Contributions of Japanese Hospitalists During the COVID-19 Pandemic and the Need for Infectious Disease Crisis Management Education for Hospitalists: An Online Cross-Sectional Study.
Hospitalists in Japan have been at the forefront of the COVID-19 pandemic. However, contributions of Japanese hospitalists during the COVID-19 pandemic and hospitalists' awareness of crisis management education remain unclear. We conducted a questionnaire survey to investigate the role of Japanese hospitalists during the COVID-19 pandemic. The questionnaire was conducted using email and Google Forms targeting the chairpersons of facilities certified by the Japanese Society of Hospital General Medicine (JSHGM). Members of the academic committee of the JSHGM and several hospitals conducted a narrative review and determined the questions for the survey in a discussion. We conducted descriptive statistics based on the responses of 97 hospitals that agreed to participate in this survey. In total, 91.8% of general medicine departments in the included hospitals were involved in the medical care of COVID-19 patients. Furthermore, in 73.2% of hospitals, hospitalists were involved in infection control for COVID-19 inside or outside the hospital. Our survey revealed that Japanese hospitalists were responsible for COVID-19 treatment in over 60% of hospitals and contributed to hospital management, infection control, and vaccination. In total, 79.4% of hospitals answered that "training of personnel who can provide practical care for emerging infectious diseases is necessary", 78.4% indicated that "the establishment of an infection control system in advance to prepare emerging infectious diseases in the hospital is necessary", and 74.2% stated that "the establishment of an educational system for responding to emerging infectious diseases is necessary.". In conclusion, during the pandemic, in addition to inpatient care, Japanese hospitalists provided outpatient care for COVID-19, which is the role of primary care physicians in other countries. Furthermore, Japanese hospitalists who experienced the COVID-19 pandemic expressed the need for personnel development and education to prepare for future emerging infectious disease pandemics.


Pharmacodynamic basis for altered drug action in the elderly.
The elderly have the highest incidence of medical and psychiatric disorders. These conditions frequently occur simultaneously and are often chronic, lasting the lifetime of the individual. Consequently, the elderly require more medications than do younger patients. Consumption of over-the-counter drugs is considerable among the aged. There is considerable evidence that the elderly patient in most cases responds differently to drugs than do young adults. Many factors contribute to these differences. Among them are reduced protein binding, reduced biotransformation, diminished renal elimination, changes in receptor density or affinity, or both, diminished receptor adaptability, changes in the coupling between receptors and effector systems, impairment of responding organs resulting from the pathologic state, reduction in the reactivity of homeostatic mechanisms, and the aging process itself. These components may have different weight, depending on the drug and the individual considered. Because of the physiologic age-related changes in the distribution and elimination of drugs and in the sensitivity to medications, adverse side effects develop frequently in the elderly. Accordingly, dosages and dosage intervals must be adjusted carefully. In addition, since the elderly often take multiple medications, they frequently experience ADRs. Psychotropic drugs are often involved in such interactions and cause twice the incidence of side effects in elderly patients as they do in younger patients. Drug-nutrient and drug-drug interactions, programs to enhance patient compliance, and sociogenic factors should be taken into account in any well-designed dose regimen for the elderly. Physician awareness of problems that exist in the elderly population's use of drugs is essential if rational drug therapy for the aged is to evolve. The proper use of drugs in the elderly largely depends on taking into account both the pharmacokinetic and the pharmacodynamic properties of the drug and how these parameters are altered with age; such information can be obtained only by investigating drug action in older people.


Canine CD20 gene.
The human CD20 antigen, a 35kDa cell surface nonglycosylated hydrophobic phoshpoprotein is expressed consistently on almost all human B-cells, and its monoclonal antibody is used for the therapy on human B-cell lymphoma. In the present study, canine CD20 gene was cloned and sequenced, and the expression of CD20 mRNA was investigated in canine peripheral blood mononuclear cells (PBMCs), and lymph nodes from healthy dogs, and canine lymphoma cells. Using canine cDNA as a template, full-length of canine CD20 gene was sequenced by 5'-RACE and 3'-RACE methods. The full-length of the cDNA sequence of canine CD20 was 1239bp encoding 297 amino acids. The amino acid sequences of canine CD20 showed 73 and 68% sequence similarities with those of human and mouse, respectively. Canine CD20 was predicted to contain domains of amino acid sequences consisting of two extracellular domains (EM), four transmembrane domains (TM), and three intracellular domains (IC) as in human CD20. Canine CD20 mRNA was detected in PBMCs and lymph node from healthy dogs, and B-cells of canine lymphoma, but not in T-cell lymphoma cells and non-T and non-B-cell lymphoma cells by RT-PCR analysis. From these results, canine CD20 might be targeted for monoclonal antibody therapy against B-cell lymphoma of dogs.


Technology and the nurse educator: are you ELITE?
Faced with an increasingly varied technology environment, nurse faculty and students often see the value of technology but struggle with its effective use. To address this issue, our school of nursing created an innovative program that provided faculty with tools and training needed to effectively implement educational technology. The authors discuss program content, implementation strategies, and results.


