Reinforcement of variations and repetitions along three independent response dimensions.
Reinforcement was presented contingent upon human subjects simultaneously varying three dimensions of an operant response. The response was drawing rectangles on a computer screen. The dimensions were area of the rectangle, its location on the screen, and its shape. In Experiment 1, an experimental group was reinforced for satisfying the three-part variability contingency. A control group was equally reinforced for drawing rectangles but independently of levels of variability. Results showed that the experimental group varied significantly more along each of the dimensions than did the control group. In Experiment 2, another group of subjects was reinforced for repeating instances along one of the dimensions, e.g. repeatedly draw a rectangle in approximately the same location, while simultaneously varying along the other two dimensions. The subjects learned to satisfy these contingencies as well. These results show reinforcement simultaneously and independently controls the variability of three orthogonal dimensions of a response.


Soil fungus causes sporadic bovine abortions in Scotland.
Abortions in cattle due to the soil fungus Scedosporium apiospermumTickborne fever in ewe hoggsCopper toxicity in a five-week-old lambDuck virus enteritisToxoplasmosis in a ring-tailed lemur These are among matters discussed in the disease surveillance report for May from SAC Consulting: Veterinary Services (SAC C VS).


Protoribosome by quantum kernel energy method.
Experimental evidence suggests the existence of an RNA molecular prebiotic entity, called by us the "protoribosome," which may have evolved in the RNA world before evolution of the genetic code and proteins. This vestige of the RNA world, which possesses all of the capabilities required for peptide bond formation, seems to be still functioning in the heart of all of the contemporary ribosome. Within the modern ribosome this remnant includes the peptidyl transferase center. Its highly conserved nucleotide sequence is suggestive of its robustness under diverse environmental conditions, and hence on its prebiotic origin. Its twofold pseudosymmetry suggests that this entity could have been a dimer of self-folding RNA units that formed a pocket within which two activated amino acids might be accommodated, similar to the binding mode of modern tRNA molecules that carry amino acids or peptidyl moieties. Using quantum mechanics and crystal coordinates, this work studies the question of whether the putative protoribosome has properties necessary to function as an evolutionary precursor to the modern ribosome. The quantum model used in the calculations is density functional theory--B3LYP/3-21G*, implemented using the kernel energy method to make the computations practical and efficient. It occurs that the necessary conditions that would characterize a practicable protoribosome--namely (i) energetic structural stability and (ii) energetically stable attachment to substrates--are both well satisfied.


Flight polymorphism in the field cricket Gryllus pennsylvanicus.
Wing length polymorphisms are common in many groups of insects. In the field cricket Gryllus pennsylvanicus the long-winged morph occurs in low frequency in most populations but seems not to occur at all in certain areas and to become relatively abundant in others. Laboratory rearing experiments and single-pair crosses suggest that both inter-and intrapopulation variation can be explained at least in part by genetic differences. A model of genetic variation in threshold response is consistent with all available data. One possible mechanism for maintenance of the flight polymorphism is discussed.


[Observations on the life biology of Pycnogonum litorale (Ström) (Pantopoda)].
Pycnogonum litorale lives in an interstitial system, of the mussel zone on the embankment of the Jadebusen. Hard substrate, high humidity at low tide, sufficient Metridium senile as food, and active currents together with protection from drifting, constitute favourable conditions for this pycnogonid.Prior to laying egg in February, the male remains in a riding position upon the female for approximately 24 days. Under artificial short-day conditions the riding position may also be assumed outside of the reproductive period. The eggs are transported to the ovigers of the male by trunk movements of both partners. At 12°C the larvae hatch about 41-46 days after egg-laying. No larvae hatched from eggs laid during summer at 19°C.The larvae live endoparasitically in Hydrozoa for about 1/2 year. Following metamorphosis, the freeliving juvenile phase lasts barely a year. The maturation moult normally takes place in the summer of the second year, the reproductive period beginning about 6 months later, in winter.


Combination of Curcumin with an Anti-Transferrin Receptor Antibody Suppressed the Growth of Malignant Gliomas In vitro.
Transferrin receptor (TfR) has been used as a target for the molecular cancer therapy due to its higher expression in a variety of tumors. Anti-TfR antibodies combined with chemotherapeutic drugs has showed great potential as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with curcumin in vitro. We detected the apoptosis, proliferation and cell cycle of glioma cells after treated with anti-TfR mAb and curcumin alone or the combinations by flow cytometer. Anti-TfR mAb or curcumin could inhibit proliferation of tumor cells. Anti-TfR mAb marked S phase arrest and curcumin induced G2/M arrest in tumor cells. When anti-TfR mAb and curcumin were used simultaneously, a synergistic effect was detected in relation to tumor growth inhibition and the induction of cells necrosis. These results provided a potential role of anti-TfR mAb-containing curcumin in the treatment for gliomas.


Metabolic rate and cost of growth in juvenile pike (Esox lucius L.) and perch (Perca fluviatilis L.): the use of energy budgets as indicators of environmental change.
Energy budgets of juvenile pike and perch (weighing approximately 3 g) were determined in experiments lasting up to 4 days, by simultaneously measuring oxygen consumption, food consumption, and growth of individual fish. Although the basic pattern of energy allocation was identical in the two species, perch subjected to constant light (PEL) showed faster growth, higher assimilation and conversion efficiency, and higher oxygen consumption than perch subjected to a short daylength regime (PED). The efficiency with which food energy was converted into body mass was 39±5% in PED but 49±4% in PEL. However, the "work coefficient" (increment of body mass/post-prandial increase of oxygen consumption: mg · μmol O inf2sup-1 ) differed only insignificantly between the two groups of perch, indicating that the metabolic cost of growth was unaffected by the manipulation of experimental conditions. This identifies the higher assimilation efficiency, i.e. the increased flow of food energy into the tissues as being the cause of accelerated growth of perch under the constant-light regime. In both species the maximum feeding-induced metabolic rate was 4 times higher than the lowest preprandial rate. In perch (which were kept on low rations before the experiments) the post-prandial metabolic rate increased steadily from day to day during the 4-day experiments, so that on the last day the rate of oxygen consumption exceeded the rate on the first day by about 41%. This investigation provides further evidence that the allocation of metabolic energy in fish is based on a flexible strategy which responds sensitively to changes in both internal and external conditions.


Investigation of ABCA1 C69T and G-191C polymorphisms in coronary artery disease.
Defects of lipoprotein metabolism are common risk factors for coronary artery disease. The ATP binding cassette transporter 1 (ABCA1) plays an important role in carrying cholesterol from peripheral tissues to the liver. The role of ABCA1 C69T and G-191C gene polymorphisms on plasma lipid levels of patients with coronary artery disease was investigated. Seventy-seven patients with coronary artery disease and fifty healthy controls were studied. Gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism method. No differences in the distribution of C69T and G-191C polymorphisms were observed in the study groups. Plasma triacylglycerol and VLDL-cholesterol levels were shown to be higher in the patient group with the C69T CC genotype compared to these patients with the CT genotype. The C69T polymorphism was associated with HDL-cholesterol levels, which insignificantly increased in the order of the CC>CT>TT genotypes in our study. No association was found between G-191C genotype and lipid levels. The results of our study suggested that polymorphisms of ABCA1 C69T polymorphism may be associated with plasma triacylglycerol and VLDL-cholesterol levels in coronary artery patients.


Effect of human lymphoblastoid interferon on human yolk sac tumors in nude mice.
The effect of human lymphoblastoid interferon on the growth of human tumors heterotransplanted into nude mice was examined. The human tumor lines examined, named YST-1, YST-2 and YST-3, were derived from yolk sac tumors of the ovary. Daily intraperioneal injection of 3 X 10(4) U interferon per mouse for 14 days did not inhibit the growth of any of these three human tumor lines. A close correlation was observed between the tumor volume and the level of alpha-fetoprotein in sera of mice bearing the YST-1 tumor (r = 0.55) or YST-2 tumor (r = 0.70). No histological differences were detected between tumor cells of interferon-treated and control mice. Tumor-bearing mice treated with interferon showed no marked weight loss.


Energy taxes, energy innovation, and green sustainability: empirical analysis from a China perspective.
The idea that energy taxes and innovation may contribute to lowering greenhouse gas emissions and fostering the development of a more sustainable energy future is gaining popularity. Therefore, the study's main goal is to explore the asymmetric impact of energy taxes and innovation on CO2 emissions in China by employing linear and nonlinear ARDL econometric methods. The outcomes of the linear model demonstrate that long-term increases in energy taxes, energy technological innovation, and financial development cause CO2 emissions to reduce, while increases in economic development cause CO2 emissions to climb. Similarly, energy taxes and energy technological innovation cause CO2 emissions to fall in the short run, while financial development promotes CO2 emissions. On the other hand, in the nonlinear model, the positive energy changes, positive energy innovation changes, financial development, and human capital help reduce the long-run CO2 emissions, and economic development increase the CO2 emissions. In the short run, the positive energy and innovation changes are negatively and significantly connected to CO2 emissions, while financial development is positively linked to CO2 emissions. The negative energy innovation changes are insignificant in both the short and long run. Therefore, Chinese policymakers should try to promote energy taxes and innovations as tools to achieve green sustainability.


Substance abuse and withdrawal in the critical care setting.
Substance use is common among individuals admitted to the critical care setting and may complicate treatment of underlying disorders. It is imperative for the critical care team to have a high index of suspicion for substance intoxication and withdrawal. This article reviews the epidemiology of substance use in this population and the treatment of common withdrawal syndromes. General principles regarding the management of substance withdrawal syndromes include general resuscitative measures, use of a symptom-triggered approach, and substitution of a long-acting replacement for the abused drug in gradual tapering dose. The authors stress the importance of long-term planning as part of the overall treatment protocol beyond the acute presentation.


