Beam monitor calibration in scanned light-ion beams.
To propose a formalism for the reference dosimetry of scanned light-ion beams consistent with IAEA TRS-398 and Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)]. To identify machine-specific reference (msr) fields and plan-class specific reference (pcsr) fields consistent with the definitions given by Alfonso et al. To review the literature of beam monitor calibration in scanned beams using three different methods in terms of this common formalism. Four types of msr fields are identified as those that are meant to calibrate the beam monitor for scanned beams with particular energies. Two types of pcsr fields are identified as those that are meant to apply one or more tuning factors to the entire delivery chain. The formalism establishes the energy-dependent relation between the number of particles incident on the phantom surface and the beam monitor reading and distinguishes three routes to determine the beam monitor calibration function: (i) the use of a calibrated reference ionization chamber in a single-layer scanned beam, (ii) the use of a cross-calibrated large-area parallel plate ionization chamber in a single-energy beamlet, and (iii) the use of a calibrated reference ionization chamber in a box field to adjust a calibration curve obtained by a Faraday cup or an ionization chamber. Examples of all three methods and comparisons between them from the literature are analysed. The formalism can form the basis of future dosimetry recommendations for scanned particle beams and the analysis of the literature data in terms of this formalism can form the basis of data compilations for the application of the dosimetry procedures.


The protective antibodies induced by a novel epitope of human TNF-alpha could suppress the development of collagen-induced arthritis.
Tumor necrosis factor alpha (TNF-alpha) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-alpha (hTNF-alpha) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-alpha. We performed screening peptide library against anti-hTNF-alpha antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-alpha. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80-91 aa) of hTNF-alpha proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-alpha biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-alpha. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-alpha and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies.


Comparative Measurement of In Vitro T-2 Toxin Cytotoxicity using Three Different Cytotoxicity Assays.
T-2 toxin is a secondary fungal metabolite produced by various species of fusarium. In this study, the in vitro cytotoxicity of T-2 toxin in the human hepatoma cell line (HepG2) was determined using three methods, including neutral red dye adsorption, trypan blue dye exclusion, and uptake of radiolabeled 3 H-thymidine. The 50% lethal concentration of T-2 toxin was found to be similar for all three, accounting for 2.39, 2.96, and 3.44 ng/mL, respectively, as determined by these assays. Significant correlations were also observed among the three methods (p <. 05 through p <. 005). These results suggest that all three methods are reliable and are comparable for determining the 50% lethal concentration of T-2 toxin. It is concluded that the neutral red cytotoxicity assay may be preferable to other methods because of its simplicity, its use of nonradioactive materials, and its objectivity.


Concomitant coronary artery disease among Asian ischaemic stroke patients.
Coronary artery disease (CAD) is the leading cause of death following ischaemic stroke. We aimed to study the prevalence and associations of concomitant CAD among ischaemic stroke patients in Singapore. We prospectively studied 2686 consecutive Asian ischaemic stroke patients. CAD was prevalent among 24% of the study patients. Older age, hypertension, diabetes, hyperlipidaemia, atrial fibrillation, large stroke and South Asian ethnicity were independently associated with CAD. The variables found to be associated with CAD are known atherosclerotic risk factors (older age, hypertension, diabetes, hyperlipidaemia) or associations of cardioembolic stroke (atrial fibrillation, large stroke). The over-representation of South Asians with concomitant CAD is consistent with the high burden of CAD in this ethnic group.


Mannose receptor induces T-cell tolerance via inhibition of CD45 and up-regulation of CTLA-4.
The mannose receptor (MR) is an endocytic receptor involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8(+) T-cell activity. We demonstrate that MR expression on dendritic cells (DCs) impaired T-cell cytotoxicity in vitro and in vivo. This regulatory effect of the MR was mediated by a direct interaction with CD45 on the T cell, inhibiting its phosphatase activity, which resulted in up-regulation of cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) and the induction of T-cell tolerance. Inhibition of CD45 prevented expression of B-cell lymphoma 6 (Bcl-6), a transcriptional inhibitor that directly bound the CTLA-4 promoter and regulated its activity. These data demonstrate that endocytic receptors expressed on DCs contribute to the regulation of T-cell functionality.


Properties of chemical-vapor-deposited silicon carbide for optics applications in severe environments.
Important data on chemical-vapor-deposited (CVD) SiC concerning the elastic modulus, polishability, scattering measurement, thermal and cryogenic stability, and degradation owing to the effects of atomic oxygen and electron beams have been obtained with the aim of assessing the suitability of SiC as an optical substrate for severe environments. These measurements show that CVD SiC substrates exhibit excellent polishability (<0.1 nm rms) with low scatter, good retention of mechanical properties up to 1500 degrees C, superior thermal and cryogenic stability (-190 degrees to 1350 degrees C) and high resistance to atomic-oxygen and electron-beam degradation. These results suggest that CVD SiC optical substrates will perform extremely well in severe environments such as outer space, and when used in lasers, combustion, and synchrotron x rays.


Pathogen cross-transmission via building sanitary plumbing systems in a full scale pilot test-rig.
The WHO Consensus Document on the epidemiology of the SARS epidemic in 2003, included a report on a concentrated outbreak in one Hong Kong housing block which was considered a 'super-spreading event'. The WHO report conjectured that the sanitary plumbing system was one transmission route for the virus. Empty U-traps allowed the aerosolised virus to enter households from the sewerage system. No biological evidence was presented. This research reports evidence that pathogens can be aerosolised and transported on airstreams within sanitary plumbing systems and enter buildings via empty U-traps. A sanitary plumbing system was built, representing two floors of a building, with simulated toilet flushes on the lower floor and a sterile chamber with extractor fan on the floor above. Cultures of a model organism, Pseudomonas putida at 106-109 cfu ml-1 in 0·85% NaCl were flushed into the system in volumes of 6 to 20 litres to represent single or multiple toilet flushes. Air and surface samples were cultured on agar plates and assessed qualitatively and semi-quantitatively. Flushing from a toilet into a sanitary plumbing system generated enough turbulence to aerosolise pathogens. Typical sanitary plumbing system airflows (between 20-30 ls-1) were sufficient to carry aerosolised pathogens between different floors of a building. Empty U-traps allowed aerosolised pathogens to enter the chamber, encouraging cross-transmission. All parts of the system were found to be contaminated post-flush. Empty U-traps have been observed in many buildings and a risk assessment indicates the potential for high risk cross-transmission under defect conditions in buildings with high pathogen loading such as hospitals. Under defective conditions (which are not uncommon) aerosolised pathogens can be carried on the airflows within sanitary plumbing systems. Our findings show that greater consideration should be given to this mode of pathogen transmission.


A comprehensive review of myelodysplastic syndrome patients with autoimmune diseases.
Primary myelodysplastic syndromes (MDS) are heterogeneous clonal hemopoietic disorders clinically presented with a varying degree of peripheral cytopenias and an increased probability of leukemic evolution. A distinct subset of MDS patients manifests overt autoimmune-inflammatory manifestations, the underlying pathogenesis and prognostic significance of which still remain controversial. In this review we attempt to analyze clinical aspects of MDS-related rheumatoid disease, and discuss pathophysiologic associations between autoimmunity and distorted BM function in preleukemic states in light of recent findings, in vivo and in vitro. We further explore the potential of recent biological and molecular advances to forward therapeutic targeting against both autoimmune and malignant process.


An immunofluorescence test to determine the occurrence of type II collagen in muscle biopsies from cattle with rectovaginal constriction.
Type II collagen occurs in the muscles of rectovaginal constriction (RVC) affected and carrier cattle but not in normal cattle. Muscle biopsies from known RVC affected and carrier cattle and normal cattle were examined for the presence of Type II collagen using affinity purified goat anti-collagen II serum in a fluorescent antibody test. Type II collagen was consistently found in RVC affected animals (22 of 23 samples score positive). Rectovaginal constriction carrier animals had variable staining for the Type II collagen (25 of 47 samples scored positive). Some positive staining was also observed in the control animals (8 of 34 samples scored positive). Because of the variable occurrence of Type II collagen, the value of fluorescent antibody staining to identify RVC carrier animals is uncertain.


Current issues in cochlear gene transfer.
Cochlear gene therapy represents a potential experimental and therapeutic tool to understand and treat deafness. In designing cochlear gene transfer studies, the chosen route of delivery of vector and the choice of gene therapy vector have to be given careful consideration. Several different routes of delivery have been tested in our laboratory including infusion with osmotic minipump, direct microinjection into the cochlea and application of vector-transgene complex-soaked Gelfoam((R)) into the direct contact with the round window membrane. In our experience, the latter is an easy, safe and atraumatic technique to deliver gene into the cochlea. A number of different gene transfer vectors have been investigated in vivo for their efficacy, utility and safety in intracochlear gene transfer. Vectors successfully studied include cationic liposomes, adeno-associated virus, adenovirus, lentivirus, herpes simplex virus and vaccinia virus. While the viral vectors offer clear experimental advantages, human gene therapy in the future will likely utilize nonviral vectors to maximize safety. Finally, safety issues regarding dissemination of gene transfer vectors beyond the target cochlea will need to be adequately addressed.


Inhibition of tumor necrosis factor alpha (TNFalpha) activity in rat brain is associated with cerebroprotection after closed head injury.
We recently demonstrated that closed head injury (CHI) in the rat triggers the production of tumor necrosis factor alpha (TNFalpha) in the contused hemisphere. Other investigations have shown that this cytokine plays a role in the inflammatory response following trauma. The present study was designed to determine whether inhibition of TNFalpha production or activity affects the development of cerebral edema as well as neurological dysfunction and hippocampal cell loss after CHI. To this end, we used two pharmacological agents, each acting via a different mechanism: pentoxifylline (PTX), which attenuates the production of TNFalpha, and tumor necrosis factor binding protein (TBP), a physiological inhibitor of TNFalpha activity. Both agents significantly lessened peak edema formation at 24 h and facilitated the recovery of motor function for < or = 4 days postinjury. In addition, TBP attenuated disruption of the blood-brain barrier and protected hippocampal cells. PTX significantly lowered the brain TNFalpha level (by approximately 80%), and TBP completely abolished the activity of recombinant human TNF when they were added at the same time in the in vitro bioassay. We suggest, therefore, that a decrease in TNFalpha level or the inhibition of its activity is accompanied by reduced brain damage.


