Anatomical study of the human anterior cruciate ligament stump's tibial insertion footprint.
The aim of this study is to define the topographical relationship of the anatomical bundles of the human anterior cruciate ligament's (ACL) stump over the tibial insertion site. Between January and April 2007, a total of 36 resected tibial plateaus were retrieved from patients who underwent total knee replacements. These samples had intact cruciate ligaments with no major osteophyte around the ACL tibial insertion footprint. The anatomical bundles of the ACL were identified and mapped, based on the topographical relationship over the tibial insertion footprint. Measurements of the dimensions of the ACL tibial footprint and tibial plateau were performed. The mean width and midsagittal depth of the tibia plateau was 78.7 +/- 6.5 and 46.4 +/- 5.0 mm, respectively. The mean width and midsagittal depth of the ACL tibial footprint was 10.3 +/- 1.9 and 19.5 +/- 2.6 mm, respectively. Out of the 36 freshly dissected ACL stumps, it was not possible to distinguish separate bundles in 14 (38.9%) cases. The average distance between the centers of the two bundles was 9.3 +/- 1.8 mm. The mean AP alignment of the tibial footprint was 89.6 degrees +/- 26.4 degrees , with a very wide range of 23 degrees -158 degrees . Of the 22 specimens with separate anatomical bundles, the alignment of the tibial footprint was AM-PL in six (27.3%), sagittal (85 degrees -95 degrees ) in five (22.7), AL-PM in nine (40.9%), and lateral-medial (L-M) in two (9.1%) cases. This study provides new information about the topographical anatomy of the ACL tibial insertion footprint. Based on gross anatomy, separate anatomical bundles of the ACL can be distinguished in 61.1% [22] of the specimens. The topographical alignment of the separate bundles is varied on a very wide range.


Ear temperature measurements in healthy children using the arterial heat balance method.
This study was undertaken to determine the upper limit of normal ear temperatures, defined as the 95th percentile for infants, children, and adolescents, using the arterial heat balance method for measuring ear temperatures. Ear temperatures were measured in 62 infants, 0-2 months of age; 346 children, 3-47 months; 226 children, 48-119 months; and 172 adolescents, 120-227 months using the LighTouch Pedi-Q (Exergen Corp, Watertown, MA) ear thermometer. The 95th percentiles for the four age groups were 100.1 degrees F (37.8 degrees C), 100.3 degrees F (37.9 degrees C), 99.8 degrees F (37.7 degrees C), and 99.8 degrees F (37.7 degrees C), respectively. Temperatures above 100.0 degrees F (37.8 degrees C) using the LighTouch Pedi-Q ear thermometer should be considered elevated.


Determination of intermediates, products and cleavage site in the reaction between plasminogen activator inhibitor type-2 and urokinases.
Several specific inhibitors for plasminogen activators have been isolated from various organs and cell lines, those from human placenta and the human monocyte-like cell line U-937 being virtually identical. The reaction between this type of inhibitor, designated as type-2, and high-Mr and low-Mr urokinase-type plasminogen activators was followed by reversed-phase high-performance liquid chromatography and gel electrophoresis. The components, their stable complexes and their dissociation and cleavage products could be clearly identified in both systems. The amino acid sequence of the inhibitor at the cleavage site was determined to be -Met-Thr-Gly-Arg decreases Thr-Gly-His-Gly-. A 35-residue carboxy-terminal fragment was found to be released.


Cerebral blood flow during high frequency ventilation in cats.
Cerebral blood flow (CBF) was compared during conventional low frequency ventilation (LFV) [tidal volume 15 ml/kg, respiratory rate 12] and high frequency ventilation (HFV) [tidal volume 3 ml/kg, respiratory rate 100] in normal cats. The intra-arterial 133Xenon technique was used to determine CBF. No significant difference in CBF was present between the 2 groups. The mean CBF was 46.6 +/- 14.2 ml/dl X min during LFV and 44.4 +/- 12.2 ml/dl X min during HFV. Additionally, mean arterial pressure, CVP, intracranial pressure (ICP), cerebral perfusion and airway pressures were not significantly different between the groups. HFV has little effect on cerebral hemodynamics.


Structural and mechanical remodelling of the common bile duct after obstruction.
Biliary obstruction in man, most often caused by cholelithiasis, induces remodelling of the bile ducts. Obstruction-induced structural remodelling of the common bile duct (CBD) has been previously described. The mechanical changes that accompany the structural remodelling, however, have not been studied in detail. The aim of this study is to quantify the structural and mechanical changes in the CBD at different time intervals after acute obstruction. The CBD was ligated in the pig, near the duodenum, and studied after 3 h, 12 h, 2 days, 8 days and 32 days (n=5 in each group). One additional animal in each group was sham-operated. At each scheduled time, the CBD was mechanically tested in vitro with a computer-controlled volume infusion system to study the pressure-volume relationship of the CBD segment. A video camera provided simultaneous measurements of the outer dimensions of the CBD at the various pressures. The diameter and wall thickness of the CBD increased about three-fold in the 32-day group compared to the sham group (P < 0.001). The circumferential stress-strain relationship differed between groups (P < 0.001); it was shifted to the right, indicating softening, in the 3-h, 12-h, and 2-day groups and to the left, indicating stiffening, in the 8-day and 32-day group, compared to the sham group. The longitudinal stress-strain curves were all shifted to the left of the circumferential stress-strain curves (P < 0.05). The collagen area increased during obstruction (P < 0.001) but no correlation between the size of the collagen area and the biomechanical parameters was found. A practical implication of the present study serves as a warning to surgeons. A reduction in the wall stiffness in the first several days of obstruction along with an increased duct diameter and a decreased wall thickness suggest that operative procedures such as suturing, anastomosis and procedures related to ERCP must be performed with special care to avoid damage to the CBD.


Disentangling protist communities identified from DNA and RNA surveys in the Pearl River-South China Sea Continuum during the wet and dry seasons.
Little is known about the mechanisms that regulate the assembly of microbial communities in the river-sea continuum. Here, we performed HiSeq paired-end sequencing of the V4 region of 18S rRNA gene, using both DNA and RNA extracts, to identify protist communities in the surface and bottom water layers along a transect of the Pearl River-South China Sea Continuum (PSC) during the wet (summer) and dry (winter) seasons. We found that during the summer but not during the winter, protist communities, identified from their DNA or RNA signatures, could be better explained by mass effects and species sorting, respectively. Moreover, protist diversity in the DNA and RNA surveys exhibited similar trends along the transect, that is, a linear upstream-to-downstream decrease during the summer and a weakly U-shaped curve during the winter. In contrast, the taxonomic compositions in the DNA- and RNA-derived communities were remarkably different during either the summer or the winter. In summary, the results of our DNA and RNA surveys revealed the temporal assembly of protist communities in the PSC, which suggests that protist diversity and composition are highly responsive to the hydrographic conditions of the river-sea continuum.


A deep learning, image based approach for automated diagnosis for inflammatory skin diseases.
As the booming of deep learning era, especially the advances in convolutional neural networks (CNNs), CNNs have been applied in medicine fields like radiology and pathology. However, the application of CNNs in dermatology, which is also based on images, is very limited. Inflammatory skin diseases, such as psoriasis (Pso), eczema (Ecz), and atopic dermatitis (AD), are very easily to be mis-diagnosed in practice. Based on the EfficientNet-b4 CNN algorithm, we developed an artificial intelligence dermatology diagnosis assistant (AIDDA) for Pso, Ecz & AD and healthy skins (HC). The proposed CNN model was trained based on 4,740 clinical images, and the performance was evaluated on experts-confirmed clinical images grouped into 3 different dermatologist-labelled diagnosis classifications (HC, Pso, Ecz & AD). The overall diagnosis accuracy of AIDDA is 95.80%±0.09%, with the sensitivity of 94.40%±0.12% and specificity 97.20%±0.06%. AIDDA showed accuracy for Pso is 89.46%, with sensitivity of 91.4% and specificity of 95.48%, and accuracy for AD & Ecz 92.57%, with sensitivity of 94.56% and specificity of 94.41%. AIDDA is thus already achieving an impact in the diagnosis of inflammatory skin diseases, highlighting how deep learning network tools can help advance clinical practice.


Strain Relaxation in Misfitting Transition Metal Dichalcogenide Monolayer Superlattices: Wrinkling vs Misfit Dislocation Formation.
Two-dimensional (2D) superlattices composed of chemically heterogeneous transition-metal dichalcogenides (TMDs) have been proposed as key components in next-generation optoelectronic devices. For potential applications, coherent, defect-free compositional interfaces are usually required. In this paper, a combination of scaling theory and numerical analysis is employed to investigate strain relaxation mechanisms in misfitting, chemically heterogeneous TMDs. We demonstrate that, in free-standing superlattices, wrinkling of the monolayer is asymptotically preferred over misfit dislocation formation in both binary and ternary superlattices. For substrate-supported monolayers, however, misfit dislocation formation is thermodynamically favored above a critical superlattice width, implying the presence of an upper limit to the thermodynamic stability of coherent, misfitting 2D superlattices. Finally, it is shown numerically that the critical superlattice width is only weakly dependent on the misfit.


Microscopic evaluation of the sequential degeneration and repair of the retinae of albino mice after high-dose laser irradiation.
After irradiation of the retinae of albino mice with a dose of 13 J, using a ruby pulse laser, the lesions were followed for a period of 60 days. Severe degenerations were observed in the outer layer 2-9 days after irradiation. By the 21st day after irradiation, the pigment epithelium started to regenerate and outer segments began to reform. Progressive recovery and repair were by and large completed by the 60th day after irradiation.