Exosomes secreted by stem cells from human exfoliated deciduous teeth contribute to functional recovery after traumatic brain injury by shifting microglia M1/M2 polarization in rats.
Traumatic brain injury (TBI) is one of the major causes of mortality and disability for all ages worldwide. Mesenchymal stem cells (MSCs)-originated exosomes have provided therapeutic effects. However, as an indispensable component of MSCs, whether odontogenic stem cell-generated exosomes could benefit TBI is still unclear. Thus we aimed to explore the potential of stem cells from human exfoliated deciduous teeth-originated exosomes (SHED-Ex) for the management of TBI. First, a transwell system was used to co-culture activated BV-2 microglia cells with SHED. The secretion levels of neuroinflammatory factors and nitrite were evaluated by enzyme-linked immunosorbent assay (ELISA) and Griess assay. Furthermore, purified SHED-Ex were co-cultured with activated BV-2. ELISA, Griess assay, flow cytometry, immunofluorescence, and qRT-PCR were performed to test the levels of inflammatory factors as well as the microglia phenotype. Finally, SHED and SHED-Ex were locally injected into TBI rat models. Basso, Beattie, and Bresnahan (BBB) scores were chosen to evaluate the motor functional recovery. Histopathology and immunofluorescence were performed to measure the lesion volume and neuroinflammation. As a result, SHED-Ex could reduce neuroinflammation by shifting microglia polarization. The administration of SHED-Ex improves rat motor functional recovery and reduces cortical lesion compared with the control group 2 weeks post-injury (P < 0.05). The current study demonstrates for the first time that SHED-Ex contribute a therapeutic benefit to TBI in rats, at least in part by shifting microglia polarization to reduce neuroinflammation. The use of odontogenic stem cells, and indeed their exosomes, may be expanded for the treatment of TBI or other neurological disorders.


Gingival metastasis of angiosarcoma of the breast as a first manifestation of spreading disease: Case report and review of the literature.
Angiosarcoma is an aggressive malignant neoplasm of vascular origin. Oral metastases of angiosarcoma are rare and have a non-specific clinical presentation, thus the diagnosis may be challenging. Herein we report a case of a 34-year-old female patient after treatment of a high-grade angiosarcoma of the breast, who presented an asymptomatic bleeding purplish nodule in the maxillary interdental papilla between the first and second premolar. A biopsy was performed, and the histological examination revealed infiltration by malignant neoplasm of epithelioid and fusocellular pattern. Immunohistochemical analysis demonstrated that neoplastic cells were positive for ERG and CD31, and negative for cytokeratins AE1/AE3, confirming the diagnosis of metastatic angiosarcoma. After investigation, multiple metastases were discovered. The patient is under management with chemotherapy and palliative radiotherapy for the bone lesions. Metastases should be considered in the differential diagnosis of oral lesions in patients with a previous history of cancer. Due to the morphology of angiosarcomas, the metastatic lesions may resemble benign vascular lesions, therefore, biopsy is mandatory to exclude malignancy.


Pretreatment with transcutaneous electrical acupoint stimulation to prevent postoperative ileus in patients undergoing laparoscopic colon surgery: study protocol for a randomised controlled trial.
Postoperative ileus (POI), a common complication after surgery, severely affects postoperative recovery. It is unclear whether pretreatment with transcutaneous electrical acupoint stimulation (TEAS) can improve recovery from POI. This trial will evaluate the effects of pretreatment with TEAS on POI. This will be a prospective, randomised controlled trial. American Society of Anesthesiologists (ASA) physical status classification I-III level patients, aged 18-75 years and scheduled for laparoscopic colon surgery, will be included in the study. It is planned that 146 subjects will be randomised to the TEAS and sham TEAS (STEAS) groups. The groups will undergo two sessions of TEAS/STEAS daily for 3 days before surgery, with a final TEAS/STEAS treatment 30 min before anaesthesia. The primary endpoint of the study will be time to first defaecation. Secondary endpoints will include time to first flatus, time to tolerance of oral diet, GI-2 (composite outcome of time to first defaecation and time to tolerance of oral diet), time to independent walking, length of hospital stay, postoperative pain Visual Analogue Scale score on the first 3 days after surgery, analgesic requirements, complications and plasma concentrations of interferon-β (IFN-β), IFN-γ, interleukin-6 (IL-6) and IL-1β. Multiple linear regression will be used to identify independent predictors of outcome measures. This study has been approved by the Chinese Registered Clinical Trial Ethics Review Committee (No. ChiECRCT-20170084). The results of the trial will be published in an international peer-reviewed journal. This study has been registered with the Chinese Clinical Trial Registry (No. ChiCTR-INR-17013184). The study was in the recruitment phase at the time of manuscript submission.


Sex hormones and oesophageal adenocarcinoma: influence of childbearing?
The male predominance of oesophageal adenocarcinoma might be explained by oestrogen protection in women. If true, female patients might have sex hormonal disturbances rendering impaired fertility. The influence of childbearing on the risk of oesophageal adenocarcinoma was investigated in a Swedish population-based case (n=63) -control (n=141) study. Childless women were not at increased risk compared to childbearing (OR=0.82; 95% CI=0.25-2.72), as neither were women with 0-1 children compared to women with at least three children (OR=0.93; 95% CI=0.35-2.49). In conclusion, we found no inverse association between childbearing and oesophageal adenocarcinoma.


Development and validation of digital health literacy competencies for citizens (DHLC), an instrument for measuring digital health literacy in the community.
COVID-19 is a new disease in human life and has become pandemic. Pandemic Coronavirus Disease (COVID-19) has been speeding up digital transformation in every sector. Implementation of digital technology in health should be supported by the community's readiness, such as digital health literacy to achieve the goals, optimize health service performance, and blockage infodemics and miss information. Implementation of digital technology in health should be supported by the community's readiness, such as digital health literacy to achieve the goals, optimize health service performance, and blockage infodemics and miss information. This study aims to develop a tool to measure digital health literacy in the community through three stages such as expert review, pre-test and field test. DHLC adopted the five competencies areas into 18 questions and put eight questions related to health literacy; the total items question of DHLC are 26 items questions. This study reveals that all of the score digital competencies areas below 4. Score 4 in DHLC indicates that the community still need guidance to doing activity in the digital environment. Elevating digital health literacy in the citizens is urgent to control the spreading misinformation and disinformation that could worsen pandemics. Future studies need to conduct to test the validity and reliability of DHLC in various settings.


Is Surgery Warranted for Oligometastatic Disease?
The development of metastases after curative treatment can be seen as a failure. A common justification for the removal of metastases is that the knowledge that they are there may cause psychological distress, a real symptom that may be relieved by their removal. Although it is a commonly used justification for metastasectomy, the authors are unaware of any studies confirming or quantifying the health gain. This article strongly challenges the belief in clinical effectiveness and demonstrates that it is supported neither by a sound biological rationale nor by any good evidence. Reasons are suggested why this unfounded belief has become so prevalent.


Branched chain amino acids in heptatic encephalopathy.
Early theories or hepatic encephalopathy focused on ammonia-driven disruption of the Krebs cycle and cellular energy production. The "false-neurotransmitter" theory directed attention toward the interactions of amino acids, metabolism, the blood-brain barrier and neurotransmission. As they evolved, these studies revealed surprising and subtle effects of ammonia on brain amino acid uptake. Research over a 15-year period in Josef E. Fischer's laboratory explored many aspects of these interactions. Subsequent studies by others have confirmed and extended them into other areas. Insights from this work continue to stimulate attempts to confirm or disprove the clinical utility of branched chain amino acids. Increased understanding of the factors affecting ammonia, amino acid and neurotransmitter disturbances in chronic liver failure have made a significant and ongoing contribution to the study of metabolism in health and disease.


In vitro labeling of the sialic acid moiety of glycoconjugates with carbon-14.
Labeling of sialoglycoproteins with carbon-14 in vitro was performed by reacting the aldehyde groups, generated by mild periodate oxidation of the terminal sialyl groups, with 14C-labeled sodium cyanide to produce the labeled cyanohydrin derivatives (Kiliani reaction). Labeling with tritium was carried out by reduction of the aldehyde groups generated on the sialyl residues with 3H-labeled sodium borohydride following standard procedures. The behavior of both types of labeled specimens of fetuin and ovine submaxillary mucin, individually and in mixtures, was investigated by gel-filtration chromatography, gel electrophoresis, and cesium bromide gradient ultracentrifugation. The labeled sialyl residues were subjected to partial characterization: color yield with the resorcinol and thiobarbituric acid reagents, behavior on ion-exchange chromatography, and susceptibility to mild acid and enzymatic hydrolyses. In addition to these model glycoproteins, this procedure was also utilized to label the sialoglycoproteins present in human tracheobronchial secretions collected from normal subjects and patients with chronic bronchitis. The potential uses of this approach for comparative studies of normal and pathological sialoglycoconjugates available in minute amounts is described. The extension of this approach to the labeling of the galactosyl and N-acetylgalactosaminyl moieties of glycoconjugates following treatment with galactose oxidase is outlined.


Aortic valve-sparing reimplantation and mitral repair in a pregnant, second trimester Marfan patient: surgical decision.
We describe a combined aortic valve-sparing reimplantation procedure and mitral valve repair in a 20-year-old pregnant Marfan patient who presented at 12 weeks' gestation with an asymptomatic 5.3-cm aortic root aneurysm and moderate mitral regurgitation. Because the risk of aortic dissection and worsening mitral regurgitation becomes significant in the third trimester, elective intervention was undertaken at 14 weeks' gestation. The mother recovered uneventfully, and the baby was delivered at term by cesarean section. This case supports early elective surgery in pregnant Marfan patients with aortic and mitral diseases to avoid potentially fatal cardiovascular complications later in the pregnancy.


[Non-Hodgkin lymphomas of the head and neck, stages I and II. Apropos 35 cases].
35 cases of non-Hodgkin malignant lymphomas of head and neck, stages I and II. All were treated in Pitié-Salpêtrière Hospital in Paris, by radiotherapy alone or combination chemotherapy and radiotherapy, with or without surgery. The authors discuss the prognostic and therapeutic aspects.


Radiological evidence for the polyp/cancer sequence in the colon.
Three cases of frank malignancy developing in pre-existing colonic polyps are presented. Although this sequence of events is well recognised, it is rarely demonstrated radiologically. The cases illustrate the importance of identifying and appropriately treating polypoid colonic lesions.


An empirical study of student perception towards pedagogy, teaching style and effectiveness of online classes.
With online education taking centerstage in recent times, the primary objective of this study is to find out the student perception of online classes from teachers who had no past experience of online teaching, with respect to their teaching effectiveness, teaching style and pedagogy in an online classroom. This study is exploratory in nature. Using a structured questionnaire, 356 completed responses were received and analysed using the available research tools. The dynamics of education have changed overnight. The findings of the study indicate that pedagogy, teaching style and teaching effectiveness significantly affect student perception towards online classes by first time online teachers. The role of the teachers has changed drastically and there is a need for them to prepare themselves for the new normal using the suitable pedagogical tools for creating an effective online classroom.