Dielectric particle and void resonators for thin film solar cell textures.
Using Mie theory and Rigorous Coupled Wave Analysis (RCWA) we compare the properties of dielectric particle and void resonators. We show that void resonators-low refractive index inclusions within a high index embedding medium-exhibit larger bandwidth resonances, reduced peak scattering intensity, different polarization anisotropies, and enhanced forward scattering when compared to their particle (high index inclusions in a low index medium) counterparts. We evaluate amorphous silicon solar cell textures comprising either arrays of voids or particles. Both designs support substantial absorption enhancements (up to 45%) relative to a flat cell with anti-reflection coating, over a large range of cell thicknesses. By leveraging void-based textures 90% of above-bandgap photons are absorbed in cells with maximal vertical dimension of 100 nm.


Genome wide genetic dissection of wheat quality and yield related traits and their relationship with grain shape and size traits in an elite × non-adapted bread wheat cross.
The genetic gain in yield and quality are two major targets of wheat breeding programs around the world. In this study, a high density genetic map consisting of 10,172 SNP markers identified a total of 43 genomic regions associated with three quality traits, three yield traits and two agronomic traits in hard red spring wheat (HRSW). When compared with six grain shape and size traits, the quality traits showed mostly independent genetic control (~18% common loci), while the yield traits showed moderate association (~53% common loci). Association of genomic regions for grain area (GA) and thousand-grain weight (TGW), with yield suggests that targeting an increase in GA may help enhancing wheat yield through an increase in TGW. Flour extraction (FE), although has a weak positive phenotypic association with grain shape and size, they do not share any common genetic loci. A major contributor to plant height was the Rht8 locus and the reduced height allele was associated with significant increase in grains per spike (GPS) and FE, and decrease in number of spikes per square meter and test weight. Stable loci were identified for almost all the traits. However, we could not find any QTL in the region of major known genes like GPC-B1, Ha, Rht-1, and Ppd-1. Epistasis also played an important role in the genetics of majority of the traits. In addition to enhancing our knowledge about the association of wheat quality and yield with grain shape and size, this study provides novel loci, genetic information and pre-breeding material (combining positive alleles from both parents) to enhance the cultivated gene pool in wheat germplasm. These resources are valuable in facilitating molecular breeding for wheat quality and yield improvement.


Calcaneal fractures - the orthopaedic challenge.
Calcaneal fractures, since their description in 1843 by Malgaigne, still remain a challenge in orthopaedic surgery. They are significant from an epidemiological point of view - they represent 60% of all tarsal fractures, and of an increasing number of fractures due to traffic accidents and their outcome is unpredictable. In contrast to the disappointing results after nonoperative treatment and at the beginnings of calcaneal surgery, the outcome is promising nowadays. New imaging and fixation devices, with proper classification and indication for certain surgical procedures have led to the improved outcome. But, there are still controversies, and we emphasize the most rationale treatment for the calcaneal fractures, as well as best surgical options.


Preliminary experience with Madopar HBS: clinical observations and plasma levodopa concentrations.
The therapeutic efficacy of Madopar HBS was investigated in 5 patients with advanced parkinsonism. They were under treatment with standard Madopar and suffered from marked fluctuations, mainly end-of-dose akinesia. All patients were abruptly switched from standard Madopar to the HBS formulation. For the first few days (up to 1 week) dosage and number of daily intakes of HBS were the same as those of the standard formulation. Under this treatment there was some deterioration of the clinical state. The dosage was then gradually increased, on average to about twice the daily amount. After 4 weeks therapy with Madopar HBS there was an improvement of akinesia and rigidity. End-of-dose akinesia was also improved, but all patients reported prolonged periods of early-morning akinesia; tremor remained unchanged. Hourly measurements of plasma levodopa and 3-O-methyldopa concentrations showed markedly increased values under Madopar HBS. The concentrations still were found to fluctuate in a similar extent as before and did not closely correlate with the actual stage of mobility. In contrast to the initial benefit, follow-up observation up to 40 weeks revealed a marked deterioration, either with permanent akinesia, or reappearance of fluctuations with a tendency from predictable to unpredictable forms.


Emotion regulation as a transdiagnostic factor in eating disorders and gambling disorder: Treatment outcome implications.
A first approach addressed to ascertain whether emotion regulation (ER) could be a transdiagnostic construct between eating disorders (EDs) and gambling disorder (GD) (through a joint clinical clustering analysis of both disorders) was performed by Munguía et al. (2021). Both conditions were represented by a severe, moderate, and low ER profile subgroups, according to the degree of ER difficulties. Results showed a linear relationship between the severity of ER difficulties and the severity of the disorder and the psychopathological state. Based on the aforementioned cross-sectional study, the objective of this longitudinal research was to explore the treatment response of the different ER subgroups. 459 adult patients (n = 277 ED; n = 182 GD) were included. Several clinical variables, as well as outcome indicators (after completing 16 weeks of cognitive-behavioral therapy), were evaluated. The three subgroups found in the previous cross-sectional study were taken for the performance of the present research. ED and GD distribution in each subgroup replicates the one exposed by Munguía et al. (2021), as well as their characterization, considering psychopathology, disorder severity and personality traits. The low ER subgroup reported a better response to treatment, whereas the severe group had the highest rates of non-remission and dropouts. Our results suggest that greater difficulties in ER lead to poorer treatment outcomes. Therefore, tailored treatments for patients with poor ER abilities would be recommended to improve adherence and treatment outcomes.


Membranoproliferative glomerulonephritis associated with hypocomplementemic urticarial vasculitis after complete remission of membranous nephropathy.
A 49-year-old-man developed proteinuria in 1978. He was diagnosed as having membranous nephropathy by renal biopsy and was treated with prednisolone. The proteinuria disappeared completely and the treatment was stopped. In 1995, after complete remission, he developed nephrotic syndrome with chronic urticaria and hypocomplementemia. Renal biopsy revealed membranoproliferative glomerulonephritis (type I) and skin biopsy showed leukocytoclastic vasculitis, which was compatible with hypocomplementemic vasculitis syndrome. Steroid therapy was very effective.


Shrinkage of sound and demineralized human coronal dentine slabs.
In this article a method is presented for dentine shrinkage measurements. The relative shrinkage of sound dentine slabs is assessed using a Perthometer with respect to a steel reference. The relative shrinkage of lesions in dentine slabs can be estimated using combined Perthometer/microradiography measurements. The results show that the relative lesion shrinkage of lesions in thick slabs is quite different from the shrinkage of lesions in thin sections used for microradiography. The relative lesion shrinkage is, for periods up to 30 min, linear with the air drying period and increases strongly with the demineralization period. The previously published diol treatment is capable of reducing the relative lesion shrinkage in thick dentine slabs to negligible values.


Chronic hypernatremia due to impaired osmoregulated thirst and vasopressin secretion.
We report the case of a young man who became adipsic following a subarachnoid hemorrhage and subsequently had two episodes of life-threatening hypernatremia. Investigations demonstrated that he had defective osmoregulated thirst and AVP release, but normal AVP responses to hypotension and nausea. There is also evidence that he had intact baroregulated thirst. We discuss the results of our investigations in the context of current models of hypothalamic-neurohypophysial function.


Prothrombin index is an indirect marker of severe liver fibrosis.
The non-invasive diagnosis of liver fibrosis is based mainly on biochemical markers. The main aim was to validate whether the prothrombin index is an indirect marker of the severity of liver fibrosis. The predictive value of the prothrombin index for liver fibrosis was first assessed in 243 patients with chronic liver disease, then validated in 193 other patients with chronic liver disease. The reproducibility of measurement of the prothrombin index in different laboratories was evaluated in 82 other patients. In the first group, the prothrombin index was predicted accurately by serum hyaluronate (R(2)= 0.67 at the first step by multiple regression). The relationship between the prothrombin index and the area of fibrosis was not influenced significantly by non-fibrotic pathological lesions. The prothrombin index began to decrease when the Metavir fibrosis score was 2 versus 3 for albumin. In the second group, the prothrombin index and the histological fibrosis score were well correlated (r= -0.70, P< 10(-4)). Prothrombin index < or =80% or < or =70% diagnosed severe fibrosis or cirrhosis, respectively, and prothrombin index > or =105% or > or =100% excluded a diagnosis of severe fibrosis or cirrhosis, respectively, at the 95% probability level. The prothrombin indices measured in different laboratories were similar (78+/-18% v. 78+/-14%) and well correlated (r= 0.91, P< 10(-4)). The prothrombin index was well correlated with pathological liver fibrosis score, had a high diagnostic accuracy for severe fibrosis or cirrhosis especially due to alcohol, and was not influenced by other pathological lesions. The prothrombin index was reproducible. Thus, the prothrombin index expressed as a percentage is an accurate, reproducible, inexpensive and easily available marker of severe liver fibrosis.


Human synthetic lethal inference as potential anti-cancer target gene detection.
Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates. Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.


Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy.
Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMP-activated protein kinase (AMPK) and peroxisome proliferator activated receptor-α (PPARα) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPARα and expression of its downstream targets, i.e., acyl-CoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser(565), and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future.


