A workflow for annotating the knowledge gaps in metabolic reconstructions using known and hypothetical reactions.
Advances in medicine and biotechnology rely on a deep understanding of biological processes. Despite the increasingly available types and amounts of omics data, significant knowledge gaps remain, with current approaches to identify and curate missing annotations being limited to a set of already known reactions. Here, we introduce Network Integrated Computational Explorer for Gap Annotation of Metabolism (NICEgame), a workflow to identify and curate nonannotated metabolic functions in genomes using the ATLAS of Biochemistry and genome-scale metabolic models (GEMs). To resolve gaps in GEMs, NICEgame provides alternative sets of known and hypothetical reactions, assesses their thermodynamic feasibility, and suggests candidate genes to catalyze these reactions. We identified metabolic gaps and applied NICEgame in the latest GEM of Escherichia coli, iML1515, and enhanced the E. coli genome annotation by resolving 47% of these gaps. NICEgame, applicable to any GEM and functioning from open-source software, should thus enhance all GEM-based predictions and subsequent biotechnological and biomedical applications.


The CT scan appearance of the brain in the normal elderly population: a correlative study.
Atrophy of the brain as depicted on CT scan was correlated with social and psychological testing in 100 selected volunteers with no known neurologic or psychiatric impairment. The data indicated cognitive impairment based on psychometric test results in those with atrophy, independent of its severity. No organic or biochemical changes could be found that could explain these findings. Repeat examinations at 1-year intervals are planned to evaluate the evolution of these findings.


Concurrent variations of cerebral blood flow and arterial blood pressure in simulated sleep apnea.
Obstructive Sleep Apnea (OSA) is one of the most common sleep disordered breathing which affects about 15 % of US adult population. OSA is considered to be an important risk factor for the development of cardiac dysfunction and stroke. In this paper, we present the initial results of our investigation of the relationship between arterial blood pressure and cerebral blood flow velocity in simulated apnea. Sixteen healthy subjects (9 male, 7 female) of 29 ± 4.89 yrs age and body mass index of 24.07 ± 4.84 kg/m(2) participated in the study. Our findings indicate that cerebral blood flow velocity variations has a relatively high correlation to changes in blood pressure during simulated apnea (r = 0.74 ± 0.06), suggesting that cerebral autoregulation may not compensate for the pressure changes during apnea.


Responses of monkey precentral neurones to passive movements and phasic muscle stretch: relevance to man.
Single cell recordings were made from movement-related neurones from the precentral cortex of two monkeys, trained to perform a simple lever-pulling task. They were also trained to remain relaxed while the arm was explored with passive movements at different joints, cutaneous stimuli and during the application of two types of phasic muscle stretch: percutaneous vibration and percussion of muscle tendons. Recordings were made of the responses of cortical neurones both to the 'natural' stimuli and to vibration of specific muscle tendons or percussion of the triceps tendon. Both tendon percussion and vibration excited neurones within area 4 with an average latency for tendon percussion of 21.0 msec. There was a high degree of consistency in the effects on single neurones of tendon percussion and vibration at the same site. Although long-term facilitation was not seen. vibration-induced discharge in the motor cortex should be considered as a potential mechanism of its effects in intact man. In contrast to the similarity of the effect of the two forms of phasic stretch, the relationship between a single neurone's response to either tendon percussion or vibration and to passive movement was complex. The dissociation seen between the effects of phasic muscle stretch and that of passive movement may underlie the failure, in man, to find uniformly increased long-latency stretch reflexes in clinical states of extrapyramidal rigidity.


Long-term imipramine treatment enhances locomotor and food intake suppressant effects of m-chlorophenylpiperazine in rats.
1 Administration of the 5-HT1B receptor agonist m-chlorophenylpiperazine (m-CPP) to rats produces dose-dependent decreases in locomotor activity and food intake. 2 The locomotor suppressant effect of m-CPP was inhibited by the 5-hydroxytryptaminergic antagonist, metergoline, but not by phentolamine, propranolol, clonidine, or haloperidol. 3 The locomotor suppressant effects of m-CPP were enhanced following long-term (but not short-term) treatment with imipramine, possibly reflecting the postulated development of a functional supersensitivity of 5-HT1B receptors mediating locomotion during longer-term antidepressant drug treatment. 4 The food intake suppressant effects of m-CPP were enhanced following both short (3-5 days) and longer-term (21 days) treatment with imipramine. Rapidly developing 5-hydroxytryptamine uptake inhibition may be responsible for this change, or it may represent an earlier adaptive change in the 5-HT1B receptors mediating food intake compared to more complexly modulated motor responses.


Fault diagnosis engineering of digital circuits can identify vulnerable molecules in complex cellular pathways.
The application of complex system engineering approaches to cell signaling networks should lead to novel understandings and, subsequently, new treatments for complex disorders. In the area of circuit fault diagnosis engineering, there are various methods to identify the defective or vulnerable components of complex digital electronic circuits. In biological systems, however, knowledge is limited regarding the vulnerability of interconnected signaling pathways to the dysfunction of each specific molecule. By developing proper biologically driven digital vulnerability assessment methods, the vulnerability of complex signaling networks to the possible dysfunction of each molecule can be determined. To show the utility of this approach, we analyzed three well-characterized signaling networks--a cellular network that regulates the activity of caspase3, a network that regulates the activity of p53, and a central nervous system network that regulates the activity of the transcription factor CREB (adenosine 3',5'-monophosphate response element-binding protein). We found important differences among the vulnerability values of different molecules. Most of the identified highly vulnerable molecules are functionally related and known key regulators of these networks. Experimental data confirmed the ability of digital vulnerability assessment to correctly predict key regulators in the CREB network. Because this approach may provide insight into key molecules that contribute to human diseases, it may aid in the identification of critical targets for drug development.


Crystal structure of the Clostridium limosum C3 exoenzyme.
C3-like toxins ADP-ribosylate and inactivate Rho GTPases. Seven C3-like ADP-ribosyltransferases produced by Clostridium botulinum, Clostridium limosum, Bacillus cereus and Staphylococcus aureus were identified and two representatives--C3bot from C. botulinum and C3stau2 from S. aureus--were crystallized. Here we present the 1.8A structure of C. limosum C3 transferase C3lim and compare it to the structures of other family members. In contrast to the structure of apo-C3bot, the canonical ADP-ribosylating turn turn motif is observed in a primed conformation, ready for NAD binding. This suggests an impact on the binding mode of NAD and on the transferase reaction. The crystal structure explains why auto-ADP-ribosylation of C3lim at Arg41 interferes with the ADP-ribosyltransferase activity of the toxin.


Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population.
Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism and it is thought to influence DNA methylation and nucleic acid synthesis. Mutations in the MTHFR gene have been associated with several autoimmune disorders in previous studies. Alopecia areata (AA) is considered to be a tissue-specific autoimmune disease as the hair follicle has been targeted and antibodies to their own hair follicle structures have been developed. Since there is a common shared pathway between AA and other autoimmune disorders, we aimed to investigate a possible association between the MTHFR gene C677T mutation and AA susceptibility in the Turkish population. The study included 136 patients affected by AA and 130 healthy controls. Genomic DNA was isolated and genotyped using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation. The distributions of genotype and allele frequencies of MTHFR gene C677T mutation were statistically different between AA patients and the control group (p=0.036 and p=0.011, respectively). High differences were also observed when the patients and controls were compared according to CC versus CT+TT (p=0.012). CT+TT genotypes and T allele of MTHFR gene C677T mutation were found to be a susceptibility factor for AA in the Turkish population. The results suggest that MTHFR gene C677T mutation may have an effect on the risk of alopecia areata in the Turkish population. This is the first study reporting the association between the MTHFR (C677T) genotype and AA.


Management of recurrent corneal ulcers: use of amniotic membrane.
Amniotic membrane (AM), or amnion, is a thin membrane on the inner side of the fetal placenta; it completely surrounds the embryo/fetus and delimits the amniotic cavity, which is filled by amniotic liquid. In recent years, the structure and function of the amnion have been investigated due to its pluripotent properties, which are an attractive source for tissue transplantation and reconstructive surgery. The pioneering use of AM in skin transplantation by Davis dates back to 1910; in 1913, Sabella and Stern employed it in the treatment of burns and superficial scars. Certain characteristics make the AM ideally suited to its application in ocular surface reconstruction. It can be easily obtained and its availability is nearly unlimited. We report a case of AM transplantation to treat ocular surface abnormality. A 28-year-old man came to our attention for persistent foreign body feeling and pain in his right eye. Because of progressive clinical worsening, we decided to perform surgical apposition of AM. Clinical and instrumental follow-up was conducted with periodic complete checkups. At 1 year follow-up, best-corrected visual acuity was 4/10. Characteristics of AM make it potentially useful to treat ocular surface abnormalities.


Rapid identification of nonblood sterile site broth cultures using the FilmArray blood culture identification panel.
The FilmArray Blood Culture Identification Panel was validated for nonblood sterile site specimens with clinical impact of rapid identification compared to conventional diagnostics. The panel accurately identified target organisms from 98% of positive broth cultures a median 1.1 day faster than conventional techniques (P < 0.0001) with potential clinical impact in 22% of cases.


High-resolution dental magnetic resonance imaging of inferior alveolar nerve responses to the extraction of third molars.
The objective of this study was to assess whether signal changes can be detected in the neurovascular bundle of the mandibular canal after the extraction of a third molar. We retrospectively analyzed MRI scans of 30 test subjects with healthy mandibles and 41 patients who had had a wisdom tooth extracted. Signal intensities were measured at particular sites in the neurovascular bundle, which were defined as regions of interest (ROI) in the sagittal T1-weighted images before and after intravenous administration of a paramagnetic contrast agent. On the basis of the signal intensity increases that were measured after contrast agent administration, we compared the signal increases obtained for the patients who had received surgical treatment with the results obtained for the population of test subjects with unremarkable mandibles ( t-test, P<0.05). Compared with the healthy test subjects, patients who had received surgical treatment showed significantly higher signal intensity increases at two measurement sites, i.e., the second molar and the second premolar ( P<0.05). We found no significant differences when the measurements were performed at the first molar ( P=0.06), the third molar ( P=0.47) and in the area of the ascending mandibular ramus ( P=0.79). Compared with a population of healthy test subjects, patients who had their third molars surgically removed show higher signal intensity increases in the neurovascular bundle after intravenous contrast agent administration. The underlying cause may be the higher blood flow in the arteries and veins and the perineural plexus, which may give evidence of the pathophysiological mechanism of nerve damage in the narrow canal as a result of osteotomy.


