice through autophagy.
Diabetes mellitus (DM) microenvironment will accelerate the accumulation of Advanced glycation end products (AGEs), adipose-derived stem cells (ASCs) have poor osteogenesis in the DM microenvironment. Studies suggest autophagy plays a vital role in osteogenesis, but the mechanism of the altered osteogenic potential of ASCs has not been elucidated. Bone tissue engineering by ASCs is widely used in the treatment of bone defects with diabetic osteoporosis (DOP). Therefore, it is meaningful to explore the effect of AGEs on the osteogenic differentiation potential of ASCs and its potential mechanism for the repair of bone defects in DOP. ASCs in C57BL/6 mice were isolated, cultured, then treated with AGEs, subsequently, cell viability and proliferation were detected through Cell Counting Kit 8 assay. 3-Methyladenine (3-MA), an autophagic inhibitor used to inhibit autophagic levels. Rapamycin (Rapa), an autophagy activator that further activated autophagy levels by inhibiting mTOR.The osteogenesis and autophagy changes of ASCs were analyzed by flow cytometry, qPCR, western blot, immunofluorescence, alkaline phosphatase (ALP) and alizarin red staining. AGEs reduced the autophagy level and osteogenic potential of ASCs. After 3-MA reduced autophagy, the osteogenic potential of ASCs also decreased. AGEs co-treatment with 3-MA, the levels of osteogenesis and autophagy reduced more significantly. When autophagy was activated by Rapa, it was found that it could rescue the reduced osteogenic potential of AGEs. AGEs reduce the osteogenic differentiation potential of ASCs through autophagy, and may provide a reference for the treatment of bone defects with diabetes osteoporosis.


A re-evaluation of squamous cell carcinoma antigen (SCC) as a serum marker for non-small cell lung cancer.
Squamous cell carcinoma antigen (SCC) is still a widely used tumor marker for monitoring non-small cell lung cancer (NSCLC), although recent reports discourage its routine use because of low sensitivity. This is a study evaluating the efficacy of SCC and CYFRA21-1 in diagnosing NSCLC. A chart review was performed in a university hospital in Japan, covering a period of 10 years, up to October 2004. During the study period, 142 (35.5%) among 400 NSCLC patients diagnosed, received serum assays of both SCC and CYFRA21-1. Elevated SCC and CYFRA21-1 levels were found in 29.6% and 59.2% of patients, respectively. SCC sensitivity was only 13.0% but CYFRA21-1 sensitivity rose to 73.9% in metastatic patients. The adjunct of SCC increased the CYFRA21-1 sensitivity by 6.3% in the overall population and by only 2.2% for patients with metastases. SCC determination should be considered an inefficient method as a potential diagnosing tool for NSCLC patients, and it provides no additional value when used in combination with CYFRA21-1.


Corrigendum: Physical activity among children and adolescents in Germany. Results of the cross-sectional KiGGS Wave 2 study and trends.
[This corrects the article DOI: 10.17886/RKI-GBE-2018-023.2.].


Anatomical bases for the radiological delineation of lymph node areas. Upper limbs, chest and abdomen.
Cancer spreads locally through direct infiltration into soft tissues, or at distance by invading vascular structures, then migrating through the lymphatic or blood flow. Although cancer cells carried in the blood can end in virtually any corner of the body, lymphatic migration is usually stepwise, through successive nodal stops, which can temporarily delay further progression. In radiotherapy, irradiation of lymphatic paths relevant to the localisation of the primary has been common practice for decades. Similarly, excision of cancer is often completed by lymphatic dissection. Both in radiotherapy and in surgery, advanced knowledge of the lymphatic pathways relevant to any tumour location is an important information for treatment preparation and execution. This second part describes the lymphatics of the upper limb, of the thorax and of the upper abdomen. Providing anatomical bases for the radiological delineation of lymph nodes areas in the axilla, in the chest and in the abdomen, it also offers a simplified classification for labeling the mediastinal and intra-abdominal nodal levels, grouped in each location inside three major functional areas (called I, II and III) which are all divided into three sublevels (named a, b or c).


The effect of adenyl compounds on the rat heart.
1 The effects of adenyl compounds were examined on the rat atrium and ventricle. 2 Adenosine, adenosine 5'-monophosphate, adenosine 5'-diphosphate, adenosine 5'-triphosphate (ATP) and beta, gamma-methylene ATP (APPCP) produced negative inotropic effects on the rat atrium. These inhibitory effects were antagonized by 8-phenyltheophylline (8-PT), a P1-purinoceptor antagonist, and potentiated by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), an adenosine deaminase inhibitor, but were not affected by dipyridamole, which blocks adenosine uptake. 3 alpha, beta-Methylene ATP (APCPP), which is resistant to degradation, did not produce a similar inhibitory response in the rat atrium. 4 Adenosine did not affect the basal developed force of the rat ventricle nor did it affect the beta-adrenoceptor-mediated positive inotropic effect. 5 Very high concentrations of ATP (0.1-3 mM) produced negative inotropic effects in the rat ventricle. APPCP (0.3 mM) also produced an inhibitory response, which was significantly smaller than that produced by ATP (0.3 mM). APCPP elicited excitation rather than the expected inhibitory response. 6 The inhibitory effect of ATP in the rat ventricle was not blocked by indomethacin, 8-PT or atropine. 7 It is possible that the action of ATP in the rat ventricle is mediated via P2-purinoceptors and that the lack of inhibitory action of APCPP on the rat ventricle is due to the difference in structural conformation between ATP and APCPP. 8 It seems likely that inhibitory P1-purinoceptors are present in the rat atrium and that the inhibitory responses produced by ATP in the rat ventricle may be mediated via P2-purinoceptors.


