Binding of Ca2+ to calbindin D9k: structural stability and function at high salt concentration.
Calcium binding constants of wild-type calbindin D9k and mutant forms with one, two, and three neutralized negative charges in the vicinity of the Ca2+ binding sites are determined at varying KCl concentrations from 2 mM to 1 M. The results indicate that the added salt does not cause significant structural changes in calbindin D9k and, along with site-directed mutagenesis, can be used as a well-controlled means for modulating electrostatic interactions. The lack of structural changes at high salt concentrations is also supported by two-dimensional 1H NMR data. High salt concentrations are observed to substantially reduce the cooperativity of calcium binding to calbindin D9k. This suggests that the cooperativity is strongly dependent on electrostatic interactions. The data have been used to test a dielectric continuum model for protein electrostatics using a macroscopic dielectric constant of water throughout the system. Excellent agreement between experiment and Monte Carlo simulations is observed for the whole set of data covering changes in the binding constant of more than 6 orders of magnitude. A simplified theoretical treatment using the Kirkwood-Tanford formula, based on the Debye-Hückel approximation, yields an almost equally good agreement with the experiment.


Activation times for "emergency back-up" programs.
A bench study was performed on 34 different pulse generators to evaluate the time necessary to actuate an "emergency back-up" (EBU) program. Pacemakers were programmed to loss of capture before the EBU was activated. Two pauses were measured that included the total pause from captured beat to captured beat and the time from the first pacing artifact showing loss of capture to the first captured beat resulting from EBU activation. Special features for threshold testing such as temporary pacing, auto threshold, Vario, and an alternating pulse ventricular threshold test were also evaluated. Activation times of the EBU ranged from 1.8 to 11.1 seconds with total pauses of 2.7 to 13.2 seconds, respectively. There were considerable variations in EBU times even within a single manufacturers' pulse generators. The special features for threshold testing resulted in pauses measuring 0.6 to 3.0 seconds with total pauses of 1.2 to 4.0 seconds, respectively, and in all cases were faster than using the EBU. Utilization of the EBU to regain capture during threshold testing in pacemaker dependent patients may result in prolonged pauses and syncope or near syncopal episodes.


[Early detection of diabetic nephropathy: serum beta 2-microglobulin].
Detection of early diabetic nephropathy is necessary to postpone or even prevent progression of irreversible kidney damage by therapeutic measures. Beta 2-microglobulin (beta 2-MG) as a parameter of the glomerular filtration rate has been measured by immunoassay in the serum of 100 diabetic subjects, 50 insulin-dependent (IDD), and 50 noninsulin-dependent (NIDD) patients. The results are compared with endogeneous creatinine-clearance, serum creatinine concentration, and proteinuria and are related to different stages of diabetic retinopathy (RD). Normal values were obtained from 50 healthy age- and sex-matched subjects. A close correlation was found between beta 2-MG levels and endogeneous creatinine clearance. Thirty-nine diabetics revealed an elevated beta 2-MG (2.5 mg/l or higher), only 16 of whom had increased serum creatinine levels (1.4 mg/dl or higher). Significant differences of beta 2-MG were obtained between each group of patients with different stages of RD. A relevant difference of serum creatinine was found only between patients with normal eye fundus and advanced proliferative retinopathy, respectively. Without RD 26% of the patients revealed elevated beta 2-MG but normal creatinine values demonstrating a "latent nephropathy", just 8% showed an increase of both parameters. Of the diabetics with proliferative retinopathy 40% suffered from impaired kidney function proven by reduced creatinine clearance and by elevation of beta 2-MG and creatinine as well, 15% just revealed an increase of beta 2-MG with normal creatinine levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative Evaluation of Two Bracket Systems' Bond Strength: Conventional and Self-Ligating.
Adhesion remains a key element in dentistry, whether approached in prosthetics, odontology, or orthodontics. It is a continuously researched aspect, as improved materials and adhesive methods keep emerging in the market. No orthodontic treatment can be effective without the proper adhesion strength of the bonded elements on the teeth. The objective of this research, in the broad context of self-ligating versus conventional brackets, was to compare active and passive self-ligating systems with a conventional one by conducting an in vitro study on human-extracted premolars. Shear bond strength tests were executed by means of an advanced materials-testing machine that generated maximum load and tensile strength values. The data obtained underwent statistical analysis with a statistical threshold of p < 0.05. The results regarding the statistical significance were acquired when comparing the passive self-ligating system with the active self-ligating and conventional systems (load-at-maximum-load mean 204.9, SD 91.09, and p < 0.05). In this study, the passive self-ligating bracket system appears to present increased shear bond strength.


Feasibility of autologous plasma gel for tonsil-derived stem cell therapeutics in hypoparathyroidism.
Hypoparathyroidism is a deficiency of the parathyroid hormone (PTH) in the body. We previously reported the possibility of treating it using tonsil-derived mesenchymal stem cells (TMSCs) differentiated into PTH-releasing cells. The purpose of this study was to evaluate the feasibility of using autologous plasma gel as scaffold material in treatment of hypoparathyroidism with TMSC. We obtained plasma by venous sampling of autologous blood and centrifuged and fabricated the plasma gel using a sinusoidal pattern heating machine. After we created the hypoparathyroidism animal model, we administered undifferentiated TMSCs and TMSCs differentiated into parathyroid cells at each rat dorsum by intramuscular injection with and without the plasma gel. In the plasma gel groups, intact PTH was detected from on day 21 after TMSC injection; we did not detect intact PTH in the groups that were only transplanted with TMSCs during the entire experimental period. Serum calcium was higher and phosphorous was lower in the TMSC with plasma gel groups than in the groups with TMSCs alone. We detected PTH and chromogranin A in the TMSC-plasma gel-transplanted areas on immunohistochemistry and immunofluorescence stain. Plasma gel can be considered as a cell-delivery scaffold for treating hypoparathyroidism with tonsil-derived mesenchymal stem cells.


Fabrication of functional metamaterials for applications in heat-shielding windows and 6G communications.
Windows with passive multilayer coatings can allow less energy to be used when maintaining comfortable indoor temperatures. As a type of effective solar energy management, these coatings can prevent the generation of excessive heat inside buildings or vehicles by reflecting near-infrared solar radiation (750-2000 nm) while retaining visible light transmission (400-750 nm) over a large range of viewing angles. To prevent overheating, they must also reflect rather than absorb near-infrared radiation. A transparent heat-shielding window is numerically and experimentally demonstrated in this study. High visual transparency (77.2%), near-infrared reflectance (86.1%), and low infrared absorption (<20%) over a wide range of oblique incident angles were achieved using nanometer-scale cross-shaped metamaterials manufactured by electron beam lithography. Furthermore, high terahertz transmittance (up to 82%) was also achieved for 6G communication system applications.


The Deletion of Hdac4 in Mouse Osteoblasts Influences Both Catabolic and Anabolic Effects in Bone.
Histone deacetylase 4 (Hdac4) is known to control chondrocyte hypertrophy and bone formation. We have previously shown that parathyroid hormone (PTH) regulates many aspects of Hdac4 function in osteoblastic cells in vitro; however, in vivo confirmation was previously precluded by preweaning lethality of the Hdac4-deficient mice. To analyze the function of Hdac4 in bone in mature animals, we generated mice with osteoblast lineage-specific knockout of Hdac4 (Hdac4ob-/- ) by crossing transgenic mice expressing Cre recombinase under the control of a 2.3-kb fragment of the Col1a1 promoter with mice bearing loxP-Hdac4. The Hdac4ob-/- mice survive to adulthood and developed a mild skeletal phenotype. At age 12 weeks, they had short, irregularly shaped and stiff tails due to smaller tail vertebrae, with almost no growth plates. The tibial growth plate zone was also thinned, and Mmp13 and Sost mRNAs were increased in the distal femurs of Hdac4ob-/- mice. Immunohistochemistry showed that sclerostin was elevated in Hdac4ob-/- mice, suggesting that Hdac4 inhibits its gene and protein expression. To determine the effect of PTH in these mice, hPTH (1-34) or saline were delivered for 14 days with subcutaneously implanted devices in 8-week-old female Hdac4ob-/- and wild-type (Hdac4fl/fl ) mice. Serum CTX, a marker of bone resorption, was increased in Hdac4ob-/- mice with or without PTH treatment. Tibial cortical bone volume/total volume (BV/TV), cortical thickness (Ct.Th), and relative cortical area (RCA) were decreased in Hdac4ob-/- mice, but PTH caused no further decrease in Hdac4ob-/- mice. Tibial trabecular BV/TV and thickness were not changed significantly in Hdac4ob-/- mice but decreased with PTH treatment. These results indicate that Hdac4 inhibits bone resorption and has anabolic effects via inhibiting Mmp13 and Sost/sclerostin expression. Hdac4 influences cortical bone mass and thickness and knockout of Hdac4 prevents the catabolic effect of PTH in cortical bone. © 2018 American Society for Bone and Mineral Research.


The respiration and cytochrome oxidase activity of rat aorta in experimental hypertension.
Oxygen consumption and cytochrome oxidase activity of aortas of rats with experimental hypertension were found to be higher than the corresponding values for aortas of normotensive animals. The higher metabolic activity of aortas of hypertensive animals appeared to be due both to an increase in the proportion of muscle cells to connective tissue fibers and to a higher activity of the intracellular portion of the tissue.


[Ion channels and tumor].
This review illuminates the current approaches of ion channels and tumor. Potassium, calcium, chloride channnels and others are abnormally expressed in the membrane of tumor cells. They are crucial for tumor development and growth. By the regulation of membrane voltage, cell cycle, cell volume, Ca2+ signaling and cytosolic pH, they can adjust the cell proliferation and apoptosis. With further study, ion channels will become a new target for cancer therapy and diagnosis.