On the stability properties of a stochastic model for phage-bacteria interaction in open marine environment.
In this paper we extend the deterministic model for the epidemics induced by virulent phages on bacteria in marine environment introduced by Beretta and Kuang [Math. Biosci. 149 (1998) 57], allowing random fluctuations around the positive equilibrium. The stochastic stability properties of the model are investigated both analytically and numerically suggesting that the deterministic model is robust with respect to stochastic perturbations.


[Pancreatic lesion in newborn mice caused by Coxsackie B1 virus].
Changes in the pancreatic gland manifested by necrosis of excretory cells and marked atrophy of insulae with the loss of beta-cells producing insulin were observed experimentally in suckling mice infected with Coxsackie B1 virus. It is suggested that the above changes of the pancreas may be a model of human diseases caused by Coxsackie viruses, including a model of development of some cases of diabetes.


A snapshot of exhaled nitric oxide and asthma characteristics: experience from high to low income countries.
Nitric oxide is a gas produced in the airways of asthmatic subjects and related to T2 inflammation. It can be measured as fractional nitric oxide (FeNO) in the exhaled air and used as a non-invasive, easy to evaluate, rapid marker. It is now widely used in many settings to determine airway inflammation. The aim of this narrative review is to report relationship between FeNO and the physiopathologic characteristics of asthmatic patients. Factors affecting FeNO levels have also been analysed as well as the impact of corticosteroid, target therapies and rehabilitation programs. Considering the availability of the test, spreading this methodology to low income countries has also been considered as a possibility for evaluating airway inflammation and monitoring adherence to inhaled corticosteroid therapy. PubMed data search has been performed restricted to English language papers. Research was limited to studies in adults unless studies in children were the only ones reported for a particular issue. This revision could be useful to summarize the role of FeNO in relation to asthma characteristics and help in the use of FeNO in different clinical settings particularly in low income countries.


The interferon-induced helicase C domain-containing protein 1 gene variant (rs1990760) as an autoimmune-based pathology susceptibility factor.
Autoimmune diseases are a group of complex diseases localized in multiple organ systems, with a wide spectrum of symptoms and still unclear causes. The aim of the present study was to analyse a possible association of three autoimmune disabilities - Multiple sclerosis (MS), LADA diabetes and Graves' disease (GD) with single nucleotide polymorphism (SNP; rs1990760) in the IF IH1 gene (also known as a melanoma differentiation-associated protein 5 - MDA5) within the Polish population. An additional goal was also to look for a correlation between this polymorphism and different clinical patient-related factors. The study population consisted of four groups of 944 unrelated Polish origin Caucasian patients - 324 with GD, 171 with MS, 49 with LADA diabetes and 400 healthy subjects as a control group. The SNP analysis was performed using the allelic discrimination technique. There were significant associations of risk T allel of the analyzed polymorphism with all studied autoimmune diseases (GDOR = 1.34, p = 7.02e-03; MSOR = 1.36, p = 2.17e-02; LADA - OR = 3.36, p = 8.73e-07). We also found that the frequency of CT and TT genotypes of the rs1990760 IFIH1 gene only in females (with LADA, GD, MS) was significantly higher than those in the female control group (47%, 41% vs 44%, 34%; p = 1.32e-03, p = 4.39e-04; OR = 2.08, 95%CI: (1.33-3.28), OR = 2.29, 95% CI: (1.44-3.65) respectively). Our research has shown significant differences regarding some clinical features (BMI, TRAb, TSH, HbA1C, anti-GAD antibodies) and age at the beginning of the studied autoimmune disabilities. This study showed an association of rs1990760 polymorphism in the IFIH1 gene in the development of GD, LADA diabetes and MS within the Polish population. To our knowledge, this is the first study to investigate the relationship between IFIH1 polymorphisms and the risk of the development of MS and LADA in Poland.


The nexus between economic growth, tourism development, energy consumption, and CO2 emissions in Mediterranean countries.
This study aims to analyze the relationship among international tourism, energy consumption, carbon dioxide emissions, and economic growth in Mediterranean countries for the 1995-2014 data period. According to the results of panel quantile regression model for 17 countries, the tourism-led growth hypothesis is valid in low growth levels, but deviations from this hypothesis are determined after the middle growth level. Also, the CO2 coefficient at low growth levels indicated that sustainable growth is achieved, but no significant results are obtained at subsequent growth levels. Finally, energy consumption supports economic growth at low and medium growth levels. Short-run causality test results illustrated that there is bidirectional causality between GDP and all explanatory variables.


The effects of microgravity on bone structure and function.
Humans are spending an increasing amount of time in space, where exposure to conditions of microgravity causes 1-2% bone loss per month in astronauts. Through data collected from astronauts, as well as animal and cellular experiments conducted in space, it is evident that microgravity induces skeletal deconditioning in weight-bearing bones. This review identifies contentions in current literature describing the effect of microgravity on non-weight-bearing bones, different bone compartments, as well as the skeletal recovery process in human and animal spaceflight data. Experiments in space are not readily available, and experimental designs are often limited due to logistical and technical reasons. This review introduces a plethora of on-ground research that elucidate the intricate process of bone loss, utilising technology that simulates microgravity. Observations from these studies are largely congruent to data obtained from spaceflight experiments, while offering more insights behind the molecular mechanisms leading to microgravity-induced bone loss. These insights are discussed herein, as well as how that knowledge has contributed to studies of current therapeutic agents. This review also points out discrepancies in existing data, highlighting knowledge gaps in our current understanding. Further dissection of the exact mechanisms of microgravity-induced bone loss will enable the development of more effective preventative and therapeutic measures to protect against bone loss, both in space and possibly on ground.


[Pathophysiology of chronic myocardial ischemia].
Myocardial ischemia is caused by a mismatch between myocardial oxygen supply and myocardial oxygen requirements. Obstructive coronary artery disease (CAD) is the most common cause for myocardial ischemia. Although coronary bypass graft (CABG) surgery und percutaneous coronary interventions (PCI) are established therapies to treat CAD, 10 years after CABG or PCI 40% of the patients still have angina pectoris. Besides obstructive CAD, chronic myocardial ischemia can be induced by small vessel disease and endothelial dysfunction that is not treatable with CABG or PCI. On the cellular basis myocardial ischemia leads to a sodium overload that is caused by an increase in the late sodium current (I Na, late). The increased intracellular sodium concentration leads to a mode switch of the sodium/calcium exchanger (NCX) that now eliminates sodium from the cell and transports calcium into the cell. The resulting calcium overload activates the contractile myofilaments causing an increased wall tension in diastole which compromises the microcirculation and intensifies myocardial ischemia.


Biological importance of glycosylation.
Glycosylation is the primary cause of microheterogeneity in proteins (glycoforms). These reflect complexity at both molecular and cellular levels. Protein sugar prints are conserved and not random under normal physiological conditions. There are many potential functions of glycosylation. For instance, physical properties include: folding, trafficking, packing, stabilisation, protease protection, quaternary structure and organization of water structure. Properties relating to recognition and biological triggering are characterized by: weak interactions, multiple presentation and precise geometry. Many of the properties may only operate in a specific biological context. Changes in sugar prints may both reflect and results in physiological changes, e.g. cancer and rheumatoid arthritis. It is necessary, in many systems, to evaluate glycosylation. This requires accurate monitoring of sugar prints of using automated and predictive technology. Glycosylation often affords a sensitive means of monitoring pharmaceutical products for Quality Control.


In-vitro shear bond strength of self-etching versus traditional adhesives for orthodontic luting.
To determine the enamel shear bond strength (SBS) of various established (Resulcin Aqua Prime & Monobond N [RA], Prompt L-Pot III [PLP]) and experimental (AC-Bond [AC], AC-Bond + Desensitizer [ACD]) self-etching adhesives in comparison to fourth (Total Etch, Primer and Bonding have separate liquids; OptiBond FL [FL]) and fifth-generation (Total Etch, Primer and Bonding "One Bottle"; Excite [EX], Gluma Comfort Bond [CB]) adhesives. All adhesives were applied on flattened human enamel surfaces following the manufacturers' instructions and light-cured using a quartz-tungsten-halogen curing device. 3.5 x 2.0 mm Tetric Ceram A2 composite cylinders were sheared off (Zwick Universal-testing-machine 1445, 1 mm/min) after thermocycling (5-55 degrees C, 5000x). Normal distribution was tested for all groups and analysis of variance was conducted. The t-test (5% level, Bonferroni-correction) was used for statistical analysis to evaluate intergroup differences. Shear bond strength in enamel: Resulcin Aqua Prime & Monobond N: 27.0 +/- 5.8 MPa, Prompt L-Pop III: 15.9 +/- 3.4 MPa, AC-Bond: 28.1 +/- 4.4 MPa, AC-Bond + Desensitizer: 22.2 +/- 4.1 MPa, OptiBond FL: 33.2 +/- 3.2 MPa, Excite: 30.5 +/- 5.1 MPa, Gluma Comfort Bond: 30.1 +/- 3.7 MPa. OptiBond FL demonstrated significantly higher SBS (p < 0.002) in enamel than Resulcin Aqua Prime & Monobond N, AC-Bond, AC-Bond + Desensitizer and Prompt L-Pop III. Resulcin Aqua Prime & Monobond N performed significantly better than Prompt L-Pop III, but did not differ from AC-Bond or AC-Bond + Desensitizer. The SBS values of Excite and Gluma Comfort Bond were both on the same level of significance as AC-Bond and Resulcin Aqua Prime & Monobond N, but the former showed superior results to AC-Bond + Desensitizer and Prompt L-Pop III. Prompt L-Pop III yielded significantly lower SBS-values than all the other products evaluated. Resulcin Aqua Prime & Monobond N and AC-Bond did not differ significantly from established 5th-generation products. Further in-vivo studies are required to investigate intra-oral stability and resistance against changing forces and force directions.