Oncologic and functional outcomes in advanced laryngeal and hypopharyngeal cancer treated with concurrent chemoradiation versus primary surgery followed by adjuvant treatment.
To compare oncologic outcomes in advanced laryngeal and hypopharyngeal cancer (LHC) patients who received either concurrent chemoradiation (CRT) or primary surgery followed by adjuvant treatment and to examine functional outcomes in the patients treated with CRT. The clinicopathological data of 136 patients, diagnosed as stage III or IV LHC, were retrospectively reviewed. The eligible patients were classified into two groups based on their primary treatment, CRT group and group of surgery followed by the adjuvant treatment. Oncologic outcomes were evaluated and compared at five years. Functional outcomes were recorded as tracheostomy and/or feeding tube dependency. Five-year overall survival rates were 66.9% for the primary surgery group and 34.8% for the CRT group (p = 0.004). Five-year disease-specific survival rates for the same two groups were 66.9% and 39.9%, respectively (p = 0.03). The three-year laryngectomy-free survival rate in the CRT group was 71.9%. At three months post-CRT 62.3% of patients depended on tracheostomy and/or a feeding tube. The primary surgery followed by adjunctive treatment among the advanced LHC cases had significantly better oncologic outcomes. Nevertheless, CRT group had a high survival rate with a preserved larynx, but with relatively inferior functional outcomes.


Phosphoenolpyruvate carboxylase from spinach leaf tissue: inhibition by sulfite ion.
Phosphoenolpyruvate carboxylase (EC 184.108.40.206), partially purified from spinach (Spinacia oleracea) leaves, is inhibited by SO(3) (2-) ion. The inhibition is competitive or mixed type with respect to HCO(3) (-) (Ki = 17 mm), and noncompetitive with respect to phosphoenolpyruvic acid (Ki = 11 mm), Mg(2+) (Ki = 10 mm), and Mn(2+) (Ki = 2.4 mm). The inhibitory effect of SO(3) (2-) is more significant in the presence of Mn(2+) than in the presence of Mg(2+). l-Malate, an inhibitor of phosphoenolpyruvate carboxylase activity, and SO(3) (2-) may bind at the same site on the enzyme. Glyoxal bisulfite and glyoxylate bisulfite are equally effective inhibitors of the enzyme activity as SO(3) (2-), but alpha-hydroxypyridinemethanesulfonate is a weak inhibitor. The data are discussed in relation to the physiological effect of the air pollutant (SO(2)) on plant leaf metabolism.


Roles of factorial noise in inducing bimodal gene expression.
Some gene regulatory systems can exhibit bimodal distributions of mRNA or protein although the deterministic counterparts are monostable. This noise-induced bimodality is an interesting phenomenon and has important biological implications, but it is unclear how different sources of expression noise (each source creates so-called factorial noise that is defined as a component of the total noise) contribute separately to this stochastic bimodality. Here we consider a minimal model of gene regulation, which is monostable in the deterministic case. Although simple, this system contains factorial noise of two main kinds: promoter noise due to switching between gene states and transcriptional (or translational) noise due to synthesis and degradation of mRNA (or protein). To better trace the roles of factorial noise in inducing bimodality, we also analyze two limit models, continuous and adiabatic approximations, apart from the exact model. We show that in the case of slow gene switching, the continuous model where only promoter noise is considered can exhibit bimodality; in the case of fast switching, the adiabatic model where only transcriptional or translational noise is considered can also exhibit bimodality but the exact model cannot; and in other cases, both promoter noise and transcriptional or translational noise can cooperatively induce bimodality. Since slow gene switching and large protein copy numbers are characteristics of eukaryotic cells, whereas fast gene switching and small protein copy numbers are characteristics of prokaryotic cells, we infer that eukaryotic stochastic bimodality is induced mainly by promoter noise, whereas prokaryotic stochastic bimodality is induced primarily by transcriptional or translational noise.


The association between drinking and smoking habits among conscripts in the Danish Navy and Army.
In 1982 an alcohol and tobacco questionnaire was given to Danish conscripts on random weekdays in the first two weeks of call-up. The conscripts were asked about the previous day's consumption of alcohol and tobacco. In the navy 94.4% (N = 162) and in the army 92.0% (N = 514) answered the questions. Both smoking and drinking in the navy were found to be more prevalent than in the army, whereas the habits among conscripts in the army and in the civilian population were identical. In the army length of education was found to be inversely related to drinking and smoking, whereas in the navy education did not seem to influence smoking or drinking habits. In the army increasing amounts of drinking were associated with higher prevalences of light to heavy smoking and vice versa. In the navy only heavy drinking was strongly associated with a pronounced rate of heavy smoking. The difference seen between the navy and the army in tobacco and alcohol habits could not be explained by differences in age or level of education. Some other sociological, psychological and life style factors may be involved. We find it relevant to pinpoint high risk populations regarding excessive alcohol and tobacco consumption, so that rational prophylaxis or intervention might be effectuated. Health education programmes ought to contain information about the illnesses of both excessive alcohol and tobacco consumption, as these habits are closely related.


Validation of a Unilateral Cleft Lip Surgical Outcomes Evaluation Scale for Surgeons and Laypersons.
A standardized evaluation tool is needed for the assessment of surgical outcomes in cleft lip surgery. Current scales for evaluating unilateral cleft lip/nose (UCL/N) aesthetic outcomes are limited in their reliability, ease of use, and application. The Unilateral Cleft Lip Surgical Outcomes Evaluation (UCL SOE) scale measures symmetry of 4 components and sums these for a total score. The purpose of this study was to validate the SOE as a reliable tool for use by both surgeons and laypersons. Twenty participants (9 surgeons and 12 laypeople) used the SOE to evaluate 25 sets of randomly selected presurgical and postsurgical standardized photographs of UCL/N patients. Interrater reliability for surgeon and laypeople was determined using an intraclass correlation coefficient (ICC). Individual surgeons and laypeople both reached an ICC in the "fair to good" range (ICC = 0.42 and 0.59, respectively). Averaging 2 evaluators in the surgeon group improved the ICC to 0.58 and in the laypeople group to 0.74, respectively. Averaging 3 evaluators increased the ICC for surgeons to the "good" range (ICC = 0.71) and the ICC for laypeople to the "very good" range (ICC = 0.82). Surgeon and layperson raters can reliably use the SOE to assess the aesthetics results after surgical repair of UCL/N, and improved reliability and reproducibility is achieved by averaging the scores of multiple reviewers.


Unveiling robustness and heterogeneity through percolation triggered by random-link breakdown.
It has been commonly recognized that heterogeneously connected networks are robust against random decays but vulnerable to malicious attacks. However, little is known about measures of heterogeneity geared towards robustness of complex networks. Here, we propose two types of percolation on general networks triggered by random-link errors, where occupied links support the nodes to be alive. Rich resilience behaviors are observed in terms of the percolation threshold and the (integrated) fraction of giant cluster. The discrepancy unraveled between the two models allows us to dynamically define compact measures that have acute discrimination in gauging network heterogeneity. The results provide a connection between network performance, structure, and dynamics.


General random matrix approach to account for the effect of static disorder on the spectral properties of light harvesting systems.
We develop a random matrix model approach to study static disorder in pigment-protein complexes in photosynthetic organisms. As a case study, we examine the ring of B850 bacteriochlorophylls in the peripheral light-harvesting complex of Rhodospirillum molischianum, formulated in terms of an effective Hamiltonian describing the collective electronic excitations of the system. We numerically examine and compare various models of disorder and observe that both the density of states and the absorption spectrum of the model show remarkable spectral universality. For the case of unitary disorder, we develop a method to analytically evaluate the density of states of the ensemble using the supersymmetric formulation of random matrix theory. Succinct formulas that can be readily applied in future studies are provided in an appendix.


Tetracarbaboranes: nido structures without bridging hydrogens.
The structures and energetics of the tetracarbaboranes C4Bn-4Hn (n = 6 to 13) have been investigated by density functional theory and coupled cluster calculations. In general, the lowest energy structures of the tetracarbaboranes C4Bn-4Hn minimize the number of C-C polyhedral edges as well as the degrees of the carbon vertices. For the C4B2H6 and C4B3H7 systems the lowest energy structures are pyramidal structures having all four carbon atoms located on the base of the pyramid. The lowest energy structure for the 9-vertex C4B5H9 system is a capped square antiprism. The frameworks of the lowest energy C4B4H8 and C4B6H10 structures resemble those of the isoelectronic experimentally known B8H12 and B10H14 structures. However, an experimentally known S4 adamantane-like 10-vertex structure found in Me4C4B6Et6 based on a tetracapped octahedron lies only ∼7 kcal mol-1 in energy above the lowest energy structure. The lowest energy structures for the 11- to 13-vertex C4Bn-4Hn (n = 11, 12, 13) systems can be derived from an (n + 1)-vertex closo deltahedron by removing a high-degree vertex. At least three of the four carbon atoms are located on edges of the resulting pentagonal or hexagonal open face in the low-energy structures. However, the structures of the experimentally known R4C4B8H8 (R = Me, Et) obtained from the dimerization of R2C2B4H42- differ from these low-energy structures. The Me4C4B8H8 polyhedron has a C4 chain and two tetragonal faces whereas the Et4C4B8H8 polyhedron has a hexagonal face with two C2 units. These structures lie within 2 kcal mol-1 of each other thereby accounting for the fluxional properties of these systems observed by NMR spectroscopy.