Changes in cholesterol kinetics following sugar cane policosanol supplementation: a randomized control trial.
Sugar cane policosanols (SCP) have been shown to exert cholesterol-modulating properties in various studies conducted in Cuba by substantially reducing cholesterol synthesis. Independent research examining changes in cholesterol kinetics in response to SCP is limited to few studies, none of which was able to replicate findings of the original research. Moreover, no data are available on the effect of SCP on cholesterol absorption to date. The present study was undertaken to determine effects on cholesterol kinetics, namely synthesis and absorption, within hypercholesterolemic individuals consuming a SCP treatment. Twenty-one otherwise healthy hypercholesterolemic subjects participated in a randomized double-blind crossover study where they received 10 mg/day of policosanols or a placebo incorporated in margarine as an evening snack for a period of 28 days. The last week of the study phase, subjects were given 13C labelled cholesterol and deuterated water for the measurement of cholesterol absorption and synthesis respectively. Blood was collected on the first two and last five days of the trial. Cholesterol absorption and synthesis were determined by measuring red cell cholesterol 13C and deuterium enrichment, respectively. There was no significant change in LDL cholesterol levels as compared to control. In addition, the area under the curve for red cell cholesterol 13C enrichment across 96 hours was not significantly different in the SCP group as compared to control. Similarly, no difference was observed in the fractional rate of cholesterol synthesis over the period of 24 hours between the two treatment groups. The findings of the present study fail to support previous research concerning efficacy and mechanism of action for policosanols.


Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.
Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.


Societal expectations and the profession's responsibility to reform the dental workforce to ensure access to care for children.
Societal expectations raise the issue of the nature of a profession and a profession's relationship with society. Influential policy leaders want reform of the oral health workforce and delivery system in such a manner as to ensure that improvements are made for accessing care, particularly for vulnerable and disadvantaged populations, especially children. This essay is based on a presentation to the House of Delegates of the California Dental Association on Nov.13, 2009.


Insulin signalling in heart involves insulin receptor substrates-1 and -2, activation of phosphatidylinositol 3-kinase and the JAK 2-growth related pathway.
Hyperinsulinemia is a common feature of obesity and hypertension and may be associated with abnormal metabolism and growth of heart muscle and vascular wall. Most of the known actions of insulin were characterised in muscle, adipose tissue and liver. In this study we investigate the initial steps of insulin signalling in rat heart. After insulin infusion in the cava vein of male Wistar rats, the insulin receptor, insulin receptor substrates-1 and -2, phosphatidylinositol 3-kinase activity and Janus kinase (JAK) 2 engagement were studied by immunoprecipitation and immunoblot of heart extracts. An insulin load induces rapid autophosphorylation of the insulin receptor which is followed by the phosphorylation of insulin receptor substrates-1 and -2. The phosphorylation of these early intracellular substrates leads to the association of the p85 subunit of phosphatidylinositol 3-kinase and subsequent activation of its catalytic p110 subunit. Besides activation of the lipid metabolising enzyme phosphatidylinositol 3-kinase, the phosphorylation of insulin receptor substrates-1 and -2 engages the intracellular kinase JAK 2 and induces JAK 2-STAT 1 complex formation. We demonstrate that the early steps of insulin signalling in heart include the phosphorylation-activation of the insulin receptor, engagement of insulin receptor substrates-1 and -2 with the consequent activation of phosphatidylinositol 3-kinase and the involvement of the recently discovered growth related pathway--JAK 2-STAT 1.


Frequency and Associated Costs of Anaphylaxis- and Hypersensitivity-Related Adverse Events for Intravenous Iron Products in the USA: An Analysis Using the US Food and Drug Administration Adverse Event Reporting System.
Intravenous iron preparations rapidly correct iron deficiency anemia, with the notable drug class effect of rare, yet potentially life-threatening, administration-related hypersensitivity or anaphylactic reactions. The objective of this comparative study was to assess adverse events associated with four intravenous iron preparations and estimated medical costs, in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Cases of hypersensitivity reactions and anaphylaxis/anaphylactic shock associated with iron dextran, iron sucrose, ferumoxytol, and ferric carboxymaltose, spontaneously reported to FAERS (1 January, 2014 to 31 December, 2019), were extracted. The reporting odds ratio lower bound 90% confidence interval (ROR05) > 1 and cases ≥ 5 defined a likely signal for a drug-adverse event association. Adverse event-associated medical costs were estimated using Agency for Healthcare Research and Quality/Healthcare Cost and Utilization Project 2016 data. For hypersensitivity reactions, ferumoxytol and iron dextran had the highest ROR05 values (5.00 and 4.35, respectively) and greatest proportions of associated deaths (7.1% and 5.3%), followed by iron sucrose (ROR05 3.94, deaths 2.4%), and ferric carboxymaltose (ROR05 3.03, deaths 0.2%). For anaphylaxis/anaphylactic shock, ROR05 for cases/deaths were: 39.32/13.4%, ferumoxytol; 37.80/4.5%, iron dextran; 17.60/4.7%, iron sucrose; and 8.77/no deaths, ferric carboxymaltose. Downstream medical costs per adverse event were highest with iron dextran (US$8615) and ferumoxytol (US$8164), followed by iron sucrose (US$4212), and ferric carboxymaltose (US$1832). Reporting rates of hypersensitivity and anaphylaxis with intravenous iron preparations were highest with ferumoxytol and lowest with ferric carboxymaltose in the US FAERS database. Adverse event-related medical costs were highest for iron dextran and ferumoxytol, and lowest for ferric carboxymaltose.


Pregnancy in MuSK-positive myasthenia gravis: A single-center case series.
Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. Our objective in this study was to describe the course of MMG during pregnancy and within 6 months postpartum, and to document any effect on fetal health. A retrospective review was performed of medical records of patients with MMG seen in the Duke Myasthenia Gravis Clinic from 2003 to 2022. MMG patients with onset of MMG symptoms before or during pregnancy as well as within 6 months postpartum were reviewed. A total of 14 pregnancies in 10 patients were included in our study cohort. Initial MG symptoms developed during pregnancy or within 6 months postpartum in six patients. Four patients had two pregnancies, three of whom developed MG during their first pregnancy. In the patients diagnosed before pregnancy, MG symptoms increased in five of eight patients during pregnancy or postpartum. Four patients required rescue therapy with plasma exchange or intravenous immunoglobulin during pregnancy or postpartum. One patient had a cesarean section after prolonged labor due to failure of progression. There were no other complications of pregnancy or delivery, and all infants were healthy at delivery. As in non-MuSK MG, women with MMG may also have worsening or may develop initial MG symptoms during pregnancy or within 6 months postpartum. More aggressive medical therapy may be required for pregnant patients with MMG. Further study is needed to identify the mechanism and risk of worsening of MMG during pregnancy or postpartum.


Learning to like it: aesthetic perception of bodies, movements and choreographic structure.
Appreciating human movement can be a powerful aesthetic experience. We have used apparent biological motion to investigate the aesthetic effects of three levels of movement representation: body postures, movement transitions and choreographic structure. Symmetrical (ABCDCBA) and asymmetrical (ABCDBCA) sequences of apparent movement were created from static postures, and were presented in an artificial grammar learning paradigm. Additionally, "good" continuation of apparent movements was manipulated by changing the number of movement path reversals within a sequence. In an initial exposure phase, one group of participants saw only symmetrical sequences, while another group saw only asymmetrical sequences. In a subsequent test phase, both groups rated all sequences on an aesthetic evaluation scale. We found that posture, movement, and choreographic structure all influenced aesthetic ratings. Separate ratings for the static body postures presented individually showed that both groups preferred a posture that maximized spatial symmetry. Ratings for the experimental sequences showed that both groups gave higher ratings to symmetrical sequences with "good" continuation and lower ratings to sequences with many path reversals. Further, participants who had been initially familiarized with asymmetrical sequences showed increased liking for asymmetrical sequences, suggesting a structural mere exposure effect. Aesthetic preferences thus depend on body postures, apparent movement continuation and choreographic structure. We propose a hierarchical model of aesthetic perception of human movement with distinct processing levels for body postures, movements and choreographic structure.


Neuropathic orofacial pain.
Neuropathic orofacial pain is a general term employed to describe a number of clinical syndromes, which may be spontaneous or triggered by local trauma or systemic disorders. Symptomatically these painful syndromes may be episodic or continuous and are often difficult to distinguish from dental pathology. In the present article, we review the diagnosis, pathophysiology and therapeutic approaches to trigeminal and glossopharyngeal neuralgias, orofacial pain associated with herpetic infection, persistent idiopathic facial pain (previously termed atypical facial pain), post-traumatic orofacial neuropathy and neuritis.


Fellowship Training: Need and Contributions.
Surgical subspecialties are now well established, and many surgery residents pursue fellowship training for various reasons. Fellowships can bridge the gaps found in many residency programs by providing graduating residents with opportunities to master surgical skills, gain confidence and progressive autonomy, and receive further mentorship. The experience also eases the transition to independent practice by allowing surgeons to tailor their training to coincide with personal interests and future practice goals. It is unlikely that the number of surgery residents pursuing fellowship training will decrease, so it is important to provide the infrastructure, oversight, and opportunities to meet their needs.