Pregnancy Recognition and Implantation of the Conceptus in the Mare.
Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following fertilization and initial development in the mare oviduct, selective transport of the embryo through the uterotubal junction driven by embryo-derived PGE2 occurs. Upon arrival in the uterus, an acellular glycoprotein capsule is formed that covers the embryo, blastocyst, and conceptus (embryo and associated extraembryonic membranes) between the second and third weeks of pregnancy. Between Days 9 and 15/16 of pregnancy, the conceptus undergoes an extended phase of mobility. Conceptus mobility is driven by conceptus-derived PGF2α and PGE2 that stimulate uterine contractions which in turn propel migration of the conceptus within the uterine lumen. Cessation of conceptus mobility is referred to as fixation and appears to be attributable to increasing size of the conceptus, preferential thickening of the endometrium near the mesometrial attachment referred to as encroachment, and a reduction in sialic acid content of the capsule. During maternal recognition of pregnancy, endometrial PGF2α release is attenuated, a consequence of reduced expression of key enzymes involved in prostaglandin production. Oxytocin responsiveness is altered during early pregnancy, and reduced expression of the oxytocin receptor appears to be regulated at the posttranscriptional level rather than the transcriptional level. Prostaglandin release is attenuated temporarily only during early pregnancy; during the third week of pregnancy, the endometrium resumes the ability to secrete PGF2α. The equine conceptus initiates steroidogenesis as early as Day 6 and synthesizes estrogens, androgens, and progesterone. Estrogens are metabolized locally, presumably regulating their bioavailability and actions. Results of experiments attempting to prove that conceptus-derived estrogens are responsible for extension of corpus luteum function have been inconclusive. By the fourth week of pregnancy, the chorionic girdle becomes visible on the trophoblast. Subsequent invasion of chorionic girdle cells leads to formation of endometrial cups which secrete equine chorionic gonadotropin. Equine chorionic gonadotropin has luteinizing hormone functions in the mare, causing luteinization of follicles resulting in the formation of secondary corpora lutea essential to production of progesterone and maintenance of pregnancy.


Sex differences in Parkinson's disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics.
Parkinson's disease (PD) is the second most frequent age-related neurodegenerative disorder. Sex is an important factor in the development of PD, as reflected by the fact that it is more common in men than in women by an approximate ratio of 2:1. Our hypothesis is that differences in PD among men and women are highly determined by sex-dependent differences in the nigrostriatal dopaminergic system, which arise from environmental, hormonal and genetic influences. Sex hormones, specifically estrogens, influence PD pathogenesis and might play an important role in PD differences between men and women. The objective of this review was to discuss the PD physiopathology and point out sex differences in nigrostriatal degeneration, symptoms, genetics, responsiveness to treatments and biochemical and molecular mechanisms among patients suffering from this disease. Finally, we discuss the role estrogens may have on PD sex differences.


[Implementation of a support system for isolated elderly people to limit the consequences of the Covid-19 epidemic in Buenos Aires].
The Covid-19 pandemic with its associated quarantine and isolation has had a dramatic impact on the elderly. In order to mitigate this, the National University of La Plata and the Agence Universitaire de la Francophonie set up a health surveillance and early warning project for the elderly in Buenos Aires, Argentina. This interventional study, has included 1,964 people. A general health and quality of life questionnaire was completed by all participants at the beginning of the isolation, and another time a year later.


Bronchial Carcinoids: From Molecular Background to Treatment Approach.
A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.


Cellular S-value evaluation based on real human cell models using the GATE MC package.
Exploring the spatial distribution of the energy loss of ionising radiation at the subcellular level is indispensable for evaluating the radiobiological effects of targeted radionuclide therapy accurately. Believing that S-values are important for obtaining the target dose, the Committee on Medical Internal Radiation Dose (MIRD) proposed a method to obtain the cellular dosimetric parameter. However, most available data on cellular S-values were calculated based on simple geometric models, such as ellipsoids or spheres, which do not accurately reflect biological reality. To investigate the influence of the cellular model on S-values, calculations were performed for two kinds of polygon-surface phantom models of realistic, individual human cells, the lung epithelial cell model (the B2B Phantom model) and the hepatocyte model (the Liver Phantom model), using the Monte Carlo (MC) software package GATE. To analyse the influence of cell geometry on the final S-value, the differences in the S-values between the realistic cell models and simple geometric sphere and ellipsoid models with similar volumes were calculated and compared for six different combinations of source and target regions. The irradiation conditions were 0.01-1.10 MeV monoenergetic electron sources and the Auger electronic therapy nuclides Ga-67, Tc-99m, In-111, I-125 and Tl-201, which are commonly used in nuclear medicine. The S-values calculated in this study are different from the results of the simple geometry models proposed by previous researchers. Two more precise polygon-surface phantom models of realistic, individual human cells were used, which provided more accurate information about the cell dose and will be very useful for the diagnostic application of radiotherapy in the future.


Mutagenic effects of dimethyl terephthalate on mouse somatic cells in vivo.
The mutagenic activity of dimethyl terephthalate (DMtP) was evaluated in the micronucleus test in mice. A clear clastogenic effect was obtained at all concentrations studied (0.2-1.0 mmole/kg body weight). The maximum number of micronuclei occurred 24 h after a single intraperitoneal (i.p.) injection. The time-course for the DMtP-induced micronuclei was in agreement with the available data on the rapid excretion of phthalates from the mammalian body. The dose-effect response was best described by a linear equation with a logarithmic component. The emergence of the latter term was related to the toxic effects of DMtP at higher concentrations on bone marrow erythropoietic function. A comparison of the effects induced by DMtP and by methyl nitrosourea indicated that DMtP cannot be considered a strong mutagenic compound. We have compared the sensitivity of the mouse micronucleus test and that of Drosophila dominant-lethal test by contrasting the effects obtained at similar exposure doses. This comparison leads to the conclusion that the micronucleus test is capable of responding to far lower phthalate concentrations than the Drosophila dominant-lethal mutation test. Our results testify to the ability of dimethyl terephthalate to cause genotoxic damages in vivo in both somatic and germinal cells of higher organisms. Thus, the chemical in question may be of potential genetic hazard to man.


TCR-engineered iNKT cells induce robust antitumor response by dual targeting cancer and suppressive myeloid cells.
Adoptive immunotherapy with T cells engineered with tumor-specific T cell receptors (TCRs) holds promise for cancer treatment. However, suppressive cues generated in the tumor microenvironment (TME) can hinder the efficacy of these therapies, prompting the search for strategies to overcome these detrimental conditions and improve cellular therapeutic approaches. CD1d-restricted invariant natural killer T (iNKT) cells actively participate in tumor immunosurveillance by restricting suppressive myeloid populations in the TME. Here, we showed that harnessing iNKT cells with a second TCR specific for a tumor-associated peptide generated bispecific effectors for CD1d- and major histocompatibility complex (MHC)-restricted antigens in vitro. Upon in vivo transfer, TCR-engineered iNKT (TCR-iNKT) cells showed the highest efficacy in restraining the progression of multiple tumors that expressed the cognate antigen compared with nontransduced iNKT cells or CD8+ T cells engineered with the same TCR. TCR-iNKT cells achieved robust cancer control by simultaneously modulating intratumoral suppressive myeloid populations and killing malignant cells. This dual antitumor function was further enhanced when the iNKT cell agonist α-galactosyl ceramide (α-GalCer) was administered as a therapeutic booster through a platform that ensured controlled delivery at the tumor site, named multistage vector (MSV). These preclinical results support the combination of tumor-redirected TCR-iNKT cells and local α-GalCer boosting as a potential therapy for patients with cancer.


A new prognostic index in surgery and parenteral feeding: the ratio of triiodothyronine to reverse triiodothyronine in serum (T3/rT3 ratio).
Serum concentrations of albumin, triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured in 46 patients on the first day after routine gastrointestinal surgery, and the molar ratio T3/rT3 was calculated. The median value of this ratio, but not of albumin, was significantly lower in 11 who subsequently suffered major septic complications than in the remainder. Measurement of the ratio correctly predicted the outcome of 80% of individuals. The T3/rT3 ratio, midarm muscle circumference (MAMC), triceps skin fold (TSF) and serum concentrations of albumin and transferrin were measured in 23 patients at referral for parenteral feeding. Median values of T3/rT3 ratio, MAMC and transferrin, but not of the other parameters, were significantly lower in nine who died than in survivors. Measurements of the ratio, MAMC and transferrin correctly predicted the outcome of 87%, 78% and 74% of individuals, respectively.


Multi-modal deep learning for automated assembly of periapical radiographs.
Periapical radiographs are oftentimes taken in series to display all teeth present in the oral cavity. Our aim was to automatically assemble such a series of periapical radiographs into an anatomically correct status using a multi-modal deep learning model. 4,707 periapical images from 387 patients (on average, 12 images per patient) were used. Radiographs were labeled according to their field of view and the dataset split into a training, validation, and test set, stratified by patient. In addition to the radiograph the timestamp of image generation was extracted and abstracted as follows: A matrix, containing the normalized timestamps of all images of a patient was constructed, representing the order in which images were taken, providing temporal context information to the deep learning model. Using the image data together with the time sequence data a multi-modal deep learning model consisting of two residual convolutional neural networks (ResNet-152 for image data, ResNet-50 for time data) was trained. Additionally, two uni-modal models were trained on image data and time data, respectively. A custom scoring technique was used to measure model performance. Multi-modal deep learning outperformed both uni-modal image-based learning (p<0.001) and time-based learning (p<0.05). The multi-modal deep learning model predicted tooth labels with an F1-score, sensitivity and precision of 0.79, respectively, and an accuracy of 0.99. 37 out of 77 patient datasets were fully correctly assembled by multi-modal learning; in the remaining ones, usually only one image was incorrectly labeled. Multi-modal modeling allowed automated assembly of periapical radiographs and outperformed both uni-modal models. Dental machine learning models can benefit from additional data modalities. Like humans, deep learning models may profit from multiple data sources for decision-making. We demonstrate how multi-modal learning can assist assembling periapical radiographs into an anatomically correct status. Multi-modal learning should be considered for more complex tasks, as clinically a wealth of data is usually available and could be leveraged.