Temporal arteritis: a cough, toothache, and tongue infarction.
Temporal arteritis, the most common form of systemic vasculitis in adults, is a panarteritis that chiefly involves the extracranial branches of the carotid artery. The condition is illustrated in this article by the case of a 79-year-old woman with a dry cough, toothache, tongue infarction, and vision loss. The mean age of onset is 72 years and the disease rarely occurs in persons younger than 50 years. The most common presenting manifestations are headache, jaw claudication, polymyalgia rheumatica, and visual symptoms. Eighty-nine percent of patients have an erythrocyte sedimentation rate greater than 50 mm/h. However, about 40% of patients present with atypical manifestations, including fever of unknown origin, respiratory tract symptoms (especially dry cough), and large artery involvement. Familiarity with such unusual manifestations of temporal arteritis facilitates early diagnosis and treatment, thereby reducing the risk of vision loss.


Controllable in situ synthesis of magnetite coated silica-core water-dispersible hybrid nanomaterials.
Magnetite nanoparticle coated silica (Fe3O4@SiO2) hybrid nanomaterials hold an important position in the fields of cell imaging and drug delivery. Here we report a large scale synthetic procedure that allows attachment of magnetite nanoparticles onto a silica surface in situ. Many different silica nanomaterials such as Stöber silica nanospheres, mesoporous silica nanoparticles, and hollow silica nanotubes have been coated with a high density layer of water-dispersible magnetite nanoparticles. The size and attachment efficiency of the magnetite nanoparticle can be well tuned by adjusting the precursor concentration and reflux time. The functionalization of Fe3O4@SiO2 nanoparticles with dye molecules and biocompatible polymers impart optical imaging modality and good colloidal stability in either buffer solution or serum. The functionalized materials also exhibited strong potential as negative contrast agents in T2 weighted magnetic resonance imaging.


Diabetic foot infections: a comprehensive overview.
Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.


pH Sensitive Hydrogels in Drug Delivery: Brief History, Properties, Swelling, and Release Mechanism, Material Selection and Applications.
Improving the safety efficacy ratio of existing drugs is a current challenge to be addressed rather than the development of novel drugs which involve much expense and time. The efficacy of drugs is affected by a number of factors such as their low aqueous solubility, unequal absorption along the gastrointestinal (GI) tract, risk of degradation in the acidic milieu of the stomach, low permeation of the drugs in the upper GI tract, systematic side effects, etc. This review aims to enlighten readers on the role of pH sensitive hydrogels in drug delivery, their mechanism of action, swelling, and drug release as a function of pH change along the GI tract. The basis for the selection of materials, their structural features, physical and chemical properties, the presence of ionic pendant groups, and the influence of their pKa and pKb values on the ionization, consequent swelling, and targeted drug release are also highlighted.


Proteomic profile of serum from patients with schizophrenia spectrum disorders.
This article describes the most likely classes of proteins and molecular processes that specifically characterize schizophrenic spectrum disorders such as simple and paranoid schizophrenia, schizotypal disorder, and acute polymorphic psychotic disorder (APPD). The identification of patients' serum proteins was carried out using mass spectrometry. For patients with paranoid schizophrenia, the proteins responsible for translation and transcription are characteristic. A significant part of the proteins of patients with simple schizophrenia regulate the cell's main metabolic and transport processes. These are proteins of the receptor system, vesicular transport, and extracellular matrix, which mainly carry out catabolic processes. The proteins of patients with schizotypal disorder mostly coincided with the classes of other patients, apart from chaperone proteins, which were not found in other studied groups. These proteins are mainly involved in anabolic processes. The main classes of proteins found in patients with APPD are responsible for the metabolism of nucleic acids. Active apoptosis processes were also revealed in these patients. These results from our basic knowledge about the molecular mechanisms of the pathogenesis of these disorders.


Halothane does not alter Ca2+ affinity of troponin C.
Troponin C has been suggested as a possible target for the negative inotropic action of volatile anesthetics. This study has examined the effect of halothane on the structure and response of isolated cardiac troponin C to Ca2+ and the response of skinned soleus and cardiac muscle fibers to Ca2+. The high-affinity Ca(2+)-binding sites of cardiac troponin C were assessed by measurement of the change in intrinsic tyrosine fluorescence and ultraviolet circular dichroism in response to Ca2+ in the presence and absence of halothane. Halothane (0.9 mM, 1.4%) did not alter the 45% enhancement in intrinsic tyrosine fluorescence that occurs with saturation of the high-affinity sites or change the Ca2+ concentration at which half-maximal enhancement occurred. The molar ellipticity in the far ultraviolet region, a measure of the secondary structure, increased to a similar extent with addition of 10(-6) M Ca2+ in the absence and presence of 1.0 mM (1.6%) halothane. The binding rate of the sulfhydryl reagent, 5,5'-dithiobis (2-nitrobenzoic acid), to troponin C in response to Ca2+ titration was used as a measure of the integrity of the low-affinity Ca(2+)-binding site in troponin C in the presence and absence of 1.0 mM (1.6%) halothane. The rate of reaction was stimulated twofold, and the half maximal effect was observed at pCa 4.8 +/- 0.2 in both control and halothane-treated samples. Halothane (5 mM; 7.8%) did not change the pCa/tension response of skinned soleus fibers; the data were fit to the Hill equation and yielded dissociation constants of 6.2 x 10(-7) M for control and halothane-treated specimens.(ABSTRACT TRUNCATED AT 250 WORDS)


Successful treatment of early myoclonic encephalopathy using lidocaine and carbamazepine.
We report two female infants with early myoclonic encephalopathy (EME) whose intractable focal seizures were suppressed with lidocaine and carbamazepine (CBZ). Although EME is a form of early-onset epileptic encephalopathy characterised by myoclonus and focal seizures that are highly resistant to treatment, lidocaine and CBZ may prove effective in treating this disorder. Future studies should be performed in order to determine whether there are common specific mechanisms of seizure generation related to the sodium channel in these patients.


Parent and nurse perceptions of parent stressors in the pediatric intensive care unit.
This study examined parent and nurse perceptions of parent stressors in a pediatric intensive care unit using the Parental Stressor Scale: Pediatric Intensive Care Unit (PSS:PICU) and standardized interviews of parents. A total of 41 parents and 34 nurses participated. Nurses expected parents to be more stressed by every dimension of the PSS:PICU than parents rated their own stress. Parents felt most stressed by the dimension relating to their child's behavioral and emotional responses, although nurses expected parents to be most concerned about staff communication and parental role alteration issues. Implications for clinical practice are discussed.


Effect of arginine aspartate on the exercise-induced hyperammoniemia in humans: a two periods cross-over trial.
To investigate the effect of the ingestion of arginine aspartate (AA) in the decrease of the exercise-induced accumulation of ammonia in plasma, 11 voluntary subjects took part in a cross-over study where AA effect was tested against placebo. Both treatments were randomly administered in a double-blind procedure. To ensure the subjects would be able to present reproducible exercise-testing results during repetitive sessions, they were involved before the experiment in a cycle ergometer training program during 8 weeks. This training determined a significant 14% increase (P less than 0.001) in maximal oxygen uptake (VO2 max). The treatments were administered during 10 days and the two treatments were separated by a 10 day-wash-out period. A 45 min-cycle ergometer test was performed at 80% VO2 max during the 10th day of each treatment to measure plasma ammonia (p[NH4+]) and total blood lactate (b[lact]) concentrations at rest and at the 15th, 30th and 45th min of exercise (determinations of changes from rest; delta p[NH4+] and delta b[lact]). Both concentrations were unchanged between AA and placebo at rest but a significant lesser delta p[NH4+] was found under AA at the 15th min of exercise only (P less than 0.05). On the other hand, an order effect was found for delta p[NH4+] between the two periods of randomized treatment that was interpreted as a remaining training effect. This effect was highly significant at the 30th and 45th min of exercise (P less than 0.001). It was concluded that AA effect was minor with regard to the training effect. As it was not located at the same time of exercise, AA effect would not consequently have the same functional origin (postulated increase in the peripheral clearance of ammonia) than those of training (decrease in muscle production of ammonia).


Human chronic myeloid leukemic cell line with positive Philadelphia chromosome exhibits megakaryocytic and erythroid characteristics.
A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of chromosome markers. LAMA-84 cells have morphological features of undifferentiated blast cells, but analyses have indicated that they belong to the megakaryocytic lineage; platelet peroxidase (PPO) was found in 8.5% of cells; LAMA-84 cells reacted spontaneously with poly- and monoclonal antibodies against the platelet glycoproteins (GP) IIb, IIIa, and the GPIIb/IIIa complex, whose presence was confirmed by crossed immunoelectrophoresis. LAMA-84 cells lack the membrane characteristics of lymphoid and mature granulocytic cells but do, however, react with certain antibodies to immature myeloid cells. Furthermore, they are positive with an antiglycophorin antibody, and contain alpha- and gamma-globin mRNA, thus demonstrating erythroid marker expression. Thus LAMA-84 is a tripotent, megakaryocytic, erythroid, and granulocytic cell line. The megakaryocytic and erythroid markers were enhanced by the addition of DMSO, butyrate, TPA, and hemin. The LAMA-84 cell line represents an interesting tool for the study of megakaryocytic and erythroid differentiation and the mechanisms of neoplastic growth.