Expansion and deletion of CTG repeats from human disease genes are determined by the direction of replication in E. coli.
Several human hereditary neurological and neurodegenerative disease genes are associated with the expansion of CTG repeats. Here we show that the frequency of genetic expansions or deletions in Escherichia coli depends on the direction of replication. Large expansions occur predominantly when the CTGs are in the leading strand template rather than the lagging strand. However, deletions are more prominent when the CTGs are in the opposite orientation. Most deletions generated products of defined size classes. Strand slippage coupled with non-classical DNA structures may account for these observations and relate to expansion-deletion mechanisms in eukaryotic chromosomes for disease genes.


Postgraduate specialties interest, career choices and qualifications earned by male dentists graduated from King Saud University.
To study the career development of male graduates of King Saud University (KSU), College of Dentistry in terms of pursuit of postgraduate dental education, higher degrees or Board Certification, choice of universities and countries of study, and place of work after qualification. A questionnaire survey was carried out through face to face or telephone interview among 666 KSU graduates of 1982-2004. 80% (532 graduates) response rate. (77%) finished postgraduate dental education. 17% specialized in Prosthodontics, 16% in Saudi Board Advanced Restorative Dentistry, 14% in Advanced General Dentistry, 10.5% in Orthodontics, 10% in Oral and Maxillofacial Surgery, 8.3% in Pediatric Dentistry, 7.7% in Endodontics, 6% in Periodontics, 5.5% in Operative Dentistry, 5% in other Specialties. 61% had a Master's degree and 16% had a Doctorate degree. 23% had Board Certificates and 8% had a Fellowship Certificate. (78%) are working in the government, 15% at the university and 6% in private, and 19% in administrative positions. Most of the dental graduates were motivated and eager to continue their postgraduate education to get either clinical specialty or academic degrees from nationally and internationally well recognized and known Universities and programs.


Problematic alcohol use among fathers in Kenya: Poverty, people, and practices as barriers and facilitators to help acceptance.
In Kenya, the prevalence of alcohol use disorder (AUD) is close to 6%, but a notable treatment gap persists. AUD is especially pronounced among men, leading to negative consequences at both individual and family levels. This study examines the experiences of problem-drinking fathers in Kenya regarding previous treatment-seeking related to alcohol use. Experiences and dynamics of the family are also explored as they pertain to treatment-seeking experiences. In Eldoret, Kenya, semi-structured qualitative interviews were conducted with 11 families with a male exhibiting problem drinking, his spouse, and one child. Thematic content analysis was used to examine themes related to barriers and facilitators to treatment. Participants only reported informal help received from family and community members; they exhibited little awareness of available formal treatments. Families were both deeply affected by alcohol use and actively involved in help-seeking. Indeed, fathers' experiences are described as help-accepting rather than help-seeking. Three overarching themes emerged from the results: poverty, people, and practices. Poverty could be a motivator to accept help to support one's family financially, but stress from lack of work also drove drinking behaviours. People were also crucial as both barriers and facilitators of help-accepting. Negative help strategies or peer influence deterred fathers from accepting help to quit. Positive motivation, social support, and stigma against drinking were motivators. Practices that were culturally salient, such as religiosity and gender roles, facilitated help acceptance. Overall, most help efforts were short-term and only lead to very short-term behaviour change. Families and communities are active in help provision for problem-drinking men in Kenya, though results confirm remaining need for effective interventions. Future interventions could benefit from recognizing the role of family to aid in treatment-engagement and attending to the importance of poverty, people, and practices in designing treatment strategies.


Measurement of upper limb ulcers in patients with systemic sclerosis: reproducibility and correlation with pain, function, and quality of life.
There are a large number of studies addressing the treatment and assessment of chronic ulcers. Despite the fact that ischemic ulcers are frequent and difficult to manage in cases of systemic sclerosis, there is minimal literature on assessment measures regarding these wounds or on their reproducibility. The aim of this study was to investigate intraobserver and interobserver reproducibility regarding ulcer dimension measurements in patients with systemic sclerosis. Correlations between pain, upper limb function, pinch strength, and quality of life were also determined. A prospective 11-week follow-up study was carried out to assess active upper limb ulcers. Ulcer diameter, ulcer area, and interobserver reproducibility were performed weekly. Quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey), upper limb function (disabilities of the arm, shoulder, and hand), pinch strength, pain, visual analog scale, and intraobserver reproducibility were assessed at baseline, 3, 7, and 11 weeks. Fifty-one active ulcers were recorded. Larger ulcer diameter, smaller ulcer diameter, and ulcer area demonstrated excellent intraobserver (r > .81, p < .001) and interobserver reproducibility (r > .76, p < .001). There was significant correlation between ulcer dimension and visual analog scale scores for pain (r = .42; p < .001) and some Medical Outcomes Study 36-Item Short-Form Health Survey; pinch strength; and disabilities of the arm, shoulder, and hand domains (r >or= .40; p < .01). Simple measurement instruments for the assessment of ischemic ulcers were reproducible in patients with SSc and correlated to other variables of interest for these wounds.


Model-Based Dose Selection of Fostemsavir for Pediatric Populations With Multidrug-Resistant HIV-1 and Relative Bioavailability Assessment in Healthy Adults.
Fostemsavir, a prodrug of the first-in-class HIV-1 attachment inhibitor temsavir, is approved for the treatment of multidrug-resistant HIV-1 in adults; its use in pediatric populations is currently being studied. Population pharmacokinetic modeling across pediatric weight bands was used to guide pediatric fostemsavir dose selection. Dosing simulations demonstrated that twice-daily fostemsavir 600-mg (adult dose) and 400-mg doses met safety and efficacy criteria for 35 kg or greater and 20 or greater to less than 35 kg pediatric weight bands, respectively. Temsavir relative bioavailability of 2 low-dose fostemsavir extended-release formulations (3 × 200 mg; formulations A and B) and reference formulation (600 mg extended release) was assessed in a 2-part, open-label, randomized, crossover study in healthy adults. Part 1 (N = 32) compared single-dose temsavir relative bioavailability, and Part 2 (N = 16) evaluated the impact of fed versus fasted conditions using the selected low-dose formulation. Temsavir geometric mean ratios for the area under the plasma concentration-time curve from time zero to infinity and maximum concentration for formulation B were bioequivalent to the reference formulation. Temsavir maximum concentration for formulation B was similar in fed and fasted states, but area under the plasma concentration-time curve from time zero to infinity geometric mean ratio was increased under fed conditions, consistent with previous results in adults. These analyses demonstrated efficient pediatric dose selection using a model-based approach.