Folate-conjugated liposomes target and deliver therapeutics to immune cells in a rat model of rheumatoid arthritis.
We endeavored to create a folate-targeted liposome (Fol-liposome) that could selectively target areas of inflammation. Fol-liposomes were prepared with encapsulated DiD fluorophore or betamethasone (BM) to image and treat an adjuvant-induced rat model of rheumatoid arthritis. Fol-liposomes selectively accumulated in arthritic rat paws to a greater extent than nontargeted liposomes. When these Fol-liposomes were used to encapsulate BM and administered to arthritic rats, animals exhibited less paw swelling, lower arthritis scores, a reduction in bone erosion, less splenomegaly and better maintenance of body weight when compared with nontreated or nontargeted BM-containing liposome groups. Fol-liposomes can selectively deliver imaging and therapeutic agents to sites of inflammation in a rat model of rheumatoid arthritis.


The role of viral infections in the development of dilated cardiomyopathy.
Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium. Viral sequences were extracted from five different regions of the hearts. Nested PCR was used to amplify conservative regions of AdV3, HHV6 and EVs. Histological examination was performed on routinely processed myocardial samples. AdV3 was verified in one fourth of the patients. ADV3 and HHV6 sequences coexisted in one case with inflammatory cardiomyopathy. Some patients had more than one positive area of their heart. AdV3 positive right ventricular samples were double in amount compared to the left ones. None of the patients had positive result for EV. This is the first occasion to identify AdV3 (a mainly respiratory infective virus) sequence in explanted hearts of cardiomyopathy patients. Though the clinical importance of our results is still unclear, AdV3 could be a new member of the viral group with possible pathogenic effect on the myocardium. Regional distribution of viral sequence location confirmed that the right ventricular wall as a biopsy sampling site might be adequate for endomyocardial biopsy pro diagnostic purposes.


Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse.
Somatosensory axon outgrowth is repulsed when soluble semaphorin D (semD) binds to growth cone neuropilin-1 (Npn-1). Here, semD ligand binding studies of Npn-1 mutants demonstrate that the sema domain binds to the amino-terminal quarter, or complement-binding (CUB) domain, of Npn-1. By herpes simplex virus- (HSV-) mediated expression of Npn-1 mutants in chick retinal ganglion cells, we show that semD-induced growth cone collapse requires two segments of the ectodomain of Npn-1, the CUB domain and the juxtamembrane portion, or MAM (meprin, A5, mu) domain. In contrast, the transmembrane segment and cytoplasmic tail of Npn-1 are not required for biologic activity. These data imply that the CUB and MAM ectodomains of Npn-1 interact with another transmembrane growth cone protein that in turn transduces a semD signal into axon repulsion.


Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.
Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. Stryker and Amsterdam University Medical Centers, University of Amsterdam.


Long-duration spike afterhyperpolarizations in neurons from the guinea pig superior cervical ganglion.
Intracellular recordings from guinea pig superior cervical ganglia maintained in vitro have revealed a protracted spike afterhyperpolarization in approximately 18% of the principal neurons that is substantially longer (greater than 1 s duration) than those previously reported. This long afterhyperpolarization is distinct from shorter duration afterpotentials in these cells because it can be selectively and reversibly blocked by cooling and by bath applied histamine. Cellular excitability is increased when the long-duration afterhyperpolarization is abolished and thus it deserves consideration as a site for modulation of synaptic transmission through the superior cervical ganglion.


Percutaneous coronary intervention in native vessels with angiographically visible thrombus temporal trends and impact of drug-eluting stents.
The aim of our study was to evaluate the temporal trends in outcomes following percutaneous coronary intervention in lesions with angiographically visible thrombus and to assess the impact of drug-eluting stents (DES) on long-term outcomes. Percutaneous coronary intervention in the presence of angiographically visible thrombus is associated with worse clinical outcomes. Whether recent advances in devices and adjunctive pharmacotherapy have made any significant impact on clinical outcomes is unknown. Moreover, concerns have been raised about the safety of DES in thrombotic lesions. We conducted a retrospective analysis of 6,227 consecutive patients who had angiographically visible thrombus. Patients were grouped into 3 eras depending on the dominant interventional strategy of that time: early stent era (1990 to 1996), bare-metal stent era (1997 to 2003), and DES era (2003 to 2006). Procedural success rates, although much improved, have remained unchanged in the last 2 cohorts (43%, 85%, 86%; p < 0.001). Adjusted in-hospital mortality (4.7%, 3.0%, 3.6%; p < 0.001), and major adverse cardiovascular events (7.8%, 5.0%, 5.3%; p < 0.001) decreased modestly. During long-term follow-up, mortality and the combined end point of death or myocardial infarction were similar in the 3 cohorts; but the combined end point of death, myocardial infarction, or target lesion revascularization (p < 0.001) was lower in the 2 most recent eras. There has been a marked improvement in procedural success accompanied by a reduction in in-hospital mortality and major adverse cardiac event rates. Importantly, the introduction of DES has not been associated with a greater risk of death or myocardial infarction among patients with angiographically visible thrombus.


Global metabolomics reveals metabolic dysregulation in ischemic retinopathy.
Proliferative diabetic retinopathy (PDR) is the most severe form of diabetic retinopathy and, along with diabetic macular edema, is responsible for the majority of blindness in adults below the age of 65. Therapeutic strategies for PDR are ineffective at curtailing disease progression in all cases; however a deeper understanding of the ocular metabolic landscape in PDR through metabolomic analysis may offer new therapeutic targets. Here, global and targeted mass spectrometry-based metabolomics were used to investigate metabolism. Initial analyses on vitreous humor from patients with PDR (n = 9) and non-diabetic controls (n = 11) revealed an increase of arginine and acylcarnitine metabolism in PDR. The oxygen-induced-retinopathy (OIR) mouse model, which exhibits comparable pathological manifestations to human PDR, revealed similar increases of arginine and other metabolites in the urea cycle, as well as downregulation of purine metabolism. We validated our findings by targeted multiple reaction monitoring and through the analysis of a second set of patient samples [PDR (n = 11) and non-diabetic controls (n = 20)]. These results confirmed a predominant and consistent increase in proline in both the OIR mouse model and vitreous samples from patients with PDR, suggesting that over activity in the arginine-to-proline pathway could be used as a therapeutic target in diabetic retinopathy.


Giant cell tumor of soft tissues of low malignant potential: A rare diagnosis on fine needle aspiration cytology.
Primary giant cell tumors of soft tissues (GCT-ST) are extremely rare soft tissue tumors, located in both superficial and deep soft tissues. They resemble osseous giant cell tumors morphologically and immunohistochemically. The tumor exhibits strong positive immunoreactivity for cluster of differentiation 68 (CD68) within multinucleated osteoclast-like giant cells and focal staining of mononuclear cells. Case reports describing the cytohistological features of this entity are very few. We report a case of GCT-ST of low malignant potential diagnosed on fine needle aspiration (FNA) and confirmed on histological and immunohistochemical studies.


School outcome, cognitive functioning, and behaviour problems in moderate and late preterm children and adults: a review.
A large number of children (6 to 11% of all births) are born at a gestational age between 32 and 36 weeks. Little is known of long term outcomes for these moderate and late preterm children. In this review, results of 28 studies on school outcome, cognitive functioning, behaviour problems, and psychiatric disorders are presented. Overall, more school problems, less advanced cognitive functioning, more behaviour problems, and higher prevalence of psychiatric disorders were found in moderate and late preterm born infants, children, and adults compared with full term peers. Suggestions for future research are discussed.


Intraocular lens implantation in Terrien's marginal corneal degeneration.
A patient with Terrien's corneal marginal degeneration and a previous trabeculectomy had planned extracapsular cataract extraction with intraocular lens implantation. A corneal incision was made with a diamond blade on the degeneration furrow superiorly and was closed with a 10-0 nylon double-running suture with keratoscopic control.


Compass-like manipulation of electronic nematicity in Sr3Ru2O7.
Electronic nematicity has been found in a wide range of strongly correlated electron materials, resulting in the electronic states having-4.5pc]Please note that the spelling of the following author name(s) in the manuscript differs from the spelling provided in the article metadata: Izidor Benedičič. The spelling provided in the manuscript has been retained; please confirm. a symmetry that is lower than that of the crystal that hosts them. One of the most astonishing examples is [Formula: see text], in which a small in-plane component of a magnetic field induces significant resistivity anisotropy. The direction of this anisotropy follows the direction of the in-plane field. The microscopic origin of this field-induced nematicity has been a long-standing puzzle, with recent experiments suggesting a field-induced spin density wave driving the anisotropy. Here, we report spectroscopic imaging of a field-controlled anisotropy of the electronic structure at the surface of [Formula: see text]. We track the electronic structure as a function of the direction of the field, revealing a continuous change with the angle. This continuous evolution suggests a mechanism based on spin-orbit coupling resulting in compass-like control of the electronic bands. The anisotropy of the electronic structure persists to temperatures about an order of magnitude higher compared to the bulk, demonstrating novel routes to stabilize such phases over a wider temperature range.