Arthritis self-efficacy scale scores in knee osteoarthritis: a systematic review and meta-analysis comparing arthritis self-management education with or without exercise.
Systematic literature review and meta-analysis. To evaluate studies that used arthritis self-management education alone or with exercise to improve Arthritis Self-Efficacy Scale scores of patients with knee osteoarthritis. Increasing self-efficacy may improve patient knee osteoarthritis symptom management and function. MEDLINE (1946-March 2013), CINAHL (1981-March 2013), and PsycINFO (1967-March 2013) databases were searched. Twenty-four studies, including 3163 subjects (women, n = 2547 [80.5%]; mean ± SD age, 65.3 ± 6.5 years), met the inclusion criteria. A meta-analysis was performed to compare the standardized mean difference effect sizes (Cohen d) of randomized controlled studies that used the Arthritis Self-Efficacy Scale pain (13 studies, n = 1906), other symptoms (13 studies, n = 1957), and function (5 studies, n = 399) subscales. Cohen d effect sizes were also calculated for cohort studies that used the Arthritis Self-Efficacy Scale pain (10 studies, n = 1035), other symptoms (9 studies, n = 913), and function (3 studies, n = 141) subscales. Both randomized controlled studies and cohort studies were grouped by intervention type (intervention 1, arthritis self-management education alone; intervention 2, arthritis self-management education with exercise), and effect sizes were compared (Mann-Whitney U tests, P<.05). Interventions that used arthritis self-management education with exercise displayed higher methodological quality scale scores (76.8 ± 13.1 versus 61.6 ± 19.6, P = .03). Statistically significant standardized effect-size differences between intervention 1 and intervention 2 were not observed. Small to moderate effect sizes were observed regardless of whether the intervention included exercise. Exercise interventions used in conjunction with arthritis self-management education programs need to be developed to better enhance the self-efficacy of patients with knee osteoarthritis. Therapy, level 2b-.


The effects of thiamine and oxythiamine on the survival of cultured brain neurons.
The effects of treatment with thiamine (Vitamin B1) alone or together with its antagonist oxythiamine on the survival of brain neurons in primary culture were investigated. Treatment with thiamine significantly promoted the survival of hippocampal neurons in high cell density culture, but had no effects on the neuronal survival in low cell density culture. In addition, the survival-promoting activity exerted by thiamine was remarkably decreased by the co-application of oxythiamine, although oxythiamine used alone revealed neither a trophic nor toxic effect on the neurons of examined brain regions. The neurotrophic function of thiamine may be due to its coenzymatic role in a biochemical reaction and/or its specific function on neurotransmission and nerve conduction.


Country estimates of social discount rates based on changes in life expectancies.
"When time is the numeraire in a social evaluation of public projects, life expectancies are essentially the unit of account. Since different generations have different life expectancies, pursuing intergenerational equity requires discounting the extra time that future generations are likely to obtain. The result is a Social Discount Rate set by the growth rate in life expectancies. This is called the Life Expectancy Discount Rate (LEDR). After providing estimates of the LEDR for 120 countries, the paper discusses some of the implications of using this rate." (SUMMARY IN FRE AND GER)


Theoretical studies of blue-emitting iridium complexes with different ancillary ligands.
The structural and electronic properties of two heteroleptic iridium complexes Ir(dfppy)2(pic) (FIrpic) and Ir(dfppy)2(acac) (FIracac) have been investigated theoretically, where dfppy = 2-(2,4-difluorophenyl) pyridine, pic = picolinic acid, and acac = acetoylacetonate. The geometries of ground and excited states are optimized at PBE0/LANL2DZ and CIS/LANL2DZ levels, respectively. Time-dependent density functional theory (TDDFT) method is employed to explore the absorption and emission properties. In the ground state, the highest-occupied molecular orbital has a significant mixture of metal Ir(d) and dfppy(pi), the lowest-unoccupied orbital locates primarily on pi* of pic for FIrpic and pi* of dfppy for FIracac. The luminescence of each complex originates from the lowest triplet excited state, which is assigned to the mixing of metal-to-ligand charge transfer and intraligand charge transfer characters. The effects of ancillary ligands pic and acac on absorption and emission spectra are observed by analysis of TDDFT results. The connection between the nature of excited states and the behavior of the complexes with different ancillary ligands is elucidated.


Synthesis of α-S-glycosphingolipids based on uronic acids.
The synthesis of S-glycosphingolipids based on uronic acids is described. These compounds are analogous to the highly immunostimulatory antigens isolated from the cell walls of bacteria of the Sphingomonas family. Key to the synthetic route is a stereoselective anomerization to give α-glycosyl thiol precursors. A route to a sphinganine precursor from pseudoephedrine glycinamide is also described.


Rapidly progressive destructive arthropathy of the shoulder--a viewpoint on pathogenesis.
Two cases of rapidly progressive destructive shoulder arthropathy are described. Both patients were elderly women with generalized osteoarthropathy who had used forearm crutches for walking. Their shoulder disease was characterized by large, relatively painless effusions, low numbers of infiltrating leukocytes, biopsy evidence of mild inflammation, and radiological evidence of severe joint damage. Case 1 developed persistent drainage from a joint sinus, eventually necessitating arthrodesis. This complication has not previously been described in this condition. Hydroxyapatite crystals were demonstrated in the joint fluid in both cases but their pathological role is uncertain. We suggest that bearing weight through the upper limbs may hasten the development of degenerative arthritis in the shoulder, possibly by contributing to mechanical disruption of the rotator cuff.


Nebivolol attenuates maladaptive proximal tubule remodeling in transgenic rats.
The impact of nebivolol therapy on the renal proximal tubular cell (PTC) structure and function was investigated in a transgenic (TG) rodent model of hypertension and the cardiometabolic syndrome. The TG Ren2 rat develops nephropathy with proteinuria, increased renal angiotensin II levels and oxidative stress, and PTC remodeling. Nebivolol, a beta(1)-antagonist, has recently been shown to reduce albuminuria, in part, through reductions in renal oxidative stress. Accordingly, we hypothesized that nebivolol therapy would attenuate PTC damage and tubulointerstitial fibrosis. Young Ren2 (R2-N) and SD (SD-N) rats were treated with nebivolol (10 mg/kg/day) or vehicle (R2-C; SD-C) for 3 weeks. PTC structure and function were tested using transmission electron microscopy and functional measurements. Nebivolol treatment decreased urinary N-acetyl-beta-D-glucosaminidase, tubulointerstitial ultrastructural remodeling and fibrosis, NADPH oxidase activity, 3-nitrotyrosine levels, and increased megalin and lysosomal-associated membrane protein-2 immunostaining in PTCs. Ultrastructural abnormalities that were improved with therapy included altered canalicular structure, reduced endosomes/lysosomes and PTC vacuoles, basement membrane thickening, and mitochondrial remodeling/fragmentation. These observations support the notion that nebivolol may improve PTC reabsorption of albumin and other glomerular filtered small molecular weight proteins in association with the attenuation of oxidative stress, tubulointerstitial injury and fibrosis in this rat model of metabolic kidney disease.


Induction of manganese superoxide dismutase in cultured human trophoblast during in vitro differentiation.
The antioxidant responses of human cell differentiation and membrane fusion are not known and may be important in understanding cellular response to injury in the human placenta. We studied the regulation of antioxidant enzymes in human trophoblasts which differentiate from mononucleated cellular trophoblasts to synctium in vivo and in culture. We characterized morphological and biochemical differentiation of cultured trophoblasts from term placenta in the presence or absence of serum, on different growth surfaces, and with a range of plating densities. Culture of cellular trophoblasts consistently and transiently induced the mRNAs of the mitochondrial antioxidant manganese superoxide dismutase (Mn SOD) but not the mRNAs for the antioxidant enzymes copper zinc SOD or catalase. Fibrin and type I collagen substrates modulated only the expression of the placental specific proteins, human chorionic gonadotropin, and human placental lactogen. Both Mn SOD induction and terminal differentiation, as reflected by human chorionic gonadotropin expression, were dependent on trophoblastic plating density. Increased levels of a smaller Mn SOD mRNA species correlated temporally with an increase in Mn SOD enzyme activity in cultured trophoblasts. These results demonstrate that Mn SOD gene expression and enzyme activity precede or are coordinately regulated with morphological and biochemical trophoblastic differentiation.


Toward the introgression of PvPdh1 for increased resistance to pod shattering in common bean.
A common bean shattering-resistance allele of PvPdh1 reduces pod twists during dehiscence, shows dominance that varies by phenotyping method, is part of a selective sweep, and can be introgressed using CAPS markers. Some varieties of common bean (Phaseolus vulgaris L.) suffer from pod shattering, which can severely reduce yields, especially in arid conditions. The PvPdh1 locus on chromosome Pv03 has recently been described as a major locus controlling pod shattering in common bean and could be used to mitigate pod shattering in the future. Despite this, the role of a possible second locus on chromosome Pv08 remains unclear and patterns of dominance and epistasis between alleles of these genes have not been resolved. This information will be vital for efficient selection to decrease pod shattering. Further, the genetic diversity around the PvPdh1 gene has not yet been thoroughly explored, and there are not yet genetic screens that can be used to evaluate pod shattering in segregating populations. Here, we have developed a recombinant inbred population to determine the roles of genes implicated in pod shattering and evaluate the patterns of dominance among the relevant alleles. Our results suggest that a PvPdh1 allele reduces pod valve twisting, and its dominance varies by phenotyping method. This allele is the only genetic variant that provides environmentally stable and widespread resistance to pod shattering in Middle American common beans grown for grain. Further analyses identified a selective sweep around PvPdh1 with greater nucleotide diversity in individuals with the ancestral, shattering-susceptible allele. Finally, we developed simple, effective CAPS markers to facilitate the introgression of PvPdh1 into new varieties of common bean. These genetic resources will be critical for improving the aridity resilience of a major global staple.


Stochastic state-space temperature regulation of biochar production. Part I: Theoretical development.
The concept of a designer biochar that targets the improvement of a specific soil property imposes the need for production processes to generate biochars with both high consistency and quality. These important production parameters can be affected by variations in process temperature that must be taken into account when controlling the pyrolysis of agricultural residues such as manures and other feedstocks. A novel stochastic state-space temperature regulator was developed to accurately match biochar batch production to a defined temperature input schedule. This was accomplished by describing the system's state-space with five temperature variables--four directly measured and one change in temperature. Relationships were derived between the observed state and the desired, controlled state. When testing the unit at two different temperatures, the actual pyrolytic temperature was within 3 °C of the control with no overshoot. This state-space regulator simultaneously controlled the indirect heat source and sample temperature by employing difficult-to-measure variables such as temperature stability in the description of the pyrolysis system's state-space. These attributes make a state-space controller an optimum control scheme for the production of a predictable, repeatable designer biochar.