The interaction of fusidic acid with peptidyl-transfer-ribonucleic-acid - ribosome complexes.
The inhibitory action of fusidic acid on peptide-chain elongation was studied with systems in vitro directed by either polyuridylic acid or endogenous messenger (Escherichia coli polysomes washed with 1 M NH4Cl) or R17 RNA, and supplemented with either crude or purified elongation factors. In all cases strong inhibition of synthesis required high concentrations of the antibiotic (approx. 1 mM), while a similar inhibition of the EF-G-plus-ribosome-dependent GTP hydrolysis required between 10 and 100 times less antibiotic. Since most of the GTP hydrolysis observed was presumably due to free ribosomes (without aminoacyl-tRNA or peptidyl-tRNA), fusidic acid seemed to interact far more easily with these ribosomes than with ribosomes engaged in peptide-chain elongation. The role of the GDP-EF-G-ribosome-fusidic acid complex in the inhibition of polypeptide synthesis was assessed by measuring formation of this complex on polysomes engaged in peptide-chain elongation. Using purified elongation factors the complex formed on only 25-35% of ribosomes, as measured either by retention of [3H]GDP or by hydrolysis of [3H, gamma-32P]GTP. In contrast, with crude factors (S 100 extract) it formed on more than 70% of ribosomes. The results are compatible with the postulated role of the complex in polypeptide synthesis inhibition (blockade of the ribosomal acceptor site and subsequent inhibition of aminoacyl-tRNA binding) and indicate that formation of the complex takes place by overriding the control that prevents interaction of EF-G when the donor site is occupied by peptidyl-tRNA. In the polyuridylic-acid-directed system for synthesis of oligophenylalanine the antibiotic inhibits every round of peptide elongation, including dipeptide formation, to roughly the same extent.


Interim results: state-specific influenza A (H1N1) 2009 monovalent vaccination coverage - United States, October 2009-January 2010.
In July 2009, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for the use of influenza A (H1N1) 2009 monovalent vaccine. Distribution of 2009 H1N1 vaccine in the United States began on October 5, using a system that allocated available vaccine to states proportional to their populations. By the end of 2009, approximately 61 million persons had been vaccinated. By January 29, 2010, approximately 124 million doses had been distributed. To provide preliminary state-specific estimates of 2009 H1N1 vaccination coverage as of the end of January, CDC analyzed results from the Behavioral Risk Factor Surveillance System (BRFSS) and the National 2009 H1N1 Flu Survey (NHFS), using data collected during November 2009--February 2010. This report summarizes the results of that analysis, which found that, by state, estimated 2009 H1N1 vaccination coverage as of the end of January among persons aged >/=6 months ranged from 12.9% to 38.8% (median: 23.9%). Median coverage was 36.8% for children aged 6 months--17 years, 20.1% for adults aged >/=18 years, and 33.2% for persons in the ACIP initial target group. The wide variation in 2009 H1N1 vaccination rates among states suggests opportunities for improvement in future seasons, such as maintaining and increasing the reach of networks of private providers as vaccinators and distributing more vaccine through public venues (e.g., schools).


Estimation of clinical axial extension of Class II caries lesions with ultraspeed and digital radiographs: an in-vivo study.
This study compared the newly introduced direct digital radiographic (DDR) system (RVG-6000) with conventional bitewing radiographs (D-speed film) to estimate the extension of Class II caries lesions. The patient's discomfort related to placement of each radiographic packet was also evaluated. Fifty-one Class II caries lesions were selected. Affected teeth were radiographed with D-speed film and t he RVG-6000 size 2sensor. Patients were asked to complete a one-page questionnaire regarding discomfort during the radiographic examination. The true caries depth was validated clinically from intra-operative photographs that captured the cross-sectional views of the lesion at its deepest point. During the operative procedures, the cavitation status was also recorded. A reference device was placed on the occlusal surface of the treatment or the adjacent tooth before taking radiographs and during the operative procedure. The caries lesion extension from the dentino-enamel junction (DEJ) was measured in mm on eachradiograph and the results were compared to the true clinical depth. Both radiographs significantly underestimated the clinical depth (p < 0.0001), but the RVG-6000 images were significantly closer to the actual depth of the lesion than the D-speed film (p = 0.0031). All of the lesions which were diagnosed radiographically to be deeper than 1 mm into dentin were cavitated. Size, sharp edges of the sensor or both comprised the source(s) of most of the discomfort caused by D-speed film (64%) and RVG-6000 sensor (79%). The results of this study showed that both types of radiographic images tend to underestimate caries depth; however, the RVG-6000 image was more accurate than the D-speed film. This study also provides information about sources of the patient's discomfort associated with these radiographs.


[Fresh osteochondral transplants in the treatment of advanced giant cell tumors].
Eighteen patients with advanced giant cell tumors were treated with complete tumor resection and reconstruction using fresh osteochondral allografts. All patients had one or more of the following indications for tumor resection (as opposed to curettage): tumor recurrence, pathological fracture, or destruction of the subchondral bone plate. At the 4- to 16-year follow-up (mean 9 years), two grafts were revised to a second fresh graft because of fracture, one graft was converted to an allograft implant composite and two joints were fused because of infection. The functional results were assessed in 14 patients: 9 were good or excellent, 4 fair and 1 poor. We conclude that the fresh osteochondral allograft is a viable treatment alternative to prosthetic replacement in advanced benign, aggressive bone tumors.


Cell-mediated and humoral immune responses to total hip replacement under spinal or general anaesthesia.
Regional anaesthesia has many advantages over general anaesthesia in hip surgery. When the effects of total hip replacement under spinal or general anaesthesia were compared in 22 patients, the only difference between the groups occurred in PHA-induced lymphocyte proliferative responses. In contrast, no differences between the groups were observed in leucocyte or differential counts, lymphocyte or subtype counts, most mitogen-induced lymphocyte proliferative responses, NK-cell activity, IgG, IgM or IgA production by unstimulated or PWM-stimulated lymphocytes, proliferative responses of control lymphocytes with 15% patient serum, or chemiluminescence values in phagocytosis of zymosan opsonized with patient serum. Thus, regional anaesthesia is indicated in total hip replacement for reasons other than the immune response.


L-Arginine-Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function.
Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L-arginine-loaded selenium-coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)-induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.


Destruction of human microvascular endothelial cell capillary-like microtubules by Brazilian purpuric fever-associated Haemophilus influenzae biogroup aegyptius.
When grown in the presence of Matrigel, monolayers of an immortalized human microvascular cell line (HMEC-1) form capillary-like microtubule networks. Previous work, using HMEC-1 monolayers, demonstrated a significant difference in in vitro cytotoxicity between Brazilian purpuric fever (BPF)-associated Haemophilus influenzae biogroup aegyptius (HAE) strains and non-BPF-associated HAE strains. The present study demonstrates that BPF-related cytotoxic differences can also be observed in HMEC-1 microtubule networks. At a multiplicity of infection (MOI) of 2 x 10(-2) bacteria/tissue culture cell, BPF-associated strain F3031 disrupted the microtubule network, producing random clumps of rounded cells at 48 h of incubation. Infection with non-BPF-associated strain F1947 at the same MOI produced no observable microtubule disruption. The ability of HMEC-1 microtubule model to differentiate virulent and avirulent HAE in vitro will further aid in the study of BPF pathogenesis. In addition, the fact that the HMEC-1 cells can be induced to form microtubules make it an excellent model system for the general study of many of the agents of vascular purpura.


Robust light beam diffractive shaping based on a kind of compact all-optical neural network.
A kind of compact all-optical learning-based neural network has been constructed and characterized for efficiently performing a robust layered diffractive shaping of laser beams. The data-driven control lightwave strategy demonstrates some particular advantages such as smart or intelligent light beam manipulation, optical data statistical inference and incident beam generalization. Based on the proposed method, several typical aberrated light fields can be effectively modulated into the desired fashion including the featured flat-top beams, an arrayed sub-beam arrangement and complex annular fringes compared with conventional GS-based DOEs. An actual THz laser is utilized to evaluate the effectiveness of the method developed.


Sea lice infestation levels decrease with deeper 'snorkel' barriers in Atlantic salmon sea-cages.
Salmon lice (Lepeophtheirus salmonis) are the most important parasites of farmed salmon. Infective larvae position themselves in the upper part of the water column to increase encounter probabilities with potential hosts. Previous studies have shown that a 'snorkel' sea-cage technology protects salmon from infection in surface waters. We tested whether deep snorkels would more effectively reduce lice infestation than shallow snorkels and still uphold adequate conditions for the fish. Five sea-cages (12 m × 12 m) each holding approximately 3000 Atlantic salmon (Salmo salar) (53 ± 10 g) were fitted with snorkels that gave protection from infection for 0, 4, 8, 12 or 16 m. We tested whether reductions in the settlement of new salmon lice copepodids were consistent among four separate infection periods. Lice infestation decreased exponentially with depth in all time periods. Infection levels in shallow snorkels (0 and 4 m) were consistently 4-10 times higher than those in deep snorkels (12 and 16 m). Key welfare and production performance indices were similar across all snorkel depths. Deeper snorkels dramatically and consistently reduced infection levels of salmon lice compared with shallow snorkels, without consequences for fish welfare and production performance. Therefore, reducing salmon sea lice encounters using a depth-based barrier is a powerful management tool for salmon farming. © 2017 Society of Chemical Industry.


Anaesthesia for elective abdominal aortic surgery.
This paper presents the purely personal attempts of one anaesthetist in a district general hospital to achieve a compromise from the widely varying advice given in print on the management of anaesthetics for elective abdominal aortic surgery.


How Narrative Engagement with Young Adult Literature Influences Perceptions of Anorexia Nervosa.
Narratives have been shown to alter health beliefs through a process called narrative engagement; however, this process has yet to be empirically investigated for how the increasingly popular young adult (YA) novel format can impact health beliefs about anorexia nervosa among emerging adults. Using an experimental design, we found that the YA format fosters narrative engagement through mechanisms of transportation, which is associated with greater endorsement of accurate social and emotional beliefs about anorexia nervosa. Compared to an informational brochure, the narrative format where the main character was a "supportive peer" (but not experiencing the illness herself) increased self-referencing and was perceived as more relevant among emerging adult participants. Results suggest narratives may be viable tools to communicate about little understood social and emotional aspects of chronic diseases with emerging adults, who are more likely to provide support for sick peers than experience chronic illnesses. Encouraging narrative engagement could facilitate a better understanding of the social and emotional complexity of anorexia nervosa and improve the quality of peer interactions.