Building the niche: the role of the S100 proteins in metastatic growth.
Communication between cancer cells and stromal cells, often mediated by extracellular molecules in the tumor microenvironment, plays a central role in tumorigenesis and metastasis. The establishment of a pro-inflammatory milieu is increasingly recognized as an important consequence of these interactions. The family of S100 Ca2+-binding proteins has been implicated in many aspects of the interaction between cancer cells and stromal cells, and contributes to the formation of an inflammatory tumor microenvironment. Focusing on S100A4, S100A8 and S100A9, in this review we discuss the role these proteins play in primary tumors and in the development of metastases, in particular during the formation of pre-metastatic niches.


Predatory trumpetfish conceal themselves from their prey by swimming alongside other fish.
Many animals use camouflage to avoid detection by others, yet even the most inconspicuous objects become detectable against the background when moving1,2. One way to reduce detection while moving would be to 'hide' behind the movements of objects or other animals3. Here, we demonstrate experimentally that a common marine predator, the trumpetfish (Aulostomus maculatus), can conceal its approach from its prey by performing a behaviour known as 'shadowing' - swimming closely next to another, larger and non-predatory fish3,4,5. Our findings reveal how predators can actively use another animal as a form of concealment to reduce detection by prey.


The effect of surgical stress on insulin sensitivity, glucose effectiveness and acute insulin response to glucose load.
Hyperglycemia after stress is a very common clinical phenomenon. It is generally hypothesized that the underlying cause is a neuroendocrine-mediated deterioration in glucose metabolism. However, the detailed roles of insulin sensitivity, glucose effectiveness and acute insulin response to glucose load in response to stress have not been well established. Hernioplasty was used as a minor stress model for studying stress-induced hyperglycemia. Eleven healthy young men were enrolled voluntarily in this study. Their mean age was 22.0 +/- 0.9 yr and BMI 23.3 +/- 0.6 kg/m2. Frequently sampled i.v. glucose tolerance tests were performed one day before and one day after the surgery. Insulin sensitivity (SI), glucose effectiveness (EG) and area under acute insulin response (AIR) were calculated from "minimal model" algorithms. We also measured fasting concentrations of human GH, ACTH and F on the days of the test. Compared to the pre-operation data, levels of ACTH and F did not change significantly after the surgery. Only GH levels were marginally significant. On the other hand, the SI (0.75 +/- 0.1, 0.52 +/- 0.9 x 10(-5) min(-1)/pmol, p = 0.04), EG (0.023 +/- 0.03, 0.016 +/- 0.003 min(-1), p = 0.01) and AIR (6738.5 +/- 1111.6, 5130.0 +/- 1047.2 pmol, p = 0.005) were all significantly decreased after surgery. The percentages of decrease were 16.3 +/- 15.5, 32.1 +/- 10.3 and 17.8 +/- 10.3%, respectively. Finally, only the changes of EG positively correlate with the changes of ACTH before and after surgery. No significant changes were noted among other stress hormones and the changes of SI, EG and AIR. In conclusion, hernioplasty results in reduced SI, EG and AIR. Among them, although not statistically significant, the EG showed the most distinct decrease after the surgery, which has not been found in previous literature.


Retracted: Decomposition of Clinical Significance of FSH, LH, E2, AMH, and AFC Standards in Females at Lofty Elevation Based on HIF1α.
[This retracts the article DOI: 10.1155/2022/6112659.].


Holistic Monte-Carlo optical modelling of biological imaging.
The invention and advancement of biological microscopy depends critically on an ability to accurately simulate imaging of complex biological structures embedded within complex scattering media. Unfortunately no technique exists for rigorous simulation of the complete imaging process, including the source, instrument, sample and detector. Monte-Carlo modelling is the gold standard for the modelling of light propagation in tissue, but is somewhat laborious to implement and does not incorporate the rejection of scattered light by the microscope. On the other hand microscopes may be rigorously and rapidly modelled using commercial ray-tracing software, but excluding the interaction with the biological sample. We report a hybrid Monte-Carlo optical ray-tracing technique for modelling of complete imaging systems of arbitrary complexity. We make the software available to enable user-friendly and rigorous virtual prototyping of biological microscopy of arbitrary complexity involving light scattering, fluorescence, polarised light propagation, diffraction and coherence. Examples are presented for the modelling and optimisation of representative imaging of neural cells using light-sheet and micro-endoscopic fluorescence microscopy and imaging of retinal vasculature using confocal and non-confocal scanning-laser ophthalmoscopes.


Selective Lysosome Membrane Turnover Is Induced by Nutrient Starvation.
Lysosome function is essential for cellular homeostasis, but quality-control mechanisms that maintain healthy lysosomes remain poorly characterized. Here, we developed a method to measure lysosome turnover and use this to identify a selective mechanism of membrane degradation that involves lipidation of the autophagy protein LC3 onto lysosomal membranes and the formation of intraluminal vesicles through microautophagy. This mechanism is induced in response to metabolic stress resulting from glucose starvation or by treatment with pharmacological agents that induce osmotic stress on lysosomes. Cells lacking ATG5, an essential component of the LC3 lipidation machinery, show reduced ability to regulate lysosome size and degradative capacity in response to activation of this mechanism. These findings identify a selective mechanism of lysosome membrane turnover that is induced by stress and uncover a function for LC3 lipidation in regulating lysosome size and activity through microautophagy.


Two C-terminal ankyrin repeats form the minimal stable unit of the ankyrin repeat protein p18INK4c.
Ankyrin repeat proteins (ARPs) appear to be abundant in organisms from all phyla, and play critical regulatory roles, mediating specific interactions with target biomolecules and thus ordering the sequence of events in diverse cellular processes. ARPs possess a non-globular scaffold consisting of repeating motifs named ankyrin (ANK) repeats, which stack on each other. The modular architecture of ARPs provides a new paradigm for understanding protein stability and folding mechanisms. In the present study, the stability of various C-terminal fragments of the ARP p18(INK4c) was investigated by all-atomic 450 ns molecular dynamics (MD) simulations in explicit water solvent. Only motifs with at least two ANK repeats made stable systems in the available timescale. All smaller fragments were unstable, readily losing their native fold and alpha-helical content. Since each non-terminal ANK repeat has two hydrophobic sides, we may hypothesize that at least one hydrophobic side must be fully covered and shielded from the water as a necessary, but not sufficient, condition to maintain ANK repeat stability. Consequently, at least two ANK repeats are required to make a stable ARP.


Behçet's disease.
The reliability and ease of use of any activity form has to be balanced against the content validity of the questions being asked. Clinical experience over several years suggests that presence of a high disease activity score is consistent both with the clinician's and patient's overall impression of disease activity. If the onset of the more serious manifestations can be predicted by more readily measured symptoms such as oral and genital ulceration, skin lesions, arthritis and superficial thrombophlebitis, then these organ system subscores could be expanded to provide a more accurate representation of activity. Other organ systems such as auditory system may also provide a measure of disease activity. For the purpose of clinical trials it is likely that if treatment is targeted at a specific organ system then a more comprehensive measure of activity within that organ system would have to be used (e.g. the role of thalidomide in oral ulceration) (Revuz et al, 1990). This would require the use of a form which measured many facets of oral ulceration (duration of ulcers, number of ulcers, size of ulcers, number of crops of ulcers, site of ulcers, etc). However it is recommended that such a form should be used in conjunction with a validated general disease activity form to alert the clinician conducting any trials of the advantageous or deleterious effects of the trial drug on other organ systems.


The elicitation of visual hallucinations via brief instructions in a normal sample.
College students tested in groups were given brief suggestions either to "see" or to "imagine" a kitten. Subjects responded twice, once with eyes open and once with eyes closed. They rated the duration, transparency, and vividness of their imagery, and also their involvement in and belief in the reality of their imaginings under both eye closure conditions. "Imagine" suggestions elicited imagery of longer duration than "see" suggestions. Although subjects reported longer, more vivid, and less transparent imagery with their eyes closed, this effect was dependent on the order of eye closure (i.e., whether the eyes closed instruction preceded or followed the eyes open instruction). The three dimensions of imagery intercorrelated, and each dimension also correlated with subjects' degree of involvement in and belief in their imaginings. A minority of subjects given both the "see" and "imagine" suggestions reported believing that their imaginings were real events during the suggestion period. Furthermore, belief in imaginings was the only variable that correlated with hypnotic susceptibility. These data indicate that hallucinations (i.e., believed-in imaginings) can be elicited from a minority of "norman" subjects with brief instructions.


Preferential location of sex chromosomes, their aneuploidy in human sperm, and their role in determining sex chromosome aneuploidy in embryos after ICSI.
In babies born after ICSI procedures, an increase of de-novo sex chromosome abnormalities has been observed. Several hypotheses have been proposed to explain these findings: an increased rate of sex chromosome aneuploidy in sperm of oligozoospermic men, or a preferential location of the sex chromosomes in the sub-acrosomal region of the sperm nucleus which leads to a reduced DNA decondensation of this region. In order to investigate which theory may be more reliable, we studied the localization of sex chromosomes and their aneuploidy rate in sperm in men undergoing ICSI. Using fluorescent in-situ hybridization we studied sex chromosome localization and the aneuploidy rate for sex chromosomes and chromosome 18 in 20 oligospermic men undergoing ICSI and in 10 controls. In 40.94 and 52.92% of cases, the X and Y chromosomes respectively were localized in the sub-acrosomal region of the sperm nucleus compared with only 14.29% of cases of chromosome 18 (P < 0.001). An increase of sex chromosome aneuploidy in sperm of oligospermic men was observed; 2.91 versus 0.69% of controls (P < 0.001). Sex chromosomes are localized preferentially in the sub-acrosomal region of sperm and sex chromosome aneuploidy rate in the sperm of oligozoospermic men is higher than in controls.