Ouchterlony double immunodiffusion method demonstrates absence of ferritin immunoreactivity in visceral organs from nine patients with Niemann-Pick disease type C.
Ouchterlony double immunodiffusion clearly demonstrated absence of ferritin, the principal iron storage protein, in spleen and/or liver extracts from nine patients with Niemann-Pick disease type C (NPC). The patients died from different clinical forms of this disease of still unknown etiology. The absence of ferritin immunoreactivity was shown using two different antisera raised in rabbits against ferritin from human spleen or liver, organs which predominantly contain light chain subunits (L-ferritin). A diagnostic double immunodiffusion assay of ferritin is, therefore, feasible with small amounts of NPC liver tissue, e.g., needle biopsy specimens. Furthermore, SDS-polyacrylamide gel electrophoresis after Coomassie blue staining revealed an almost complete absence of the L-ferritin protein band in crude spleen heat extracts from two NPC patients. The absence of visceral ferritin in all nine patients studied is suggestive of a biochemical abnormality that is as characteristic as the known impairment of cellular trafficking of LDL-derived cholesterol in this complex lysosomal storage disorder. According to recent data a relationship exists between ferritin-dependent lipid peroxidation and oxidative modification of LDL. We suggest that deficiency of the antioxidant ferritin-whatever the nature of this deficiency might be-could lead to uncontrolled LDL oxidation with subsequent multisubstrate lipidosis in NPC disease.


Exercise-induced upregulation of endothelial adhesion molecules in human skeletal muscle and number of circulating cells with remodeling properties.
Multipotent cells have received great interest because of their potential capacity to repair and remodel peripheral tissues. We examined the effect of an acute exercise bout on the number of circulating cells with known remodeling properties and the level of factors in plasma and skeletal muscle tissue with potential to recruit these cells. Twenty healthy male subjects performed a 60-min cycling exercise. Blood samples for flow cytometry were drawn from 10 subjects (group 1) before and up to 2 h after exercise, and absolute cell counts of the classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocyte (MO) subpopulations and of CD45dimCD34+VEGFR2+ endothelial progenitor cells (EPCs) were measured by bead-based determination. Plasma samples and vastus lateralis muscle biopsies were obtained from the other 10 subjects (group 2). In group 1, all MO subsets were increased directly after exercise, with CD14+CD16++ MOs showing the greatest fold increase. After 2 h, only CD14++CD16- MOs were increased compared with resting levels. The number of EPCs showed a trend toward increasing with exercise (P = 0.08). In group 2, the mRNA levels of the endothelial adhesion molecules ICAM-1, VCAM-1, and E-selectin increased in the skeletal muscle tissue. VEGF-A increased in exercised skeletal muscle and stimulated the expression of VCAM-1 and E-selectin in human umbilical vein endothelial cells. In conclusion, exercise increases MO subsets with different temporal patterns and enhances the capacity of skeletal muscle tissue to recruit circulating cells as shown by increased expression of endothelial adhesion molecules.NEW & NOTEWORTHY In the present study we showed for the first time that the adhesion molecules ICAM-1, VCAM-1, and E-selectin, known to be able to recruit circulating cells to the peripheral tissue, increased in exercised human skeletal muscle concurrently with increased circulating levels of cells shown to have importance for skeletal muscle remodeling. These findings support the concept of cell recruitment from the circulation playing a role in skeletal muscle adaptation to exercise.


Optimal planar leg geometry in robots and crabs for idealized rocky terrain.
Natural terrain is uneven so it may be beneficial to grasp onto the depressions or 'valleys' between obstacles when walking over such a surface. To examine how leg geometry influences walking across obstacles with valleys, we (1) modeled the performance of a two-linkage leg with parallel axis 'hip' and 'knee' joints to determine how relative segment lengths influence stepping across rocks of varying diameter, and (2) measured the walking limbs in two species of intertidal crabs,Hemigrapsus nudusandPachygrapsus crassipes, which live on rocky shores and granular terrains. We idealized uneven terrains as adjacent rigid hemispherical 'rocks' with valleys between them and calculated kinematic factors such as workspace, limb angles with respect to the ground, and body configurations needed to step over rocks. We first find that the simulated foot tip radius relative to the rock radius is limited by friction and material failure. To enable force closure for grasping, and assuming that friction coefficients above 0.5 are unrealistic, the foot tip radius must be at least 10 times smaller than that of the rocks. However, ratios above 15 are at risk of fracture. Second, we find the theoretical optimal leg geometry for robots is, with the distal segment 0.63 of the total length, which enables the traversal of rocks with a diameter that is 37% of the total leg length. Surprisingly, the intertidal crabs' walking limbs cluster around the same limb ratio of 0.63, showing deviations for limbs less specialized for walking. Our results can be applied broadly when designing segment lengths and foot shapes for legged robots on uneven terrain, as demonstrated here using a hexapod crab-inspired robot. Furthermore, these findings can inform our understanding of the evolutionary patterns in leg anatomy associated with adapting to rocky terrain.


Turning down the system: counter-regulatory mechanisms in bone and adaptive immunity.
Major advances have been made in recent years toward the identification of transcription factors that control cell-type-specific gene expression in the skeletal and adaptive immune systems. However, the identification of factors necessary and sufficient to drive production of effector cell proteins such as matrix components and cytokines represents the first step toward understanding how cells in bone and the adaptive system achieve their highly specialized functions. Here, we provide selected examples of counter-regulatory mechanisms that serve to turn down cells involved in extracellular matrix biosynthesis and adaptive immunity at the level of the transcription factors Runx2 and nuclear factor for the activation of T cells.


Right Common Iliac Artery Occlusion in a Patient with Severe COVID-19.
In patients with coronavirus disease 2019 (COVID-19), thromboembolism is a frequently reported complication. However, it is reported that the incidence of arterial occlusion is rare. We experienced a case of 70-year-old male patient who developed a complication of Right common iliac arterial occlusion while treating him for confirmed COVID-19 who did not have any risk factors, such as diabetes or smoking. As in our case, it is necessary to carefully observe whether this complication occurs while treating COVID-19 patients.


Nogo-A expression in the brain of mice with cerebral malaria.
Cerebral malaria (CM) is associated with a high rate of transient or persistent neurological sequelae. Nogo-A, a protein that is highly expressed in the endoplasmic reticulum (ER) of the mammalian central nervous system (CNS), is involved in neuronal regeneration and synaptic plasticity in the injured CNS. The current study investigates the role of Nogo-A in the course of experimental CM. C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. Brain homogenates of mice with different clinical severity levels of CM, infected animals without CM and control animals were analyzed for Nogo-A up-regulation by Western blotting and immunohistochemistry. Brain regions with Nogo-A upregulation were evaluated by transmission electron microscopy. Densitometric analysis of Western blots yielded a statistically significant upregulation of Nogo-A in mice showing moderate to severe CM. The number of neurons and oligodendrocytes positive for Nogo-A did not differ significantly between the studied groups. However, mice with severe CM showed a significantly higher number of cells with intense Nogo-A staining in the brain stem. In this region ultrastructural alterations of the ER were regularly observed. Nogo-A is upregulated during the early course of experimental CM. In the brain stem of severely affected animals increased Nogo-A expression and ultrastructural changes of the ER were observed. These data indicate a role of Nogo-A in neuronal stress response during experimental CM.


Myocardial fibrosis in aging germ-free and conventional Lobund-Wistar rats: the protective effect of diet restriction.
The influences of diet restriction and germ-free environment on aging were studied in 127 male Lobund-Wistar rats ranging in age from 7 to 48 months. There was an age-related increase in collagen deposition of the heart, particularly involving the left ventricle. The degree of fibrosis was significantly less extensive in middle and old age rats (18 mo, 30 mo, 32+ mo) maintained on a restricted diet. No clear-cut influence of germ-free environment was apparent. No amyloid was detected in 175 tissue sections examined from hearts, lungs, and livers.


Bilateral pulmonary embolism in a patient with pulmonary tuberculosis: a rare association in Yaoundé, Cameroon.
Pulmonary embolism is a complication of pulmonary tuberculosis that has received little emphasis in the literature. We describe a 52 year old male, with no risk factors for thromboembolic disease referred to our service for an in depth clinical review for cardiomegaly and dyspnea on exertion. Echocardiography and CT scans revealed dilated heart cavities and bilateral proximal pulmonary emboli respectively and a cavitation in the apical lobe of the right lung. Bronchial aspirate and culture revealed the presence of mycobacterium tuberculosis. There was no evidence of malignancy. Elsewhere, a clinical review and a lower limb ultrasound showed no evidence of deep venous thrombosis. Clinical course on anti - tuberculosis and anti - coagulant therapies was remarkably favorable. Clinicians need to be conscious of the risk of developing thromboembolic disease in patients treated for tuberculosis, in especially high prevalence settings like ours.


Using Kl LAC4 as a Reporter Gene in Candida albicans.
The lacZ gene which codes for beta-galactosidase from E.coli does not work in Candida albicans. In this work a reporter system with Kl LAC4 gene was contructed, coding for beta-galactosidase from Kluyveromyces lactis. Kl LAC4 gene was fused to the promoter of ADH1 of Candida albicans with the terminator sequence of ADH1 at the tail. The constructed plasmid, named pYPB1-LAC4, was used to transform Candida albicans. beta-galactosidase activity was measured by plate assay, when cultured on solid medium, and by photometric assay, when cultured in liquid medium. The results suggest that LAC4 of Kluyveromyces lactis can serve as a reporter gene in Candida albicans.