Development of a compact tunable diode laser absorption spectroscopy based system for continuous measurements of dissolved carbon dioxide in seawater.
Robust marine carbon sensors with small size, low power consumption, and high sensitivity provide greater insight into the carbon cycle studies and resolve environmental variability. We report here the development of a diminutively integrated tunable diode laser absorption spectroscopy (TDLAS) system with a specially designed multipass gas cell for small amounts of dissolved gas extractions and measurements. It was used to detect and monitor carbon dioxide (CO2) dissolved in water and seawater. Systematic experiments have been carried out for system evaluation in the lab. Extracted CO2 was determined via its 4989.9 cm-1 optical absorption line. The achieved TDLAS measurement precision was 4.18 ppm for CO2, measured by averaging up to 88 s. The integrated absorbance was found to be linear to gas concentrations over a wide range. Comparison measurements of the atmospheric CO2 values with a commercial instrument confirmed a good accuracy of our TDLAS-based system. The first test campaign was also accomplished with a hollow fiber membrane contactor, and concentrations of CO2 were quantitatively detected with partial degasification operations. The results clearly show the ability to continuously measure dissolved gases and highlight the potential of the system to help us better understand physical and geochemical processes in a marine environment.


Auditory brain stem responses to air- and bone-conducted clicks in the audiological assessment of at-risk infants.
Auditory brain stem responses (ABRs) to air- and bone-conducted clicks were used to assess the auditory status of 170 at-risk neonates. During the perinatal period, 20.6% (35/170 cases) of the at-risk infants failed ABRs to air-conducted clicks at 30 dB nHL in at least one ear. Ear-specific results indicated an initial failure rate of 15.0% (51/340 ears). Approximately two-thirds (32/51 ears) of these initial failures showed purely conductive deficits, whereas the remaining one-third (19/51 ears) involved suspected sensorineural components. Follow-up audiological evaluations were performed for 87.1% (148 cases) of these at-risk infants at 4 mo and/or 1 yr corrected age. Based on the initial tests and follow-up assessments, the tentative operating characteristics of ABRs to both air- and bone-conducted clicks for identification of sensorineural deficits in at-risk neonates were calculated. It was found that the ABR to bone-conducted clicks yielded better specificity, predictive value of positive results, and overall efficiency. It is suggested that the ABR to bone-conducted stimuli should be viewed as a valuable addition in the assessment of cochlear reserve in infants who fail a newborn auditory screening to air-conducted stimuli.


Granulocytopoiesis in children with acute lymphoblastic leukaemia.
Numbers, proliferative potential, and differentiative capacity of bone marrow granulocyte-macrophage precursor cells were studied in 130 children with acute lymphoblastic leukaemia (ALL), including 77 children in an acute phase of the disease and 53 in remission. Bone marrow samples from 65 children without haematopoietic abnormalities were used as controls. The numbers of clonogenic precursors were found to be below normal in all phases of ALL, particularly during the acute period when the bone marrow was heavily infiltrated with leukaemic cells. It is shown that the decreases in the numbers and proliferative potential of the precursor cells during the acute phases was associated with the effects of leukaemic blast cells, but that in remission the observed reduction in the precursor cell pool was due to the cytostatic effect of therapy. The differentiative capacity of clonogenic granulocyte and macrophage precursors was not altered in children with ALL.


Prph2 disease mutations lead to structural and functional defects in the RPE.
Prph2 is a photoreceptor-specific tetraspanin with an essential role in the structure and function of photoreceptor outer segments. PRPH2 mutations cause a multitude of retinal diseases characterized by the degeneration of photoreceptors as well as defects in neighboring tissues such as the RPE. While extensive research has analyzed photoreceptors, less attention has been paid to these secondary defects. Here, we use different Prph2 disease models to evaluate the damage of the RPE arising from photoreceptor defects. In Prph2 disease models, the RPE exhibits structural abnormalities and cell loss. Furthermore, RPE functional defects are observed, including impaired clearance of phagocytosed outer segment material and increased microglia activation. The severity of RPE damage is different between models, suggesting that the different abnormal outer segment structures caused by Prph2 disease mutations lead to varying degrees of RPE stress and thus influence the clinical phenotype observed in patients.


Perineal muscles: possible androgen regulation of glucocorticoid receptor sites in the rat.
The glucocorticoid receptor population of the androgen-dependent levator ani-bulbo cavernosus muscle complex in response to both androgen withdrawal and androgen replacement was examined in rats. After castration the concentration of receptor sites more than doubled. The increase in the sites began within the first 24 h after castration and reached a plateau level within 7 days. Parallel dry weight studies demonstrated that no loss in muscle mass is observed until 48 h after castration. In a second series of experiments, both the regrowth of the muscle and the number of receptor sites in response to androgen injections were examined. By day 11 of injection, the muscle had increased in dry weight to a point where it was equal to the size of this muscle in normal intact male controls. During this process, the concentration of receptor sites began to decline 5 days after the beginning of injections and reached control or below control values by 11 days.


Effect of cold exposure (-15 degrees C) and salbutamol treatment on physical performance in elite nonasthmatic cross-country skiers.
The effects of whole-body exposure to ambient temperatures of -15 degrees C and 23 degrees C on selected performance-related physiological variables were investigated in elite nonasthmatic cross-country skiers. At an ambient temperature of -15 degrees C we also studied the effects of the selective beta2-adrenergic agonist Salbutamol (0.4 mg x 3) which was administered 10 min before the exercise test. Eight male cross-country skiers with known maximal oxygen uptakes (VO2max) of more than 70 ml x kg(-1) x min(-1) participated in the study. Oxygen uptake (VO2), heart rate (fc), blood lactate concentration ([La-]b) and time to exhaustion were measured during controlled submaximal and maximal running on a treadmill in a climatic chamber. Lung function measured as forced expiratory volume in 1 s (FEV1) was recorded immediately before the warm-up period and at the conclusion of the exercise protocol. Submaximal VO2 and [La-]b at the two highest submaximal exercise intensities were significantly higher at -15 degrees C than at 23 degrees C. Time to exhaustion was significantly shorter in the cold environment. However, no differences in VO2max or fc were observed. Our results would suggest that exercise stress is higher at submaximal exercise intensities in a cold environment and support the contention that aerobic capacity is not altered by cold exposure. Furthermore, we found that after Salbutamol inhalation FEV1 was significantly higher than after placebo administration. However, the inhaled beta2-agonist Salbutamol did not influence submaximal and maximal VO2, fc, [La-]b or time to exhaustion in the elite, nonasthmatic cross-country skiers we studied. Thus, these results did not demonstrate any ergogenic effect of the beta2-agonist used.


State mental health policy: Physical health screening in state mental health clinics: the New York health indicators initiative.
The New York State Office of Mental Health recently mandated that all adult outpatient clinics regularly monitor three health indicators--body mass index, blood pressure, and smoking status. After the population was defined, medical equipment was distributed. Regular training and quality improvement meetings were held to improve the electronic database for indicator data. Clinical directors were provided regular feedback on performance monitoring. Learning collaboratives allowed sharing of implementation strategies. After only four months of this coordinated effort, approximately 7,500 people with mental illnesses had been screened for the three health indicators across New York State.


Virome comparison (VC): A novel approach to comparing viromes based on virus species specificity and virome specificity diversity.
The human virome, or the viral communities distributed on or in our body, is estimated to contain about 380 trillion of viruses (individuals), which has far reaching influences on our health and diseases. Obviously, the sheer numbers of viruses alone make the comparisons of two or multiple viromes extremely challenging. In fact, the theory of computation in computer science for so-termed NP-hard problems stipulates that the problem is unsolvable when the size of virome is sufficiently large even with fastest supercomputers. Practically, one has to develop heuristic and approximate algorithms to obtain practically satisfactory solutions for NP-hard problems. Here, we extend the species-specificity and specificity-diversity framework to develop a method for virome comparison (VC). The VC method consists of a pair of metrics: virus species specificity (VS) and virome specificity diversity (VSD) and corresponding pair of random search algorithms. Specifically, the VS and VS permutation (VSP) test can detect unique virus species (US) or enriched virus species (ES) in each virome (treatment), and the VSD and VSD permutation (VSDP) test can further determine holistic differences between two viromes or their subsets (assemblages of viruses). The test with four virome data sets demonstrated that the VC method is effective, efficient, and robust.


A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase.
The flaviviruses pose serious threats to human health. Being a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP), NS5 is the most conserved flavivirus protein and an important antiviral target. Previously reported NS5 structures represented by those from the Japanese encephalitis virus (JEV) and Dengue virus serotype 3 (DENV3) exhibit two apparently different global conformations, defining two sets of intra-molecular MTase-RdRP interactions. However, whether these NS5 conformations are conserved in flaviviruses and their specific functions remain elusive. Here we report two forms of DENV serotype 2 (DENV2) NS5 crystal structures representing two conformational states with defined analogies to the JEV-mode and DENV3-mode conformations, respectively, demonstrating the conservation of both conformation modes and providing clues for how different conformational states may be interconnected. Data from in vitro polymerase assays further demonstrate that perturbing the JEV-mode but not the DENV3-mode intra-molecular interactions inhibits catalysis only at initiation, while the cell-based virological analysis suggests that both modes of interactions are important for virus proliferation. Our work highlights the role of MTase as a unique intra-molecular initiation factor specifically only through the JEV-mode conformation, providing an example of conformation-based crosstalk between naturally fused protein functional modules.