Mortality predictors of snake bite envenomation in southern India--a ten-year retrospective audit of 533 patients.
Snake bite incidence is highest in Asia and sub-Saharan Africa. This retrospective audit of 533 adult patients, who had presented to the Emergency Department, collates clinical features, effect of pharmacologic interventions and the risk factors that influence morbidity and mortality. Dual toxicity, neurological and haematological, was observed in 30.4% of patients. Laboratory evidence of haematotoxicity was demonstrated in 314 (58.9%) and 40% demonstrated clinical evidence of bleeding. However, 7.3% of these patients did not have laboratory evidence of bleeding disorder (p < 0.001). Conversely, 60% did not have clinical evidence of bleeding, but demonstrated laboratory evidence of abnormal parameters. Acute kidney injury (AKI) was evident in 28% of patients and 15.3% required haemodialysis. About 25% with no haematotoxicity showed evidence of AKI. The majority received 6-12 vials of poly-valent anti-snake venom. Hypersensitivity reaction rate was 8% and predominantly anaphylactoid in nature. The length of hospital stay ranged from 2 to 28 days and 20% required mechanical ventilation. Overall mortality rate was 7.5% with significant association to AKI, haematotoxicity and assisted ventilation. The mortality rate was 18% in patients with pre-hospital delay more than 24 h, as against 5% when admitted within the above specified period (p = <0.001). The strength of this study is the accrued information of over a period of 10 years of snake-bite management through the Emergency Department of a university hospital setting. The limitations are the retrospective study design and the rejection percentage of 15.5% due to insufficient information from the total chart pool.


The influence of fungal food quality on the growth and fecundity of Folsomia candida (Collembola: Isotomidae).
The Basidiomycete fungi Coriolus versicolor and Hypholoma fasciculare were grown in liquid media containing 2, 20, 200 and 2,000 ppm nitrogen (as asparagine) and fed to cultures of Folsomia candida. Collembola feeding on both species of fungi exhibited trends of increased moulting and egg laying rates up to 200 ppm N and an inhibition of growth and fecundity at 2,000 ppm N. The differences in moulting rates between individual treatments were small for both species of fungi and not all the pair wise comparisons of treatments were significantly different. Egg laying rates of collembola fed C. versicolor showed a highly significant response to all levels of N in the growth medium and egg production at 200 ppm N was over three times higher than at 2 ppm N. Collembola fed H. fasciculare showed a less marked fecundity response to the different nitrogen levels and egg production at 200 ppm was approximately 1.5 times higher than at 2 ppm N. Both moulting and egg laying rates were significantly affected by the species of fungus presented as food to the collembola. The patterns of growth and reproduction of starved control groups of F. candida as well as those fed the test fungi demonstrate the adaptability of this species to changes in the quality and quantity of available food.


Fabrication and Determination of the Sun Protection Factor and Ultraviolet Protection Factor for Piscean Collagen/Bischalcone Derivative (B1) Composite Films with Wide-Range UV Shielding.
The present study investigates the development of distinct UV-A and UV-B radiation filtering materials through the introduction of a heterocyclic bischalcone derivative [(3,5-bis{[4-(methylsulfanyl)phenyl]methylidene}piperidin-4-one] (B1) into the matrix of PVA/Piscean collagen blend films (1:1) prepared through the solution casting method and characterized. The dopant concentration varied from 0.25 to 4%. The scanning electron microscopy images showed the rough surface due to the uniform dispersion of dopant B1. The addition of different concentrations of B1 altered the mechanical strength with a proportional increase in Young's modulus (146-317 MPa), tensile strength (23.3-39.21 MPa), and decrease in its elongation at break (158.8-105.2%). As the dopant B1 belongs to the bischalcone class of compounds which absorb in the UV-vis region (370 nm λmax) due to the α, β unsaturated keto group, it was selected for doping. Dopant concentration-dependent increase in density was observed in films (31-162 mg/cm3). The bathochromic shift in UV absorption from 370 to 390 nm for λmax as well as hyperchromism was evidenced with proportional increase in the concentration of B1, indicating its capacity to block UV rays. On determining the UV filtering ability for all the prepared films, the one with 4% dopant showed a higher sun protection factor (SPF) with a value of 27.53 and ultraviolet protection factor (UPF) with a value of 58.23. In addition, the degradation of supercoiled PBR322 DNA on UV irradiation was effectively inhibited by these films with a dopant concentration of 0.5-4.0%, which might cause less harm to the skin. The inferences of the experiments would indicate the use of these water-insoluble films as UV blocking potential materials with a merit of SPF and UPF characteristics.


Dispersed FeOx nanoparticles decorated with Co2SiO4 hollow spheres for enhanced oxygen evolution reaction.
Oxygen evolution reaction (OER) has drawn ever-increasing attention because of its essential role in various renewable-energy technologies. In spite of tremendous research efforts, developing high-performance OER catalysts at low cost remains a great challenge. Inspired by two earth-abundant elements Fe and Si, herein, we report a Fe-Co2SiO4 composite consisting of well dispersed iron oxide (FeOx) decorated Co2SiO4 hollow nanospheres as an economical and promising OER catalyst. Although Co2SiO4 or FeOx alone has little OER activity, their composite exhibits satisfied performance, that is highly related to geometric effect and bimetal component electronic interactions. The Fe-Co2SiO4 composite exhibits comparable catalytic activity to most of transition mental oxide/hydroxide relevant composites at 10 mA cm-2. It is even 1.6 times higher than commercial RuO2 electrocatalyst at high current density 100 mA cm-2 in alkaline solution. In this work, surface decoration of transition metal silicate provides a new horizon to design high-performance and economical OER catalysts.


State-dependent effectiveness of cathodal transcranial direct current stimulation on cortical excitability.
The extensive use of transcranial direct current stimulation (tDCS) in experimental and clinical settings does not correspond to an in-depth understanding of its underlying neurophysiological mechanisms. In previous studies, we employed an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG) to track the effect of tDCS on cortical excitability. At rest, anodal tDCS (a-tDCS) over the right Posterior Parietal Cortex (rPPC) elicits a widespread increase in cortical excitability. In contrast, cathodal tDCS (c-tDCS) fails to modulate cortical excitability, being indistinguishable from sham stimulation. Here we investigated whether an endogenous task-induced activation during stimulation might change this pattern, improving c-tDCS effectiveness in modulating cortical excitability. In Experiment 1, we tested whether performance in a Visuospatial Working Memory Task (VWMT) and a modified Posner Cueing Task (mPCT), involving rPPC, could be modulated by c-tDCS. Thirty-eight participants were involved in a two-session experiment receiving either c-tDCS or sham during tasks execution. In Experiment 2, we recruited sixteen novel participants who performed the same paradigm but underwent TMS-EEG recordings pre- and 10 min post- sham stimulation and c-tDCS. Behavioral results showed that c-tDCS significantly modulated mPCT performance compared to sham. At a neurophysiological level, c-tDCS significantly reduced cortical excitability in a frontoparietal network likely involved in task execution. Taken together, our results provide evidence of the state dependence of c-tDCS in modulating cortical excitability effectively. The conceptual and applicative implications are discussed.


[Radiation exposure of the eye lens in orthopedics and trauma surgery : A pilot study].
On 27 June 2017 the Act on new regulation of the law for the protection against the harmful effects of ionizing radiation was passed. One of the main innovations in daily surgical practice in the now legally stipulated provisions is the lowering of the eye lens dose to 20 mSv/year (§§ 78, 212 Radiation Protection Act, StrlSchG). To estimate the level of exposure of the eye lens to ionizing radiation that is to be expected in the course of surgical interventions, the dose that surgeons receive during surgery was determined. For this, the radiation exposure adjacent to the eye lens was measured using a forehead dosimeter while performing surgical interventions over a period of 8 weeks in 2 different operating rooms. As a result, a mean estimated eye lens radiation dose Hp (3) of 190 µSv could be determined during the 2‑month study period. Thus, the estimated cumulative radiation dose in 1 year of approximately 1.2 mSv was significantly below the threshold of 20 mSv/year. By complying with the common radiation protection measures in the context of operative interventions in orthopedics and trauma surgery, the legal limit value of 20 mSv/year is generally not expected to be exceeded.


Resting-state functional connectivity in normal brain aging.
The world is aging and, as the elderly population increases, age-related cognitive decline emerges as a major concern. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), allow the investigation of the neural bases of age-related cognitive changes in vivo. Typically, fMRI studies map brain activity while subjects perform cognitive tasks, but such paradigms are often difficult to implement on a wider basis. Resting-state fMRI (rs-fMRI) has emerged as an important alternative modality of fMRI data acquisition, during which no specific task is required. Due to such simplicity and the reliability of rs-fMRI data, this modality presents increased feasibility and potential for clinical application in the future. With rs-fMRI, fluctuations in regional brain activity can be detected across separate brain regions and the patterns of intercorrelation between the functioning of these regions are measured, affording quantitative indices of resting-state functional connectivity (RSFC). This review article summarizes the results of recent rs-fMRI studies that have documented a variety of aging-related RSFC changes in the human brain, discusses the neurophysiological hypotheses proposed to interpret such findings, and provides an overview of the future, highly promising perspectives in this field.


Renal effects of propranolol, practolol and butoxamine in pentobarbital-anesthetized rats.
The renal effects of the beta-adrenergic blockers, propranolol, practolol and butoxamine, were examined in pentobarbital-anesthetized rats. All the beta-blockers, infused i.v., increased urine volume (V), urinary sodium excretion (UNaV) and p-aminohippuric acid clearance without change in inulin clearance. Indomethacin, an inhibitor of prostaglandin biosynthesis, did not affect the renal effects of these beta-blockers. Phentolamine abolished the renal effects of practolol, but not those of propranolol and butoxamine. Haloperidol abolished the renal effects of propranolol and butoxamine, but not those of practolol. A high correlation was found between the increased UNaV and the increased urinary phosphate excretion by butoxamine but not by propranolol and practolol. Therefore, it is suggested that alpha-adrenergic stimulation is involved in the mechanism of diuresis by practolol, a beta1-blocker, and that dopaminergic stimulation is involved in the diuresis caused by butoxamine, a beta2-blocker. Propranolol is similar to butoxamine, and partially similar to practolol.


Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude-mouse-passaged nasopharyngeal carcinoma.
After nude-mouse-passage, a carcinoma of the nasopharynx was found to contain a few scattered C-type retrovirus particles. Culture of this nude-mouse-grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C-type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent.


Population pharmacokinetic model selection assisted by machine learning.
A fit-for-purpose structural and statistical model is the first major requirement in population pharmacometric model development. In this manuscript we discuss how this complex and computationally intensive task could benefit from supervised machine learning algorithms. We compared the classical pharmacometric approach with two machine learning methods, genetic algorithm and neural networks, in different scenarios based on simulated pharmacokinetic data. Genetic algorithm performance was assessed using a fitness function based on log-likelihood, whilst neural networks were trained using mean square error or binary cross-entropy loss. Machine learning provided a selection based only on statistical rules and achieved accurate selection. The minimization process of genetic algorithm was successful at allowing the algorithm to select plausible models. Neural network classification tasks achieved the most accurate results. Neural network regression tasks were less precise than neural network classification and genetic algorithm methods. The computational gain obtained by using machine learning was substantial, especially in the case of neural networks. We demonstrated that machine learning methods can greatly increase the efficiency of pharmacokinetic population model selection in case of large datasets or complex models requiring long run-times. Our results suggest that machine learning approaches can achieve a first fast selection of models which can be followed by more conventional pharmacometric approaches.


Data in support of proteomic analysis of pneumococcal pediatric clinical isolates to construct a protein array.
Surface proteins play key roles in the interaction between cells and their environment, and in pathogenic microorganisms they are the best targets for drug or vaccine discovery and/or development. In addition, surface proteins can be the basis for serodiagnostic tools aiming at developing more affordable techniques for early diagnosis of infection in patients. We carried out a proteomic analysis of a collection of pediatric clinical isolates of Streptococcus pneumoniae, an important human pathogen responsible for more than 1.5 million child deaths worldwide. For that, cultured live bacterial cells were "shaved" with trypsin, and the recovered peptides were analyzed by LC/MS/MS. We selected 95 proteins to be produced as recombinant polypeptides, and printed them on an array. We probed the protein array with a collection of patient sera to define serodiagnostic antigens. The mass spectrometry proteomics data correspond to those published in [1] and have been deposited to the ProteomeXchange Consortium [2] via the PRIDE partner repository [3] with the dataset identifier PXD001740. The protein array raw data are provided as supplemental material in this article.


Nuclear changes in apoptosis.
Specific proteinases of the Ced-3/interleukin-1 beta converting enzyme family trigger a multi-enzyme cascade that drives apoptotic events. Studies with newly developed cell-free systems have begun to identify the substrates of these and other proteinases in apoptosis. Studies with intact cells have revealed that cleavage of the genome into domain-sized fragments precedes the activation of a second nuclease that fragments the DNA into nucleosome-sized pieces.


Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response.
Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during the first wave of the pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, poorly neutralized Beta, and failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these mAbs in complex with trimeric spike protein showed that all three mAbs bivalently bind spike with two mAbs targeting class 1 and one targeting a class 4 receptor binding domain epitope. The immunogenetic makeup, structure, and function of these mAbs revealed specific molecular interactions associated with the potent multi-variant binding/neutralization efficacy. This knowledge shows how mutational combinations can affect the binding or neutralization of an antibody, which in turn relates to the efficacy of immune responses to emerging SARS-CoV-2 escape variants.


A new paradigm of sewage collection in rural areas.
Rural sewage collection networks play extremely important roles in rural sewage treatment, and the lack of a suitable collection model makes this task difficult. Hence, there is an urgent need to develop a new method to collect and deal with rural sewage. This paper establishes a rural sewage optimal collection model (RSOCM) with critical distance (d) and sewage quota per unit area (qs) as the constraint factors. The implementation of critical distance for rural sewage collection pipeline networks was demonstrated for 38 rural areas in the Huicheng District, Huizhou City, Guangdong Province of China. The average critical distances of 22 m, 38 m, 29 m, 29 m, 41 m, and 55 m were demonstrated for Sandong Town, Ma'an Town, Luzhou Town, Ruhu Town, Hengli Town, and Shuikou Subdistrict, respectively. The qs is used to create the best possible pipe network layout, determine the appropriate treatment method, and reduce construction costs. This model can be widely applied to sewage collection in rural areas of China, where the overall sewage collection system can implement different regional strategies to maximize rural pollution control and protect the environment.


Law and ethics of deep brain stimulation.
Deep brain stimulation (DBS) is a non-destructive, adjustable, and mainly reversible method of continuously giving electrical impulses into a small area of the brain via implanted electrodes. It has been established as a standard form of treatment for specific cases of Parkinson's disease, essential tremor and dystonia. It is currently being evaluated for several mental disorders, dementia and even alcoholism. In spite of its growing practical importance, the legal issues have so far undergone almost no analysis. The article outlines both the essential legal questions of DBS from the perspective of German Law as well as major issues of the current ethical debate, and the correlation of both fields.


Control of rRNA expression by small molecules is dynamic and nonredundant.
The control of ribosomal RNA transcription is one of the most enduring issues in molecular microbiology, having been subjected to intense scrutiny for over 50 years. Rapid changes in rRNA expression occur during transitions in the bacterial growth cycle and following nutritional shifts during exponential growth. Genetic approaches and measurements of initiating nucleoside triphosphate (iNTP) and guanosine 5'-diphosphate, 3'-diphosphate (ppGpp) concentrations and of rRNA promoter activities showed that rapid changes in the concentrations of iNTPs and ppGpp account for the rapid changes in rRNA expression. The two regulatory signals are nonredundant: changes in iNTP concentration dominate regulation during outgrowth from stationary phase, whereas changes in ppGpp concentration are responsible for regulation following upshifts and downshifts during exponential phase. The results suggest a molecular logic for the use of two homeostatic regulatory mechanisms to monitor different aspects of ribosome activity and provide general insights into the nature of overlapping regulatory circuits.


Effect of meal size on the specific dynamic action of the juvenile snakehead (Channa argus).
The effect of meal size on the specific dynamic action (SDA) of the juvenile snakehead (Channa argus) was assessed at 25 °C. The fish were fed with test diets at meal sizes of 0.5, 1, 2, 3, 4, and 5% body mass and the postprandial oxygen consumption rate was determined at 1-h intervals until it returned to the pre-prandial level. The peak metabolic rate increased from 237.4 to 283.2 mg O(2) kg(-1) h(-1) as the relative meal size increased from 0.5% to 3% and leveled off at 4% and 5%. Factorial metabolic scope increased from 1.53 to 1.99 and SDA duration increased from 11.7 to 32.3h as the relative meal size increased from 0.5% to 5%. The relationship between SDA duration (D) and relative meal size (M) was described as: D=4.28 M+10.62 (r(2)=0.752, P<0.05, n=50). The energy expended on SDA increased while the SDA coefficient decreased with increasing meal size. The results of the present study suggest that the snakehead may adopt different feeding strategies when taking in different amounts of food.


[Study on correlations between total saponins content in rhizome or mycorrhizal infection rate of Pairs polyphylla var. yunnanensis and soil factors].
Through correlation and path analysis between total saponins content in rhizome/mycorrhizal infection rate in roots of Pairs polyphylla var. yunnanensis and soil factors, to make an inquiry into the role of soil factors in the quality formation of P. polyphylla var. yunnanensis. Tested total saponins in rhizome, mycorrhizal fungal infection rate in root and physical and chemical properties in rhizosphere soil in 25 different growth areas, and statistically analyzed the relationship between total saponins in rhizome/mycorrhizal infection rate in roots of P. polyphylla var. yunnanensis and soil factors by using correlation and path analysis. The symbiosis relationship between AM mycorrhizal and roots of P. polyphylla var. yunnanensis were better established under natural condition, of which the infection ratio between 36.41%, 83.37%. There were significantly positive correlation between total saponins content in rhizome and urease activity or alkaline phosphatase activities or organic matter in soil, but there was significantly negative correlation between total saponins content and bulk density. There was significantly positive correlation between AM infection ratio and alkaline nitrogen. Path analysis indicated that total saponins of rhizome mainly affected by alkaline nitrogen in soil rhizosphere, secondly by soil organic matter and soil urease activity. While the mycorrhizal fungal colonization ratio was mainly affected by soil pH, secondly by alkaline nitrogen, urease activity, and available phospherus in soil. There is closed relationship between quality formation of P. polyphylla var. yunnanensis and soil factors. Path analysis is better for reflecting the contribution of soil factors to total saponins and mycorrhizal infection ratio.


The Shape Bias is Affected by Differing Similarity Among Objects.
Previous research has demonstrated that visual properties of objects can affect shape-based categorization in a novel-name extension task; however, we still do not know how a relationship between visual properties of objects affects judgments in a novel-name extension task. We examined effects of increased visual similarity among the target and test objects in a shape bias task in young children and adults. Experiment 1 assessed college students with sets of objects whose similarity between target and test objects was either low or high similarity. Adults preferred shape when the similarity among objects was minimized. Experiment 2 tested 24- month-olds in their use of the shape bias using the Intermodal Preferential Looking Paradigm. Children showed a shape bias only with items whose similarity to each other was low. These findings suggest that the visual properties of objects affect shape bias performance.


The effect of fibrin formulation on cell migration in an in vitro tendon repair model.
The purpose of this study was to determine the effect of fibrinogen concentration on cell viability and migration in a tissue culture tendon healing model. Forty-eight canine flexor digitorum profundus tendons were randomly divided into three groups. In each group the tendons were lacerated and repaired augmented with a canine bone marrow stromal cell seeded fibrin interposition patch using either 5 mg/ml fibrinogen and 25 U/ml thrombin (physiological as a control), 40 mg/ml fibrinogen and 250 U/ml thrombin (low adhesive), or 80 mg/ml fibrinogen and 250 U/ml thrombin (high adhesive). The sutured tendons were cultured for two or four weeks. Failure load was not significantly different among the groups. Cell-labeling staining showed that the stromal cells migrated across the gap in the control and low adhesive groups, but there was no cell migration in the high adhesive group at two weeks. A high fibrinogen concentration in a fibrin patch or glue may impede early cell migration. Not applicable because this study was a laboratory study.