Colicin N binds to the periphery of its receptor and translocator, outer membrane protein F.
Colicins kill Escherichia coli after translocation across the outer membrane. Colicin N displays an unusually simple translocation pathway, using the outer membrane protein F (OmpF) as both receptor and translocator. Studies of this binary complex may therefore reveal a significant component of the translocation pathway. Here we show that, in 2D crystals, colicin is found outside the porin trimer, suggesting that translocation may occur at the protein-lipid interface. The major lipid of the outer leaflet interface is lipopolysaccharide (LPS). It is further shown that colicin N binding displaces OmpF-bound LPS. The N-terminal helix of the pore-forming domain, which is not required for pore formation, rearranges and binds to OmpF. Colicin N also binds artificial OmpF dimers, indicating that trimeric symmetry plays no part in the interaction. The data indicate that colicin is closely associated with the OmpF-lipid interface, providing evidence that this peripheral pathway may play a role in colicin transmembrane transport.


The fentanyl family: A distinguished medical history tainted by abuse.
Beginning in the 1950s, a family of potent opioids was synthesized and developed (fentanyl and analogues). They continue to serve as valuable analgesic agents. But the recent spike and notoriety of their abuse has raised alarm, even calls for tighter control. We review the trajectory of these compounds. To rectify shortcomings of the then available opioid analgesics, an analogue family of compounds was synthesized having a piperidine ring (presumptive principal active moiety in morphine and meperidine). The result was more potent and rapid-acting compounds, including alfentanil, carfentanil, fentanyl, sufentanil and others. These properties, plus availability in formulations for multiple routes of administration, impart broad therapeutic utility. They also unfortunately favour abuse. The abuse of fentanyl and its analogues (legal and illicit) serves as a case study for the dilemma and difficulties balancing a medical need against psychosocial realities. The fentanyl family provides relief for severe pain, but their very properties also engender abuse.


Indigenous filamentous fungi on the surface of Argentinean dry fermented sausages produced in Colonia Caroya (Córdoba).
Some producers of dry fermented sausages use fungal starter cultures with the aim to achieve a desirable surface appearance and avoid the growth of mycotoxigenic fungi. These commercial cultures are mainly composed of Penicillium nalgiovense biotype 6. In contrast, in the case of producers who do not use starters, sausages are spontaneously colonized by the house mycobiota, which generally consists of heterogeneous molds corresponding to different genera and species. In this work, the surface mycobiota of dry fermented sausages produced in Colonia Caroya (Córdoba, Argentina) was determined in both summer and winter seasons. All the sausages sampled had been made without the use of surface fungal starters. In the 57 sausages analyzed in the two winter seasons studied (2010 and 2012), we found a total of 95 isolates of filamentous fungi belonging to six genera (Penicillium, Aspergillus, Mucor, Cladosporium, Scopulariopsis and Eurotium) and ten fungal species, whereas in the 36 sausages analyzed in the two summer seasons studied (2011 and 2012), we found 89 isolates belonging to five genera (Penicillium, Aspergillus, Mucor, Cladosporium and Geotrichum) and ten fungal species. Although 16 different species were found in both winter and summer seasons, only 2 of them predominated completely. P. nalgiovense was found in almost 100% of the sausages analyzed, where biotype 4 was the most frequent. This species gives a whitish gray coloration to the sausages. Considering that the factories sampled do not use fungal starter cultures, this predominance is very interesting since mycotoxin production by this fungus has not been reported. Aspergillus ochraceus was isolated with a frequency of 80-90% in the summer seasons, but in none of the winter samples. The presence of this fungus in sausages produced in the summer was attributed to the high environmental temperatures and the uncontrolled temperature in the ripening rooms during the night. In all cases, A. ochraceus was responsible for the undesirable yellowish gold color of the casing. This fungus thus causes significant economic losses to the producers of Colonia Caroya during the months of high temperatures.


Evaluation of dimensional stability, accuracy and surface hardness of interocclusal recording materials at various time intervals: an in vitro study.
To evaluate and compare the dimensional stability, accuracy and surface hardness of three interocclusal recording materials at various time intervals. Polyvinylsiloxane, Zinc oxide eugenol, Aluwax were taken for this study. A stainless steel die of ADA specification no 19. was prepared. A total of ten samples were made with each group. The samples were measured using a travelling microscope of 10× magnification at 1, 24, 48 and 72 h time intervals. Five readings were taken for each sample, the mean was considered to measure the dimensional change, accuracy and surface hardness. The values obtained were statistically analysed by ANOVA and Tukey HSD-Honestly significant difference. Polyvinylsiloxane was the most dimensionally stable, accurate and had the highest surface hardness among the three inter-occlusal materials.


Role of epigenetics in cancer initiation and progression.
The epigenome which comprises DNA methylation, histone modifications, chromatin structures and non-coding RNAs controls gene expression patterns. In cancer cells, there are aberrant changes in the epigenome. The question in cancer epigenetics is that whether these changes are the cause of cell transformation, or rather the consequence of it. We will discuss the epigenetic phenomenon in cancer, as well as the recent interests in the epigenetic reprogramming events, and their implications in the cancer stem cell theory. We will also look at the progression of cancers as they become more aggressive, with focus on the role of epigenetics in tumor metastases exemplified with the urokinase plasminogen activator (uPA) system. Last but not least, with therapeutics intervention in mind, we will highlight the importance of balance in the design of epigenetic based anti-cancer therapeutic strategies.


The Use of Smartphone Keystroke Dynamics to Passively Monitor Upper Limb and Cognitive Function in Multiple Sclerosis: Longitudinal Analysis.
Typing on smartphones, which has become a near daily activity, requires both upper limb and cognitive function. Analysis of keyboard interactions during regular typing, that is, keystroke dynamics, could therefore potentially be utilized for passive and continuous monitoring of function in patients with multiple sclerosis. To determine whether passively acquired smartphone keystroke dynamics correspond to multiple sclerosis outcomes, we investigated the association between keystroke dynamics and clinical outcomes (upper limb and cognitive function). This association was investigated longitudinally in order to study within-patient changes independently of between-patient differences. During a 1-year follow-up, arm function and information processing speed were assessed every 3 months in 102 patients with multiple sclerosis with the Nine-Hole Peg Test and Symbol Digit Modalities Test, respectively. Keystroke-dynamics data were continuously obtained from regular typing on the participants' own smartphones. Press-and-release latency of the alphanumeric keys constituted the fine motor score cluster, while latency of the punctuation and backspace keys constituted the cognition score cluster. The association over time between keystroke clusters and the corresponding clinical outcomes was assessed with linear mixed models with subjects as random intercepts. By centering around the mean and calculating deviation scores within subjects, between-subject and within-subject effects were distinguished. Mean (SD) scores for the fine motor score cluster and cognition score cluster were 0.43 (0.16) and 0.94 (0.41) seconds, respectively. The fine motor score cluster was significantly associated with the Nine-Hole Peg Test: between-subject β was 15.9 (95% CI 12.2-19.6) and within-subject β was 6.9 (95% CI 2.0-11.9). The cognition score cluster was significantly associated with the Symbol Digit Modalities Test between subjects (between-subject β -11.2, 95% CI -17.3 to -5.2) but not within subjects (within-subject β -0.4, 95% CI -5.6 to 4.9). Smartphone keystroke dynamics were longitudinally associated with multiple sclerosis outcomes. Worse arm function corresponded with longer latency in typing both across and within patients. Worse processing speed corresponded with higher latency in using punctuation and backspace keys across subjects. Hence, keystroke dynamics are a potential digital biomarker for remote monitoring and predicting clinical outcomes in patients with multiple sclerosis. Netherlands Trial Register NTR7268; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7268.


Development and characterization of chitosan nanoparticles containing an indanonic tricyclic spiroisoxazoline derivative using ion-gelation method: an in vitro study.
Biodegradable nanoparticulate carriers are potentially applicable compounds in the administration of therapeutic agents and drug delivery. They have received much attention due to their biological characteristics such as biodegradability, biocompatibility, and bioadhesive. The objectives of this work are first, investigating the impact of two important parameters (i.e. chitosan or sodium tripolyphosphate (TPP) solution concentration and chitosan to TPP mass ratio) on the chitosan nanoparticles (CNPs) formation by ionic-gelation method and then, the synthesis and characterization of chitosan-based, biodegradable drug-loaded nanoparticles in the encapsulation of novel 4'-(4-(methylsulfonyl)phenyl)-3'-(3,4,5-trimethoxyphenyl)-4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one (MTS) indanonic tricyclic spiroisoxazoline, which is a potent anticancer drug. The particle size, shape, zeta potential, drug loading capacity, in vitro release characteristics, and stability of the formulated drug-loaded nanoparticles of the different drug:carrier ratio has been studied. The results indicated that the particle size increased at the higher chitosan or TPP concentration while the mass ratio did not appear to be a significant parameter during the cross-linking process. The particle diameter and zeta potential of CNPs including MTS were approximately in the range of 256-350 nm and 24.08-38.70 mV, respectively. The entrapment efficiency steadily increased with increasing the concentration of the polymer in formulizations. Throughout 24 h, the in vitro release behavior was provided a sustained release from all the drug-loaded formulizations. The optimal formulization of CNPs based on drug content with a drug:carrier ratio of 1:2 did not change appreciably during 60-day storage at either 4 °C or the ambient temperature.