Comparative analysis of glucose-6-phosphate dehydrogenase levels in pre-term and term babies delivered at University of Ilorin Teaching Hospital.
Glucose-6-phosphate (G6P) is an enzyme in the hexose monophosphate shunt required for the production of reducing equivalents needed to mop up free radicals. thereby keeping hemoglobin in its free state. Deficiency of the enzyme can cause severe neonatal jaundice. The aim of this study was to compare G6PD levels in pre-term and term babies, and evaluate the extent to which G6PD deficiency determines the severity of jaundice in various gestational age groups. Samples of cord blood collected from consecutively delivered babies in the University of Ilorin Teaching Hospital, Nigeria, were assayed for G6PD levels, and the babies were observed for jaundice during the first week of life. Those who developed jaundice had serial serum bilirubin measured. Nine hundred and thirty-three babies had G6PD assayed, with 348 being G6PD deficient, giving a hospital based prevalence of 37.3%. Of the 644 who were followed up, 143 (22.2%) were pre-term and 501(77.8%) were term babies. Babies with gestational age (GA) 27-29 weeks had the highest G6PD levels. However, there was no significant variation among the different gestational age groups (F=0.64, P=0.64). Jaundice occurred more in pre-term compared to term babies with a relative risk of 2.41 (χ(2)=60.95, P=0.00001). Occurrence of jaundice in pre-term babies was irrespective of G6PD status (χ(2)=0.2, P=0.66, RR=1.09, CI=0.83<RR<1.43). There is an inverse relationship between gestational age and the occurrence of jaundice (R(2)=-0.874). Pre-term babies are more likely to have higher G6PD levels, but occurrence of jaundice in pre-term babies is irrespective of G6PD status. More severe jaundice (especially for gestational age) occurring in pre-term babies requires critical care.


Transport and secretion in plant-microbe interactions.
Microbial elicitors and effectors, as well as plant receptors and defence compounds, traffic at the interface of plants and microbes in pathogenic or mutualistic interactions. Net exocytosis appears to be required for surface enlargement of plasma membrane during accommodation of microbes in intact plant cells. By contrast, ligand-induced endocytosis of surface receptors operates in basal defence. The first layer of plant defence appears to depend on polarized transport of small molecules and on local secretion of defence proteins. In return, pathogen effectors target plasma membrane bound and intracellular proteins to inhibit extracellular host defences.


Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids.
Sphingolipids and glycosphingolipids are membrane components of eukaryotic cell surfaces. Their constitutive degradation takes place on the surface of intra-endosomal and intra-lysosomal membrane structures. During endocytosis, these intra-lysosomal membranes are formed and prepared for digestion by a lipid-sorting process during which their cholesterol content decreases and the concentration of the negatively charged bis(monoacylglycero)phosphate (BMP)--erroneously also called lysobisphosphatidic acid (LBPA)--increases. Glycosphingolipid degradation requires the presence of water-soluble acid exohydrolases, sphingolipid activator proteins, and anionic phospholipids like BMP. The lysosomal degradation of sphingolipids with short hydrophilic head groups requires the presence of sphingolipid activator proteins (SAPs). These are the saposins (Saps) and the GM2 activator protein. Sphingolipid activator proteins are membrane-perturbing and lipid-binding proteins with different specificities for the bound lipid and the activated enzyme-catalyzed reaction. Their inherited deficiency leads to sphingolipid- and membrane-storage diseases. Sphingolipid activator proteins not only facilitate glycolipid digestion but also act as glycolipid transfer proteins facilitating the association of lipid antigens with immunoreceptors of the CD1 family.


Exciton linewidth broadening induced by exciton-phonon interactions in CsPbBr3 nanocrystals.
Quantum dephasing of excitonic transitions in CsPbBr3 nanocrystals has been studied using two-dimensional electronic spectroscopy at cryogenic temperatures. The exciton-phonon interactions for acoustic and optical modes exhibit different effects on the coherent dynamics of excitonic transitions. The homogeneous linewidth shows a proportional dependence on the temperature, suggesting the primary dephasing channel of the elastic scattering between exciton and acoustic modes. The exciton-optical mode interaction is manifested as the beatings of off-diagonal signals in the population time domain at the frequencies of 29 and 51 cm-1, indicating phonon replicas of excitonic transitions arising from coherent exciton-phonon interaction. The insight information of exciton homogeneous broadening in perovskite nanocrystals is essential for the potential application of quantum light sources.


Impact of oral hygiene instructions on plaque index in adolescents.
The objective of the study, which consisted of a motivational lecture and hands-on training, was to evaluate the role of oral hygiene education for adolescents. The study population included sixty-two high school students between fourteen and fifteen years of age (thirty males and thirty-two females). The response rate was 76.5%. The measurement of oral hygiene level was performed using the modified Green Vermilion Index (GVI). The values were recorded at baseline, one week, three months, and six months after education through motivational lecture and hands-on training was performed. Descriptive and nonparametric statistical methods were used in statistical analysis. Level of significance was 0.05. At the beginning of the study, the GVI of all examined subjects was 3.52 (SD = 0.70). One week after the motivational lecture and training, it decreased to 2.64 (SD = 0.69). Three months later, the level of plaque index had the lowest value (1.44; SD = 0.66). At the end of the study the level of plaque index increased to 2.52 (SD = 0.86). A significant oral hygiene improvement in adolescents as a result of education was presented. However, due to a decline in oral hygiene level six months after the education, there is a need for educational programmes continuity.


Tunable, dual wavelength and self-Q-switched Alexandrite laser using crystal birefringence control.
We present a red-diode-pumped Alexandrite laser with continuous wavelength tunability, dual wavelength and self-Q-switching in an ultra-compact resonator containing only the gain medium. Wavelength tuning is obtained by varying the geometrical path length and birefringence by tilting a Brewster-cut Alexandrite crystal. Two crystals from independent suppliers are used to demonstrate and compare the performance. Wavelength tuning between 750 and 764 nm is demonstrated in the first crystal and between 747 and 768 nm in the second crystal. Stable dual wavelength operation is also obtained in both crystals with wavelength separation determined by the crystal free spectral range. Temperature tuning was also demonstrated to provide finer wavelength tuning at a rate of -0.07 nm K -1. Over a narrow tuning range, stable self-Q-switching is observed with a pulse duration of 660 ns at 135 kHz, which we believe is the highest Q-switched pulse rate in Alexandrite to date. Theoretical modelling is performed showing good agreement with the wavelength tuning and dual wavelength results.


HIV/AIDS risk perception, HIV risk behaviors, and HIV seropositivity among injection drug users in Puerto Rico.
This paper assesses the factors related to self perception of developing AIDS among a group of 1,568 Puerto Rican injection drug users (IDUs). Incarceration history, years of drug injection, sharing needles, renting and borrowing needles, sharing rinse water or cooker, and having an IDU sex partner yielded a moderate association with HIV/AIDS risk perception. Use of sterile needles, shooting drugs alone, having had previous treatment episodes, and all the variables related to health status were also moderately associated with HIV/AIDS risk perception. A logistic regression model based on backwards elimination procedure, which included statistically significant variables in the bivariate analyses, yielded the variables living with children, sex with an IDU partner, shooting drugs alone, perception of health, having had a sexually transmitted disease, and results of HIV testing as statistically significant (p < 0.05).


Regional importation and asymmetric within-country spread of SARS-CoV-2 variants of concern in the Netherlands.
Variants of concern (VOCs) of SARS-CoV-2 have caused resurging waves of infections worldwide. In the Netherlands, Alpha, Beta, Gamma and Delta variants circulated widely between September 2020 and August 2021. To understand how various control measures had impacted the spread of these VOCs, we analyzed 39,844 SARS-CoV-2 genomes collected under the Dutch national surveillance program. We found that all four VOCs were introduced before targeted flight restrictions were imposed on countries where the VOCs first emerged. Importantly, foreign introductions, predominantly from other European countries, continued during these restrictions. Our findings show that flight restrictions had limited effectiveness in deterring VOC introductions due to the strength of regional land travel importation risks. We also found that the Alpha and Delta variants largely circulated more populous regions with international connections after their respective introduction before asymmetric bidirectional transmissions occurred with the rest of the country and the variant dominated infections in the Netherlands. As countries consider scaling down SARS-CoV-2 surveillance efforts in the post-crisis phase of the pandemic, our results highlight that robust surveillance in regions of early spread is important for providing timely information for variant detection and outbreak control.


Nutritional treatment of a patient with hepatic cirrhosis with the novel low glycemic index liquid food (Inslow).
A sixty-six year-old patient with liver cirrhosis and diabetes was nutritionally treated by administration of the low glycemic index liquid food (Inslow) as a late evening sack (LES) for 6 weeks. The mean energy intake increased from 825+/-48 kcal/d to 1567+/-66 kcal/d after the 6-week treatment period. The fasting glucose level did not change, remaining at about 100 mg/dl throughout this period. Interestingly, the amount of insulin administered was reduced from 38 units before treatment to 28 units in the fifth week of treatment without a change in the fasting glucose level. This indicates a marked improvement in insulin sensitivity due to Inslow administration in this patient. In conclusion, the long-term administration of Inslow as an LES may be an effective treatment for cirrhotic patients.


Subclass restriction of human enterovirus antibodies.
We studied antibodies to enteroviruses in four groups of serum specimens: those from healthy adults, cord blood specimens, serum specimens known to contain immunoglobulin M (IgM) to coxsackie B (CB) viruses by radioimmunoassay, and serum specimens from children with symptomatic enteroviral infections. Enzyme-linked immunosorbent assays (ELISAs) were developed to detect the IgG class- and subclass (IgG1, IgG2, IgG3, and IgG4)-specific responses to CB3. The CB3 virus ELISA was not type specific. There was very poor correlation between CB3 virus neutralizing titer and IgG anti-CB3 virus ELISA results, indicating that antibodies to heterologous picornaviruses cross-react with CB3 virus in the assay. All serum specimens tested except one were IgG positive for CB3 virus. All 32 cord serum specimens were positive for IgG1 and IgG3. No enterovirus-specific IgG2 or IgG4 was detected in any serum specimen tested. Most serum specimens from the IgM-positive group, healthy adults, and children with enterovirus infections were positive for IgG1 and IgG3. Class and subclass antibody titers remained constant over time. IgG antibodies to enteroviruses appear to be restricted to the IgG1 and IgG3 subclasses. This pattern is similar to results obtained by other investigators evaluating IgG subclass antibodies to protein antigens.


Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.
In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey.