Adaptation of a high-voltage electron microscope for routine biological dark-field imaging.
Relative merits of different objective aperture geometries for generating dark-field images in a high-voltage electron microscope (an AEI EM7) are considered. Using metal-bar beam stops in the objective lens diffraction plane, with large (500 micron diameter) limiting apertures, effective resolution in the 2-4 nm range can be demonstrated for biological specimens.


If the shoe fits: development of an on-line tool to aid practitioner/patient discussions about 'healthy footwear'.
A previous study highlighted the importance of footwear to individuals' sense of their identity, demonstrating that shoes must 'fit' someone socially, as well as functionally. However, unhealthy shoes can have a detrimental effect on both foot health and mobility. This project utilises qualitative social science methods to enable podiatrists to understand the broader contribution of footwear to patients' sense of themselves and from this an online toolkit was developed to aid footwear education. Semi-structured interviews were conducted with six podiatrists/shoe-fitters and 13 people with foot pathologies, some of whom also completed shoe diaries. These were supplemented with some follow-up interviews and photographs of participants' own shoes were taken to allow in-depth discussions. Four areas related to 'fit' were identified; practicalities, personal, purpose and pressures, all of which need to be considered when discussing changes in footwear. These were incorporated into an online toolkit which was further validated by service users and practitioners in a focus group. This toolkit can support podiatrists in partnership with patients to identify and address possible barriers to changing footwear towards a more suitable shoe. Enabling patients to make healthier shoe choices will help contribute to improvements in their foot health and mobility.


Quality of dispatcher-assisted vs. automated external defibrillator-guided cardiopulmonary resuscitation: a randomised simulation trial.
Quality of hands-only cardiopulmonary resuscitation (CPR) is an important determinant of resuscitation outcome for cardiac arrest patients cared for by lay rescuers. We designed a simulation trial to assess and compare the quality of CPR among untrained lay people under two different scenarios: automated external defibrillator (AED)-guided and dispatcher-assisted CPR. A simulation study was performed involving 42 volunteers selected by non-probabilistic sampling. Participants were randomized into two CPR simulation scenarios with a manikin: (A) AED-guided CPR and (T) dispatcher-assisted CPR. The quality of CPR was evaluated by metric monitoring of the chest compressions and timing of actions. Content analysis of the telephone instructions was performed by two independent researchers using a checklist. CPR was started in 20 of the 21 cases in scenario A and in all cases in scenario T. In total, 12 053 chest compressions were applied, 57.6% corresponding to scenario A. The proportion of compressions that were of an adequate depth was low in both cases, 15.3% in scenario A vs. 31.7% in scenario T (P < 0.001), while complete chest recoil was allowed in 66 and 72% (P < 0.001) of compressions, respectively. The AED advised to shock 91 times, and shocks were delivered in all cases. Although guided CPR helps untrained people to initiate resuscitation manoeuvres, the quality of CPR was poor in both groups. Telephone guidance improved the proportion of compressions that achieved adequate chest compression and recoil but did not optimise the compression rate.


Cell cycle analysis during retinoic acid induced differentiation of a human embryonal carcinoma-derived cell line.
Several subclones of the human embryonal carcinoma (EC) cell line Tera-2 can be induced to differentiate in monolayer culture by retinoic acid (RA) to a flattened cell type with reduced growth rate. Using a method based on the transition probability model, we have analysed changes in cell cycle kinetics of Tera-2 cells during the differentiation process. Growth inhibition was shown to occur without a lag period and to be partly due to an increase in the duration of the S-phase, but with a relatively greater contribution from an increase in the duration of G1-phase. Since the fraction of the cell population in the G1-phase then doubled, cells accumulated in this part of the cycle. In contrast, the reduced proliferation rate of two murine EC cell lines, PC13 and P19, treated with RA occurs after a lag period of about two cell cycles and is mainly attributable to an increase in the duration of the S-phase. The results illustrate a differential response of human and murine EC cells to growth regulation by RA and again emphasize that although the stem cells of murine teratocarcinomas may provide a useful model, they are not identical to their human counterparts.


Developmental toxicity of domoic acid in zebrafish (Danio rerio).
Domoic acid (DA) is a rigid analog of the excitatory amino acid glutamate. It is produced by the diatom genus Pseudo-nitzschia and is a potent neurotoxin in both adult and developing animals. We have used zebrafish (Danio rerio) as a model to investigate and characterize the developmental toxicity of DA. Domoic acid was administered by microinjection to fertilized eggs at the 128- to 512-cell stages in concentrations ranging from 0.12 to 17 mg/kg (DA/egg weight). DA reduced hatching success by 40% at 0.4 mg/kg and by more than 50% at doses of 1.2 mg/kg and higher. Fifty percent of embryos treated with 1.2 mg/kg DA showed marked tonic-clonic type convulsions at 2 days post fertilization. Four days post fertilization (dpf), all embryos treated with 4.0 mg/kg DA and higher showed a complete absence of touch response reflexes. Commencing 5 dpf, rapid and constant pectoral fin movements were observed, a response which may be related to the hallmark effect in rodents of stereotypic scratching. These data indicate that zebrafish show symptoms of developmental DA toxicity as well as a similar sensitivity comparable to the effects of DA characterized in laboratory rodents.