Specific Milk Composition of miR-30b Transgenic Mice Associated with Early Duodenum Maturation in Offspring with Lasting Consequences for Growth.
Milk composition is complex and includes numerous components essential for offspring growth and development. In addition to the high abundance of miR-30b microRNA, milk produced by the transgenic mouse model of miR-30b-mammary deregulation displays a significantly altered fatty acid profile. Moreover, wild-type adopted pups fed miR-30b milk present an early growth defect. This study aimed to investigate the consequences of miR-30b milk feeding on the duodenal development of wild-type neonates, a prime target of suckled milk, along with comprehensive milk phenotyping. The duodenums of wild-type pups fed miR-30b milk were extensively characterized at postnatal day (PND)-5, PND-6, and PND-15 using histological, transcriptomic, proteomic, and duodenal permeability analyses and compared with those of pups fed wild-type milk. Milk of miR-30b foster dams collected at mid-lactation was extensively analyzed using proteomic, metabolomic, and lipidomic approaches and hormonal immunoassays. At PND-5, wild-type pups fed miR-30b milk showed maturation of their duodenum with 1.5-fold (P < 0.05) and 1.3-fold (P < 0.10) increased expression of Claudin-3 and Claudin-4, respectively, and changes in 8 duodenal proteins (P < 0.10), with an earlier reduction in paracellular and transcellular permeability (183 ng/mL fluorescein sulfonic acid [FSA] and 12 ng/mL horseradish peroxidase [HRP], respectively, compared with 5700 ng/mL FSA and 90 ng/mL HRP in wild-type; P < 0.001). Compared with wild-type milk, miR-30b milk displayed an increase in total lipid (219 g/L compared with 151 g/L; P < 0.05), ceramide (17.6 μM compared with 6.9 μM; P < 0.05), and sphingomyelin concentrations (163.7 μM compared with 76.3 μM; P < 0.05); overexpression of 9 proteins involved in the gut barrier (P < 0.1); and higher insulin and leptin concentrations (1.88 ng/mL and 2.04 ng/mL, respectively, compared with 0.79 ng/mL and 1.06 ng/mL; P < 0.01). miR-30b milk displays significant changes in bioactive components associated with neonatal duodenal integrity and maturation, which could be involved in the earlier intestinal closure phenotype of the wild-type pups associated with a lower growth rate.


Experiences with head injuries in a regional neurosurgical unit.
A review of all patients with major head injuries transferred to a regional neurosurgical unit for the years 1975 and 1976 has been carried out for comparison with the total number of patients with head injury admitted to district general hospitals of the region. Fifty-four per cent of patients admitted to the neurosurgical unit have resumed their old occupation and 20 per cent died. The significance of these figures is discussed, particularly in the light of the need for a more comprehensive policy for treating head injuries within the United Kingdom.


Toxic shock syndrome in nasal surgery: a physiochemical and microbiologic evaluation of Merocel and NuGauze nasal packing.
A prospective comparison of the microbiologic safety of Merocel versus NuGauze nasal packing in 119 surgical patients is presented. Presurgical and postsurgical nasal cultures were obtained, analyzed, and compared. The importance of a preoperative nasal culture isolate of Toxic Shock Syndrome Toxin Number 1 (TSST-1) producing Staphylococcus aureus in predicting postoperative toxigenic S. aureus isolation and Toxic Shock Syndrome symptomatology is demonstrated. An in vitro comparison of the ability of NuGauze and Merocel to amplify TSST-1 production was performed.


Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure.
Estimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020. Participants (n=7935) were recruited through electronic advertising and received materials for a self-sampled dried blood spot assay through the mail or a minimal contact in person method. IgG to the receptor binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay. Overall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR positive test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3-4 months. Quantitative IgG measurements with a highly specific and sensitive assay indicate more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentration produced from these asymptomatic exposures is similar to IgG levels occurring after documented non-hospitalized COVID-19, which is considerably lower than that produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.


Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo.
Pro-inflammatory chemokines and their receptors exhibit elementary functions in cell migration and in Th1-driven inflammatory conditions. One therapeutic strategy to prevent accumulation of pro-inflammatory immune cells is the use of specific chemokine receptor antagonists. An interesting and promising candidate in this context is the viral antagonist MIP-II (vMIP-II) that acts on a broad spectrum of chemokine receptors. To study the in vitro and in vivo effects of vMIP-II on pro-inflammatory chemokine receptor function, we further characterized an ovalbumin-specific murine central memory Th1IF12 clone by using RT-PCR, cDNA array and cytometry. Using in vitro chemotaxis assays we show that eukaryotically generated vMIP-II strongly inhibited migration of CCL2- or CCL5-stimulated Th1 IF12 cells. Using intravital microscopy, we observed that CCL5 induced rolling of Th1 cells in the ear vasculature of C57Bl/6 mice. Pre-treatment with vMIP-II significantly reduced CCL5-induced rolling of Th1 cells to basal levels, indicating, that vMIP-II is also active in vivo (proportion of rolling cells: 19.4 +/- 3.8%, 39.8 +/- 2.9% and 26.1 +/- 3.2%). In addition, investigating the anti-inflammatory action of vMIP-II in adoptive transfer of immunity and dinitrofluorobenzene-induced cutaneous hypersensitivity reaction using C57Bl/6 mice, we show a direct inhibitory effect of vMIP-II on the sensitization phase [Delta ear swelling 62 and 37 cm x 10(-3) for controls and vMIP-II treated mice (2.5 mg/kg), respectively] and effector phase (Delta ear swelling 14.8 and 3.6 cm x 10(-3) for controls and vMIP-II treated mice (2.5 mg/kg), respectively) of cutaneous hypersensitivity. These data indicate that vMIP-II is a promising agent to interfere with chronic inflammatory (skin) diseases.


Digestion time and reemergence in the desert grassland scorpion Paruroctonus utahensis (Williams) (Scorpionida, Vaejovidae).
The desert grassland scorpion Paruroctonus utahensis spends most of its life in its burrow. During the active season, only about 5% of the individuals in a population appear on the surface each night. Individuals do not appear on the surface for several nights following a meal. To determine if physiological digestion time could account for this delay in reemergence after eating, I measured changes in oxygen consumption immediately following a meal. Oxygen consumption exceeded 125 μl O2g-1h-1 just after completion of a meal, then dropped to normal levels (53 μl O2g-1h-1) within 6 h. I also measured the interval between completion of the meal and subsequent defecation. All individuals defecated by 72 h following ingestion (median 12 h). In field enclosures, scorpions returned to the surface after a mean of 20.3 days (median=16) following a successful predation event. Lack of correspondence between estimates of physiological digestion time and the reappearance interval lead me to reject the idea of a long digestive pause in Paruroctonus utahensis. This conclusion lends support to the hypothesis that scorpions remain in their burrows to minimize exposure to predation.


English stops after /s/ at medial word-boundary.
Subjects listened to a speech perception test. It consisted of a series of items obtained by tape splicing from one recorded English utterance it's still. The subjects assigned one of four possible English utterance choices to each item. Combined duration of the /s/ friction and closure of the following stop account for their choice between it's dill, it still or it's still. A delay in voice onset of the stop is primarily responsible for items consistently heard as it's till. There is no difference in closure duration between the traditionally fortis and lenis stops following the /s/.


Cobomarsen, an Oligonucleotide Inhibitor of miR-155, Slows DLBCL Tumor Cell Growth In Vitro and In Vivo.
miRNA-155 is an oncogenic miRNA highly expressed in B-cell malignancies, particularly in the non-germinal center B-cell or activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of cobomarsen in a patient diagnosed with aggressive ABC-DLBCL. Preclinical studies included the delivery of cobomarsen to highly miR-155-expressing ABC-DLBCL cell lines to assess any phenotypic changes, as well as intravenous injections of cobomarsen in NSG mice carrying ABC-DLBCL xenografts, to study tumor growth and pharmacodynamics of the compound over time. To begin to test its safety and therapeutic efficacy, a patient was recruited who underwent five cycles of cobomarsen treatment. Cobomarsen decreased cell proliferation and induced apoptosis in ABC-DLBCL cell lines. Intravenous administration of cobomarsen in a xenograft NSG mouse model of ABC-DLBCL reduced tumor volume, triggered apoptosis, and derepressed direct miR-155 target genes. Finally, the compound reduced and stabilized tumor growth without any toxic effects for the patient. Our findings support the potential therapeutic application of cobomarsen in ABC-DLBCL and other types of lymphoma with elevated miR-155 expression.


Postintensive Care Syndrome.
Patients admitted to the intensive care unit (ICU) are at an extremely high risk for developing intensive care syndrome. Increased illness severity often result in prolonged immobility, altered cognition, and the development of psychotic manifestations. Any constellation of these problems can result in prolonged patient impairment long after transfer from the ICU. Quick recognition of these symptoms leads to the development of a targeted rehabilitation to minimize long-term sequelae and optimize functional recovery.


Brittle cornea syndrome: an heritable connective tissue disorder distinct from Ehlers-Danlos syndrome type VI and fragilitas oculi, with spontaneous perforations of the eye, blue sclerae, red hair, and normal collagen lysyl hydroxylation.
We report a patient with the characteristic features of the brittle cornea syndrome, a rare, autosomal recessively inherited disorder, namely brittle corneae, blue sclerae, and red hair. The patient also showed joint hyperextensibility, a soft skin, and dysplastic auricles with unusually soft cartilage. Phenotypically, the disorder bears a certain resemblance to fragilitas oculi and the type VI (ocular) form of the Ehlers-Danlos syndrome, two conditions which are, themselves, not readily distinguishable. However, the hydroxylysine content of dermal collagen was normal, as was the activity of lysyl hydroxylase in cultured dermal fibroblasts, thus supporting the distinction of the brittle cornea syndrome as an independent entity. No abnormality was discernible in types I or III collagens synthesised by cultured fibroblasts, but electron microscopy revealed dramatic ultrastructural alterations in dermis in that distributed over its whole thickness were 20-60 microns wide "holes" or fibre-free spaces, filled with an amorphous material.