Functional disruption of HypB, a GTPase of Helicobacter pylori, by bismuth.
Bismuth (Bi(3+)) binds equal molar amounts of HypB from Helicobacter pylori at the conserved metal site with a dissociation constant of 0.94 (±0.25) × 10(-17) μM, and concomitantly induces the protein dimerization similarly to Ni(2+). Excess Bi(3+) causes HypB further oligomerization, leading to HypB GTPase dysfunction. The results extend our understanding on the inhibitory mechanism of bismuth drugs against the pathogen.


Correlation between the length of gracilis and semitendinosus tendon and physical parameters in Thai males.
As anterior cruciate ligament (ACL) injuries became more common, ACL reconstruction using hamstring tendons autograft (i.e. semitendinosus and gracilis) has become increasingly popular. One of the problems encountered during operation is insufficient size of the graft. In order to determine the size of hamstring graft preoperatively, the authors collect anthropometric data from the patients and compare them with the actual hamstring tendon length harvested from the patient during ACL reconstruction. Cross sectional diagnostic study. Seventy-five consecutive patients with torn ACL scheduled for reconstruction using hamstring autograft were prospectively evaluated. Preoperatively the authors recorded height, weight, body mass index, age, leg length, thigh length, thigh circumference, length and width of the femur. Intraoperative measurements of both the gracilis and semitendinosus tendons length were made after trimming the useless thin border of the graft and final diameter of the quadrupled graft. Bivariate correlation coefficients (Pearson r) were calculated to identify relationships among clinical data and hamstring graft length and diameter measured intraoperatively. Strongest correlations for graft lengths were height and leg length measurements from both physical examination and x-rays. In contrast, graft diameter was not correlated with any physical parameters. Simple parameter such as height can be used for preoperative identification of patients at risk for insufficient graft tissue and would be useful for patient counseling and alternative graft source planning. Thai male who is taller than 170 cm have a good potential to have semitendinosus tendon longer than 250 mm and maybe candidates to have ACL reconstruction with semitendinosus alone. X-ray of the whole leg did not provide any better prediction of graft length.


The Impact of 68Ga-DOTATATE PET/CT Imaging on Management of Patients with Neuroendocrine Tumors: Experience from a National Referral Center in the United Kingdom.
(68)Ga-DOTATATE PET/CT scanning is a widely accepted method for imaging of neuroendocrine tumors. This cross-sectional study was performed to review the first 8 y of patient data from a large (68)Ga-DOTATATE PET/CT database in order to establish the impact of the modality on patient treatment and survival. Demographic data, clinical outcome, survival, and change in management after (68)Ga-DOTATATE PET/CT were evaluated. Between May 2005 and August 2013, 1,258 (68)Ga-DOTATATE PET/CT scans were obtained in 728 patients with confirmed or suspected neuroendocrine tumors. In most patients, the primary site was located in the midgut (26.4%). Analysis of NET grading in patients with known histopathologic data revealed that 35.7% had NET grade G1, 12.2% G2, and 8.7% G3. The most common indications for (68)Ga-DOTATATE PET/CT were follow-up (24.4%) and initial tumor staging (23.4%). Of the 1,258 (68)Ga-DOTATATE PET/CT scans completed, 75.7% were positive and 24.3% negative; there were 14 false-positive and 29 false-negative scans. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97%, 95.1%, 96.6%, 98.5%, and 90.4%, respectively. In 40.9% of patients, the treatment plan was changed after the scans, owing mainly to new, unexpected findings. Statistically significant differences in survival were shown between patients with G1, G2, and G3 grade tumors (P < 0.0001) and also between patients with bone metastasis versus patients with soft-tissue metastasis (P < 0.0001). (68)Ga-DOTATATE PET/CT scanning is safe and influences management in a large proportion of patients. Prognosis was dependent on tumor grade, and the presence of bone metastasis was associated with worse overall survival.


Microbial and genetically engineered oils as replacements for fish oil in aquaculture feeds.
As the global population grows more of our fish and seafood are being farmed. Fish are the main dietary source of the omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, but these cannot be produced in sufficient quantities as are now required for human health. Farmed fish have traditionally been fed a diet consisting of fishmeal and fish oil, rich in n-3 LC-PUFA. However, the increase in global aquaculture production has resulted in these finite and limited marine ingredients being replaced with sustainable alternatives of terrestrial origin that are devoid of n-3 LC-PUFA. Consequently, the nutritional value of the final product has been partially compromised with EPA and DHA levels both falling. Recent calls from the salmon industry for new sources of n-3 LC-PUFA have received significant commercial interest. Thus, this review explores the technologies being applied to produce de novo n-3 LC-PUFA sources, namely microalgae and genetically engineered oilseed crops, and how they may be used in aquafeeds to ensure that farmed fish remain a healthy component of the human diet.


Prothrombotic Fibrin Clot Phenotype in Patients with Deep Vein Thrombosis and Pulmonary Embolism: A New Risk Factor for Recurrence.
Prothrombotic fibrin clot phenotype, involving faster formation of dense meshwork composed of thinner and highly branched fibers that are relatively resistant to plasmin-induced lysis, has been reported in patients with not only myocardial infarction or stroke, but also venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT), and/or pulmonary embolism (PE). Prothrombotic fibrin clot phenotype, in particular prolonged clot lysis time, is considered a novel risk factor for VTE as well as venous thrombosis at unusual location, for example, cerebral sinus venous thrombosis, retinal vein obstruction, and Budd-Chiari syndrome. Growing evidence from observational studies indicates that abnormal fibrin clot properties can predict recurrent DVT and PE and they are involved in serious complications of VTE, for example, thromboembolic pulmonary hypertension and postthrombotic syndrome. The purpose of this article is to review our current understanding of the role of fibrin clot structure and function in venous thrombosis with emphasis on clinical issues ranging from prognosis to therapy.


Learning Additional Languages as Hierarchical Probabilistic Inference: Insights From First Language Processing.
We present a framework of second and additional language (L2/Ln) acquisition motivated by recent work on socio-indexical knowledge in first language (L1) processing. The distribution of linguistic categories covaries with socio-indexical variables (e.g., talker identity, gender, dialects). We summarize evidence that implicit probabilistic knowledge of this covariance is critical to L1 processing, and propose that L2/Ln learning uses the same type of socio-indexical information to probabilistically infer latent hierarchical structure over previously learned and new languages. This structure guides the acquisition of new languages based on their inferred place within that hierarchy, and is itself continuously revised based on new input from any language. This proposal unifies L1 processing and L2/Ln acquisition as probabilistic inference under uncertainty over socio-indexical structure. It also offers a new perspective on crosslinguistic influences during L2/Ln learning, accommodating gradient and continued transfer (both negative and positive) from previously learned to novel languages, and vice versa.


Proteinase specificity and functional diversity in point mutants of plasminogen activator inhibitor 1.
Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin superfamily. The alternative behavior of PAI-1 as an inhibitor, a non-inhibitory substrate, or a non-reactive latent form has been shown to be dependent on the initial conformation. In this study, we have evaluated the effect of a substitution outside the reactive site loop (P18) or in the reactive site loop (P6 and P10) on proteinase specificity and conformational transitions in PAI-1. Wild-type PAI-1 (wtPAI-1) revealed the same conformational distribution pattern toward tissue-type plasminogen activator (t-PA) as toward urokinase-type plasminogen activator (u-PA) (i.e. 53 +/- 6. 9% active, 36 +/- 6.8% latent, and 12 +/- 1.9% substrate). Inactivation of wtPAI-1 resulted in the conversion of the labile active form into the latent form while the stable substrate form remained unchanged. PAI-1-P6 (Val --> Pro at P6) revealed a target specificity for t-PA (39 +/- 7% versus 3 +/- 2% of the theoretical maximal value toward t-PA and u-PA, respectively), PAI-1-P10 (Ser --> Pro at P10) was 4-fold more active toward u-PA than toward t-PA, and PAI-1-P18 (Asn --> Pro at P18) exhibited inhibitory properties exclusively toward u-PA (41 +/- 10%). Surprisingly, inactivation of these mutants revealed functional and conformational transitions distinct from those observed for wtPAI-1. Inactivation of PAI-1-P6(Val --> Pro) resulted in a total conversion of the active form into the latent form and in a partial conversion of the substrate form into the latent form. The active forms of both PAI-1-P10(Ser --> Pro) and PAI-1-P18(Asn --> Pro) are also labile but, in contrast to the active form of wtPAI-1, convert into substrate forms. Based on the existence of various conformations of PAI-1, we propose an alternative reaction scheme describing the putative interactions between serpins and their target proteinases. The unusual conformational and functional flexibility of PAI-1 that, according to the current study, appears not to be restricted to the reactive site loop further underlines the importance of potential structural rearrangements (e.g. upon binding to cofactors) in PAI-1 (or serpins in general) for its functional behavior at particular biological sites.


[Double homicide with a damning bite mark on the offender´s body - case report].
The authors deal with a case of a double homicide, the parental murder made by their older son, which was committed by a combination of stabbing and cutting wounds. The perpetra-tor tried to hide the bodies, so he doused them with gasoline and set fire to them on a lonely forest road. Then he ran over the remains by his car. The cause of death was in both cases open wound of the neck - autopsy findings of the woman´s body testified for a blood aspi-ration, on the man´s body it was not clear for a partial charring, so the possibilities were blood aspiration, air embolism or external bleeding with haemorrhagic shock. There were also many other injuries on the bodies, especially of the post-mortem origin. During the combat, one of the victims - the mother - bit the assailant´s left forearm. So a few days after creation the injury on murderer´s left upper extremity, the police technicians took photos and during the forensic autopsies of both bodies, authors created the impressions of the teeth. The utilities were loaned from Department of Stomatology of University Hospital Královské Vinohrady in Prague and they were designed for the general adult population. The work was more difficult for the state of mortal remains, which were damaged by combination of fire and blunt violence. However finally the impressions of each arch were made, and they were given to the experts from Institute of Criminalistic Prague, who compared them with pictures of the bite mark. The results of this analysis were used in a court as evidence against the perpetrator.