Epiglottis collapse in adult obstructive sleep apnea: A systematic review.
To systematically review the international literature evaluating the role of the epiglottis in snoring and obstructive sleep apnea and to explore possible treatment options available. PubMed, Scopus, Embase, Google Scholar, Book Citation Index-Science, CINAHL, Conference Proceedings Citation Index-Science, The Cochrane Collaboration Databases, and Web of Science. The searches were performed from the first year of each database through March 5, 2015. Fourteen studies about the prevalence of epiglottis collapse in obstructive sleep apnea (OSA) were found. Most involved drug-induced sleep endoscopy studies that indirectly reported their findings about epiglottis collapse. The data suggests that the prevalence of epiglottis collapse in OSA is higher than previously described. The epiglottis has been implicated in 12% of cases of snoring, and sound originating from it has a higher pitch than palatal snoring. Continuous positive pressure (CPAP) surgery and positional therapy in the treatment of epiglottis collapse were also considered. Lateral position of the head may reduce the frequency of epiglottis collapse. With regard to CPAP, available reports suggest that it may accentuate collapse of the epiglottis. Surgery may help reduce snoring in some patients with a lax epiglottis and improve OSA in patients undergoing multilevel surgery. Knowledge regarding the role of the epiglottis in adult OSA and snoring patients is limited. The prevalence of this phenomenon in OSA seems to be greater than previously reported, and more research is needed to understand its role in OSA and the best way to treat it. NA.


Stimulation of calcium absorption and reduction in susceptibility to fasting-induced hypocalcaemia in pregnant ewes fed vegetable oil.
To test the hypothesis that susceptibility to fasting-induced hypocalcaemia could be reduced by prior stimulation of the ability of late-pregnant ewes to absorb calcium (Ca) from the gastrointestinal tract (GIT) by feeding a vegetable oil supplement. The supplement was expected to decrease the availability of the Ca supplied from a pasture diet, and stimulate the animals' homeostatic system. Mature ewes pregnant with twins (n=28) and grazing at pasture, were randomly allocated to Treated or Control groups, 6 weeks prior to their expected date of parturition (Day 0). Treated ewes (n=14) were drenched with 25 ml soya bean oil twice daily for 3 weeks. Plasma Ca concentrations were determined on Days 0, 8, and immediately before and after a 20-hour fast that began on Day 21, which was intended to simulate the reduced feed intakes that occur on the day of parturition. An index of the ewes' ability to absorb Ca from the GIT was obtained using orally dosed strontium (Sr) as a tracer and the extent of Ca mobilisation from bone was assessed by measuring hydroxyproline concentrations in plasma before fasting on Day 21. Plasma Ca concentrations were significantly higher in Treated than Control ewes after fasting (p0.001). The Ca absorption index was also higher in Treated than Control ewes at the end of the 3-week treatment period (p=0.014), but degree of bone mobilisation assessed by concentration of hydroxyproline in plasma did not differ significantly between groups. Susceptibility of late-pregnant ewes to fasting-induced hypocalcaemia was reduced using a soya bean oil supplement. The inclusion of one or more dietary ingredients capable of binding or forming complexes specifically with Ca in the diet of late pregnant ruminants may provide a novel, practical method of reducing periparturient hypocalcaemia.


Integrative network analysis interweaves the missing links in cardiomyopathy diseasome.
Cardiomyopathies are progressive disease conditions that give rise to an abnormal heart phenotype and are a leading cause of heart failures in the general population. These are complex diseases that show co-morbidity with other diseases. The molecular interaction network in the localised disease neighbourhood is an important step toward deciphering molecular mechanisms underlying these complex conditions. In this pursuit, we employed network medicine techniques to systematically investigate cardiomyopathy's genetic interplay with other diseases and uncover the molecular players underlying these associations. We predicted a set of candidate genes in cardiomyopathy by exploring the DIAMOnD algorithm on the human interactome. We next revealed how these candidate genes form association across different diseases and highlighted the predominant association with brain, cancer and metabolic diseases. Through integrative systems analysis of molecular pathways, heart-specific mouse knockout data and disease tissue-specific transcriptomic data, we screened and ascertained prominent candidates that show abnormal heart phenotype, including NOS3, MMP2 and SIRT1. Our computational analysis broadens the understanding of the genetic associations of cardiomyopathies with other diseases and holds great potential in cardiomyopathy research.


Prediction of severity of isolated aortic regurgitation by echocardiography: an aortic regurgitation index study.
No single precise qualitative method is recommended for evaluating the severity of aortic regurgitation (AR). Quantitative methods for AR assessment are, typically, cumbersome and time-consuming. The purpose of this study was to develop a more comprehensive method for predicting the severity of AR. In all, 79 patients with normal left ventricular systolic function and at least mild AR were included in this prospective study. The standard references for evaluating AR severity were quantitative methods. The AR index consisted of 5 echocardiographic parameters: jet width ratio, vena contracta width, pressure half-time, jet density, and diastolic flow reversal in the descending aorta. Each parameter was scored on a 3-point scale from 1 to 3. The AR index was calculated as the sum of each score divided by the number of parameters. Thus, an increasing AR index score from 1 to 3 was indicative of increasing regurgitation. The study demonstrated that the numeric value of AR index increased proportionately to the quantitative grading of AR severity, and proved to be an accurate predictor for AR severity. A 1.8 threshold for the AR index offered a high level of sensitivity and negative predictive value for severe AR. The possibility of missing severe AR was low with AR index less than 1.8. A 2.6 threshold for the AR index provided high specificity and positive predictive value for severe AR. The possibility of diagnosing severe AR was extremely high with AR index of 2.6 or more. AR index provided a more comprehensive method for predicting the degree of AR severity in this study. We suggest that the AR index should be considered for any evaluation of the severity of AR.