Barriers to early identification of autism in Brazil.
Parents of children with autism spectrum disorders (ASD) seem to perceive that their child's development is not following the normal pattern as early as the first year of life. However, ASD children may not receive a diagnosis until they are of preschool age, especially in low- and middle-income countries. The objective of this study was to evaluate the pathway between initial parental concerns about atypical child development and ASD diagnosis in Brazil. Nineteen mothers whose children had been diagnosed with ASD participated and were interviewed. The ASD group consisted of two girls and 17 boys, with a mean age of 93.0 months (SD 48.4 months; range 39-197 months). Mothers had their first concerns regarding ASD when children were 23.6±11.6 months old, but formal diagnosis occurred at a mean ± SD age of 59.6±40.5 months, corresponding to a 3-year delay. Most mothers felt discouraged to address their concerns due to negative experiences with health professionals. In Brazil, mothers perceived the first signs of ASD in their children at an age similar to that reported in other countries, but the diagnosis of ASD seemed to be delayed. Consistent with the literature, mothers reported negative experiences with health professionals during the pathway to achieving ASD diagnosis.


Identification of a novel monocyte cell surface molecule involved in the generation of antigen-induced proliferative responses.
A monocyte molecule, identified by a monoclonal antibody (mAb) named 24, is involved in the antigen-specific proliferation of T cells. Several types of antigen-induced responses are blocked by mAb24, but mitogen responses, even at low doses, are not. The 24 molecule is found on circulating monocytes and no other cell type. Normally only a proportion of monocytes express the 24 molecule but it can be induced rapidly on monocytes in culture, possibly from intracellular sources. The epitope is present on a heterodimer of 175 and 95 kDa which is similar to the leukocyte cell adhesion molecule (Leu-CAM) family. These findings suggest that although the 24 molecule shows some functional and biochemical similarities with the Leu-CAM family of molecules, it represents a novel structure primarily associated with mononuclear phagocytes.


Dual-metal-organic-framework derived CoP/MoP hybrid as an efficient electrocatalyst for acidic and alkaline hydrogen evolution reaction.
Searching for efficient and cost-effective electrocatalysts for hydrogen evolution reaction (HER) is significantly desirable and challenging. Herein, N, P co-doped carbon-encapsulated CoP/MoP hybrid (CoP/MoP@NPC) is fabricated using dual-metal-organic-framework (dual-MOF) as precursor by a simple one-step phosphating process. When applied as an electrocatalyst toward the HER, the as-designed CoP/MoP@NPC hybrid shows efficiently catalytic performance with a lower overpotential of 183 mV to deliver a current density of 10 mA cm-2, smaller Tafel slope of 53.3 mV dec-1 as well as long-time stability for 10 h in 0.5 M H2SO4 owing to the distinctive component and structural advantages. Furthermore, the electrode material also displays enhanced electrocatalytic HER activity in alkaline media. Importantly, this work provides an effective and feasible route for the construction of bimetallic phosphide electrocatalysts toward hydrogen production.


Phylogeny-wide conservation and change in developmental expression, cell-type specificity and functional domains of the transcriptional regulators of social amoebas.
Dictyostelid social amoebas self-organize into fruiting bodies, consisting of spores and up to four supporting cell types in the phenotypically most complex taxon group 4. High quality genomes and stage- and cell-type specific transcriptomes are available for representative species of each of the four taxon groups. To understand how evolution of gene regulation in Dictyostelia contributed to evolution of phenotypic complexity, we analysed conservation and change in abundance, functional domain architecture and developmental regulation of their transcription factors (TFs). We detected 440 sequence-specific TFs across 33 families, of which 68% were upregulated in multicellular development and about half conserved throughout Dictyostelia. Prespore cells expressed two times more TFs than prestalk cells, but stalk cells expressed more TFs than spores, suggesting that gene expression events that define spores occur earlier than those that define stalk cells. Changes in TF developmental expression, but not in TF abundance or functional domains occurred more frequently between group 4 and groups 1-3, than between the more distant branches formed by groups 1 + 2 and 3 + 4. Phenotypic innovation is correlated with changes in TF regulation, rather than functional domain- or TF acquisition. The function of only 34 TFs is known. Of 12 TFs essential for cell differentiation, 9 are expressed in the cell type for which they are required. The information acquired here on conserved cell type specifity of 120 additional TFs can effectively guide further functional analysis, while observed evolutionary change in TF developmental expression may highlight how genotypic change caused phenotypic innovation.


Role of CCAAT enhancer-binding protein beta in the thyroid hormone and cAMP induction of phosphoenolpyruvate carboxykinase gene transcription.
Transcription of the gene for phosphoenolpyruvate carboxykinase (PEPCK) is stimulated by thyroid hormone (T3) and cAMP. Two DNA elements in the PEPCK promoter are required for T3 responsiveness including a thyroid hormone response element and a binding site called P3(I) for the CCAAT enhancer-binding protein (C/EBP). Both the alpha and beta isoforms of C/EBP are highly expressed in the liver. C/EBPalpha contributes to the liver-specific expression and cAMP responsiveness of the PEPCK gene. In this study, we examined the ability of C/EBPbeta when bound to the P3(I) site to regulate PEPCK gene expression. We report that C/EBPbeta can stimulate basal expression and participate in the induction of PEPCK gene transcription by T3 and cAMP. The cAMP-responsive element-binding protein and AP1 proteins that contribute to the induction by cAMP are not involved in the stimulation by T3. A small region of the transactivation domain of C/EBPbeta is sufficient for the stimulation of basal expression and cAMP responsiveness. Our results suggest that C/EBPalpha and C/EBPbeta are functionally interchangeable when bound to the P3(I) site of the PEPCK promoter.


Vaginal birth after caesarean section before and during COVID-19 pandemic. Factors associated with successful vaginal birth.
The ratio of caesarean has been increasing considerably in many countries. Planning a vaginal birth after a previous caesarean is considered an important option for women in a subsequent pregnancy. To analyse obstetric and neonatal outcomes in women in labour after caesarean section before and during the COVID-19 pandemic, and to determine factors associated with successful vaginal birth after caesarean (VBAC). Observational cohort study of women in labour with history of caesarean section who gave birth between March 2019 and December 2020 in a tertiary hospital in southern Spain. Consecutive sampling was performed using the maternal birth database and a descriptive and inferential analysis of the study variables was carried out. Socio-demographic, obstetric and neonatal variables were compared between the pre-pandemic and pandemic periods. Multiple logistic regression analysis was performed to determine variables associated with VBAC success. The VBAC success rate was 67.4%. The caesarean section rate was significantly higher during the COVID-19 pandemic period. Factors associated with VBAC success were: birth before the pandemic (OR 0.32) and at night (OR 0.45), use of epidural analgesia (OR 2.14), and having had a previous vaginal birth (OR 1.98). The success rate of VBAC was lower during the pandemic. Knowledge of the factors related to VBAC success is critical for practitioners when supporting women in decision-making about mode of birth after a previous caesarean section.


The less they know, the better: abstinence-only HIV/AIDS programs in Uganda.
Young people in Uganda have never known a world without HIV/AIDS. Ignorance and denial fuel HIV, leaving young people without the critical information that could help them prevent infection. As of 2002, according to government estimates, HIV prevalence among young people in Uganda stood at an estimated 4.9 percent, with rates of 6.5 percent in major towns and 4.1 percent in rural areas. This is the summary and excerpts from the recommendations of this publication.


The effect of chlorpromazine on monoamine levels in the rat cerebellum and hippocampus: a developmental study.
Acute and chronic alterations of the monoamine levels in the rat cerebellum and hippocampus after late prenatal and early postnatal administration of chlorpromazine, were examined using high performance liquid chromatography with electrochemical detection. During a critical phase of development (one week postnatal), chlorpromazine produced increased levels of both serotonin and dopamine in both brain regions. At 24 weeks postnatal, or 21 weeks after cessation of drug administration, the levels of all 3 monoamines were decreased in the cerebellum and increased in the hippocampus. The early disruption in the normal monoamine levels may be related to abnormal growth patterns observed in previous studies.


Bioguided extraction of polyphenols from grape marc by using an alternative supercritical-fluid extraction method based on a liquid solvent trap.
The biological activity of polyphenols extracted from grape marc was studied with a view to finding a new use for this winery waste. Polyphenols were extracted by using an alternative supercritical-fluid extraction method based on the use of a liquid trap that allows extracted polyphenols to be retained in a saline buffer, thus avoiding the need for the organic solvent required to elute polyphenols from a solid trap. The major extraction variables influencing the performance of the liquid trap (viz. CO(2) modifier content, flow-rate, extraction time and trap volume) were optimized. The proposed method was applied to the supercritical-fluid extraction extraction of 0.3 g grape marc with CO(2) modified with 3% methanol at 350 bar at 50 degrees C (CO(2) density 0.9 g mL(-1)) for 20 min, using a liquid flow-rate of 0.9 mL min(-1). The polyphenol extracts thus obtained exhibited cytotoxic effects that induced apoptosis in tumour cells.


Inhibition of KIF20A suppresses the replication of influenza A virus by inhibiting viral entry.
The influenza A virus (IAV) has caused several pandemics, and therefore there are many ongoing efforts to identify novel antiviral therapeutic strategies including vaccines and antiviral drugs. However, influenza viruses continuously undergo antigenic drift and shift, resulting in the emergence of mutated viruses. In turn, this decreases the efficiency of existing vaccines and antiviral drugs to control IAV infection. Therefore, this study sought to identify alternative therapeutic strategies targeting host cell factors rather than viruses to avoid infection by mutated viruses. Particularly, we investigated the role of KIF20A that is one of kinesin superfamily proteins in the replication of IAV. The KIF20A increased viral protein levels in IAV-infected cells by regulating the initial entry stage during viral infection. Furthermore, the KIF20A inhibitor significantly suppressed viral replication, which protected mice from morbidity and mortality. Therefore, our findings demonstrated that KIF20A is highly involved in the viral replication process and viral propagation both in vitro and in vivo, and could thus be used as a target for the development of novel antiviral drugs.


Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney.
Aristolochic acid (AA) is known to be a potent mutagen and carcinogen. Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major components of AA, differ from each other by a single methoxy group. However, their individual mutagenic characteristics in vivo are unclear. In the present study, we compared their DNA adduct formation and mutagenicities in the gpt delta transgenic mouse kidney. The dA-AAI, dG-AAI, dA-AAII and dG-AAII were identified in the kidney two days after intragastric administration of AAI or AAII at 5mg/kg. The concentration of DNA adducts formed by AAII was approximately 2.5-fold higher than that formed by AAI (p<0.05). The mutant frequency induced by AAII was nearly two-fold higher than that induced by AAI (p<0.05) following administration of 5mg/kg AAI or AAII, five times per week for six weeks. Investigation of the mutation spectra showed no statistically significant difference between AAI- and AAII-treated mice (p>0.05). A:T to T:A transversion was the predominant type of mutation in both treated groups, the GC-associated mutation rates, however, differed between the AAI and AAII treatments. The in vivo metabolic pathways of AAI and AAII are different, and this may affect their mutagenicity. In the present study, we measured the levels of AAI and AAII in the kidney and plasma of gpt delta transgenic mice at multiple time points after a single intragastric dose of 1 or 5mg/kg of either component. Our results showed that the levels of AAII in both kidney and plasma were considerably higher than those of AAI (p<0.01). The present study indicated that AAII showed more carcinogenic risk than AAI in vivo, and this may be, at least partly, the result of its increased levels in kidney and plasma.


Use of high resolution thin section CT scanning of the petrous bone in temporal bone anomalies.
High resolution thin section axial CT scans (REVIEW reconstruction ARRANGE reformation--General Electric copyright were utilized to evaluate the petrous bone of 17 patients, ages 3 to 60, with congenital hearing loss. Two scanning protocols were evaluated: 1.5 mm thick sections at 1.5 mm intervals, and 1.5 mm thick sections at 1.0 mm intervals. These protocols were qualitatively compared with regard to 1. visualization of small anatomical structures, and 2. computer reformatted images in coronal and sagittal planes. Our experience suggests this imaging capability is highly useful in th evaluation of congenital ear abnormalities. Seventeen patients were examined with high resolution CT scans. The inner ear abnormalities included varying degrees of Mondini's dysplasia. The large vestibule, the large fenestra into the internal auditory canal, as well as the poor cochlear formation, were seen in these malformations. These studies have allowed a greater degree of accuracy in counseling parents of patients with inner ear malformations. Middle and external ear deformities were also encountered. The imaging technique is capable of demonstrating ossicular deformities, as well as the nature of canal atresias. It is particularly useful in the planning of surgery on some of these patients in that location of the plane of the facial nerve canal can be determined prior to surgery. This provides the ability to determine whether surgery is possible, and if so, the probability of opening the middle ear adequately to obtain appropriate reconstruction. Illustrative cases demonstrate the ease of visualizing the small structures of the inner and middle ear and the ability to review these structures in any plane utilizing the ARRANGE program.


Suggested bacteriological standards for air in ultraclean operating rooms.
Bacteriological standards for the air in ultraclean operating rooms are needed since physical tests alone cannot guarantee satisfactory results. 10 m-3 is suggested as the highest acceptable value for an ultraclean system. Methods are described for determining this.


Somatostatin is increased in the basal ganglia in Huntington disease.
Huntington disease (HD) is an autosomal dominant hereditary disorder characterized by premature cell death, predominantly in the neostriatum. Decreased concentrations of several neurotransmitters and neuropeptides have been reported in the basal ganglia in Huntington disease. We now report that concentrations of radioimmunoassayable somatostatin are increased in extracts of the caudate (mean +/- standard error of the mean, ng/gm net weight; 247 +/- 24 versus 85 +/- 11), putamen (275 +/- 48 versus 74 +/- 11), external globus pallidus (100 +/- 10 versus 27 +/- 6), and internal globus pallidus (108 +/- 21 versus 21 +/- 8) in the disease. The concentrations of immunoreactive substance P measured in the same extracts were markedly reduced in caudate (mean +/- standard error of the mean, pmol/gm wet weight; 25 +/- 3 versus 109 +/- 20), putamen (28 +/- 7 versus 88 +/- 28), external globus pallidus (39 +/- 9 versus 196 +/- 62), and internal globus pallidus (60 +/- 17 versus 263 +/- 39), as well as in both subdivisions of the substantia nigra. Gel permeation chromatography and high-performance liquid chromatography showed radioimmunoassayable somatostatin to include peptides with physicochemical properties of the tetradecapeptide somatostatin and larger substances, including somatostatin-28-like material. A single peak of immunoreactive substance P corresponding to synthetic substance P was found by high performance liquid chromatography. These results suggest that immunoassayable somatostatin-containing neuronal elements in the neostriatum and globus pallidus in Huntington disease are affected differentially by the disease process from neurons that contain immunoreactive substance P.


Effect of antisense oligodeoxynucleotide targeted against NF-κB/P65 on cell proliferation and tumorigenesis of gastric cancer.
To study the inhibitory effect of nuclear transcription factor-kappa B(NF-κB) antisense oligodeoxynucleotide(ASODN) on the growth and tumorgenesis of human gastric cancer. We synthesized and transfected the ASODN of NF-κB/P65 to gastric cancer cell line. The effect of ASODN of NF-κB/P65 on the proliferation of gastric cancer cells was measured by MTT method. The subcutaneous xenograft model of human gastric cancer was established in nude mice, and the tumor growth curve was observed. The cell proliferation was significantly inhibited in P65 ASODN-transfected group in vitro (P<0.05). In vivo, tumor formation test showed that the tumor volume in nude mice in ASODN group was obviously smaller than in other groups (P<0.05); the apoptosis index (AI) was significantly higher (P<0.001). Simultaneously, MVD in ASODN group was markedly lower than in other groups (P<0.01). NF-κB could be used as a new biological therapeutic target of gastric cancer.


An intricate web - designing and authoring a web-based course.
The Internet offers a great opportunity to deliver dental education in new ways. However, to achieve the maximum benefit from this medium, it is necessary to understand its strengths and weaknesses and, above all, not to lose sight of the key principle that in education it is the message and not the messenger (the content and not the medium) that should be given priority. After a brief introduction, this paper considers the principles of designing online programmes. It stresses the need for ensuring that students have easy access to the materials that have been designed and then describes 'learning objects' and virtual learning environments (VLEs). It concludes that with some notable exceptions, dental educators have hardly begun to grasp the benefits of web-based teaching and learning.


Hepatoprotective Activity.
The liver performs a vital role in metabolism, secretion, storage, and detoxification of endogenous and exogenous substances. Oxidative stress and free radicals enhance the severity of hepatic damage, which can be overcome by the antioxidant mechanism. Plant extracts can be the best source of such antioxidants and mediate hepatoprotective activity. In this chapter, high-dose paracetamol-induced hepatotoxicity in rat model is discussed with explanations of biochemical and histopathological studies.


Dynamic expression of p75NTR and Lingo-1 during development of mouse retinofugal pathway.
Our previous studies showed interaction of Nogo at the midline with its receptor (NgR) on optic axons plays a role in axon divergence at the mouse optic chiasm. Since NgR lacks a cytoplasmic domain, it needs transmembrane receptor partners for signal transduction. In this study, we examined whether the co-receptors of NgR, low-affinity neurotrophic receptor (p75NTR) and Lingo-1, are localized on axons in the mouse optic pathway. In the retina, p75NTR and Lingo-1 were observed on neuroepithelial cells at E13 and later on the retinal ganglion cells at E14 and E15. At the optic disc, p75NTR was observed on the retinal axons, whereas Lingo-1 was found on glial processes surrounding the axon fascicles. Both p75NTR and Lingo-1 were found on axons in the optic stalk, optic chiasm and optic tract. Furthermore, a transient expression of Lingo-1 was observed on the SSEA-1 positive chiasmatic neurons at E13, but not at later developmental stages. The presence of p75NTR and Lingo-1 on optic axons provides further supports to the contribution of Nogo/NgR signaling in axon divergence at the mouse optic chiasm.


Resolution of serous macular detachment after intravitreal triamcinolone acetonide treatment of patients with branch retinal vein occlusion.
To evaluate the effect of intravitreal triamcinolone acetonide on serous macular detachment in patients with branch retinal vein occlusion (BRVO). Eight eyes of 8 patients with BRVO (6 men and 2 women; age range, 52-76 years) made up the study population. The eligibility criteria for this study included clinically and angiographically detectable cystoid macular edema (CME) in which the presence of serous macular detachment was documented by optical coherence tomography (OCT). After intravitreal injection of 0.1 mL (4 mg) of triamcinolone acetonide, the visual and anatomical responses were observed. In all eyes, after injection of triamcinolone acetonide, CME and serous macular detachment regressed. At 3 and 6 months, CME and serous macular detachment had recurred in 1 eye (12.5%) and 2 eyes (25%), respectively. Patients with recurrence were retreated. No eyes lost vision at 1 month, and all eyes showed improvement. At 3 months, no eyes had lost vision from baseline, and 7 eyes (87.5%) showed improvement. At 6 months, again no eyes had lost vision from baseline, and 7 eyes (87.5%) maintained improved visual acuity. The preliminary results of our study showed prompt resolution of serous macular detachment with corresponding improved visual acuity in patients with CME secondary to BRVO. Further study with longer follow-up and a larger series is warranted to assess the long-term efficacy and safety.