Prevalence and Trends of Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter Species Isolated from Clinical Specimens at the Ethiopian Public Health Institute, Addis Ababa, Ethiopia: A Retrospective Analysis.
Carbapenem-resistant Acinetobacter species and P. aeruginosa are the leading cause of nosocomial infections. Therefore, the objective of this study was to analyze the prevalence, antimicrobial susceptibility profile, and trends of carbapenem-resistant P. aeruginosa and Acinetobacter species isolated from clinical specimens. This retrospective study included data from Ethiopian Public Health Institute from 2017 to 2021. BD phoenix M50, Vitek 2 compact, and conventional identification methods were used to identify the organisms. The Kirby-Bauer disc diffusion, BD phoenix M50, and Vitek 2 compact methods were used to determine the antimicrobial susceptibility profiles of the isolates. Chi-square for linear trends using Epi Info was employed to test the significance of carbapenem resistance trends over time. The p-values of ≤0.05 were considered statistically significant. Following data cleaning, 7110 reports were used. Out of this, (N=185, 2.6%) and (N=142, 2%), Acinetobacter species and P. aeruginosa were isolated, respectively. Twenty-four Acinetobacter species and fourteen P. aeruginosa species were omitted because carbapenem antimicrobial agents were not tested for them. The overall prevalence of carbapenem-resistant Acinetobacter species and P. aeruginosa were 61% and 22%, respectively. The prevalence of carbapenem-resistant Acinetobacter species increased significantly from 50% in 2017 to 76.2% in 2021 (p=0.013). The trend of carbapenem-resistant P. aeruginosa was fluctuating (p=0.99). Carbapenem-resistant Acinetobacter had a lower resistance rate to amikacin (44%) and tobramycin (55%); similarly, carbapenem-resistant P. aeruginosa had a lower resistance rate to amikacin (27%) and tobramycin (47%). This study revealed a high prevalence of carbapenem-resistant Acinetobacter species and P. aeruginosa, both of which showed better sensitivity to amikacin and tobramycin. Furthermore, Acinetobacter species showed a statistically significant increasing trend in carbapenem resistance.


Applying functional genomics research to the study of pig reproduction.
Functional genomics is an experimental approach that incorporates genome-wide or system-wide experimentation, expanding the scope of biological investigation from studying single genes to studying potentially all genes at once in a systematic manner. This technology is highly appealing because of its high throughput and relatively low cost. Furthermore, analysis of gene expression using microarrays is likely to be more biologically relevant than the conventional paradigm of reductionism, because it has the potential to uncover new biological connections between genes and biochemical pathways. However, functional genomics is still in its infancy, especially with regard to the study of pig reproduction. Currently, efforts are centred on developing the necessary resources to enable high throughput evaluation and comparison of gene expression. However, it is clear that in the near future functional genomics will be applied on a large scale to study the biology and physiology of reproduction in pigs, and to understand better the complex nature of genetic control over polygenic characteristics, such as ovulation rate and litter size. We can look forward to generating a significant amount of new data on differences in gene expression between genotypes, treatments, or at various temporal and spatial coordinates within a variety of reproductively relevant systems. Along with this capability will be the challenge of collating, analysing and interpreting datasets that are orders of magnitude more extensive and complex than those currently used. Furthermore, integration of functional genomics with traditional genetic approaches and with detailed analysis of the proteome and relevant whole animal phenotypes will be required to make full use of this powerful new experimental paradigm as a beneficial research tool.


[Causes of death in cancer patients].
Causes of death of 260 tumorous patients autopsied in 1974 were analyzed. Most common causes were inflammation and tumorous and non-tumorous organ insufficiencies; the others, in order of decreasing incidence, massive tumorous dissemination, infarct and haemorrhage. Pneumonia was predominating over the inflammatory causes although peritonitis and sepsis were also not rarely encountered. Death due to inflammation occurred most frequently in cases of myeloid-lymphoid, urogenital and gastro-intestinal tumours and in postoperative states. The incidence of insufficiencies due to tumorous or non-tumorous origin differed but slightly. Of the various organ insufficiencies, massive hepatic metastases, occlusion of the biliary duct and cardiac failure were the most common. In cases of tumors of the small pelvis, compression of the ureters led most often to death. Massive dissemination was observed most of all in breast and ovarian carcinomas. Myeloid-lymphoid tumors led to death through extensive organ infiltration in about one thirds of the cases. After hearth infarction, venous thrombosis was often followed by pulmonary embolism, however, coronary occlusion was also not rare. Death due to haemorrhage originated from acute or chronic ulcers of the gastrointestinal tract or from vascular invasion of tumors in the head and neck regions or from thrombocytopaenia induced by cytostatics.


Sartre and Freud.
The approaches to understanding a person's life represented by Freud's psychoanalysis and Sartre's "existential psychoanalysis" are fundamentally opposed. Starting from entirely different epistemological premises, they reach irreconcilable views on the nature of man and psychopathology, and lead to quite dissimilar and opposed formulations for psychotherapy.


RNA-Seq-based transcriptome analysis of aflatoxigenic Aspergillus flavus in response to water activity.
Aspergillus flavus is one of the most important producers of carcinogenic aflatoxins in crops, and the effect of water activity (a(w)) on growth and aflatoxin production of A. flavus has been previously studied. Here we found the strains under 0.93 a(w) exhibited decreased conidiation and aflatoxin biosynthesis compared to that under 0.99 a(w). When RNA-Seq was used to delineate gene expression profile under different water activities, 23,320 non-redundant unigenes, with an average length of 1297 bp, were yielded. By database comparisons, 19,838 unigenes were matched well (e-value < 10⁻⁵) with known gene sequences, and another 6767 novel unigenes were obtained by comparison to the current genome annotation of A. flavus. Based on the RPKM equation, 5362 differentially expressed unigenes (with |log₂Ratio| ≥ 1) were identified between 0.99 a(w) and 0.93 a(w) treatments, including 3156 up-regulated and 2206 down-regulated unigenes, suggesting that A. flavus underwent an extensive transcriptome response during water activity variation. Furthermore, we found that the expression of 16 aflatoxin producing-related genes decreased obviously when water activity decreased, and the expression of 11 development-related genes increased after 0.99 a(w) treatment. Our data corroborate a model where water activity affects aflatoxin biosynthesis through increasing the expression of aflatoxin producing-related genes and regulating development-related genes.


Enhanced radiation effect on SMCC7721 cells through endoplasmic reticulum stress induced by C225-GNPs in vitro and in vivo.
The high atomic number of gold nanoparticles (GNPs) enables them to offer potential as practical and efficient radiosensitizing agents for cancer radiotherapy applications. In the present study, it was demonstrated that GNPs can significantly modulate the irradiation response of hepatocellular carcinoma (HCC) cells in vitro and in vivo, of which the underlying mechanisms were investigated. Cetuximab (C225) is a targeting agent, which binds to the extracellular domain of epidermal growth factor receptor (EGFR). Hepatocyte-targeting, EGFR-specific C225 was synthesized onto GNP surfaces (C225-GNPs) to increase the GNP targeting specificity. C225-GNPs was synthesized successfully and characterized. The cytotoxicity was tested using a Cell Counting Kit-8 assay and 50% inhibition concentration of SMCC7721 cells was calculated. Cell uptake assay was detected using transmission electron microscopy. Radiosensitization was tested using a cell colony formation assay and cell cycle was detected using flow cytometry. The expression of a number of apoptotic proteins were tested by western blot analysis. Orthotropic SMCC7721 xenografts were used in order to verify its radiosensitizing effect. The results revealed that a higher number of C225-GNPs were effectively uptaken by SMCC7721 cells and markedly enhanced cancer cell death. The sensitization mechanism of C225-GNPs was associated with the apoptotic gene signalling process activated by endoplasmic reticulum stress and the unfolded protein response in cancer cells. In orthotopic SMCC7721 xenografts, the C225-GNPs significantly enhanced the radiation-induced suppression of tumour growth. The results of the present study provided evidence that C225-GNPs are potent radiosensitizers with radiotherapeutic value for HCC with the overexpression of EGFR.


Use of antibodies against dodecylsulfate-denatured heavy meromyosins to probe structural differences between muscular myosin isoenzymes.
Heavy meromyosin, a tryptic myosin fragment, was purified from rabbit fast twitch muscles and rat cardiac ventricles. Both types of heavy meromyosin were denatured by sodium dodecylsulfate and used to immunize guinea-pigs after chromatography on Sephadex G-10 to remove excess dodecylsulfate. Micro-complement fixation analysis showed that the antisera were specific to a denatured configuration of heavy meromyosin and myosin, and hardly recognized the native proteins. Cross-reactions performed with both rabbit skeletal and rat cardiac antisera indicated that the antigenic structures of denatured myosins varied according both to species (man, rabbit, rat or mouse), and to muscle-type (red skeletal slow twitch, while skeletal fast twitch, cardiac atria or cardiac ventricles). Denatured heavy meromyosin chromatography on Sephadex G-200 in the presence of 0.1% sodium dodecylsulfate enabled separation of several polypeptides groups. Of these, a polypeptide of Mr 29000 was the most reactive and exhibited the same immunological specificities as the whole myosin molecule. The use of antibodies against denatured heavy meromyosin in conjunction with micro-complement fixation therefore provides a discriminant means, not only for estimating the structural relationship between several myosin isoenzymes, but also for localizing constant and variable regions in the heavy chains of these isoenzymes.


[Recents advances in the pharmacology of immunosuppressive drugs used in organ transplantation].
Individualization of immunosuppressive drugs may be helped by the use of therapeutic drug monitoring determining the best unique time point for concentration to be controlled or using limited sample strategy to perform abbreviated area under the curve (AUC). Pharmacogenetic analyzes the role of enzymes genetic polymorphisms on pharmacokinetic characteristics. Recent studies have demonstrated that cyclosporine concentration obtained 2 hours after oral intake is the best single point. However, a recent analysis of published data did not sustain the clinical benefit of this approach. Regarding mycophenolate mofetil, the targeted AUC has been defined between 30 and 60 mg/h/l. Clinical results are contradictory and it is not possible for the time being to give a clear answer to its clinical relevance. For tacrolimus, it has been demonstrated that the daily dose needed to achieve adequate trough levels are correlated with cytochrome P450 3A5 expression and therefore the presence of *1 allele. A prospective study has been conducted to demonstrate the clinical consequences of this pharmacogenetic approach.