Conversion of chirality to twisting via sequential one-dimensional and two-dimensional growth of graphene spirals.
The properties of two-dimensional (2D) van der Waals materials can be tuned through nanostructuring or controlled layer stacking, where interlayer hybridization induces exotic electronic states and transport phenomena. Here we describe a viable approach and underlying mechanism for the assisted self-assembly of twisted layer graphene. The process, which can be implemented in standard chemical vapour deposition growth, is best described by analogy to origami and kirigami with paper. It involves the controlled induction of wrinkle formation in single-layer graphene with subsequent wrinkle folding, tearing and re-growth. Inherent to the process is the formation of intertwined graphene spirals and conversion of the chiral angle of 1D wrinkles into a 2D twist angle of a 3D superlattice. The approach can be extended to other foldable 2D materials and facilitates the production of miniaturized electronic components, including capacitors, resistors, inductors and superconductors.


Misleading long post-pacing interval after entrainment of typical atrial flutter from the cavotricuspid isthmus.
The purpose of this study was to evaluate the prevalence and mechanism of a misleading long post-pacing interval (PPI) upon entrainment of typical atrial flutter (AFL) from the cavotricuspid isthmus (CTI). In typical AFL, the PPI from entrainment at the CTI is expected to closely match the tachycardia cycle-length (TCL). Sixty patients with confirmed CTI-dependent AFL were retrospectively analyzed and grouped into short (≤30 ms) or long (>30 ms) PPI-TCL. Thereafter, we prospectively studied 16 patients to acquire the PPI-TCL at 4 CTI sites with entrainment at pacing cycle-lengths (PCLs) 10 to 40 ms shorter than the TCL. Conduction times during AFL and entrainment were compared in 5 segments of the AFL circuit. Eleven patients (18%) in the retrospective analysis had a long PPI-TCL after entrainment from the CTI. Subjects with long PPI-TCL had similar baseline characteristics but greater beat-to-beat TCL variability. In the prospective cohort, PPI-TCL was influenced by the difference between PCL and TCL and site of entrainment. Conduction delays associated with a long PPI-TCL were located predominantly in the segment activated first by the paced orthodromic wave front, and were mainly due to local pacing latency, as confirmed by the use of monophasic action potential catheters. A long PPI upon entrainment of typical AFL from the CTI is common and due to delayed conduction with entrainment. Whether these findings apply to other macro-re-entrant tachycardias warrants further investigation.


Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer.
We describe here the existence of a heregulin-HER3 autocrine loop, and the contribution of heregulin-dependent, HER2-mediated HER3 activation to gefitinib insensitivity in non-small cell lung cancer (NSCLC). ADAM17 protein, a major ErbB ligand sheddase, is upregulated in NSCLC and is required not only for heregulin-dependent HER3 signaling, but also for EGFR ligand-dependent signaling in NSCLC cell lines. A selective ADAM inhibitor, INCB3619, prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. These results show that ADAM inhibition affects multiple ErbB pathways in NSCLC and thus offers an excellent opportunity for pharmacological intervention, either alone or in combination with other drugs.


Parallel Simulated Annealing Using an Adaptive Resampling Interval.
This paper presents a parallel simulated annealing algorithm that is able to achieve 90% parallel efficiency in iteration on up to 192 processors and up to 40% parallel efficiency in time when applied to a 5000-dimension Rastrigin function. Our algorithm breaks scalability barriers in the method of Chu et al. (1999) by abandoning adaptive cooling based on variance. The resulting gains in parallel efficiency are much larger than the loss of serial efficiency from lack of adaptive cooling. Our algorithm resamples the states across processors periodically. The resampling interval is tuned according to the success rate for each specific number of processors. We further present an adaptive method to determine the resampling interval based on the adoption rate. This adaptive method is able to achieve nearly identical parallel efficiency but higher success rates compared to the fixed interval one using the best interval found.


A study of efficacy of Nigella sativa in treatment of Meniere's disease: A randomized, placebo controlled clinical trial.
Meniere's disease (MD), first introduced by Prosper Meniere, is characterized mainly by vertigo, tinnitus, aural fullness and sensorineural hearing loss. Though the exact pathophysiology of MD is unknown, immunologic and inflammatory interactions are possible underlying mechanisms involved in MD. This study is aimed to investigate the immunomodulatory and anti-inflammatory effect of Nigella sativa on MD as a therapeutic agent. We divided 40 patients with definite MD into two groups of 20 cases. The study group received 1 g of Nigella sativa oil daily for three months and the control group received a placebo. Changes in hearing, tinnitus and vertigo were estimated by pure tone audiometry, tinnitus handicap inventory questionnaire and dizziness handicap inventory questionnaire, respectively. At the end of the study we did not observe any significant improvement in study's group hearing threshold, tinnitus and vertigo compared to the control group. In this study, statistical analysis showed that Nigella sativa failed to improve signs and symptoms of MD. However, further investigations with a larger study population are needed to ascertain the current conclusion.


The 532-nm 180-W (GreenLight®) laser vaporization of the prostate for the treatment of lower urinary tract symptoms: how durable is the new side-fire fiber with integrated cooling system?
The 532-nm side-fire laser vaporization is established for the treatment of symptomatic benign prostate hyperplasia. Meanwhile, the third generation of this system is offered by American Medical Systems, Inc. The laser power increased from 80 and 120 to 180 W from the first to the third generation. Despite good functional results, with the 80- and 120-W systems, the removal of prostate tissue is limited because of fiber degradation. To overcome this problem, the fiber was designed newly with an integrated cooling system and a sensor for decreasing the laser energy in case of overheating. We evaluate whether the new fiber still suffers from degradation with consecutive drop of power transmission during the procedure. The power output of the cooled fiber was measured in vitro and during prostate vaporization in ten patients. Laser beam power was measured at baseline and after the application each of 50 kJ during laser vaporization. Power emission of the fiber remains constant at 20, 80, and 180 W of power settings over the whole 40-kJ lifespan. During the transurethral procedure, a median total energy of 276 kJ (standard deviation 153 kJ) was applied for vaporization. Median power output from the fiber at the end of the procedure was 97% from the baseline value. There were no fiber malfunctions observed. In contrast to former generations, the third-generation laser fiber is durable without significant power loss during prostate vaporization.