CHANGES IN THE NUMBER OF NEURONS, ASTROCYTES AND MICROGLIA IN THE BRAIN AFTER ISCHEMIC STROKE ASSESSED BY IMMUNOHISTOCHEMISTRY AND IMMUNOBLOTTING.
It is known that the mechanisms of damage in the brain after stroke are regulated by combination of several types of cells, primarily of neurons, astrocytes, endothelium and microglia. Ischemic exposure disrupts the balance in the cellular composition of the brain; in the lesion, cells die by necrosis while in tissue surrounding ischemic zone the delayed induction of apoptosis occurs, and namely the ratio of death of different cells determines the clinical outcome of the disease. Thus, the assessment of death of various cell types of the neurovascular unit is an important part of fundamental studies of the mechanisms of brain damage and pre-clinical studies of potential neuroprotective drugs. In this line, we have conducted a comparative study of the two most often used methods: immunohistochemical staining of brain sections, allowing to determine the number and localization of specific cells in the tissue among other types of cells, and immunoblotting that detects specific proteins in the tissue homogenate. We have found that, depending on the type of cells, changes in their number and composition after stroke can be diffuse or localized, which imposes restrictions on the use of any method of estimation of the number of cells in brain tissue. In general, the most preferable is the use of immunohistochemistry, however, with certain limitations, immunoblotting can be used in estimating amounts of astroglia and microglia.


The relationship between single radial hemolysis, hemagglutination inhibition, and virus neutralization assays used to detect antibodies specific for equine influenza viruses.
Antibodies specific for equine influenza viruses are usually quantified using single radial hemolysis (SRH), hemagglutination inhibition (HI) or virus neutralization (VN). Neutralizing antibodies are thought to provide optimum protection to challenged animals. The purpose of this study was to determine the extent to which SRH and HI assays detect antibodies which neutralize equine influenza viruses. Acute and convalescent sera from 41 horses were analyzed using VN, SRH, and HI assays. These horses were present in a population of Thoroughbred racehorses during an epidemic of upper respiratory tract disease associated with influenza A/equine/Saskatoon/1/91 (H3N8), infections. Concentrations of antibodies binding to influenza A/equine/Kentucky/1/81 (H3N8), A/equine/Miami/1/63 (H3N8), and A/equine/Prague/1/56 (H7N7) were determined. Results of the VN assay were compared with results from the SRH and HI assays for acute antibody levels, changes in antibody concentrations between acute and convalescent sampling, and the occurrence of seroconversion. The correlation between assays for pre-exposure antibody levels ranged from 88% to 96%. The correlation between assays for change in antibody concentration ranged from 83% to 90% for the H3N8 viruses. This study shows that antibody concentrations specific for equine influenza virus, measured using SRH and HI assays, are highly correlated with concentrations detected using a VN assay.


Antihypertensive action and serotonin-induced platelet aggregation during long-term ketanserin treatment in hypertensive patients.
Ketanserin (3 X 40 mg daily) was administered during 6 weeks in 14 patients with mild to moderate essential hypertension using a double-blind, placebo-controlled, crossover design. Ketanserin decreased (p less than 0.01) the recumbent blood pressure from 159/104 to 153/97 mm Hg and the recumbent heart rate from 75 to 72 beats/min. Platelet aggregation induced by 5-hydroxytryptamine (5-HT), whether or not amplified by threshold doses of collagen, was not inhibited; however, it was reduced in 10 normal volunteers after a single oral dose of 40 mg ketanserin. The results suggest that long-term treatment with ketanserin reduces blood pressure; whereas 5-HT receptor inhibition could not be demonstrated when assessed by platelet aggregation.


Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease.
The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer.


Stability of heating temperature on cytotoxicity.
Chinese hamster V79 cells were used to test the cytotoxic effect of heat which alternates between high and low temperatures during the treatment period. This type of temperature fluctuation is often encountered in clinical hyperthermia. Two sets of heating protocols were used in the experiments: Temperature alternates (a) between 42 and 43 degrees and (b) between 42 and 44 degrees in cycle with equal total "thermal dose," that is heating temperature X heating time. The effectiveness of these heating protocols expressed in average percentage of cell survival depend on the initial temperature attained and the length of the time of this temperature alternation. If the period of temperature change is short such as every 5 or 10 minutes, the cytotoxicity shows very little difference whether the initial treatment temperature is low or high. However, when the period is longer than 20 minutes, the difference in cell survival between the initial temperature at 42 degrees and at higher temperatures is substantial. Cells obtained from logarithmic or plateau phases of growth yield the same result. The difference is likely resulted from a combination of thermotolerance and step-down heating mechanisms. In addition, the effects of heating temperature fluctuation on cytotoxicity is not altered by a 500 cGy of gamma-ray radiation applied either immediately before or after the heat treatment.


Transient tactile allodynia following intrathecal puncture in mouse: contributions of Toll-like receptor signaling.
Studies of spinal drug action in mice often involve percutaneous intrathecal drug administration delivered in a lightly anesthetized animal. A successful lumbar intrathecal (IT) needle stick of a lightly anesthetized (isoflurane) mouse evokes a tail flick, which is an indication of local spinal nerve stimulation. Immediately upon arousal, a hind paw tactile allodynia, as measured with von Frey hairs (pre 1.55±0.11 g vs. injected 0.66±0.08 g) lasts 3-4 h. In a similarly anesthetized mouse without the needle stick, a 1-h allodynia was noted. In studies on spinal Toll-like receptor (TLR) signaling, we observed that following intrathecal puncture and mechanical stimulation of the nerve roots mice deficient in TLR down-stream signaling (Myd88(-/-)/Trif(lps2)), displayed only the transient (1-h) allodynia otherwise observed following isoflurane alone. These data suggest that the extended period of hyperalgesia observed with needle penetration of the dura and mechanical stimulation of the nerve roots requires signaling through the MyD88/TRIF pathways and supports the intrinsic role of Toll-like receptors in the allodynia secondary to the minor nerve activation occurring during the intradural puncture.


Community-based infections and the potential role of common touch surfaces as vectors for the transmission of infectious agents in home and community settings.
Community-based pathogens that can survive on common touch surfaces include those that can cause gastrointestinal, respiratory, and skin infections. Our hands play an obvious role in the transmission of many of these pathogens, but common touch surfaces are also part of the transmission equation. Traditionally, common touch surfaces have not been the main focus of cleaning and sanitation in household and community settings. Infectious disease continues to be of concern globally due in part to emergence of new pathogens, antibiotic-resistant organisms, and a growing immunocompromised community. As a result, it is important to prevent and minimize the infection risk in homes and in the community. Understanding the role of common touch surfaces should inform surface hygiene practices and these surfaces should be the subject of future intervention studies.


[Peculiar bone injuries by grinding in a corpse with a long immersion period (author's transl)].
Injuries frequently occur after immersion of corpses in water. Depending on the type of water different sorts of injuries, caused by drifting and being dragged, can lead to more or less severe abrasions of the soft parts of the body predominantly skin abrasions. This case is unique among hover 3000 corpses in water found in the last 4 decades in the Elbe. The corpse was found with very severe and extensive bone injuries; in fact the bones were ground down (among other injuries was a large opening in the skull). The origin is discussed: it is assumed that the corpse changed its position only minimally in the half-year period after immersion and did not drift with the stream, but on the contrary had stuck fast on or under a pontoon and was rubbed and ground against a pole or something similar. The special conditions of the Elbe River appear to have played an important role in this process.


Correction: Why are listeners sometimes (but not always) egocentric? Making inferences about using others' perspective in referential communication.
[This corrects the article DOI: 10.1371/journal.pone.0240521.].


Autoimmune lymphoproliferative syndrome due to FAS mutations outside the signal-transducing death domain: molecular mechanisms and clinical penetrance.
Autoimmune lymphoproliferative syndrome is a disorder of lymphocyte apoptosis. Although FAS molecules bearing mutations in the signal-transducing intracellular death domain exhibit dominant-negative interference with FAS-mediated apoptosis, mechanisms for pathology of non-death domain FAS mutations causing autoimmune lymphoproliferative syndrome are poorly defined. RNA stability, protein expression, ligand binding, and ability to transmit apoptosis signals by anti-FAS antibody or FAS ligand were determined for a cohort of 39 patients with non-death domain autoimmune lymphoproliferative syndrome. Correlations between mutation type and disease penetrance were established in mutation-positive family members. Frameshifts or transcriptional stop mutations before exon 7 resulted in messenger RNA haploinsufficiency, whereas an amino-terminal signal sequence mutation and certain intracellular truncations prevented cell surface localization of FAS. All resulted in decreased FAS localization, inability to bind FAS ligand, and reduced FAS ligand-induced apoptosis. Extracellular missense mutations and in-frame deletions expressed defective FAS protein, failed to bind FAS ligand, and exhibited dominant-negative interference with FAS-mediated apoptosis. Mutation-positive relatives with haploinsufficient or extracellular mutations had lower penetrance of autoimmune lymphoproliferative syndrome clinical phenotypes than did relatives with death domain mutations. We have defined molecular mechanisms by which non-death domain FAS mutations result in reduced lymphocyte apoptosis, established a hierarchy of genotype-phenotype correlation among mutation-positive relatives of patients with autoimmune lymphoproliferative syndrome, and demonstrated that FAS haploinsufficiency can lead to autoimmune lymphoproliferative syndrome.


A procedure for determining the number and pattern of digestible starch fractions in multiphasic food digestograms.
Plant-based foods are frequently heterogenous systems, containing multiple starch fractions with distinct digestion rate constants. An unbiased determination of the number and digestion pattern of these fractions is a prerequisite for understanding the digestive characteristics of food. A non-linear least-squares procedure based on a conditional selection of simple first-order kinetics or a combination of parallel and sequential kinetics models was developed. The procedure gave robust results fitting manually generated data, and was applied to in vitro experimental digestion data of retrograded rice starches. By correlating fitting parameters with starch structural parameters, it showed that rice starches with a lower amylose content, longer amylose chains, and amylopectin intermediate chains had more digestible starch fractions after long-term retrogradation. This procedure enables the structural basis of starch digestibility and the development of food products with slow starch digestibility to be better understood. © 2022 Society of Chemical Industry.