Accountable Care Organizations: roles and opportunities for hospitals.
Federal health reform has established Medicare Accountable Care Organizations (ACOs) as a new program, and some states and private payers have been independently developing ACO pilot projects. The objective is to hold provider groups accountable for the quality and cost of care to a population. The financial models for providers generally build off of shared savings between the payers and providers or some type of global payment that includes the possibility of partial or full capitation. For ACOs to achieve the same outcomes with lower costs or, better yet, improved outcomes with the same or lower costs, the delivery system will need to become more oriented toward primary care and care coordination than is currently the case. Providers of clinical services, in order to be more effective, efficient, and coordinated, will need to be supported by a variety of shared services, such as off-hours care, easy access to specialties, and information exchanges. These services can be organized by an ACO as a medical neighborhood or community. Hospitals, because they have a management structure, history of developing programs and services, and accessibility 24/7/365, are logical leaders of this enhancement of health care delivery for populations and other providers.


Hydrocolloid dressings can be used to treat hypertrophic scars: An outpatient dermatology service devoted to treat keloids and challenging scars.
Since we first described the rationale for the use of hydrocolloid dressings to treat keloids and hypertrophic scars, this technique has been used as an occlusive therapy alternative to the use of silicone sheets in our outpatient clinic. In this paper, we describe the use of these dressings on two patients with challenging scars: a large postburn hypertrophic scar on a young patient's hand and arm, with a growing keloid on the wrist, and a progressive scar on the lower eyelid, developing after a complication of a cosmetic blepharoplasty procedure, leading to ectropium. The methods on the proper use of these dressings are reviewed here in detail. Larger clinical trials are needed to further evaluate this technique in the treatment of hypertrophic scars and keloids.


Demonstration of the lateral casimir force.
The lateral Casimir force between a sinusoidally corrugated gold coated plate and large sphere was measured for surface separations between 0.2 to 0.3 microm using an atomic force microscope. The measured force shows the required periodicity corresponding to the corrugations. It also exhibits the necessary inverse fourth power distance dependence. The obtained results are shown to be in good agreement with a complete theory taking into account the imperfectness of the boundary metal. This demonstration opens new opportunities for the use of the Casimir effect for lateral translation in microelectromechanical systems.


A study of immune profile in human hydatid diseases.
A clinico haematological and immunological study was undertaken in 90 patients clinically suspected to be suffering from hydatid disease over a period of 1 year. The parameters studied included age of presentation, site of cyst localisation, haematological profile, total immunoglobins of different classes (IgG, IgM, IgA & IgE) and complement component C3, rosette forming lymphocytes, blast cell formation in response to phytohaemagglutinin (PHA-P) and concanavalin A (Con-A) and casoni test using standard methods. Twenty two out of 90 (22.44%) clinically suspected patients were surgically confirmed as hydatid disease cases. Hydatid disease occured in all age groups. Youngest case was 8 years and oldest 70 years. In 17/22 cases the cyst localised in the liver followed by lungs (3) neck (1) and kidney (1). Majority of patients (63.65%) belonged to blood group B. The mean total leucocyte and eosinophill counts were raised significantly (p < 0.001 and p < 0.05, respectively) in confirmed patients. The mean ESR value was raised in hydatid patients though, not significantly (P > 0.08). All the four classes of immunoglobulins viz. IgG, IgA, IgM, IgE and complement C3 were significantly raised in patients of hydatid disease compared to controls (P < 0.001, P < 0.002, p < 0.01 and p < 0.01, P < 0.02 respectively). The percentage of lymphocytes in peripheral blood in hydatid patients was reduced though, not significantly (P > 0.2). The absolute lymphocyte count was raised and mean percentage of T cells was reduced in patients with hydatid disease (P < 0.001 and P < 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Individual molecular response to elevated intraocular pressure in perfused postmortem human eyes.
Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. In the clinic, the response to elevated pressure and thus the risk for development of glaucoma differs among individuals. We took advantage of our ability to subject postmortem human eyes from the same individual to physiological and elevated pressure in a perfused outflow model and compared individual patterns of gene expression under pressure. The architecture of the trabecular meshwork, tissue responsible for the maintenance of IOP, was conserved. We performed two sets of experiments. The first set (n = 5, 10 eyes) used Affymetrix GeneChips, identified the 20 most pressure-altered genes in each individual, and compared their pressure response in the other four. The second set (n = 5, 10 eyes) selected 21 relevant trabecular meshwork genes and examined, by real-time TaqMan-PCR, the rank of their abundance and of their pressure differential expression in each individual. The majority of the up- and downregulated top-changers of each individual showed an individual response trend. Few genes were general responders. Individual responders included STATH, FBN2, TF, OGN, IL6, IGF1, CRYAB, and ELAM1 (marker for glaucoma). General responders included MMP1, MMP10, CXCL2, and PDPN. In addition, we found that although the relative abundance of selected genes was very similar among nonstressed individuals, the response to pressure of those same genes had a marked individual component. Our results offer the first molecular insight on the variation of the individual response to IOP observed in the clinical setting.


Cochet-Bonnet aesthesiometer-determined corneal sensitivity in neonatal foals and adult horses.
Corneal touch threshold (CTT) was measured in sick neonatal foals, healthy foals, and healthy adult horses with a Cochet-Bonnet aesthesiometer. The mean overall CTT for the adult horses, sick foals, and healthy foals was 4.82 +/- 0.87 cm, 3.21 +/- 0.24 cm, and 5.01 +/- 0.61 cm, respectively. The central cornea of adult horses was more sensitive than the limbal cornea. Corneal sensitivity was significantly reduced in sick neonatal foals compared to adults. The mean Schirmer I tear test values were significantly lower in foals than adults, and were 14.2 +/- 1.0 mm, 12.8 +/- 2.4 mm, and 18.3 +/- 2.1 mm wetting in sick neonatal foals, normal neonatal foals, and adult horses, respectively. Reduced corneal sensation and lower tear production may be associated with ulcerative keratitis and slow corneal healing in some foals.


Minimum indoor temperature threshold recommendations for English homes in winter - A systematic review.
To identify and assess the available evidence on the impacts of cold indoor temperature thresholds on human health and make evidence-based recommendations for English homes. Systematic literature review. A systematic search of peer-reviewed published literature from the UK and countries with similar climates, and grading of the evidence using the National Institute of Health (NIH) framework was followed by a discussion with experts and formulation of recommendations. Twenty papers were included. Studies were included if they were conducted outside England but were from countries considered to have similar climates. Studies included two small randomised controlled trials, two cohort studies and one case control study; other studies were cross-sectional, largely laboratory-based studies. Health effects in the general population start to occur at around 18 °C. Effects in older people are more profound than in younger adults. Older people are less able to perceive low temperatures. Although evidence was limited, a strong argument for setting thresholds remains. The effects observed on the general population and the effects on those more vulnerable makes a case for a recommended minimum temperature for all. Health messages should be clear and simple, allowing informed choices to be made. A threshold of 18 °C was considered the evidence based and practical minimum temperature at which a home should be kept during winter in England. There is limited evidence available on minimum temperature thresholds for homes. However a recommendation of at least 18 °C for the whole population with nuancing of messages for those more vulnerable to the effects of cold can be made from the results of the retrieved studies. Heating homes to at least 18 °C (65 °F) in winter poses minimal risk to the health of a sedentary person, wearing suitable clothing.


Severe hemoperitoneum after patient self-induced fecal evacuation.
An increasing incidence of rectal injuries following patient self-induced harmful acts, aimed to sexual or laxatives porpouses, is a fact reported in literature (El-Ashaal et al., 2008). We herein report a case of severe hemoperitoneum related to a middle and upper rectal third seromuscolar tear caused by a self-induced fecal evacuation by means of an arrow with a covered cork tip. An urgent intestinal diversion by means of a Hartmann's operation was performed. The clinical case is presented in relation to the literature debate, regarding the issue of primary repair or resection and anastomosis versus fecal diversion for penetrating rectal injuries (Fabian, 2002; Cleary et al., 2006; Office of the Surgeon General, 1943; Busic et al., 2002). In conclusion, the importance of avoiding an anastomotic breakdown in a patient undergoing a hemorrhagic shock is highlighted.


The effects of weight levels and gloves on the ability to discriminate weight difference.
In this study, six different types of gloves commonly used in industry (surgical, cotton, nylon, leather, rubber, and whizard knife hand gloves) were evaluated at four different weight levels (8.2, 3, 1.5 and 0.25 kg). Six males and six females voluntarily took part in this study. The dependent variable was the difference limen (or difference threshold) (abbreviated as DL(%)) of the discriminating weight difference (DWD). A nested-factorial design with the subject nested under gender was employed. The results indicate that the weight level had a negatively significant effect on the DL(%). The mean difference thresholds were 3.49, 5.39, 6.08, and 9.45 for the weight levels at 8.2, 3, 1.5, and 0.25 kg, respectively. The individual difference becomes obvious when the weight level is relatively light (0.25 kg). However, the effects of gender, glove, gender x weight, and weight x glove were found to be insignificant, and there was no significant correlation between the DL(%) and glove characteristics (thickness and weight). Subsequently, four additional weight levels (0.01, 0.5, 1 and 15 kg) were considered, and a psychophysical equation was derived: DL(%) = 34.33 x W(0.238) (R2 = 0.98), where W represents the weight level. These results support the power function. A minimum weight difference with 90% confidence of correct detection was suggested.