Fusion of family 2b carbohydrate-binding module increases the catalytic activity of a xylanase from Thermotoga maritima to soluble xylan.
A family 2b carbohydrate-binding module from Streptomyces thermoviolaceus STX-II was fused at the carboxyl-terminus of XynB, a thermostable and single domain family 10 xylanase from Thermotoga maritima, to create a chimeric xylanase. The chimeric enzyme (XynB-CBM2b) was purified and characterized. It displayed a pH-activity profile similar to that of XynB and was stable up to 90 degrees C. XynB-CBM2b bound to insoluble birchwood and oatspelt xylan. Whereas its hydrolytic activities toward insoluble xylan and p-nitrophenyl-beta-xylopyranoside were similar to those of XynB, its activity toward soluble xylan was moderately higher than that of XynB.


Felodipine in ischaemic heart disease.
The effects of felodipine on haemodynamics and exercise capacity have been studied in patients with angina pectoris. In a study of 11 patients undergoing cardiac catheterisation with concomitant beta-blockade, oral felodipine (0.075 mg/kg) increased resting heart rate by 16%. During atrial pacing at 100 beats per minute, felodipine decreased mean systemic arterial pressure by 9.6% and systemic vascular resistance by 30% and increased cardiac index by 30%. There was no significant effect on pulmonary haemodynamics or left ventricular end-diastolic pressure and the isovolumic and ejection phase indices of left ventricular contractility were unchanged. In a randomised double-blind study of 14 patients, felodipine, when added to regular beta-blockade, reduced the frequency of episodes of angina and the amount of glyceryl trinitrate consumed. At a similar plasma concentration to that in the above study, felodipine significantly increased exercise tolerance by 16%, without producing a change in the maximal double product. Resting supine heart rate was increased by 7.3% after felodipine administration; supine systolic and diastolic blood pressures were decreased by 13% and 12%, respectively, and erect systolic and diastolic blood pressures by 14% and 10%, respectively. Only minor adverse effects were reported. Because of its systemic vasodilating properties, felodipine should be a useful adjunct to beta-blockade in patients with angina pectoris.


[Effect of change in occlusal contact areas of the mandibular second molar on temporomandibular joint stress distribution: a 3-dimensional finite element analysis].
To investigate the regulation of stress distribution on TMJ when the location of occlusal load on the mandibular second molar was changed by using the 3-dimensional Finite Element Method (FEM). A 3-dimensional FEM TMJ model including left mandibular second molar and mandible was established. In finite element analysis software ANSYS the same boundary constraints were applied to the TMJ FEM model with different load cases. The occlusal loads were applied to simulate ICO load, distal load, and buccal load and the stress values of condyles of the FEM model were calculated. As the occlusal load was applied to different tooth contact areas with various shapes, the stress distributions of bilateral condyles were found different and asymmetrical. The condyle stress on TMJ FEM model in three loading cases was diverse, not only in stress character but also in stress distribution style. The maximum value of Von Mises in the opposite condyle was 51.513 MPa when ICO load was applied. But when the distal load or the buccal load was applied, the maximum value of Von Mises in the opposite condyle increased to 72.145 MPa or 69.566 Mpa respectively. The same level but in different direction of occlusal load that resulted from difference of loading spots by changing the occlusal contact area, would induce different stress features on bilateral condyles.


Multiple GTP-binding proteins from cholinergic synaptic vesicles.
Cholinergic synaptic vesicles purified from the electric organ of the marine ray, Discopyge ommata, contain 2 different size classes of GTP-binding proteins: one or more with an apparent molecular weight (MW) between 37 and 41 kDa, and 3 major and at least 2 minor proteins with MW between 20 and 29 kDa. These GTP-binding proteins were detectable using the alpha 32P-GTP overlay technique and covalent modification with bacterial toxins. The higher MW GTP-binding proteins are ADP-ribosylated by pertussis toxin and 2 of the lower MW GTP-binding proteins are sensitive to botulinum toxin.


Double-chambered right ventricle presenting significant outflow tract obstruction only in the right decubitus position.
A 75-year-old man was referred to our echocardiography laboratory for presurgical evaluation. His past history included ventricular septal defect closure. He reported chest discomfort in the right decubitus position. Two-dimensional and Doppler echocardiography revealed an anomalous muscle bundle with accelerated blood flow in the right ventricle. The peak flow velocity of the flow increased from 1.4 m/s in the left decubitus position to 2.9 m/s in the right decubitus position. Double-chamber right ventricle with intermittent mid-ventricular obstruction during the right decubitus position was confirmed by transesophageal echocardiography.


Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease.
To test the hypothesis of an association between polymorphism in FCGR3A (the gene coding for FcgammaRIIIa, which is expressed on macrophages and natural killer cells, is involved in antibody-dependent cell-mediated cytotoxicity and has recently been associated with a positive response to rituximab, a recombinant immunoglobulin G1 antibody used in non-Hodgkin's lymphomas) and response to infliximab in Crohn's disease. FCGR3A-158 polymorphism was determined using an allele-specific polymerase chain reaction assay in 200 Crohn's disease patients who had received infliximab for either refractory luminal (n = 142) or fistulizing (n = 58) Crohn's disease. Clinical and biological responses (according to C-reactive protein levels) were assessed in 200 and 145 patients, respectively. There were 82.9% clinical responders in V/V patients vs. 72.7% in V/F and F/F patients (N.S.). Globally, the decrease in C-reactive protein was significantly higher in V/V patients than in F carriers (P = 0.0078). A biological response was observed in 100% of V/V patients, compared with 69.8% of F carriers (P = 0.0002; relative risk, 1.43; 95% confidence interval, 1.27-1.61). In the sub-group of patients with elevated C-reactive protein before treatment, the multivariate analysis selected the use of immunosuppressive drugs and FCGR3A genotype as independent factors influencing the clinical response to infliximab (P = 0.003). Crohn's disease patients with FCGR3A-158 V/V genotype have a better biological and, possibly, clinical response to infliximab.


Bath-PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB-UVB phototherapy.
Photochemotherapy with bathwater delivery of psoralens plus UVA exposures (bath-PUVA) is mainly used for those psoriatic patients who are not responsive to narrowband (NB)-UVB phototherapy and oral-PUVA therapy and belong to two categories (1) patients with psoriasis without systemic comorbidities who do not need long-term continuous treatment and (2) patients who have contraindications to immunosuppressive drugs and oral-PUVA or refuse systemic drugs, including oral ingestion of psoralens, for personal reasons. However, it is not known how many patients belong to the second group and how much bath-PUVA is effective and safe for them. We have reviewed the treatment results of a cohort of 120 patients with clinical indication to bath-PUVA for the above-mentioned reasons between 2010 and 2019. These patients were selected among 2640 patients with moderate and severe psoriasis who were treated in our department in the same time interval. Ninety-six patients completed at least one treatment cycle with bath-PUVA. A per-protocol analysis showed that average number of treatment sessions was 21.3 ± 9.0 and the cumulative UVA dose was 80.4 ± 60.0 J/cm2 . The average PASI scores decreased from 20.8 ± 7.9 to 5.1 ± 5.4 (p < .01). Sixty-seven (69.7%) patients achieved at least a 75% improvement (PASI75 ) and, of them, 38 (39.6%) had an improvement greater than 90% (PASI90 ). Adverse effects were mild and transitory. These findings demonstrate that bath-PUVA is still a valuable treatment option for a high number of patients who reject systemic treatments or have contraindications to systemic immune-modifying drugs and have had a limited or no improvement with NB-UVB phototherapy.


Direct on-line hyphenation of capillary liquid chromatography to nuclear magnetic resonance spectroscopy: practical aspects and application to drug metabolite identification.
In combining the high peak concentrations of capillary liquid chromatography (CapLC) with the high mass sensitivity of micro scale nuclear magnetic resonance (NMR) the hyphenation of CapLC to micro NMR offers a substantial gain in overall sensitivity. This paper deals with our experiences gained using a commercial CapLC-NMR system which has very recently become available. The limits of detection (SNR > 3) for a test compound of a molecular weight of M 318 were found to be approximately 100 ng (0.35 nmol) within an hour acquisition time and approximately 25 ng over night (85 pmol). Practical aspects such as the feasibility of stopped-flow experiments and sample handling issues are discussed in detail and first possible drug metabolite applications to hepatocyte incubations and direct analysis of plasma samples are presented.


Neurodegeneration-associated protein fragments as short-lived substrates of the N-end rule pathway.
Protein aggregates are a common feature of neurodegenerative syndromes. Specific protein fragments were found to be aggregated in disorders including Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Here, we show that the natural C-terminal fragments of Tau, TDP43, and α-synuclein are short-lived substrates of the Arg/N-end rule pathway, a processive proteolytic system that targets proteins bearing "destabilizing" N-terminal residues. Furthermore, a natural TDP43 fragment is shown to be metabolically stabilized in Ate1(-/-) fibroblasts that lack the arginylation branch of the Arg/N-end rule pathway, leading to accumulation and aggregation of this fragment. We also found that a fraction of Aβ42, the Alzheimer's disease-associated fragment of APP, is N-terminally arginylated in the brains of 5xFAD mice and is degraded by the Arg/N-end rule pathway. The discovery that neurodegeneration-associated natural fragments of TDP43, Tau, α-synuclein, and APP can be selectively destroyed by the Arg/N-end rule pathway suggests that this pathway counteracts neurodegeneration.