Comparison of the malnutrition-inflammation score in chronic kidney disease patients and kidney transplant recipients.
Protein-energy wasting (PEW) is a common condition in patients with chronic kidney disease (CKD) including dialysis and kidney transplant recipients (TX) and frequently assessed with malnutrition-inflammation score (MIS). We hypothesized that (1) the MIS and PEW parameters are correlated with kidney function and (2) the MIS and PEW parameters are more severe in TX than in non-dialysis (ND) CKD patients with similar eGFR. In this study, we matched 203 ND-CKD and 203 TX patients from two independently assembled cohorts of patients based on estimated glomerular filtration rate (eGFR) and compared various PEW parameters between the two groups using unadjusted and case-mix adjusted linear regression and conditional logistic regression analysis models. In the combined cohort (n = 406) of patients, the mean ± SD age was 57 ± 12 years; included 55 % men and 35 % diabetics; and demonstrated a mean ± SD baseline eGFR of 29 ± 11 ml/min/1.73 m(2). The eGFR correlated positively with serum albumin (ρ = 0.26, p < 0.001) and negatively (ρ = -0.33, p < 0.001) with MIS. ND-CKD and TX patients had similar MIS, PEW parameters such as waist circumference, serum CRP, albumin, and leptin levels. After case-mix adjustment, TX status was associated with higher waist circumference (standardized coefficient: 0.187, p < 0.001), lower BMI (standardized coefficient: -0.204, p < 0.001), and lower SGA score (standardized coefficient: 0.156, p = 0.006). We found associations between lower eGFR and various PEW measures in both the ND-CKD and TX populations. Additionally, we did not observe significant differences in the burden of PEW parameters between the CKD and TX populations.


[Identification and isolation of mesenchymal stem cells from human fetal pancreas].
To isolate and identify the phenotype and biological characteristics of pancreas derived mesenchymal stem cell. Fresh pancreas of 4-5 months old aborted fetus was dissected free from connective tissue, and was cut into small pieces. The adherent cells were harvested and subcultured, after the third subculture, the cells were used for examination. Cell cycle was analyzed by measuring DNA content by FACScan flow cytometer. Phenotype of MSCs was analyzed by immunohistochemical SA technique and differentiated cells were identified by relevant specific staining. Fetal pancreas derived cells gave rise to a population of adherent cells characterized by the presence of a predominant cell type with a typical fibroblast like morphology. By transmission electron microcopy, MSC had few endoplasmic reticulums and mitochondrias. During the log phase of growth, MSC proliferated with a two fold population at 30 h. MSC can be ex vivo expanded by successive cycles of trypsinization, seeding, and culture. Under these conditions, MSC had capability of passaging up to 30 times without displaying significant changes in morphology, with 2-fold increase in cell number after each passage. This indicates the high ex vivo expansion potential of MSC. The results showed that the yield of CFU-Fs was above 200 clones even after the 6th passage. Cell cycle analysis by flow cytometry revealed that more than 83% of cells were in the G0/G1 phases, while a small population of cells were actively engaged in proliferation (S + G2 + M = 17%). We also showed that more than 86% of cells were positive stained by FITC labeled CD44, CD29, CD13, and only about 1% of cells were positive for CD34, HLA-DR. Expression of collagen I, III was positive while vWF was negative. In the differentiation study, we found culture-expanded pancreas MSCs could be directed into the osteogenic lineage as detected by osteoblastic morphology, expression of alkaline phosphatase, modulation of osteocalcin mRNA production and the formation of a mineralized extracellular matrix. We also found that MSCs could give rise to the adipogenic and chondrogenic lineage as evidenced by accumulation of lipid-rich vacuoles within cells and the expression of lipoprotein lipase mRNA or the expression of collagen II and the deposition of proteoglycans. Mesenchymal stem cells existing in human pancreas can be isolated by their adherent ability and should be essential to sustain a steady supply of primitive cells in tissue remodeling.


Math at home adds up to achievement in school.
With a randomized field experiment of 587 first-graders, we tested an educational intervention designed to promote interactions between children and parents relating to math. We predicted that increasing math activities at home would increase children's math achievement at school. We tested this prediction by having children engage in math story time with their parents. The intervention, short numerical story problems delivered through an iPad app, significantly increased children's math achievement across the school year compared to a reading (control) group, especially for children whose parents are habitually anxious about math. Brief, high-quality parent-child interactions about math at home help break the intergenerational cycle of low math achievement.


Small, round-structured viruses (SRSVs) associated with acute gastroenteritis outbreaks in Gifu, Japan.
Two outbreaks of non-bacterial gastroenteritis occurred in Gifu prefecture in January 1989 and in January 1991. Both outbreaks were closely related to the consumption of raw oysters, and showed similar clinical features. Small, round-structured virus particles were found in patient stools in both outbreaks by electron microscopy. The role of these particles as the causative agents of the outbreaks were strongly suggested by immune electron microscopy and/or western-blotting immunoassay. When compared with SRSV-9 (Tokyo/SRSV/86-510) reported previously (Hayashi et al, J. Clin. Microbiol., 27: 1728-1733, 1989), it was found that these viral particles were antigenically similar to SRSV-9, and had a major structural protein of 63 kilodaltons (kDa). Further, the prevalence of this agent in Gifu area was examined by western blot antibody assay using 67 serum samples collected from the inhabitants in 1991. The results indicated the circulation of the same or antigenically similar agent in this area.