Isolation and characterization of 25Kd fibronectin-binding growth factor.
A high recovery protocol was devised for the isolation of a 25Kd protein in a pure form from bovine serum using successive affinity and gel permeation chromatography techniques. Structural characterization of the resulting isolate shows that it is a Mr 25Kd polypeptide consisting of two chains held together with disulphide bonds. 25Kd is an acid- and heat-stable molecule, requiring the disulphide bonds for full activity. The biological activity of 25Kd is in a latent form that requires acidification, alkinisation or exposure to urea for activation. When tested on different cell lines for mitogenicity, 25Kd shows a 7.2- and a 3-fold increase over basal at 50ng/ml with CH23 and SV3T3 fibroblasts respectively. However, it shows a considerable inhibition (up to 90% at 10ng/ml with 3T3 cultures. Active 25Kd stimulates colony formation on soft agar of CH23, 3T3 and SV3T3 which requires the presence of 5ng/ml epidermal growth factor (EGF). The concentration of purified 25Kd required to elicit a half-maximal response for formation of colonies is 0.1-5ng/ml when assayed in the presence of 5ng/ml EGF. Both anti- 25Kd antibodies and synthetic pentapeptide Gly-Arg-Gly-Asp-Ser inhibit colony-stimulating activity of 25Kd. The finding that 25Kd is not a fibronectin fragment provides more supporting evidence that 25Kd is a serum growth factor. The structural properties, chromatographic behaviour, immunological and biological activities of 25Kd suggest a close relationship to transforming growth factor type beta (TGF-B).


Evidence-based complementary and alternative medicine in inpatient care: take a look at Europe.
The aim of this report is to provide the reader an overview of the complex therapy currently used within the German health system. Complex therapies in inpatient care in Germany establish the basis for an integrative and interdisciplinary provision of services. They define minimal criteria for the organization of a hospital, enable the integration of different therapeutic approaches, and therefore, lead to an intensive and holistic treatment by a specially trained team. The German model can be viewed as a pilot program for the introduction of integrative patient-centered care in other hospitals around the world.


Application of reflectometry power flow for magnetic field pitch angle measurements in tokamak plasmas (invited).
Reflectometry has successfully demonstrated measurements of many important parameters in high temperature tokamak fusion plasmas. However, implementing such capabilities in a high-field, large plasma, such as ITER, will be a significant challenge. In ITER, the ratio of plasma size (meters) to the required reflectometry source wavelength (millimeters) is significantly larger than in existing fusion experiments. This suggests that the flow of the launched reflectometer millimeter-wave power can be realistically analyzed using three-dimensional ray tracing techniques. The analytical and numerical studies presented will highlight the fact that the group velocity (or power flow) of the launched microwaves is dependent on the direction of wave propagation relative to the internal magnetic field. It is shown that this dependence strongly modifies power flow near the cutoff layer in a manner that embeds the local magnetic field direction in the "footprint" of the power returned toward the launch antenna. It will be shown that this can potentially be utilized to locally determine the magnetic field pitch angle at the cutoff location. The resultant beam drift and distortion due to magnetic field and relativistic effects also have significant consequences on the design of reflectometry systems for large, high-field fusion experiments. These effects are discussed in the context of the upcoming ITER burning plasma experiment.


[Therapeutic evaluation of an ampicillin suppository (KS-R1) used against acute suppurative otitis media in children: a comparison with an oral preparation].
A comparative well-controlled study was performed to evaluate the efficacy and tolerability of KS-R1 (ampicillin rectal suppository, 125 mg X 4/day) administered to the rectum as compared with those of orally administered ampicillin (ABPC) with same dosage. The results obtained were as follows. The clinical effect of the drug was judged in 100 cases (suppository group in 45 cases, oral group in 55 cases) out of 111 cases. The overall efficacy rates evaluated on standard criteria were 93.3% for the suppository group and 89.1% for the oral group. There was no statistically significant difference between 2 groups. Evaluation by stratification according to the dose, disease type and age also revealed a slightly higher efficacy rate on each parameter in the suppository group, but no significant difference between 2 groups. The bacteriological effects evaluated in 84 cases (suppository group in 38 cases, oral group in 46 cases) were 94.7% and 93.5%, respectively. There was no statistically significant difference between 2 groups. Side effects were evaluated in 101 cases (suppository group in 46 cases, oral group in 55 cases), but the incidence rate showed no significant difference between the 2 groups; 3 cases (each 1 of abdominal pain, periproctal redness and periproctal erosion) were observed in suppository group and 2 cases (each 1 of stomach pain + soft stool and diarrhea) in oral group. The results indicate that KS-R1 is equally effective and tolerable against acute suppurative otitis media compared to oral administration of ABPC, and considered to be useful.


Tensin1 positively regulates RhoA activity through its interaction with DLC1.
DLC1 is a RhoGAP-containing tumor suppressor and many of DLC1's functions are absolutely dependent on its RhoGAP activity. Through its RhoGAP domain, DLC1 inhibits the activity of RhoA GTPase, which regulates actin cytoskeleton networks and dis/assembly of focal adhesions. Tensin1 (TNS1) is a focal adhesion molecule that links the actin cytoskeleton to integrins and forms signaling complexes through its multiple binding domains. Here, we report that TNS1 enhances RhoA activity in a DLC1-dependent manner. This is accomplished by binding to DLC1 through TNS1's C2, SH2, and PTB domains. Point mutations at these three sites disrupt TNS1's interaction with DLC1 as well as its effect on RhoA activity. The biological relevance of this TNS1-DLC1-RhoA signaling axis is investigated in TNS1 knockout (KO) cells and mice. Endothelial cells isolated from TNS1 KO mice or those silenced with TNS1 siRNA show significant reduction in proliferation, migration, and tube formation activities. Concomitantly, the RhoA activity is down-regulated in TNS1 KO cells and this reduction is restored by further silencing of DLC1. Furthermore, the angiogenic process is compromised in TNS1 KO mice. These studies demonstrate that TNS1 binds to DLC1 and fine-tunes its RhoGAP activity toward RhoA and that the TNS1-DLC1-RhoA signaling axis is critical in regulating cellular functions that lead to angiogenesis.


Supported phospholipid membrane interactions with 1-butyl-3-methylimidazolium chloride.
Quartz crystal microbalance with dissipation measurements were conducted for a 98/2 mole ratio of 1,2-dielaidoylphosphocholine (DEPC) and 1,2-dimyristoylphosphoglycerol (DMPG) on silica, gold, and a self-assembled monolayer of 11-mercapto-1-undecanol (11MU) and 11-mercaptoundecanoic acid (11MUA) at 50 mol % each. This study demonstrates that vesicles composed of DEPC and DMPG at 98 and 2 mol %, respectively, formed a supported bilayer with unruptured vesicles present when adsorbed onto the self-assembled monolayer. Also, the partially formed supported bilayer apparently deadsorbed in the presence of 1-butyl-3-methylimidazolium chloride, suggesting that surface-bilayer interactions are weaker on a hydrophilic modified gold surface composed of 50/50 11MU/11MUA than the surface-bilayer interactions on silica.


Complex sublinear burrows in the deep sea may be constructed by amphipods.
Trails, burrows, and other "life traces" in sediment provide important evidence for understanding ecology-both of the maker and of other users-and behavioral information often lacking in inaccessible ecosystems, such as the deep sea or those that are already extinct. Here, we report novel sublinear rows of openings in the abyssal plains of the North Pacific, and the first plausible hypothesis for a maker of these constructions. Enigmatic serial burrows have now been recorded in the Pacific and Atlantic deep sea. Based on image and specimen evidence, we propose that these Bering Sea excavations represent amphipod burrows, while the maker of the previously known Mid-Atlantic Ridge constructions remains undetermined. We propose that maerid amphipods could create the Pacific burrows by eating-digging horizontally below the surface along a nutrient-rich layer in the sediment, making the serial openings above them as they go, for conveniently removing excavated sediment as the excavation progresses. These striking structures contribute to local biodiversity, and their maker could be considered a deep-sea ecosystem engineer.


Gene expression network reconstruction by convex feature selection when incorporating genetic perturbations.
Cellular gene expression measurements contain regulatory information that can be used to discover novel network relationships. Here, we present a new algorithm for network reconstruction powered by the adaptive lasso, a theoretically and empirically well-behaved method for selecting the regulatory features of a network. Any algorithms designed for network discovery that make use of directed probabilistic graphs require perturbations, produced by either experiments or naturally occurring genetic variation, to successfully infer unique regulatory relationships from gene expression data. Our approach makes use of appropriately selected cis-expression Quantitative Trait Loci (cis-eQTL), which provide a sufficient set of independent perturbations for maximum network resolution. We compare the performance of our network reconstruction algorithm to four other approaches: the PC-algorithm, QTLnet, the QDG algorithm, and the NEO algorithm, all of which have been used to reconstruct directed networks among phenotypes leveraging QTL. We show that the adaptive lasso can outperform these algorithms for networks of ten genes and ten cis-eQTL, and is competitive with the QDG algorithm for networks with thirty genes and thirty cis-eQTL, with rich topologies and hundreds of samples. Using this novel approach, we identify unique sets of directed relationships in Saccharomyces cerevisiae when analyzing genome-wide gene expression data for an intercross between a wild strain and a lab strain. We recover novel putative network relationships between a tyrosine biosynthesis gene (TYR1), and genes involved in endocytosis (RCY1), the spindle checkpoint (BUB2), sulfonate catabolism (JLP1), and cell-cell communication (PRM7). Our algorithm provides a synthesis of feature selection methods and graphical model theory that has the potential to reveal new directed regulatory relationships from the analysis of population level genetic and gene expression data.