The glass gene encodes a zinc-finger protein required by Drosophila photoreceptor cells.
Null mutations of glass specifically remove photoreceptor cells, leaving other cell types intact. We have isolated the glass gene and have shown that its transcript encodes a putative protein of 604 amino acids with five zinc-fingers. The glass product may be a transcription factor required for the development of a single neuronal cell type.


Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis.
To investigate the association between the functional Fc gamma receptor 3 A (FCGR3A) V158F and FCGR2A R131H polymorphisms and rituximab therapy in patients with autoimmune diseases. We searched the Medline, Embase, and Cochrane databases for relevant articles. We conducted a meta-analysis of the association between FCGR3A V158F and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases. Eleven studies, consisting of 661 responders and 267 non-responders for FCGR3A V158F polymorphism and 156 responders and 89 non-responders for FCGR2A R131H polymorphism, were included. The meta-analysis revealed a significant association between the FCGR3A V allele and responsiveness to rituximab (odds ratio [OR] = 1.600, 95% confidence interval [CI] = 1.268-2.018, P < 0.001). Furthermore, associations were found using the dominant and homozygous contrast models. Subgroup analysis showed an association between the FCGR3A V allele and responsiveness to rituximab in European, RA, ITP, small (<50) and large (≥50) groups, and short- (≤6 months) and long-term follow-up periods (≥6 months). These associations were also found in recessive, dominant or homozygous contrast models. Meta-analysis revealed no association between the FCGR2A R allele and responsiveness to rituximab (OR = 1.243, 95% CI = 0.825-1.873, P = 0.229). We demonstrated that the FCGR3A F158V polymorphism is associated with better responsiveness to rituximab therapy in patients with autoimmune diseases, indicating that individuals carrying the FCGR3A V allele will likely respond better to rituximab. However, FCGR2A R131H polymorphism was not associated with better response to rituximab.


RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters.
The leukocyte integrins CD11a/CD18 (LFA-1, alphaLbeta2) and CD49d (VLA-4, alpha4beta1, alpha4beta7) mediate leukocyte transendothelial migration during immune and inflammatory responses and provides co-stimulatory signals for the activation of T lymphocytes. Our previous studies demonstrate that the CD11a gene promoter directs CD11a/CD18 integrin expression, and it depends on two overlapping sequences within the MS7 element, RUNX-110 and CEBP-100, which are recognized by RUNX and C/EBP transcription factor families, respectively. Recognition of MS7 differs in lymphoid (RUNX) and myeloid (C/EBP and RUNX) cells and its in vivo occupancy is regulated in a competitive and differentiation-dependent manner. The functional relevance of these elements are illustrated by the fact that RUNX3 overexpression leads to enhanced CD11a/CD18 levels, whereas RUNX1-ETO-expressing cells exhibit a weak/absent CD11a/CD18 integrin cell surface expression. We now provide evidence that RUNX3 also transactivates the CD49d gene promoter, and that the increased expression of CD49d mRNA and CD49d integrins on mature monocyte-derived dendritic cells correlates with an up-regulation of RUNX3 mRNA. The regulation of CD49d and CD11a integrins by RUNX3 could potentially contribute to the enhancement of transendothelial migration, antigen presentation and T cell stimulatory capabilities of mature dendritic cells.


Postnatal ontogeny of enkephalin fibers in spinal sympathetic nuclei.
The postnatal distribution of enkephalin (Enk) fibers is described in preganglionic containing sympathetic nuclei in the rat thoracolumbar spinal cord. In high thoracic spinal cord, at birth, Enk fibers are present in moderate numbers in the intermediolateralis nucleus, pars principalis (ILp), and nucleus intercalatus spinalis (IC). Enkephalin fibers first appear in the dorsal commissural nucleus (dcn) on postnatal day 2. Postnatal day 6 represents a pivotal timepoint when the basic Enk innervation pattern is established. From postnatal day 11 through day 20 there is a gradual accumulation of Enk fibers within each of the sympathetic nuclei such that the density and distribution of immunoreactive fibers approaches the adult appearance by postnatal day 20. An adult pattern is achieved by postnatal day 30. There is a rostral-caudal gradient in the developmental appearance of Enk fibers in sympathetic nuclei such that the ILp nucleus contains Enk fibers on postnatal day 0 in the high thoracic spinal levels compared to postnatal day 6 in low thoracic-high lumbar spinal levels. Examination of the location of Enk fibers during ontogeny highlighted several additional features of the distribution of Enk fibers in the adult animal. Enkephalin fibers delineate two subdivisions of the IC nucleus; a thin dense core of Enk fibers contained within a broader band of moderate numbers of Enk fibers. We also report variations in the general overall pattern of the Enk fiber distribution in high thoracic, middle thoracic, and lwo thoracic-high lumbar spinal cord levels.


Assessing barriers and solutions for Yemen energy crisis to adopt green and sustainable practices: a fuzzy multi-criteria analysis.
Currently, the renewable energy sectors have dynamically revolved around targeting green turbulence, mainly due to increased customer environmental awareness. Therefore, this paper investigates green initiatives. The results show barriers and explain the strategies for adopting green renewable energy sources in Yemen. The political barrier has the highest weight of 0.191, while technical barrier sored the second highest weight of 0.181. The weights of managerial and information energy were found to be 0.18 and 0.17, respectively. Market barrier weighed the lowest score of 0.12, while economic barrier (0.15 weight) is the barrier to develop renewable energy road map. The research developed a comprehensive decision making framework to identify major barriers, sub-barriers, and develop plans for green energy in Yemen. Fuzzy analytical hierarchal process (FAHP) results indicate that the category of political obstacles is more important than other obstacles. Yemen has undergone power reforms and achieved better energy efficiency, compared to the countries that have applied imperfect. Economic efficiency in Yemen is the lowest among the considered barriers. Twenty-five percent of the considered barriers were identified with an alarming efficiency of 0.5%. The effects of FTOPSIS show that the planned explanation "developing research methods to achieve green innovation in renewable" energy is significant to address the obstacles to green innovation in renewable energy.


Production of porcine antibodies with high specificity to [8-D-arginine] deamino-vasopressin (dDAVP).
The development of a specific radioimmunoassay for [8-D-arginine] deamino-vasopressin (dDAVP) is described.


Bronchiolitis obliterans organizing pneumonia (BOOP) after renal transplantation.
A 42-year-old renal transplant recipient was admitted with fever, anorexia, malaise, nonproductive cough, and dyspnea of 1-week duration. Multiple cultures of blood, sputum, and urine were negative. The possibility of bronchiolitis obliterans with organizing pneumonia (BOOP) was considered when pulmonary infiltrate did not respond to conventional antibiotic therapy. High-resolution computed tomography of the chest revealed patchy air-space consolidation and ground-glass opacities, predominantly located in the periphery of the lungs. Cultures and stains of bronchoalveolar lavage specimen and bronchoscopic biopsy of lung tissue were negative for organisms such as Pneumocystis (carinii) jiroveci, bacteria, Mycobacterium tuberculosis, cytomegalovirus, fungi, and atypical germs, and showed evidence of BOOP. The patient recovered completely after treatment with steroids.


Long-range focusing of magnetic bound states in superconducting lanthanum.
Quantum mechanical systems with long-range interactions between quasiparticles provide a promising platform for coherent quantum information technology. Superconductors are a natural choice for solid-state based quantum devices, while magnetic impurities inside superconductors give rise to quasiparticle excitations of broken Cooper pairs that provide characteristic information about the host superconductor. Here, we reveal that magnetic impurities embedded below a superconducting La(0001) surface interact via quasiparticles extending to very large distances, up to several tens of nanometers. Using low-temperature scanning probe techniques, we observe the corresponding anisotropic and giant oscillations in the LDOS. Theoretical calculations indicate that the quasi-two-dimensional surface states with their strongly anisotropic Fermi surface play a crucial role for the focusing and long-range extension of the magnetic bound states. The quasiparticle focusing mechanism should facilitate the design of versatile magnetic structures with tunable and directed magnetic interactions over large distances, thereby paving the way toward the design of low-dimensional magnet-superconductor hybrid systems exhibiting topologically non-trivial quantum states as possible elements of quantum computation schemes based on Majorana quasiparticles.


Oligomerization of the reversibly glycosylated polypeptide: its role during rice plant development and in the regulation of self-glycosylation.
A multigenic family of self-glycosylating proteins named reversibly glycosylated polypeptides, designated as RGPs, have been usually associated with carbohydrate metabolism, although they are an enigma both at the functional, as well as at the structural level. In this work, we used biochemical approaches to demonstrate that complex formation is linked to rice plant development, in which class 1 Oryza sativa RGP (OsRGP) would be involved in an early stage of growing plants, while class 2 OsRGP would be associated with a late stage linked to an active polysaccharide synthesis that occurs during the elongation of plant. Here, a further investigation of the complex formation of the Solanum tuberosum RGP (StRGP) was performed. Results showed that disulfide bonds are at least partially responsible for maintaining the oligomeric protein structure, so that the nonreduced StRGP protein showed an apparent higher molecular weight and a lower radioglycosylation of the monomer with respect to its reduced form. Hydrophobic cluster analysis and secondary structure prediction revealed that class 2 RGPs no longer maintained the Rossman fold described for class 1 RGP. A 3D structure of the StRGP protein resolved by homology modeling supports the possibility of intercatenary disulfide bridges formed by exposed cysteines residues C79, C303 and C251 and they are most probably involved in complex formation occurring into the cell cytoplasm.


[Percutaneous endoscopic colostomy for treatment of an antibiotic-induced pseudomembranous colitis].
A 61-year-old man was admitted with diffuse abdominal pain and diarrhea for one week. A few weeks before admission he had been given antibiotics for an exacerbation of his chronic obstructive pulmonary disease. On physical examination he presented with bronchospasm, abdominal tenderness, active bowel sounds and slight edema in both legs. Blood tests detected an acute inflammation and colonoscopy revealed a massive inflammation of the bowel with pseudomembranes. Clostridium difficile and Clostridium toxin was isolated from the feces. Oral antibiotic treatment with metronidazole and thereafter vancomycin was without effect. However, the colitis receded rapidly after vancomycin was given into the colon via a percutaneous endoscopic colostomy placed in the proximal ascending colon. There are increasing numbers of reports on severe Clostridium colitis. The percutaneous endoscopic colostomy with local application of antibiotics may improve outcome.