Ileal alkaline phosphatase is upregulated following functional amino acid supplementation in Salmonella Typhimurium-challenged pigs.
We recently showed that functional amino acid (FAA) supplementation improves growth performance and immune status of Salmonella Typhimurium (ST)-challenged pigs, which was further improved by a longer adaptation period. It is expected that the effects are associated with increased activity of intestinal alkaline phosphatase (IAP). The objective of this study was to evaluate the effects of FAA supplementation and adaptation period on the ileal, cecal, and colonic activity of IAP in weaned pigs challenged with ST. In experiment 1, a total of 32 mixed-sex weanling pigs were randomly assigned to dietary treatments in a 2 × 2 factorial arrangement with low (LP) or high protein (HP) content and basal (FAA-) or FAA profile (FAA+; Thr, Met, and Trp at 120% of requirements) as factors. In experiment 2, a total of 32 mixed-sex weanling pigs were randomly assigned to one of four dietary treatments, being FAA- fed throughout the experimental period (FAA-) or an FAA profile fed only in the post-inoculation (FAA + 0), for 1 wk pre- and post-inoculation (FAA + 1), or throughout the experimental period (FAA + 2). In experiments 1 and 2, after a 7- and 14-d adaptation period, respectively, pigs were inoculated with saline solution containing ST (3.3 and 2.2 × 109 CFU/mL, respectively). Plasma alkaline phosphatase was measured on days 0 and 7 post-inoculation in experiment 1, and IAP (ileum, cecum, and colon) was measured in experiments 1 and 2. Correlations among ileal IAP and serum albumin and haptoglobin, plasma superoxide dismutase (SOD), malondialdehyde (MDA), and reduced:oxidized glutathione, ileal myeloperoxidase, ST shedding and ileal colonization, and post-inoculation average daily gain, feed intake (ADFI), and gain:feed were also analyzed. In experiment 1, plasma alkaline phosphatase was decreased with ST inoculation and the overall content was increased in LP-FAA+ compared with LP-FAA- (P < 0.05). Moreover, ileal IAP was increased in FAA+ compared with FAA- pigs in both studies (P < 0.05) regardless of adaptation time (P > 0.05). IAP was positively correlated with MDA and ADFI and negatively correlated with SOD and ST shedding in experiment 1 (P < 0.05). These results demonstrate a positive effect of FAA supplementation, but not adaptation period, on ileal alkaline phosphatase activity in Salmonella-challenged pigs, which may be associated with improvements in antioxidant balance.


ERP abnormalities during semantic processing in schizophrenia.
To examine the neurophysiological and cognitive characteristics of thought disturbance in schizophrenic patients, we examined the amplitude, latency, and topography of a specific event-related brain potential (ERP), the N400, which is elicited by semantically incongruent words and phrases. Twelve chronic schizophrenic patients and twelve age-matched control subjects read sentences presented visually that had either semantically correct (e.g., 'People pray in their local church') or incorrect endings (e.g., 'Every Sunday morning people pray in their local nest'). Relative to normal controls, schizophrenic patients had significantly reduced N400 amplitude and increased latency to semantically anomalous endings. Additionally, a late positive component which follows the N400 was significantly reduced in amplitude in schizophrenic patients. However, patients and controls did not differ significantly in terms of the topographical distribution of either the N400 or its late positive potential, examined at 28 electrode sites. Thus, N400 topography in schizophrenic patients was not accompanied by the asymmetry which frequently characterizes the well known auditory P300 disturbance in schizophrenic patients. We concluded that these findings may reflect a profound disturbance in attentional processes in chronic schizophrenia.


Modeling and characteristic analysis of roadway profile under the influence of multiple factors.
Considering that the movement trajectory of roadheader cutting head directly affects the surface morphology characteristics of roadway forming, the creation mechanism of roadway contour obtained by cutting head cutting roadway is analyzed. The robot kinematics analysis method was used to determine the coordinates of the roadheader cutting head in the roadway space coordinate system, and the mathematical model of the cutting head cutting the roadway contour was constructed. Through numerical calculation, the differences of roadway morphology characteristics formed by three different types of cutting heads are analyzed. The orthogonal experiment was designed, and the regression equation under multiple factors was solved with the experimental results. The influence of cutting feed rate, cutting Angle, cutting head radius and cutting head cone Angle on the morphology characteristics of cutting surface was analyzed by regression calculation and theoretical calculation. The research results show that the roadway surface obtained by "spherical crown + cylinder" cutting head is the most uneven, and the roadway surface obtained by "spherical crown + cone + cylinder" cutting head is the most flat. With the decrease of cutting lifting Angle, cutting feed, cutting head cone Angle and the increase of cutting head crown radius, the smoothness of roadway obtained by cutting is higher.


The effect of sleep deprivation on the EEG in epilepsy.
Many published studies report an increased incidence of epileptiform EEG activity following sleep deprivation in persons with epilepsy in whom a previous routine EEG was normal or inconclusive. Few such studies, however, permit a clear distinction to be made between the effects of sleep deprivation per se, sleep induction following deprivation, or simply repeated EEG recording. Sixty-nine patients have been investigated in whom a routine waking record, a secobarbital-induced sleep recording and an EEG following 24 h sleep deprivation were obtained in random order irrespective of whether or not the initial EEG contained epileptiform activity. For each record the incidence of epileptiform activity if any, was quantified in terms of discharges per minute for wake, drowsiness and each sleep stage. The findings confirmed the marked activating effect of light sleep on the EEG but there was no evidence of an overall increase in discharge rate after sleep deprivation either in the waking state or in the various sleep stages when these were compared with secobarbital-induced or spontaneous sleep. There was a significant increase of generalized discharges in the waking state only, after sleep deprivation, but a decrease in incidence of focal epileptiform activity. It is concluded that although specific indications may exist for the use of sleep deprivation, as a general method of EEG activation in epilepsy it has no advantages over barbiturate-induced sleep to offset the greater inconvenience to patients.