Reliability evaluation of auxiliary feedwater system by mapping GO-FLOW models into Bayesian networks.
Bayesian network (BN) is a widely used formalism for representing uncertainty in probabilistic systems and it has become a popular tool in reliability engineering. The GO-FLOW method is a success-oriented system analysis technique and capable of evaluating system reliability and risk. To overcome the limitations of GO-FLOW method and add new method for BN model development, this paper presents a novel approach on constructing a BN from GO-FLOW model. GO-FLOW model involves with several discrete time points and some signals change at different time points. But it is a static system at one time point, which can be described with BN. Therefore, the developed BN with the proposed method in this paper is equivalent to GO-FLOW model at one time point. The equivalent BNs of the fourteen basic operators in the GO-FLOW methodology are developed. Then, the existing GO-FLOW models can be mapped into equivalent BNs on basis of the developed BNs of operators. A case of auxiliary feedwater system of a pressurized water reactor is used to illustrate the method. The results demonstrate that the GO-FLOW chart can be successfully mapped into equivalent BNs.


A simple turn-on fluorescent chemosensor based on Schiff base-terminated water-soluble polymer for selective detection of Al3+ in 100% aqueous solution.
A simple water-soluble polymer PEGBHB based on polyethylene glycol bearing a Schiff base derivative moiety was successfully designed and synthesized. PEGBHB showed high selectivity and sensitivity towards Al3+ as a turn-on fluorescent chemosensor without influence by other competitive metal ions in 100% aqueous solution. The detection limit of PEGBHB for Al3+ was found to be 9.67 × 10-9 M. A 1:1 stoichiometry between PEGBHB and Al3+ has been confirmed by Job plot analysis. PEGBHB could detect Al3+ over a wide pH range from 4 to 10. The chemosensor was reversible by adding EDTA to the solution of PEGBHB-Al3+ complex. An INHIBIT molecular logic gate was constructed with the help of OFF-ON-OFF signal on alternate addition of Al3+ and EDTA to the chemosensor. Furthermore, test papers were fabricated facilely using PEGBHB for convenient and visual detection of practical Al3+.


In vivo enhancement of general and specific transcription in Escherichia coli by DNA gyrase activity.
The effect of drugs which inhibit DNA gyrase, including nalidixic acid, oxolinic acid and coumerycin, on transcription of Escherichia coli bacteria, phage and plasmid genomes was studied. Quantitative estimates of the synthesis of RNA under drug-treatment conditions showed that synthesis of many RNA species, including trp mRNA, was subject to inhibiton by the drug. Transcription directed by the lambda promoter pR was selectively less sensitive to the drug action than transcription initiated at the lambda promoter pL. Evidence was obtained showing that diminished transcription resulted from less frequent RNA chain initiation rather than a premature arrest of the chain elongation. Inhibiton of transcription by these DNA gyrase inhibitors was observed even in the absence of DNA replication. The inhibition by oxolinic acid or coumerycin was not observed in an E. coli strain bearing a nalAr mutation or a cour mutation, respectively. The reduction of trp mRNA synthesis in oxolinic acid-treated cells cannot be attributed to the increase in the rate of nascent mRNA degradation. These results indicate that DNA gyrase is generally required for intracellular RNA synthesis, and suggest that the supercoiling of DNA by this winding enzyme enhances the initiation of transcription.


Familial congenital cornea guttata with anterior polar cataracts.
We examined 21 members of a family with a syndrome of cornea guttata and anterior polar cataracts. Twelve members had both ocular abnormalities. An affected woman underwent penetrating keratoplasty at age 28 years. Light microscopy of the corneal button showed changes consistent with cornea guttata and corneal edema. The combination of cornea guttata and anterior polar cataracts appears to form a well-defined ocular syndrome that is inherited in an autosomal dominant fashion.


Design and fabrication of porous chitosan scaffolds with tunable structures and mechanical properties.
Chitosan-based porous scaffolds are of great interest in biomedical applications because of their biodegradability and biocompatibility. However, the poor mechanical properties of these scaffolds hinder their broad utility. In the present study, a novel compression method was developed to fabricate chitosan scaffolds with high mechanical strength and tuneable topography, based on the ionic strength and pH-dependent solubility of chitosan. When the compressive ratio increases from 1 to 8, the compressive elastic modulus of the scaffold increases from 5.2kPa to 520kPa and the porosity decreases from 94.1% to 82.5%. Furthermore, the number of human adipose-derived stem cells adhering to the scaffolds increases as the compressive ratio increases, owing to the high density of the chitosan fibres. This method does not require external cross-linker agent, sophisticated instrumentation and/or technical proficiency and could be extended to other polysaccharides.


Comprehensive review of task-based neuroimaging studies of cognitive deficits in Alzheimer's disease using electrophysiological methods.
With an aging population, cognitive decline and neurodegenerative disorders are an emerging public health crises with enormous, yet still under-recognized burdens. Alzheimer's disease (AD) is the most common type of dementia, and the number of cases is expected to dramatically rise in the upcoming decades. Substantial efforts have been placed into understanding the disease. One of the primary avenues of research is neuroimaging, and while positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are most common, crucial recent advancements in electrophysiological methods such as magnetoencephalography (MEG) and electroencephalography (EEG) have provided novel insight into the aberrant neural dynamics at play in AD pathology. In this review, we outline task-based M/EEG studies published since 2010 using paradigms probing the cognitive domains most affected by AD, including memory, attention, and executive functioning. Furthermore, we provide important recommendations for adapting cognitive tasks for optimal use in this population and adjusting recruitment efforts to improve and expand future neuroimaging work.


Redox-dependent disulfide bond formation in SAP30L corepressor protein: Implications for structure and function.
Sin3A-associated protein 30-like (SAP30L) is one of the key proteins in a multi-subunit protein complex involved in transcriptional regulation via histone deacetylation. SAP30L, together with a highly homologous SAP30 as well as other SAP proteins (i.e., SAP25, SAP45, SAP130, and SAP180), is an essential component of the Sin3A corepressor complex, although its actual role has remained elusive. SAP30L is thought to function as an important stabilizing and bridging molecule in the complex and to mediate its interactions with other corepressors. SAP30L has been previously shown to contain an N-terminal Cys3 His type zinc finger (ZnF) motif, which is responsible for the key protein-protein, protein-DNA, and protein-lipid interactions. By using high-resolution mass spectrometry, we studied a redox-dependent disulfide bond formation in SAP30L ZnF as a regulatory mechanism for its structure and function. We showed that upon oxidative stress SAP30L undergoes the formation of two specific disulfide bonds, a vicinal Cys29-Cys30 and Cys38-Cys74, with a concomitant release of the coordinated zinc ion. The oxidized protein was shown to remain folded in solution and to bind signaling phospholipids. We also determined a solution NMR structure for SAP30L ZnF that showed an overall fold similar to that of SAP30, determined earlier. The NMR titration experiments with lipids and DNA showed that the binding is mediated by the C-terminal tail as well as both α-helices of SAP30L ZnF. The implications of these results for the structure and function of SAP30L are discussed.


Stress reactions in rats during immunization to serotonin.
We studied the effect of immunization with a serotonin-bovine serum albumin conjugate on parameters of stress reaction to immobilization stress in rats. Active immunization was accompanied by changes in parameters reflecting animal resistance to emotional stress. The observed changes can be interpreted as a decrease in individual resistance to emotional stress. Active immunization of rats with a serotonin-bovine serum albumin conjugate was accompanied by production of autoantibodies against serotonin and dopamine. The role of autoantibodies against dopamine in modulation of the effect of immunization with serotonin-bovine serum albumin conjugate on the stress reaction in rats is discussed.


Granular cell tumor of the optic nerve.
A case of a combined neurofibroma-granular cell tumor is presented. The tumor had developed in the left middle cranial fossa after an intracranial trigeminal nerve operation 23 years before. It had displaced and infiltrated the temporal lobe and expanded probably via the fissura orbitalis into the orbit. The thickened optic nerve revealed a marked widening of the subdural fissure by typical granular cells. The cufflike tumor cell aggregation in the subdural fissure had compressed the optic fascicle, thereby inducing a demyelinisation and axonal degeneration. A reactive gliosis in the optic fascicle masks the typical pattern of the optic nerve atrophy. The gangliocytes of the third retinal neuron are atrophic and replaced by reactively proliferated fibrillary astrocytes. A short review of the literature and theories concerning histogenesis of the granular cell tumor (neurogenic or mesoderma) is given. An intermediary type of neurofibromatous and granular cells which we found motivates us to agree with a mesodermal origin.


Emerging identity of Finnish nurse teachers: student teachers' narratives in a group exam.
In Finland students pursuing in Master's Degree Programme have a previous degree in nursing from polytechnics. Nurse teacher qualification also includes at least five year's experience of working in practice. This article concentrates on the conflicts student teachers brought up in a group exam as regards changing a nurse's identity into a teacher's identity in teacher training. The approach of the study on this group was narrative. The data were collected by videotaping two group exam situations (five hours in all) of volunteer student teachers (N= 5) during the last course (Nurse teacher's inquiring mind) of their nurse teacher studies in 2002. The material was transcribed and analysed using categorical-content reading to identify particular themes, story lines and messages within material. By abstracting these, stories that describe the content can be found. Three narratives emerged in the analysis: 1. Competence creates confidence; 2. Shared teacher identity; 3. Ethics of teacher identity. The narratives raised new ideas for developing nurse teacher education in the future. Nowadays, there are good prospects for developing a shared teacher identity if there is willingness to co-operate within a learning community of a new kind.