Aseptic survival of the 1.5-stage exchange arthroplasty for periprosthetic joint infection was acceptable when using an autoclaved femoral component and a new polyethylene insert.
To investigate the aseptic survival of 1.5-stage exchange arthroplasty for periprosthetic joint infection (PJI) after total knee arthroplasty (TKA). Eighty-eight cases of 1.5-stage exchange arthroplasty for PJI without reinfection were retrospectively analysed. The autoclaved femoral component and new polyethylene insert (PE) were implanted using antibiotic mixed cement. The explanted tibial component was not reinserted. The Western Ontario and McMaster Universities Osteoarthritis Index and range of motion were clinically evaluated preoperatively and at the last follow-up (the last time for the implant in situ). Radiographically, hip-knee-ankle angle (HKA) and component positions were measured preoperatively, postoperatively (1 month after the 1.5-stage exchange arthroplasty), and at the last follow-up. The survival rate was analysed using the Kaplan-Meier method, in which failure was defined as reoperation due to aseptic failure. Mean period to failure and failure site were analysed. Factors affecting survival were investigated in terms of demographics and inappropriateness of the postoperative HKA (HKA > 0 ± 3°) and component positions (α angle > 95 ± 3°, β angle > 90 ± 3°, γ angle > 3 ± 3°, and δ angle > 87 ± 3°). The spacer in-situ time was 3.7 years (0.2-6.4). The clinical results improved hip-knee-ankle significantly at the last follow-up. Radiographically, the average HKA was valgus 0.1° postoperatively. The average α, β, γ, and δ angles of the postoperative component positions were 95.9°, 90.4°, 3.8°, and 86.7°, respectively. The 1-, 2-, and 5-year postoperative survival rates were 90.9%, 86.4%, and 80.6%, respectively. The mean period to failure was 2.0 years (0.2-5.3). There were 18 cases of aseptic loosening (20.8%), occurring on both the femur and tibial sides in 1 knee, and only on the tibial side in 17 knees. Inappropriate coronal position of the PE (β angle > 90 ± 3°) was a significant factor affecting survival (odds ratio = 5.491; p = 0.011). The aseptic survival of the 1.5-stage exchange arthroplasty was acceptable when using an autoclaved femoral component and new PE. The appropriate coronal position of the PE helps ensure favourable survival of 1.5-stage exchange arthroplasty. IV.


Impairments in limb actions after dorsal funiculi section in cats.
A study of the forces exerted by cats against the ground when jumping from a platform equipped with force transducers, was carried out. The study, complemented by film analysis of the jump, attempted to disclose some of the mechanisms underlying the decrease in efficiency and accuracy in releasing a moving piece of liver observed after dorsal funiculi section above C1 level. The results showed that after the lesion, peak force and height of jump were significantly reduced. However, angle of take-off, an index of force distribution in the three axes of rectangular coordinates remained unchanged. Intact cats consistently extend their forelimbs in a smooth and progressive way toward the liver in order to release it. The distance between the tips of the forelimbs remained more or less constant during the flight. Postoperatively, instead of the regular pattern described, the extension of the limbs was interrupted by fast marked flexion movements and the distance between their tips increased significantly during the flight. Peak extension of the forelimbs was also decreased after surgery. The results are interpreted in terms of the different disruption of the various components (proprio and exteroceptive) that make up fasciculus gracilis and cuneatus of the dorsal funiculi.


Accuracy of the current TNM classification in predicting survival in patients with sinonasal mucosal melanoma.
The first International Union Against Cancer (UICC) TNM classification for aerodigestive malignant mucosal melanoma was not published until 2009, and since then, only a few studies have evaluated the accuracy of this staging system. Our aim was to evaluate the accuracy of this UICC staging system for sinonasal malignant mucosal melanoma (SMMM) in a nationwide survey. Retrospective, population-based, multicenter study. The hospital surgical and discharge registries were used to identify the patients. A database including demographic and clinicopathologic variable was created. Altogether, 50 SMMM patients diagnosed in Finland from 1990 to 2004 were evaluated. Three- and 5-year overall survival rates were 44% and 27%, respectively. Significant differences in overall survival according to T classification (P = .028, log rank) and stage (P = .02, log rank) were found. Tumor extension to the sphenoid sinus had a significant negative impact on survival (n = 11, P = .03, log rank). The current UICC staging system for mucosal melanoma provides a useful format for staging SMMMs in clinical settings.


Reduced crystallization inhibition by urine from women with nephrolithiasis.
Human urine is known to inhibit growth, aggregation, nucleation, and cell adhesion of calcium oxalate monohydrate (COM) crystals, the main solid phase of human kidney stones. This study tested the hypothesis that low levels of inhibition are present in women with calcium oxalate stones and, therefore, could promote stone production. In 17 stone-forming women and 17 normal women matched in age within five years, inhibition by dialyzed urine proteins of COM growth and aggregation was examined, as well as whole urine upper limits of metastability (ULM) for COM and calcium phosphate (CaP) in relation to the corresponding supersaturation (SS). Compared to normals, patient urine showed a reduced ULM in relation to SS. In contrast to men, there was no difference in growth inhibition. Reduced CaP and CaOx ULM values in relation to SS are a characteristic of female stone formers. This defect could promote stones by facilitating crystal nucleation. Abnormal inhibition may well be a very important cause of human nephrolithiasis.


Models for assessing antipsychotics: antagonism of amphetamine-induced hyperactivity and stereotypies in mice.
All classical antipsychotics, such as chlorpromazine and haloperidol, have potent dopamine receptor-blocking properties. This unit describes the rat anti-Thy-1.1 model of acute proliferative glomerulonephritis for the study of chronic renal insufficiency. A procedure is detailed for the induction of glomerulonephritis in rats as well as measurement of daily urinary excretion of protein, which is a convenient, primary screening tool. The unit also provides methods for assessment of glomerular filtration rate and effective renal plasma flow in anesthetized rats with anti-Thy-1.1-induced renal insufficiency.


Intranasal IGF-1 Reduced Rat Pup Germinal Matrix Hemorrhage.
Germinal matrix hemorrhage (GMH) is the most devastating neurological problem of premature infants. Current treatment strategies are ineffective and brain injury is unpreventable. Insulin-like growth factor 1 (IGF-1) is an endogenous protein shown to have multiple neuroprotective properties. We therefore hypothesized that IGF-1 would reduce brain injury after GMH. Neonatal rats (P7 age) received stereotactic collagenase into the right ganglionic eminence. The following groups were studied: (1) sham, (2) GMH + vehicle, (3) GMH + intranasal IGF-1. Three days later, the animals were evaluated using the righting-reflex (early neurobehavior), Evans blue dye leakage (blood-brain barrier (BBB) permeability), brain water content (edema), and hemoglobin assay (extent of bleeding). Three weeks later, juvenile rats were tested using a water maze (delayed neurobehavior), and then were sacrificed on day 28 for assessment of hydrocephalus (ventricular size). Intranasal IGF-1 treated animals had improved neurological function, and amelioration of BBB permeability, edema, and re-bleeding. IGF-1 may play a part in protective brain signaling following GMH, and our observed protective effect may offer new promise for treatment targeting this vulnerable patient population.


Translating digital anthropometry measurements obtained from different 3D body image scanners.
Body image scanners are used in industry and research to reliably provide a wealth of anthropometric measurements within seconds. The demonstrated utility of the scanners drives the current proliferation of more commercially available devices that rely on their own reference body sites and proprietary algorithms to output anthropometric measurements. Since each scanner relies on its own algorithms, measurements obtained from different scanners cannot directly be combined or compared. To develop mathematical models that translate anthropometric measurements between the three popular commercially available scanners. A unique database that contained 3D scanner measurements in the same individuals from three different scanners (Styku, Human Solutions, and Fit3D) was used to develop linear regression models that translate anthropometric measurements between each scanner. A limits of agreement analysis was performed between Fit3D and Styku against Human Solutions measurements and the coefficient of determination, bias, and 95% confidence interval were calculated. The models were then applied to normalized scanner data from four different studies to compare the results of a k-means cluster analysis between studies. A scree plot was used to determine the optimal number of clusters derived from each study. Correlations ranged between R2 = 0.63 (Styku and Human Solutions mid-thigh circumference) to R2 = 0.97 (Human Solutions and Fit3D neck circumference). In general, Fit3D had better agreement with Human Solutions compared to Styku. The widest disagreement was found in chest circumference (Fit3D (bias = 2.30, 95% CI = [-3.83, 8.43]) and Styku (bias = -5.60, 95% CI = [-10.98, -0.22]). The optimal number of body shape clusters in each of the four studies was consistently 5. The newly developed models that translate measurements between the scanners Styku and Fit3D to predict Human Solutions measurements make it possible to standardize data between scanners allowing for data pooling and comparison.


Measurement of albumin synthesis in perfused rat liver using stable isotopes: [15N] hippurate as a measure of the intracellular [15N] glycine precursor enrichment.
Rat livers were perfused by the non-recirculating technique with medium containing [15N] glycine and sodium benzoate. At various times, the 15N-concentration and the isotopic enrichment of perfusate hippurate, albumin, globulines, urea, creatinine and other fractions were measured by MS. Hippurate was used to represent the intracellular precursor pool for albumin synthesis. After start of glycine administration the ratio APE product/APE precursor pool had reached approximately maximal values. After 30 min, the precursor pool size and its use in protein synthesis decreased due to amino-acid-deficient perfusion with no further decrease between 30 and 105 min. Additionally, rates of protein synthesis were determined. The albumin synthesis rate was 3.27 mg/g liver weight per hour.