Validity and reliability of a new incremental step test for people with chronic obstructive pulmonary disease.
Incremental step tests (IST) can be used to assess exercise capacity in people with chronic obstructive pulmonary disease (COPD). The development of a new step test based on the characteristics of the incremental shuttle walk test (ISWT) is an important study to explore. We aimed to develop a new IST based on the ISWT in people with COPD, and assess its validity (construct validity) and reliability, according to Consensus-based Standards for the selection of health status Measurement Instruments (COSMIN) recommendations. A cross-sectional study was conducted in participants recruited from hospitals/clinics. During the recruitment, the participants who presented a 6-minute walk test (6MWT) report in the previous month were also identified and the respective data was collected. Subsequently, participants attended two sessions at their homes. IST was conducted on the first visit, along with the 1 min sit-to-stand (1MSTS) test. IST was repeated on a second visit, performed 5-7 days after the first one. Spearman's correlations were used for construct validity, by comparing the IST with the 6MWT and the 1MSTS. Intraclass correlation coefficient (ICC2,1), SE of measurement (SEM) and minimal detectable change at 95% CI (MDC95) were used for reliability. The learning effect was explored with the Wilcoxon signed-rank test. 50 participants (70.8±7.5 years) were enrolled. IST was significant and moderate correlated with the 6MWT (ρ=0.50, p=0.020), and with the 1MSTS (ρ=0.46, p=0.001). IST presented an ICC2,1=0.96, SEM=10.1 (16.6%) and MDC95=27.9 (45.8%) for the number of steps. There was a statistically significant difference between the two attempts of the IST (p=0.030). Despite the significant and moderate correlations with the 6MWT and 1MSTS, the inability to full compliance with the COSMIN recommendations does not yet allow the IST to be considered valid in people with COPD. On the other hand, the IST is a reliable test based on its high ICC, but a learning effect and an 'indeterminate' measurement error were shown. NCT04715659.


DNA methylation and gene activity.
The above experiments support a relatively simple model to explain the role of DNA methylation in vivo. Most tissue-specific genes are methylated. The methyl groups may generate a local chromatin configuration that renders the genes inaccessible, and thus transcriptionally inactive. This would provide a general mechanism for transcriptional repression which may operate independent of the requirement for interactions between cis-acting regulatory elements and tissue-specific factors. In contrast, house-keeping genes may not be affected by this inhibitory mechanism, and are thus available for constitutive expression in all cell types. Activation of tissue-specific genes from their generalized state of repression must first involve recognition of the genes while they are still methylated and this event initiates the process of transcription and concomitant demethylation. In their demethylated state these genes would be stably maintained in an active structure that is generally accessible to the transcriptional machinery of the cell.


Effects of sleeping position on development of infant cardiovascular control.
Sudden Infant Death Syndrome (SIDS) is associated with prone sleeping, and circulatory failure has been hypothesised to be a factor in the fatal event. We aimed to determine the effect of prone sleeping on heart rate (HR) and blood pressure (BP) control over the first 6 months of life. Term infants (n = 20) were studied longitudinally at 2-4 weeks, 2-3 months and 5-6 months with daytime polysomnography. A photoplethysmographic cuff (Finometer, FMS, Finapres Medical Systems, Amsterdam, The Netherlands) on the infant's wrist measured mean, systolic, and diastolic arterial pressure (MAP, SAP, DAP) and HR during quiet sleep (QS) and active sleep (AS) in both the supine and prone positions. BP in QS was lower compared to AS (by 3-9 mmHg) in both positions and at all three ages (p<0.05). At 2-3 months, a change from supine to prone in QS induced a fall in SAP (6 mmHg, p<0.05) and a rise in HR (4 bpm, p<0.05). An overall effect of postnatal age (PNA) on BP was identified (ANOVA) with MAP and DAP consistently averaging less (by 1-9 mmHg) at 2-3 months in both sleep states and sleeping positions compared with both other ages. Infant BP is modified by sleep state and sleeping position. A tendency for BP to fall in the prone position appears to be prevented by elevated HR at 2-4 weeks and 5-6 months, but not at 2-3 months, coincident with the age of greatest risk for SIDS. An uncompensated fall in BP in the prone position at this age could increase the possibility of circulatory failure and SIDS in vulnerable infants.


Epidural Catheter-Assisted Percutaneous Transforaminal Endoscopic Diskectomy: A Technical Note.
With advances in techniques and instruments, percutaneous endoscopic transforaminal lumbar diskectomy (PETLD) is now widely used for lumbar disk herniation. Although the indication for PETLD is expanding, the technique still has limitations. To overcome them, we performed the epidural catheter-assisted PETLD described here. A 49-year-old woman had severe radiating pain in a left L5 dermatomal distribution. Magnetic resonance imaging (MRI) revealed left paramedial disk herniation at L4-L5 and a small downward-migrated disk fragment. We performed epidural catheter-assisted PETLD. Mechanical outward pushing and normal saline injection through the epidural catheter were performed for removal of hidden disk remnants. In the second case, a 26-year-old man presented with severe radiating pain in the L5-S1 dermatoms on both sides. MRI revealed massive disk herniation at L4-L5. A unilateral approach was used, and the ruptured disk could be moved using an epidural catheter. The patients' pain improved immediately after the procedures. With this method, neural decompression can be performed more easily and effectively. Epidural catheter-assisted PETLD has several advantages and can overcome the limitations of conventional PETLD.


The prognostic value of non-perfusion variables obtained during vasodilator stress myocardial perfusion imaging.
Myocardial perfusion imaging (MPI) is an established diagnostic test that provides useful prognostic data in patients with known or suspected coronary artery disease. In more than half of the patients referred for stress testing, vasodilator stress is used in lieu of exercise. Unlike exercise, vasodilator stress does not provide information on exercise and functional capacity, heart rate recovery, and chronotropy, and ECG changes are less frequent. These non-perfusion data provide important prognostic and patient management information. Further, event rates in patients undergoing vasodilator MPI are higher than in those undergoing exercise MPI and even in those with normal images probably due to higher pretest risk. However, there are a number of non-perfusion variables that are obtained during vasodilator stress testing, which have prognostic relevance but their use has not been well emphasized. The purpose of this review is to summarize the prognostic values of these non-perfusion data obtained during vasodilator MPI.


The classic P300 encodes a build-to-threshold decision variable.
The P300 component of the human event-related potential has been the subject of intensive experimental investigation across a five-decade period, owing to its apparent relevance to a wide range of cognitive functions and its sensitivity to numerous brain disorders, yet its exact contribution to cognition remains unresolved. Here, we carry out key analyses of the P300 elicited by transient auditory and visual targets to examine its potential role as a 'decision variable' signal that accumulates evidence to a decision bound. Consistent with the latter, we find that the P300 reaches a stereotyped amplitude immediately prior to response execution and that its rate of rise scales with target detection difficulty and accounts for trial-to-trial variance in RT. Computational simulations of an accumulation-to-bound decision process faithfully captured P300 dynamics when its parameters were set by model fits to the RT distributions. Thus, where the dominant explanatory accounts have conceived of the P300 as a unitary neural event, our data reveal it to be a dynamically evolving neural signature of decision formation. These findings place the P300 at the heart of a mechanistically principled framework for understanding decision-making in both the typical and atypical human brain.


Modulation of agonistic behavior by the dual olfactory system in male mice.
This study analyzed the effects of deafferentation of the main, vomeronasal or both olfactory systems on the agonistic behavior of male mice in response to unfamiliar male intruder mice. In every animal, regardless of the technique used, disruption of the vomeronasal system led to consistent reductions in agonistic behavior. All animals receiving bulbectomies, vomeronasal tract transections or a combined treatment of vomeronasal cuts and ZnSO4 nasal flush reliably suppressed agonistic responding toward the intruder. Animals treated with intranasal ZnSO4 alone or those receiving control procedures continued to respond to the intruders at rates similar to pretreatment. These results indicate that the vomeronasal system is directly involved in the perception of the male chemosignals modulating agonistic behavior and, therefore, is capable of modulating the male's response to these signals.


Generation of a monoclonal antibody (Epenl) which binds selectively to murine ependymal cells.
In order to define surface antigens unique to ependymal cells, spleen cells from C57/B16 mice immunized with a suspension of 70-80% purified isolated ependymal cells from syngeneic animals were fused with NS-1 myeloma cells. Five hybridomas were found which secrete monoclonal antibodies that recognize ependymal cells both by indirect immunofluorescence and radioimmunoassay. One of them, Epenl, appears to be a relatively specific surface marker of murine and rat ependymal cells, whereas the 4 others also recognize neurons, astrocytes, and/or oligodendrocytes. Absorption of Epenl with murine cerebral cortex did not affect its binding, whereas absorption with ependymal cells abolished it. Labeling of in vivo sections with Epenl demonstrates prominent binding to ependymal cells lining ventricular cavities. Epenl does not bind to neurons or astrocytes in culture, and binds only minimally to isolated oligodendrocytes. It does, however, recognize an antigenic determinant present in lung tissue.


[Measurement of diaphragm compound muscle action potential with magnetic stimulation of the phrenic nerve and multipara esophageal electrode in intensive care unit].
To investigate whether magnetic stimulation of the phrenic nerve and multipara esophageal electrode can be used to measure diaphragm compound muscle action potential (CMAP) in intensive care unit (ICU). Ten normal subjects and 10 patients in ICU were studied. A newly designed multipara esophageal catheter with 5 pairs of electrodes was used to record the diaphragm CMAP elicited by magnetic stimulation and transcutaneous electrical stimulation of the phrenic nerve. Good quality CMAPs were obtained from normal subjects and patients in ICU. In normal subjects, the phrenic nerve conduction time (PNCT) and amplitude of the diaphragm CMAP measured with electrical stimulation [(7.2 +/- 0.8) ms, (1.52 +/- 0.40) mV] were similar to those measured with magnetic stimulation [(7.1 +/- 0.8) ms, (1.56 +/- 0.38) mV, all P > 0.05, pooled left and right values]. The amplitude of the diaphragm CMAP in patients [(0.73 +/- 0.38) mV] was much smaller than that in normal subjects [(1.58 +/- 0.38) mV, P < 0.01, pooled left and right values]. This study suggests that magnetic stimulation combined with a multipara esophageal electrode could be a useful technique in assessing diaphragm function in ICU.


Analyzing territory for the sustainable development of solar photovoltaic power using GIS databases.
Solar energy generated by grid-connected photovoltaic (GCPV) systems is considered an important alternative electric energy source because of its clean energy production system, easy installation, and low operating and maintenance costs. This has led to it becoming more popular compared with other resources. However, finding optimal sites for the construction of solar farms is a complex task with many factors to be taken into account (environmental, social, legal and political, technical-economic, etc.), which classic site selection models do not address efficiently. There are few studies on the criteria that should be used when identifying sites for solar energy installations (large grid-connected photovoltaic systems which have more than 100 kWp of installed capacity). It is therefore essential to change the way site selection processes are approached and to seek new methodologies for location analysis. A geographic information system (GIS) is a tool which can provide an effective solution to this problem. Here, we combine legal, political, and environmental criteria, which include solar radiation intensity, local physical terrain, environment, and climate, as well as location criteria such as the distance from roads and the nearest power substations. Additionally, we use GIS data (time series of solar radiation, digital elevation models (DEM), land cover, and temperature) as further input parameters. Each individual site is assessed using a unique and cohesive approach to select the most appropriate locations for solar farm development in the Valencian Community, a Spanish region in the east of Spain.