Establishment and validation of in-house cryopreserved CAR/TCR-T cell flow cytometry quality control.
Chimeric antigen receptor (CAR) or T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for the treatment of hematologic malignancies and solid tumors. Multiparametric flow cytometry-based assays play a critical role in monitoring cellular manufacturing steps. Since manufacturing CAR/TCR T-cell products must be in compliance with current good manufacturing practices (cGMP), a standard or quality control for flow cytometry assays should be used to ensure the accuracy of flow cytometry results, but none is currently commercially available. Therefore, we established a procedure to generate an in-house cryopreserved CAR/TCR T-cell products for use as a flow cytometry quality control and validated their use. Two CAR T-cell products: CD19/CD22 bispecific CAR T-cells and FGFR4 CAR T-cells and one TCR-engineered T-cell product: KK-LC-1 TCR T-cells were manufactured in Center for Cellular Engineering (CCE), NIH Clinical Center. The products were divided in aliquots, cryopreserved and stored in the liquid nitrogen. The cryopreserved flow cytometry quality controls were tested in flow cytometry assays which measured post-thaw viability, CD3, CD4 and CD8 frequencies as well as the transduction efficiency and vector identity. The long-term stability and shelf-life of cryopreserved quality control cells were evaluated. In addition, the sensitivity as well as the precision assay were also assessed on the cryopreserved quality control cells. After thawing, the viability of the cryopreserved CAR/TCR T-cell controls was found to be greater than 50%. The expression of transduction efficiency and vector identity markers by the cryopreserved control cells were stable for at least 1 year; with post-thaw values falling within ± 20% range of the values measured at time of cryopreservation. After thawing and storage at room temperature, the stability of these cryopreserved cells lasted at least 6 h. In addition, our cryopreserved CAR/TCR-T cell quality controls showed a strong correlation between transduction efficiency expression and dilution factors. Furthermore, the results of flow cytometric analysis of the cryopreserved cells among different laboratory technicians and different flow cytometry instruments were comparable, highlighting the reproducibility and reliability of these quality control cells. We developed and validated a feasible and reliable procedure to establish a bank of cryopreserved CAR/TCR T-cells for use as flow cytometry quality controls, which can serve as a quality control standard for in-process and lot-release testing of CAR/TCR T-cell products.


Haemorheological studies of the sickle cell phenomenon in European red deer (Cervus elaphus).
It was demonstrated that the appearance of sickle-shaped erythrocytes can be induced by oxygenating the blood of European red deer (Cervus elaphus). The process was reversible. Blood cell counts with the exception of a slight reduction in red cell number and protein fractions did not show any abnormal values. The blood, which was examined at least 18 h after sampling, exhibited considerable deviations of blood gas values. In addition, highly significant haemorheological changes due to the sickle-shaped and oxygenated erythrocytes were detected.


SF-36 scales, and simple sums of scales, were reliable quality-of-life summaries for patients with schizophrenia.
To examine the feasibility and reliability of the Medical Outcomes Study 36 Item Short Form Health Survey (SF-36) for patients with schizophrenia, focusing on the eight scales and various aggregate summary measures. Secondary analysis of data from the European multicenter QUATRO medication adherence trial and the Regional Psychosis Project from The Netherlands. Methods included exploratory and confirmatory factor analyses and estimation of aggregate score reliability using Cronbach's alpha and Tarkkonen's generalized reliability index. The aggregate scores that were compared included two sets based on factor analyses, the standard "physical and mental health component summary scores" (PCS and MCS) and scores based on the original conceptual model of the SF-36 (simple sum of first four scales for physical health, last four for mental health). The eight SF-36 scales were feasible to administer and reliable. Factor analyses of the QUATRO baseline scale data suggested two or three factors, the latter solution including a general "role limitation" factor. Aggregate scores based on the conceptual model had the highest generalized reliability of those compared. SF-36 scales are suitable for patients with schizophrenia. Aggregate scores based on the conceptual model may be preferable to the MCS and PCS for such patients. Further investigation of factor structure is advisable.


Corrigendum: An evaluation of the COVID-19 pandemic and perceived social distancing policies in relation to planning, selecting, and preparing healthy meals: An observational study in 38 countries worldwide.
[This corrects the article DOI: 10.3389/fnut.2020.621726.].


Clinical profile of klebsiella septicemia in neonates.
A detailed clinical study of 51 consecutive cases of neonatal klebsiella septicemia was carried out prospectively over a 20 months period. The incidence was 6.27 per 1000 live births. Majority (85.5%) were either preterms or small for date. Almost fifty percent babies had associated perinatal risk factors. Mean age of onset was 5.7 +/- 2.2 days. General symptoms were the earliest to occur at mean age of 5.7 days followed by respiratory, alimentary, hematological and neurological symptoms at 6.2, 6.3, 6.6 and 7.9 days respectively. About half of the neonates had associated complications; commoner being meningitis (20%), bleeding manifestations and sclerema (17.6% each) and pneumonia (15.7%). Cefatoxime was found to be the drug of choice (86% sensitivity). Nine babies (17.6%) died during the study period at a mean age of 9.1 +/- 3.2 days. Mean duration of hospital stay in rest of neonates was 27.9 +/- 12.1 days. Neurological symptoms were commoner in late onset disease. Bleeding manifestations, sclerema and granulocytopenia were seen exclusively in preterms. Presence of respiratory symptoms, bleeding, sclerema, shock and granulocytopenia were identified as poor prognostic factors in neonatal klebsiella septicemia.


Comparison of the Vineland Adaptive Behavior Scales, Second Edition, and the Bayley Scales of Infant and Toddler Development, Third Edition.
The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II), and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were administered to 65 children between the ages of 12 and 42 months referred for developmental delays. Standard scores and age equivalents were compared across instruments. Analyses showed no statistical difference between Vineland-II ABC standard scores and cognitive levels obtained from the Bayley-III. However, Vineland-II Communication and Motor domain standard scores were significantly higher than corresponding scores on the Bayley-III. In addition, age equivalent scores were significantly higher on the Vineland-II for the fine motor subdomain. Implications for early intervention are discussed.