Response of wastewater-based epidemiology predictor for the second wave of COVID-19 in Ahmedabad, India: A long-term data Perspective.
In this work, we present an eight-month longitudinal study of wastewater-based epidemiology (WBE) in Ahmedabad, India, where wastewater surveillance was introduced in September 2020 after the successful containment of the first wave of COVID-19 to predict the resurge of the infection during the second wave of the pandemic. The study aims to elucidate the weekly resolution of the SARS-CoV-2 RNA data for eight months in wastewater samples to predict the COVID-19 situation and identify hotspots in Ahmedabad. A total of 287 samples were analyzed for SARS-CoV-2 RNA using RT-PCR, and Spearman's rank correlation was applied to depict the early warning potential of WBE. During September 2020 to April 2021, the increasing number of positive wastewater influent samples correlated with the growing number of confirmed clinical cases. It also showed clear evidence of early detection of the second wave of COVID-19 in Ahmedabad (March 2021). 258 out of a total 287 samples were detected positive with at least two out of three SARS-CoV-2 genes (N, ORF- 1 ab, and S). Monthly variation represented a significant decline in all three gene copies in October compared to September 2020, followed by an abrupt increase in November 2020. A similar increment in the gene copies was observed in March and April 2021, which would be an indicator of the second wave of COVID-19. A lead time of 1-2 weeks was observed in the change of gene concentrations compared with clinically confirmed cases. Measured wastewater ORF- 1 ab gene copies ranged from 6.1 x 102 (October 2020) to 1.4 x 104 (November 2020) copies/mL, and wastewater gene levels typically lead to confirmed cases by one to two weeks. The study highlights the value of WBE as a monitoring tool to predict waves within a pandemic, identify local disease hotspots within a city, and guide rapid management interventions.


Torus palatinus and torus mandibularis in edentulous patients.
To determine the prevalence of tori in Jordanian edentulous patients, the sex variation in their distribution, and their clinical characteristics. Three hundred and thirty eight patients were examined in the Prosthodontic Clinic in the Department of Restorative Dentistry at Jordan University of Science and Technology. The location, extent, and clinical presentation of tori were recorded related to the age and sex of patients. The overall prevalence of tori was 13.9%. The prevalence of torus palatinus was 29.8% (14/47), while that of torus mandibularis was significantly higher 42.6% (20/47). Both types of tori were associated with each other in 27.7% of cases (13/47). There was no significant difference in the prevalence of tori between males and females. There seems to be a strong association between mandibular and palatal tori.


Distinguishing Familial from Acquired Traits in the Retinal Blood Vessel Arborization.
It has been suggested that retinal blood vessel arborization (RBVA) is unique to each individual. We examined this claim in a pedigree that included two pairs of monozygotic twins. Fundus photographs were taken of subjects belonging to this pedigree to compare the pattern of their RBVA. Pattern prevalence within the general population was estimated from a pre-existing clinical database. The optic nerve head (ONH) RBVA disclosed the following patterns: pattern A, outgrowth, with angle sizes ranging from 12° to 86°, toward the macula, made by the central retinal (CR) vein; pattern O, circular shape delimited by the CR artery on the nasal side and CR vein on the temporal (macula) side; and pattern Y, a double-Y shape (upright in the superior retina and upside down in the inferior retina) made by the four branches-inferior temporal and nasal and superior temporal and nasal-of the CR artery. The prevalence of patterns A, O, and Y was estimated at 11%, 2.8%, and 2.7%, respectively, from our pre-existing clinical database. Pattern A was the most frequently noted in our pedigree, with a prevalence of 26% to 29%, a value significantly larger (P < 0.05) than that measured in our sample of the general population. Of note, familial similarity is progressively lost as we move away from the ONH. Relatives appear to share similar ONH RBVA patterns, suggesting that the ONH RBVA could be genetically transmitted as a familial trait. Arrangement of the more peripheral retinal blood vessels would create individuality. Our results suggest the existence of a specific, reproducible, and transmissible retinal identifier, a feature that could potentially be associated with the prevalence of a given disease process, thus offering the possibility of identifying an underlying retinopathy long before its clinical manifestation and consequently optimize its management.


A phylogenetic study of ubiquinone-7 species of the genus Candida based on 18S ribosomal DNA sequence divergence.
To clarify phylogenetic relationships among ubiquinone 7 (Q7)-forming species of the genus Candida, we analyzed the nearly complete sequences of 18S ribosomal RNA genes (18S rDNAs) from fifty strains (including 46 type strains) of Candida species, and from 8 type strains of species/varieties of the genera Issatchenkia, Pichia and Saturnispora. Q7-forming Candida species were divided into three major groups (Group I, II, and III) and were phylogenetically distant from a group that includes the type species of the genus Candida. Group I included four clusters with basal branches that were weakly supported. The first cluster comprised C. vartiovaarae, C. maritima, C. utilis, C. freyschussii, C. odintsovae, C. melinii, C. quercuum, Williopsis saturnus var. saturnus, and W. mucosa. The second cluster comprised C. norvegica, C. montana, C. stellimalicola, C. solani, C. berthetii, and C. dendrica. Williopsis pratensis, W. californica, Pichia opuntiae and 2 related species, P. amethionina (two varieties), and P. caribaea were also included in this cluster. The third cluster comprised C. pelliculosa (anamorph of P. anomala), C. nitrativorans, and C. silvicultrix. The fourth cluster comprised C. wickerhamii and C. peltata, which were placed in the P. holstii - C. ernobii clade with Q8-containing species. Group II comprised C. pignaliae, C. nemodendra, C. methanolovescens, C. maris, C. sonorensis, C. pini, C. llanquihuensis, C. cariosilignicola, C. ovalis, C. succiphila (including its two synonyms), C. methanosorbosa, C. nitratophila, C. nanaspora, C. boidinii (including its two synonyms), W. salicorniae, and P. methanolica. Group III was composed of four clusters with strong bootstrap support. The first cluster comprised C. valida (anamorph of P. membranifaciens), C. ethanolica, C. pseudolambica, C. citrea, C. inconspicua, C. norvegensis, C. rugopelliculosa, and C. lambica. Three species and two varieties of the genus Issatchenkia were also included in this cluster. The second cluster comprised C. diversa, C. silvae, 4 Saturnispora species, and P. besseyi. The third comprised C. sorboxylosa, and the fourth comprised C. vini. Based on this 18S rDNA sequence analysis, it is evident that Q7-forming Candida species and the genera Pichia and Williopsis are polyphyletic. The genus Issatchenkia is suggested to be congeneric with the genus Pichia. The genus Saturnispora is phylogenetically definable.


Contributions of the microbiome to intestinal inflammation in a gut-on-a-chip.
The intestinal microbiome affects a number of biological functions of the organism. Although the animal model is a powerful tool to study the relationship between the host and microbe, a physiologically relevant in vitro human intestinal system has still unmet needs. Thus, the establishment of an in vitro living cell-based system of the intestine that can mimic the mechanical, structural, absorptive, transport and pathophysiological properties of the human intestinal environment along with its commensal bacterial strains can promote pharmaceutical development and potentially replace animal testing. In this paper, we present a microfluidic-based gut model which allows co-culture of human and microbial cells to mimic the gastrointestinal structure. The gut microenvironment is recreated by flowing fluid at a low rate (21 μL/h) over the microchannels. Under these conditions, we demonstrated the capability of gut-on-a-chip to recapitulate in vivo relevance epithelial cell differentiation including highly polarized epithelium, mucus secretion, and tight membrane integrity. Additionally, we observed that the co-culture of damaged epithelial layer with the probiotics resulted in a substantial responded recovery of barrier function without bacterial overgrowth in a gut-on-a-chip. Therefore, this gut-on-a-chip could promote explorations interaction with host between microbe and provide the insights into questions of fundamental research linking the intestinal microbiome to human health and disease.


Mathematical modeling and estimation for next wave of COVID-19 in Poland.
We investigate the problem of mathematical modeling of new corona virus (COVID-19) in Poland and tries to predict the upcoming wave. A Gaussian mixture model is proposed to characterize the COVID-19 disease and to predict a new / future wave of COVID-19. This prediction is very much needed to prepare for medical setup and continue with the upcoming program. Specifically, data related to the new confirmed cases of COVID-19 per day are considered, and then we attempt to predict the data and statistical activity. A close match between actual data and analytical data by using the Gaussian mixture model shows that it is a suitable model to present new cases of COVID-19. In addition, it is thought that there are N waves of COVID-19 and that information for each future wave is also present in current and previous waves as well. Using this concept, predictions of a future wave can be made.


Shear bond strength of six restorative materials.
The purpose of this study was to determine and compare the shear bond strength of a conventional glass-ionomer cement, a resin modified glass-ionomer, a composite resin and three compomer restorative materials. Dentin of the occlusal surfaces from sixty extracted human permanent molars were prepared for shear bond strength testing. The specimens were randomly divided into six groups of 10 each. Dentinal surfaces were treated according to the instructions of manufacturers for each material. Each restorative material was placed inside nylon cylinders 2 mm high with an internal diameter of 3 mm, which were placed perpendicular to dentin surfaces. Shear bond strengths were determined using an Universal Testing Machine at crosshead speed of 0.5 mm/min in a compression mode. Conventional glass-ionomer, Ketac-Molar aplicap showed the lowest mean shear bond strength 3.77+/-1.76 (X +/- SD MPa) and the composite resin, Heliomolar showed the highest mean shear bond strength 16.54+/-1.65 while the mean bond strength of Fuji II LC was 9.55+/-1.06. The shear bond strengths of compomer restorative materials were 12.83+/-1.42, 10.64+/-1.42 and 11.19+/-1.19 for Compoglass, Hytac and Dyract respectively. ANOVA revealed statistically significant differences in the mean shear bond strengths of all groups (P<0.001). No statistically significant difference was found between the three compomer materials (P>0.5). Ketac-Molar and composite resin showed statistically significant difference (P<0.0005). The mode of fracture varied between materials. It is concluded that the compomer restorative materials show higher shear bond strength than conventional glass-ionomer and resin modified glass-ionomer, but less than composite resin. The fracture mode is not related to the shear bond strengths values.