Theoretical Study of the Pyridine-Helium van der Waals Complexes.
In this study we evaluate a high-level ab initio ground-state intermolecular potential-energy surface for the pyridine-He van der Waals complex, using the CCSD(T) method and Dunning's augmented correlation consistent polarized valence double-ζ basis set extended with a set of 3s3p2d1f1g midbond functions. The potential is characterized by two symmetric global minima of -93.2 cm(-1) that correspond to geometries where the distance between the helium atom and the pyridine center of mass is 3.105 Å and the angle with respect to the pyridine c rotational axis is 3.9°. Six local minima can be observed for geometries with the helium atom in the plane cotaining the pyridine molecule. To further analyze the nature of the intermolecular interactions in the complex, we use symmetry-adapted perturbation theory (SAPT). Additional consideration of the pyridine-He2 complex provides a better insight into many-body nonadditive contributions to intermolecular interactions in systems with more helium atoms.


Psychological characteristics of patients treated by chronic maintenance hemodialysis.
Studies related to psychological aspects of dialysis patients show that depression and anxiety are the most common characteristics. The aim of our study was to analyze the personality profile in patients on chronic maintenance dialysis and to evaluate more specifically the level of depression. The total number of patients was 68 (30 females and 38 males), with mean age 62.3 and 56.5 for females and males respectively. Mean duration of dialysis was 6.73 years for females and 6.68 years for men (the period varied from 0.5 to 18 years). For the evaluation of psychological characteristics, we used two psychometric instruments: Minnesota Multiphase Personality Inventory (MMPI- 201) and Beck Depression Inventory. The obtained results confirmed the presence of depression in patients treated with hemodialysis. The level of depression is variable (minimal is present in 21.43%; mild in 35.71%; moderate in 17.85% and severe in 14.28% of patients). The depression is significantly positively correlated with age (p<0.05) as well as with educational level, and negatively with the duration of dialysis. Specific characteristics of personality obtained with MMPI are hypersensitivity, depressive mood, and withdrawal from friends and relatives. More specific emotional traits are the accentuated anxiety, low level of hostility, but very high passive aggression which destroys their social communications. Some response measures for depression such as relaxation training, psychological support, music therapy, or peripheral biofeedback are recommended.


Infant feeding indicators for use in emergencies: an analysis of current recommendations and practice.
To assess the applicability and use of infant nutrition and health indicators during emergencies. Indicators recommended by international health and nutrition organisations for assessing infant feeding practice were compiled and analysed to evaluate their consistency and applicability for use in surveys of emergency-affected populations. These indicators included measures of breast-feeding status, use of artificial feeding, anthropometric status and morbidity. Health and nutrition surveys performed on the resident or refugee population of Kosovo during the years 1996-1999 were then reviewed and the use of infant feeding and morbidity indicators were compared. A number of recommended indicators exist for assessing infant and child feeding practice which have been generated by different international organisations. A comparison of these indicators revealed a number of inconsistencies, both in target population and measurement method. Their use during the Kosovo crisis was likewise inconsistent and prevented conclusions being drawn about the effectiveness of the international response in protecting infant health and nutrition. Standard indicators need to be agreed and promoted for use during surveys of emergency-affected populations. Failure to do so will lead to a continued inability to monitor the health and nutrition of infants at a population level during international relief operations.


Single-Cell Transcriptomic Analysis in the Regenerating Cnidarian Nematostella vectensis.
Cnidarians have historically served as excellent laboratory models for regenerative development given their capacity to regrow large portions of the adult organism. This capacity is notably absent or poorly developed in the powerful genetic laboratory models Drosophila, C. elegans, and mouse. Increasingly, development of genetic and genomic resources and the application of next-generation sequencing-based techniques in cnidarian systems has further expanded the potential of cnidarian regenerative models. Here, we present a workflow for the characterization of the regenerative response in the sea anemone Nematostella vectensis utilizing fluorescence-activated cell sorting and a plate-based single-cell RNA-sequencing pipeline. This approach can characterize the transcriptional response during regeneration in distinct populations of cells, thus providing a quantitative view of a whole organism process at cellular resolution.


Uncoupling between Ig somatic hypermutation and oncogene mutation in mouse lymphoma.
Burkitt lymphoma (BL) features translocations linking c-myc to the immunoglobulin heavy chain (IgH) locus. By inserting a c-myc gene under the control of the 3'IgH locus control region (LCR) into the mouse genome, we generated c-myc-3'LCR mice that develop clonal BL or diffuse anaplastic lymphoma. We show in the present study that while BL from c-myc-3'LCR mice would be classified as pre-germinal center (GC) cells due to the absence of both BCL-6 expression and somatic hypermutation (SHM) in V(H) sequences, they show a high level of SHM focused on the c-myc oncogene itself. This observation suggests that the c-myc-3'IgH LCR tandem association drives development of lymphoma from naïve B cells by specifically recruiting AID activity on c-myc in a process that early becomes independent from antigen selection and where the successive rounds of SHM rather rely on the selection of the most efficient mutations for oncogene deregulation. Similar to the translocated c-myc gene in human BL, mutations were found in first exon and 5' flanking sequences of transgenic c-myc and specially focused on negative regulatory elements, thus leading to high and constitutive oncogene expression. In conclusion while 3'IgH transcriptional enhancers in c-myc-3'LCR mice first simply act in cis to slightly stimulate c-myc transcription in untransformed B cells, the occurrence of lymphoma appears to result from an additional mechanism necessitating AID-driven mutations within the first exon and 5' flanking sequences which does not occur in parallel but rather circumvents antigen-driven selection.


Types of aggression, responsiveness to provocation, and callous-unemotional traits in detained adolescents.
The present study investigated differences in the behavioral and psychophysiological responses to provocation and in the level of callous-unemotional traits in boys exhibiting different patterns of aggression. Eighty-five boys (ages 13-18) in a juvenile detention center played a competitive computer task against a hypothetical peer who provided low and high levels of provocation. Youth high on both self-reported reactive and proactive aggression showed different behavioral responses to provocation than youth high on only reactive aggression. Specifically, the combined group showed high levels of aggressive responses without any provocation, whereas the group high on reactive aggression showed an increase in aggressive responding to low provocation. Further, results revealed a trend for the combined group to show lower levels of skin conductance reactivity to low provocation if they were also high on callous-unemotional traits.


Recent Outbreak of Monkeypox: Implications for Public Health Recommendations and Crisis Management in India.
Monkeypox is a rare and self-limiting disease that was eradicated globally through vaccination approximately forty years ago, following the eradication of smallpox. The purpose of this article is to explore the implications of the recent monkeypox outbreak on public health recommendations and crisis management in India. An overview of the consequences of the current monkeypox epidemic on public health, epidemiology, clinical findings, management, challenges, and existing strategies for this disease, along with recommendations are discussed. It is crucial to develop evidence-based recommendations for the diagnosis and treatment of monkeypox, as well as early case identification and contact tracing. To prevent the spread of infection, travelers from affected countries should be subjected to health testing and quarantine. In order to successfully control the outbreak, a multidisciplinary team should be established to manage the monkeypox virus at tertiary care facilities, and health workers with occupational exposure to the virus should be assessed and given management plans.


Dopamine Signaling in Circadian Photoentrainment: Consequences of Desynchrony.
Circadian rhythms, or biological oscillations of approximately 24 hours, impact almost all aspects of our lives by regulating the sleep-wake cycle, hormone release, body temperature fluctuation, and timing of food consumption. The molecular machinery governing these rhythms is similar across organisms ranging from unicellular fungi to insects, rodents, and humans. Circadian entrainment, or temporal synchrony with one's environment, is essential for survival. In mammals, the central circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and mediates entrainment to environmental conditions. While the light:dark cycle is the primary environmental cue, arousal-inducing, non-photic signals such as food consumption, exercise, and social interaction are also potent synchronizers. Many of these stimuli enhance dopaminergic signaling suggesting that a cohesive circadian physiology depends on the relationship between circadian clocks and the neuronal circuits responsible for detecting salient events. Here, we review the inner workings of mammalian circadian entrainment, and describe the health consequences of circadian rhythm disruptions with an emphasis on dopamine signaling.


Factor analysis of local cerebral blood flow changes observed in physiological experiments.
Local blood flow values measured by 14C-iodoantipyrine autoradiography in 78 cerebral structures of the rat brain were compiled from 128 physiological experiments concerning neurohumoral influences and anaesthesia. The data were evaluated by common factor analysis in order to reveal correlative relationships between cerebral areas and to determine representative structures for the observed reaction patterns. The calculations showed that 92% of the regional variations could have been represented by 5 independent factors accounting for 37%, 20%, 19%, 10% and 6% of the total variance, respectively. The most closely associated structures and their loadings for the above factors were colliculus inferior (0.92), cingulum (0.89), tractus opticus (-0.86), radix tractus spinalis nervi trigemini (-0.93) and nucleus olivarius superior (0.86). The results suggest that the local blood flow response of a given cerebral area depends, above all, on the fact whether it is part of the carotid or the vertebro-basilar territory.


Nebulization with alkaline hipertonic ibuprofen induces a rapid increase in platelets circulating in COVID-19 patients but not in healthy subjects.
We analyze changes in circulating platelets in COVID-19 positive patients who received conventional treatment Dexamethasone and Enoxaparin (Dexa-Enoxa) compared to patients treated with conventional therapy plus nebulization with alkaline hypertonic ibuprofenate (AHI). Results show that after 24 h of nebulization with AHI, circulating platelets shows an increase about 40% at 24 h and reach 65% at 96 h. In patients with platelets content below 200,000 by microliter the increase was 49% and 79% at 24 and 96 h respectively. In patients with platelets above 200,000 by microliter the increase was 24% and 31% at 24 and 96 h, respectively. The increase of platelets via AHI was similar in both, men and women.To evaluate whether this action of AHI was related to platelets from COVID-19 positive patients or also for healthy people, two controls were included: one of them with 10 healthy volunteers and another one with COVID-19 positive patients hospitalized and treated only with Dexa-Enoxa. Results show that, in healthy volunteers, the number of circulating platelets remains unchanged even after 7 days of treatment with AHI. In COVID-19 positive patients treated only with Dexa-Enoxa for 4 days, platelets increased only 16%.


[The lobus venae anonymae].
A paramediastinal shadow in the right upper lobe resembled a cavitary lesion in conventional tomography. Computed tomography displayed an anomalous course of the right brachiocephalic vein in the upper lobe.