Histopathological criteria for intestinal neuronal dysplasia of the submucosal plexus (type B)
The aim of this study was to review critically the diagnostic features of intestinal neuronal dysplasia type B (IND B). Over a period of 5 years colonic mucosal biopsies of 773 children with symptoms of chronic constipation were examined. Four biopsies taken 2-10 cm above the pectinate line were cut in serial sections and histochemical lactate dehydrogenase, succinate dehydrogenase, (SDH) and acetylcholinesterase (AChE) reactions performed. Presence of giant ganglia of the submucosal plexus, being characterized by more than seven nerve cells, established the diagnosis of IND B. Giant ganglia were found to be age-independent changes, while hyperplasia of the submucosal plexus, increase of AChE activity in nerve fibres of the lamina propria and low SDH activity in nerve cells proved to be age-dependent findings which disappear during the maturation of the enteric nervous system. Using these criteria IND B was diagnosed in 209 children. In 64 of these patients a combination of IND B and aganglionosis (Hirschsprung's disease) was found. IND B seems to be related to premature expression of laminin A during embryogenesis, resulting in premature nerve cell differentiation in the myenteric and submucosal plexus, which in turn blocks neuroblast colonization of the rectum. IND B, hypoganglionosis and aganglionosis, which are often combined, may therefore be considered to be different manifestations of the same developmental abnormality.


Tight junctions of human keratinocytes in primary culture: a freeze-fracture study.
Human skin explants obtained from 2- to 5-yr-old patients with harelips were cultured in NCTC 168 medium at 37 degrees C, in a humidified atmosphere containing 5% CO2 in air. After a 2-week incubation period, the newly grown cells were studied with special reference to tight junctions by freeze-fracture electron microscopy. Many completely formed tight junctions were observed between the uppermost living cells of migrating epithelium, and fragmented tight junctions were seen between the lower layer cells. The tight junctions in the uppermost cells developed so well that they formed a belt-like network consisting of two to six rows of strands. This observation may suggest that human keratinocytes have the ability to produce tight junctions perfectly enough to serve as a barrier, although no complete tight junctions were formed in situ.


Gefitinib (ZD1839, Iressa) as palliative treatment in recurrent or metastatic head and neck cancer.
To assess the level of activity and toxicity of gefitinib (ZD1839, Iressatrade mark) in a population of patients with locally recurrent and/or metastatic head and neck cancer. Patients were recruited into an expanded access programme through the multidisciplinary head and neck clinics at the Royal Marsden and St George's Hospitals. Patients were required to have received at least one course of standard systemic chemotherapy or radiation therapy, or be medically unfit for chemotherapy. Patients were commenced on single-agent gefitinib at a dose of 500 mg day(-1). Clinical, symptomatic and radiological response, time to progression (TTP), survival and toxicity were recorded. A total of 47 patients were enrolled (35 male and 12 female) with a median age of 62 years (range 18-93 years). The observed clinical response rate was 8% with a disease control rate (complete response, partial response, stable disease) of 36%. In all, 34% of patients experienced an improvement in their symptoms. The median TTP and survival were 2.6 and 4.3 months, respectively. Acneiform folliculitis was the most frequent toxicity observed (76%) but the majority of cases were grade 1 or 2. Only four patients experienced grade 3 toxicity of any type (all cases of folliculitis). Gefitinib was well tolerated and yielded symptomatic improvement in one-third of patients. However, this agent appeared to possess limited antitumour activity in this group of patients with head and neck cancer in whom the objective response rate, median TTP and survival were all lower than has been reported in a previous study.


Carbinolamine formation and dehydration in a DNA repair enzyme active site.
In order to suggest detailed mechanistic hypotheses for the formation and dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer glycosylase (T4PDG) reaction, we have investigated these reactions using steered molecular dynamics with a coupled quantum mechanics-molecular mechanics potential (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation with and without a water molecule restrained to remain within the active site quantum region. We recovered potentials of mean force (PMF) from thirty replicate reaction trajectories using Jarzynski averaging. We demonstrated feasible pathways involving water, as well as those independent of water participation. The water-independent enzyme-catalyzed reaction had a bias-corrected Jarzynski-average barrier height of approximately (6.5 kcal mol(-1) (27.2 kJ mol(-1)) for the carbinolamine formation reaction and 44.5 kcal mol(-1) (186 kJ mol(-1)) for the reverse reaction at this level of representation. When the proton transfer was facilitated with an intrinsic quantum water, the barrier height was approximately 15 kcal mol(-1) (62.8 kJ mol(-1)) in the forward (formation) reaction and 19 kcal mol(-1) (79.5 kJ mol(-1)) for the reverse. In addition, two modes of unsteered (free dynamics) carbinolamine dehydration were observed: in one, the quantum water participated as an intermediate proton transfer species, and in the other, the active site protonated glutamate hydrogen was directly transferred to the carbinolamine oxygen. Water-independent unforced proton transfer from the protonated active site glutamate carboxyl to the unprotonated N-terminal amine was also observed. In summary, complex proton transfer events, some involving water intermediates, were studied in QM/MM simulations of T4PDG bound to a DNA abasic site. Imine carbinolamine formation was characterized using steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate to form the final imine product was observed in free, unsteered, QM/MM dynamics simulations, as was unforced acid-base transfer between the active site carboxylate and the N-terminal amine.


Experimental study on fist-ellipse for Chinese auto drivers.
Sub-workspaces and the fist-ellipse of auto drivers are new concepts in the fields of ergonomics and automotive engineering. The paper introduces measurement, generation, application and location of the 95th percentile fist-ellipse (i.e., 95th sub-workspace for gearshift) for Chinese car drivers. It is a rigorous scientific approach to locate gearshift handles in conventional motor vehicles or locate a central control handle sidestick in a recent non-steering wheel conceptual car, expanding the concepts of the design tool contours of SAE.


Mutagenic potency of chlorofuranones and related compounds in Salmonella.
One of the mutagenic byproducts associated with chlorinated humic waters and kraft pulp bleaching effluents was recently identified as 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone. This compound and several related chlorofuranones and precursors were synthesized and evaluated for direct-acting mutagenicity in Salmonella typhimurium tester strain TA100. Mutagenicity was greatest for 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, its 5-methoxy derivative, and the precursor in their synthesis, 3-(dichloromethyl)-2,4,4-trichloro-2-butenoic acid. Several of the compounds were tested in the presence of added rat liver homogenate S9 fraction, and in all cases mutagenicity was substantially reduced. An important structural feature which may govern the mutagenic response in these instances appears to be the cis arrangement of CHCl2 and Cl substituents on a carbon-carbon double bond. These compounds may also be transformed in vitro to the same acyclic chlorine substituted alpha, beta-unsaturated aldehyde derivative, which is proposed to be the agent responsible for the observed mutagenicity.


Heterologous Expression, Purification, and Biochemical Characterization of α-Humulene Synthase from Zingiber zerumbet Smith.
The α-humulene synthase from Zingiber zerumbet Smith was expressed as a polyhistidine-tagged protein in an E. coli BL21(DE3) strain. Induction time and inductor (isopropyl-β-D-thiogalactopyranoside) concentration were optimized. The enzyme was successfully purified directly from cell lysate by NTA affinity column chromatography and careful selection of coordinated metal ion and imidazole elution conditions. Bioactivity assays were conducted with the natural substrate farnesyl diphosphate (FDP) in a two-phase system with in situ extraction of products. The conversion of FDP to α-humulene (~94.5%) and β-caryophyllene (~5.5%) could be monitored by gas chromatography-flame ionization detection (GC-FID). Optimal pH and temperature as well as kinetic parameters K M and k cat were determined using a discontinuous kinetic assay.


Myofilament compliance and sarcomere tension-stiffness relation during the tetanus rise in frog muscle fibres.
The sarcomere stiffness was measured in single muscle fibres during the development of tetanic tension using a method insensitive to fibre inertia and viscosity. The stiffness was calculated as the ratio between tension changes and sarcomere length changes during a period of fast sarcomere elongation at constant velocity. The results show that, unlike previous measurements with step or sinusoidal length changes, the relation between relative force and relative stiffness on the tetanus rise is linear. Consequently, the development of stiffness upon stimulation is synchronous with the development of force. Since a substantial fraction of sarcomere compliance is localized in the myofilaments, this result can be accounted for by assuming that either myofilament compliance is highly non-linear or that crossbridges stiffness during the tetanus rise is not proportional to crossbridge tension.


Differences in pacing pattern and sub-technique selection between young and adult competitive cross-country skiers.
The present study describes differences in pacing patterns and sub-technique selection in young compared to adult competitive cross-country skiers. Eleven young male skiers (YOS) (14.4 ± 0.5 years, V ˙ O2peak 63.9 ± 2.8 mL∙kg-1 ∙min-1 ) and eight adult male skiers (ADS) (22.6 ± 4.3 years, V ˙ O2peak 77.4 ± 4.4 mL∙kg-1 ∙min-1 ) performed a free technique rollerski time trial (TT) over a distance of 4.3 km (YOS) and 13.1 km (ADS) to simulate normal racing distances. A GNSS/IMU system was used to track position, speed, and classify sub-techniques. Skiing economy and V ˙ O2peak were measured on an additional day to calculate the relative oxygen demand ( V ˙ O2dem ) in 13 segments of the TT. YOS were slower than ADS in all types of terrain (mean speed difference of 13%), with differences for uphills of 19%, undulating terrain of 11% and downhills of 8% (all P < .05). The mean relative V ˙ O2dem tended to be higher for YOS compared to ADS (120% vs 112% of V ˙ O2peak , P = .09), and the difference was more pronounced in the initial four segments of the race (130% vs 110% of V ˙ O2peak , P < .01). YOS used more of the sub-technique Gear 2 (23 ± 7 vs 14 ± 4%), less Gear 3 (36 ± 7 vs 45 ± 5%), and had more frequent transitions between sub-techniques (18 ± 2 vs 15 ± 3 km-1 ) (all P < .05) than ADS. Over an age-related distance, young skiers tend to exhibit higher mean exercise intensity than adult elite skiers, with a more pronounced positive pacing pattern. Differences in physical ability affect speed and sub-technique selections, implying a need for differentiating technical training for different ages and levels.


Joint associations of sauna bathing and cardiorespiratory fitness on cardiovascular and all-cause mortality risk: a long-term prospective cohort study.
We aimed to evaluate the joint impact of cardiorespiratory fitness (CRF) and frequency of sauna bathing (FSB) on the risk of cardiovascular and all-cause mortality. CRF measured by respiratory gas analyses and sauna exposure were assessed at baseline in a prospective study of 2277 men. CRF was categorized as low and high (median cut-offs) and FSB as low and high (≤2 and 3-7 sessions/week, respectively). During a median follow-up of 26.1 years, 520 cardiovascular and 1124 all-cause deaths occurred. Comparing high versus low CRF, the multivariate-adjusted hazard ratios (HRs) 95% CIs for cardiovascular and all-cause mortality were 0.51 (0.41-0.63) and 0.65 (0.57-0.75), respectively. Comparing high versus low FSB, the corresponding HRs were 0.74 (0.59-0.94) and 0.84 (0.72-0.97), respectively. Compared to low CRF & low FSB, the HRs of CVD mortality for high CRF & high FSB; high CRF & low FSB; and low CRF & high FSB were 0.42 (0.28-0.62), 0.50 (0.39-0.63) and 0.72 (0.54-0.97), respectively. For all-cause mortality, the corresponding HRs were 0.60 (0.48-0.76), 0.63 (0.54-0.74) and 0.78 (0.64-0.96), respectively. A combination of high CRF and frequent sauna bathing confers stronger long-term protection on mortality outcomes compared with high CRF or high FSB alone. KEY MESSAGES Cardiorespiratory fitness (CRF) and frequency of sauna bathing are independently associated with reduced mortality risk; a combination of good CRF and frequent sauna bathing may confer additional survival benefits. In a population-based prospective cohort study, a combination of high CRF levels and frequent sauna bathing (3-7 sessions per week) was associated with a substantial risk reduction in fatal cardiovascular and all-cause mortality events compared with good CRF or frequent sauna bathing alone. A combination of good fitness levels produced by aerobic exercises and frequent sauna bathing may have added health benefits and confer more protection on the risk of mortality.


Bilateral changes in neocortical [3H]pirenzepine and [3H]oxotremorine-M binding following unilateral lesions of the rat nucleus basalis magnocellularis: an autoradiographic study.
Neocortical choline acetyltransferase (ChAT) activity and muscarinic [3H]pirenzepine, [3H]oxotremorine-M, [3H]N-methylscopolamine ([3H]NMS; both high- and low-affinity agonist (carbachol) sites) and nicotinic [3H]acetylcholine binding were assessed both ipsi- and contralaterally 1 week and 13 weeks after unilateral ibotenic acid lesions of the rat nucleus basalis magnocellularis (NBM). Ipsilateral ChAT activity was reduced to 49% of control values 1 week postlesion but by 13 weeks had recovered to 80% of control values. Contralateral ChAT activity did not change significantly at either 1 week or 13 weeks postlesion. At 1 week postlesion, [3H]oxotremorine-M binding was increased by 33% and 54% in ipsilateral and contralateral neocortex, respectively. By week 13, both ipsi- and contralateral [3H]oxotremorine-M binding had returned to normal but [3H]pirenzepine binding was significantly decreased by 31% and 39% in the ipsilateral and contralateral hemispheres, respectively. The binding of [3H]NMS and [3H]acetylcholine did not differ significantly from control values at either 1 week or 13 weeks postlesion. These data suggest that none of the cholinergic binding sites studied is preferentially localized presynaptically and that there may be interhemispheric regulation of neocortical cholinergic binding sites.


A case study in communication disorders.
Often, children with language disorders exhibit other more subtle delays or deviance in social, communicative, and cognitive development. By focusing on these three areas, the clinician can understand the developmental context in which the language delay manifests. This approach includes the following: gathering information, psychological and communicative examinations, psychiatric examination, and medical evaluation.


Mammalian glutathione S-transferase: regulation of an enzyme system to achieve chemotherapeutic efficacy.
The glutathione S-transferases are a family of Phase II detoxication enzymes that catalyze the conjugation of glutathione to a large variety of electrophilic compounds. In the 1990s, there have been many advances regarding the function of these enzymes in protecting a cell from the toxic effects of these electrophiles. The complexity of this enzyme family has been realized and much work has been performed to identify the specific roles played by individual isozymes in resistance to a variety of agents. Likewise, the determination of the crystal structure of these enzymes has allowed the identification of specific amino acid residues that are involved in the catalysis of important reactions. The important role that these enzymes play in carcinogenesis and in drug resistance has warranted an attempt to bring together these different subfields of glutathione S-transferase biology to investigate possible ways that this system could be regulated in therapeutically useful ways. In this report, we have reviewed the recent advances and ways in which this knowledge could be utilized in the advancement of the treatment of cancer.


Social Isolation and Patient Experience in Older Adults.
Social isolation has been identified as a major health problem, particularly in the elderly. In the present study, we examine the association between social isolation and patient experience in elderly primary care patients. This cross-sectional study was conducted in a primary care practice-based research network (28 clinics) in Japan. We assessed social isolation using an abbreviated Lubben Social Network Scale and patient experience of primary care using a Japanese version of the Primary Care Assessment Tool (JPCAT), which comprises 6 domains: first contact, longitudinality, coordination, comprehensiveness (services available), comprehensiveness (services provided), and community orientation. We used a linear mixed effects model to adjust clustering within clinics and individual covariates. Data were analyzed for 465 elderly primary care patients aged ≥65 years. After adjustment for possible confounders and clustering within clinics, social isolation was negatively associated with the JPCAT total score, (mean difference = -3.67; 95% CI, -7.00 to -0.38). Among the JPCAT domain scores, social isolation was significantly associated with longitudinality, comprehensiveness (service provided), and community orientation scores. Social isolation was associated with negative patient experience in elderly primary care patients. Raising awareness regarding patient social networks among primary care providers and targeted interventions for socially isolated elderly patients aimed at improving the experience of primary care, especially regarding longitudinality, comprehensiveness, and community orientation, may be warranted.


Recent advances in CRISPR/Cas9-mediated knock-ins in mammalian cells.
Since its inception, the CRISPR/Cas9 technology has been widely utilized for the targeted insertion of donor DNAs into mammalian genomes. A shortcoming with the earlier knock-in (KI) approaches, however, has been the low efficiency of targeted integrations-especially in primary cells and mouse embryos. Since, a variety of novel strategies have been developed towards improving the KI efficiencies in select target cells. In this review, the current applications of CRISPR/Cas9-mediated KIs in mammalian cells are described. Furthermore, the recent strategies which have been developed in order to augment the CRISPR/Cas9-mediated KI efficiencies are summarized.


Identification of affective valence of Twitter generated sentiments during the COVID-19 outbreak.
This study aims to conduct text mining of affective valence of the sentiments generated on social media during the COVID-19 and measure their association with different outcomes of the disease. 50,000 tweets per day over 23 days during the pandemic were extracted using the VADER sentiment analysis tool. Overall, tweets could effectively be classified in terms of polarity, i.e., "positive," "negative" and "neutral" sentiments. Furthermore, on a day-to-day basis, the study identified a positive and significant relationship between COVID-19-related (a) global infections and negative tweets, (b) global deaths and negative tweets, (c) recoveries and negative tweets, and (d) recoveries and positive tweets. No significant association could be found between (e) infections and positive tweets and (f) deaths and positive tweets. Furthermore, the statistical analysis also indicated that the daily distribution of tweets based on polarity generates three distinct and significantly different numbers of tweets per category, i.e., positive, negative and neutral. As per the results generated through sentiment analysis of tweets in this study, the emergence of "positive" tweets in such a gloomy pandemic scenario shows the inherent resilience of humans. The significant association between news of COVID-19 recoveries and positive tweets seems to hint at a more optimistic scenario whenever the pandemic finally comes to an end or is controlled. Such public reactions-for good-have the potential to go viral and influence several others, especially those who are classified as "neutral" or fence-sitters.


A lysosome-targeted ruthenium(II) polypyridyl complex as photodynamic anticancer agent.
Polypyridyl ruthenium complexes as novel photosensitizers had drawn attention due to its high selectivity towards cancer cells and low toxicity to normal cells. Herein, we synthesized a lysosome-targeted polypyridyl ruthenium complex Rhein-Ru(bpy)3 (bpy = 2,2'-bipyridine, rhein = 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid), tethering with the Chinese medicine herb rhein. Rhein-Ru(bpy)3 exhibited high phototoxicity with short time of irradiation against tumor cell lines with the IC50 value of 2.4- 8.7 μM, and higher cytotoxicity against cisplatin-resistant A2780 cell lines, suggesting that Rhein-Ru(bpy)3 could overcome the cisplatin resistance. Moreover, Rhein-Ru(bpy)3 displayed low cytotoxicity towards cell lines in dark incubation, which was beneficial to reduce the toxic side effects towards normal cell lines. Besides, the confocal imaging and western blotting assay results suggested that Rhein-Ru(bpy)3 could induce cancer cell death through the autophagy pathway. These results inspired us that lysosome-targeted photosensitizers based on ruthenium complexes showed great potential for photodynamic therapy (PDT) application in cancer treatment.


Application of leaching tests for toxicity evaluation of coal fly ash.
The toxic properties of coal fly ash samples obtained from various coal combustion power plants were evaluated in this work using physicochemical analyses and bioassays. Physicochemical analyses showed that heavy metals present in solid samples included Cr, Cu, Mn, Ni, Pb, and Zn. The results of the chemical analysis of eluates deduced by the application of standard leaching tests according to EN 12457-2 and Toxicity Characteristic Leaching Procedure (TCLP) methods indicated that the compounds contained in fly ashes could potentially be transferred to the liquid phase depending upon the leaching method used. Heavy metal concentrations were higher in TCLP eluates, indicating that the initial pH value of the leaching medium significantly affected the transfer of these elements to the liquid phase. Tests conducted with the photobacterium Vibrio fischeri (Microtox test), the crustacean Daphnia magna, and the rotifer Brachionus calyciflorus were used to assess toxicity of eluates obtained by both leaching tests. Daphnia magna was the most sensitive test organism. The EN 12457-2 method proved to be more reliable for toxicity evaluation of eluates. In contrast, the TCLP method showed some interference owing to acetic acid toxicity, and precipitation occurred after pH adjustment of eluates from acid to neutral range. The toxicity of both fly ashes and the corresponding solid leaching residues of EN 12457-2 and TCLP leaching tests was also measured using the Microtox Basic Solid phase Test. The results generated with this bioassay indicated that toxicity was greatly influenced by the pH status of the solid samples.


Competitive hierarchies in marine benthic communities.
Patterns of competitive displacement by over-growth were examined in communities of sessile organisms in the low intertidal zone at three sites in Washington state and Alaska. Cruotose invertebrates and algae can be arranged into a hierarchy such that species of lower competitive rank rarely overgrow any higher ranking species. Erect and solitary species show a wide range of competitive abilities, but whether they fall into a strict hierarchy is unknown. Few of the solitary or erect species occupy substantial amounts of space in the communities examined.An approximate competitive hierarchy is well established in middle to high intertidal areas dominated by mussels, fleshy algae, and barncles, and has been an important concept in developing both an intuitive understanding and specific mathematical models of the dynamics of benthic marine communities. In particular, lower ranking species in such communities are thought to depend upon predation or chronic disturbance to the dominants to avoid competitive displacement. An alternative viewpoint, proposed on the basis of "nonstransitive" competitive relationships observed in cryptic encrusting communities on the undersides of coral plates, is that specific competitive "loops" or "networks" allow the coexistence of a number of competitors. Although the growth forms and higher taxa represented in the low intertidal bear some similarity to those in the cryptic coral reef community, there is little evidence of ecologically important competitive loops in the intertidal. A reanalysis of data from cryptic reef communities suggests that they also do not depart substantially from a competitive hierarchy, although there appear to be many more cases of local reversals in the outcome of competition. It is suggested that the ecological importance of departures from a strict hierarchy depends upon the competitive rankings of the participants, with departures involving competitively dominant species likely to contribute much more to community structure than those involving opportunistic species.


[Diagnosis of chondral injury in trauma of the knee joint (author's transl)].
Diagnosis of chondral lesions as the only injury in knee trauma is difficult: Lesions of the cartilage were found by arthroscopy, months or years after trauma, in 153 patients; the diagnosis was never suspected immediately after injury. Chondral lesions may be suspected from clinical examination but never proved. Contrast arthography may reveal the injury in exceptional cases. Only arthroscopy or arthrotomy can really prove or exclude injury to the cartilage. Arthoscopy is to he preferred because of the far lower morbidity and is more reliable because of a better view of the articular surfaces.


Adolescents' input on the development of an HIV risk reduction intervention.
Adolescence is a developmental period often associated with sexual debut as well as risk taking. Given these considerations, HIV prevention interventions need to become an important component of adolescent health care. This article describes the use of formative research to guide intervention refinement. To refine an HIV risk reduction intervention that has been used successfully with adults, the authors conducted focus groups with 30 adolescent females. These participants identified misconceptions regarding HIV-related information and factors that influence motivation to participate in risky behaviors. They also suggested strategies for recruitment and retention in a longitudinal study. Formative research such as this can be used to develop interventions that are gender specific and developmentally and culturally appropriate for adolescents.


Effect of tumor size on prognosis in patients treated with radical radiotherapy or chemoradiotherapy for non-small cell lung cancer. An analysis of the staging project database of the International Association for the Study of Lung Cancer.
Analysis of the International Association for the Study of Lung Cancer database revealed that for patients with completely resected, node-negative, non-small-cell lung cancer (NSCLC), increasing tumor size was associated with worsening survival. This analysis was performed to determine the effect of size on prognosis in patients in the same database but who were treated with radiotherapy or chemoradiotherapy. Patients were eligible if they had pathologically confirmed NSCLC, no evidence of distant metastases, intended treatment was radical radiotherapy (minimum 50 Gy) or combined chemotherapy and radiotherapy, no surgery, and tumor diameter was available. Eight hundred and sixty-eight patients were available for analysis. Patient characteristics were: sex (men) 65.3%; median age 64 years (range, 32-88); Eastern Cooperative Oncology Group performance status 0: 55%, 1: 33%, 2 or more: 5%; chemotherapy 74%; no chemotherapy 18%; weight loss less than 5 %: 70%, and more than 5%: 25%. Primary tumor size was categorized according to tumor, node, metastasis 7th edition. On univariate analysis, the following factors were prognostic for survival: age (continuous) (p = 0.0035); performance status of 1 or more (p = 0.0021); weight loss less than 5% (p < 0.0001); chemotherapy (p = 0.0189); and primary tumor size (continuous) (p = 0.0002). Sex and clinical nodal stage were not significant. On multivariate analysis, age and weight loss remained significant factors for survival, as was tumor size less than 3 cm. In patients treated with radiotherapy with or without chemotherapy, tumor size less than 3 cm was associated with longer survival than larger tumors. Evidence of the effect of size on prognosis above this was weak. Five-year survival of more than 10% was observed in all four size categories.


Small airway bronchodilator response to different doses of salbutamol in 7-year-old children.
The Global Initiative for Asthma (GINA) guidelines do not specify a bronchodilator range for bronchodilator response (BDR) testing and simply recommend a salbutamol dose of 200 to 400 μg. We determined the oscillometric BDR results of children given low-dose (2 puffs, 200 μg) and standard-dose (4 puffs, 400 μg) salbutamol to compare the small airway responses of healthy controls (defined using criteria based on the guidelines developed at the American Thoracic Society) and exclusion subjects (defined as any child that did not meet the inclusion criteria for healthy controls). The oscillometric reactance of small airways is significantly associated with the dose of salbutamol used for BDR testing in exclusion children. We suggest use of the standard-dose of salbutamol for oscillometric BDR testing.


Membrane production and yolk degradation in the early fly embryo (Calliphora erythrocephala meig.): An ultrastructural analysis.
Formation of nuclear envelopes during the last cleavage mitosis and the formation of the cell membranes during the cellularization of the blastoderm have been studied ultrastructurally in the blowfly egg. Dense bodies arising from yolk granules by budding could contain membrane material destined to be incorporated into the new membranes of the blastoderm. The presence of transitional structures indicates that these bodies can be converted into dark multivesicular bodies. Large amounts of endoplasmic reticulum are found around the mitotic nuclei. Clusters or branched chains of vesicles associated with this are interpreted as evidence for the formation of endoplasmic reticulum by the breakdown of dark multivesicular bodies. Nuclear envelopes of mitotic daughter nuclei probably originate from endoplasmic reticulum. The egg contains both intranuclear and extranuclear annulate lamellae. The main events of cytokinesis are furrow initiation and cell membrane growth during the slow first phase, but probably only cytokinetic movement during the rapid second phase. On the assumption that cell membrane growth occurs by incorporation of complete membrane pieces, the addition of coated vesicles and/or light multivesicular bodies is definitely most probable. Some intermediate profiles indicate that light and dark multivesicular bodies are related. The membrane needed for second phase cytokinesis could well be provided by the unfolding of surface microvilli and protuberances of the furrow canal.


Unbalanced form of translocation deletion between chromosomes 6 and 22 in a mentally handicapped female [45,XX,-6,-22,+der(6),t(6;22)(q25.1:q11.2)].
A case of a mentally handicapped female with unbalanced form of translocation deletion between chromosomes 6 and 22 is reported. Clinical features, mental disorder and abnormal dermatoglyphs of the propositus are described.


Comparative haemodynamic effects of clonidine administered intramuscularly or intravenously to anaesthetized rats.
1. The acute haemodynamic effects of clonidine, 0.001-1.0 mg/kg, administered intramuscularly or intravenously, were studied in anaesthetized rats. 2. The direct pressor potency of clonidine was 100-fold greater following intravenous administration than after intramuscular injection, but hypotensive efficacy was equal by either route.


An evaluation of the low-pH enzymatic assay of urinary D-glucaric acid, and its use as a marker of enzyme induction in exocrine pancreatic disease.
We have evaluated a low-pH enzymatic method for measuring urinary D-glucaric acid, and its usefulness as a marker of 'enzyme induction' in patients with exocrine pancreatic disease. The coefficient of variation lay between 7.5 and 10.9% for within-batch precision, and between 7.9 and 19.8% for between-batch precision. The useful range of the method was 20-200 mumol/l, with a lower detection limit of 11 mumol/l. The molar concentration ratio of D-glucaric acid to creatinine in urine correlated with the 8-h output of D-glucaric acid (p less than 0.005): both indices were significantly higher in a group of 29 patients with exocrine pancreatic disease than in controls (median ratios 4.6 and 2.9 X 10(-3), p less than 0.005; median outputs 14.0 and 8.8 mumol/8 h, respectively, p less than 0.005). Comparison with the results of theophylline tests in the same group of patients showed that whereas 72% of patients had theophylline clearances higher than the highest value in controls, 45% of the group had increased D-glucaric acid/creatinine ratios, whilst only 21% had increased outputs of D-glucaric acid. Paradoxically, in patients with established liver disease in whom drug metabolism was impaired urinary D-glucaric acid values were amongst the highest encountered in the study. Thus, the obvious advantages of the method--non-invasive, simple, reproducible, inexpensive, easily applied to out-patients--are offset by an unacceptably low predictive value as an indicator of microsomal 'enzyme induction'.


N-heterocyclic carbene-catalyzed highly enantioselective synthesis of substituted dihydropyranopyrazolones.
Highly optically pure multisubstituted dihydropyrano[2,3-c]pyrazol-6-(1H)-ones were synthesized via the N-heterocyclic carbene-catalyzed enantioselective [4 + 2] annulation of α-chloroaldehydes and pyrazolone-derived oxodienes.


Scaling down the analysis of environmental processes: monitoring enzyme activity in natural substrates on a millimeter resolution scale.
Natural environments often show high levels of spatial heterogeneity. With a methodology based on the immobilization of fluorescent substrates, the distribution of extracellular enzymes can be studied at a 2.3-mm resolution with a detection limit of 1.8 nmol · h(-1) · cm(-2). The method is applicable to environmental samples such as wood, litter, soil, or fungal colonies.