Longitudinal flow of macromolecules in the endolymphatic space of the rat. An autoradiographical study.
Secretion and resorption of sulphated glycoproteins by the epithelial lining of the endolymphatic space of the rat were studied autoradiographically with the use of 35SO4 as a selective marker. This isotope was found to be incorporated into the sensory area of cristae and maculae and a small area of epithelial cells adjacent to the sensory epithelium. Thereafter 35S-labelled glycoproteins were secreted into cupulae and otolithic membranes. No such process could be established in the tectorial membrane. From the gradual disappearance of 35S-labelled glycoproteins from cupulae and otolithic membrane coupled with an accumulation of this substance in the lumen of the endolymphatic sac, the existence of a longitudinal flow under physiological conditions could be concluded. Resorption of glycoproteins by the saccus epithelium was found to be very slow. Accumulation of 35S-labelled glycoproteins in the endolymphatic duct after saccus obstruction indicates that, in addition to the endolymphatic sac, also the duct contributes to the mechanism underlying the longitudinal flow of macromolecules.


Fluorescence turn-on detection of human serum albumin based on the assembly of gold nanoclusters and bromocresol green.
As the most abundant protein in plasma, human serum albumin plays a vital role in physiological processes, such as maintaining blood osmotic pressure and carrying small-molecule ligands. Since the content of albumin in the human serum can reflect the status of liver and renal function, albumin quantitation is significant in clinical diagnosis. In this work, fluorescence turn-on detection of human serum albumin (HSA) had been performed based on the assembly of gold nanoclusters and bromocresol green. Gold nanoclusters (AuNCs) capped by reduced glutathione (GSH) were assembled with bromocresol green (BCG), and the assembly was used as a fluorescent probe for HSA. After BCG assembling, the fluorescence of gold nanoclusters was nearly quenched. In acidic solution, HSA can selectively bind to BCG on the assembly and recover the fluorescence of the solution. Based on this turn-on fluorescence, ratiometric HSA quantification was realized. Under optimal conditions, HSA detection by the probe possessed a good linear relationship in the range of 0.40-22.50 mg·mL-1, and the detection limit was 0.27 ± 0.04 mg·mL-1 (3σ, n = 3). Common coexisting components in serum and blood proteins did not interfere with the detection of HSA. This method has the advantages of easy manipulation and high sensitivity, and the fluorescent response is insensitive to reaction time.


Healthcare Utilization and Costs According to Frailty Transitions After Two Years: A Korean Frailty and Aging Cohort Study.
Korea's aging population has raised several challenges, especially concerning healthcare costs. Consequently, this study evaluated the association of frailty transitions with healthcare utilization and costs for older adults aged 70 to 84. This study linked the frailty status data of the Korean Frailty and Aging Cohort Study to the National Health Insurance Database. We included 2,291 participants who had frailty measured by Fried Frailty phenotype at baseline in 2016-2017 and follow-up in 2018-2019. We conducted a multivariate regression analysis to determine the association between their healthcare utilization and costs by frailty transition groups. After 2 years, changes from "pre-frail" to "frail" (Group 6) and "frail" to "pre-frail" (Group 8) were significantly associated with increased inpatient days (P < 0.001), inpatient frequency (P < 0.001), inpatient cost (P < 0.001 and P < 0.01, respectively), and total healthcare cost (P < 0.001) than "robust" to "robust" (Group 1) older adults. A transition to frailty from "pre-frail" to "frail" (Group 6) resulted in a $2,339 total healthcare cost increase, and from "frail" to "pre-frail" (Group 8), a $1,605, compared to "robust" to "robust" older adults. Frailty among community-dwelling older adults is economically relevant. Therefore, it is crucial to study the burden of medical expenses and countermeasures for older adults to not only provide appropriate medical services but also to prevent the decline in their living standards due to medical expenses.


Determination of guanosine 3',5'-cyclic-monophosphate in tissues of the free living nematode, Panagrellus redivivus.
1. Tissue levels of guanosine 3',5'-cyclic monophosphate (c-GMP) were determined by radioimmunoassay in mixed-age populations of the free living nematode Panagrellus redivivus. 2. Cyclic-GMP was identified by chromatography (ion exchange and thin-layer) and by enzymatic degradation.


Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care.
Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU. Preliminary studies on neonates admitted to operating NICUs demonstrate performance comparable to the most advanced clinical-standard monitoring systems.


Characterization of the chirality of the monohydroxy-eicosatetraenoic acids produced by rat basophilic leukemia cells.
Incubation of rat basophilic leukemia cells with exogenous arachidonic acid and permeabilizing concentrations of ethanol resulted in the production of 5-, 12-, and 15-hydroxyeicosatetraenoic acids. With chiral phase high performance liquid chromatography, it was demonstrated that the 5-hydroxyeicosatetraenoic acid had strict (S) stereospecificity while contrary to expectation, the 12- and the 15-hydroxyeicosatetraenoic acids were non-racemic mixtures of the stereoisomers with the S/R ratios averaging 8.6 and 2.2, respectively. If the strict (S) stereospecificity of mammalian lipoxygenases holds true, these results suggest that the 15- and 12-hydroxyeicosatetraenoic acids may be derived from non-lipoxygenase sources. Examination of the chirality of the oxygenase products of unsaturated fatty acids may be of value in defining the enzymes which are activated in vivo in pathological states.


Metal complexes of natural melophlins and their cytotoxic and antibiotic activities.
Complexes of the natural melophlins A and C with Mg, Zn, Ga, La and Ru were prepared, characterized and tested for antimicrobial and cytotoxic effects. The lanthanum complex La(melophlinato C)(3) and the ruthenium complex chlorido(eta(6)-p-cymene)(melophlinato C)ruthenium(II) inhibited cells of human A-498 kidney cancer at IC(50)=0.54 microM and 1.0 microM, respectively, and so distinctly better than free melophlin C. Another synergistic effect of coordinating melophlins to bioactive metals was found in the growth inhibition of the melophlin C-resistant bacterium Micrococcus luteus by Ga, La and Ru complexes of melophlin C.


A complete suction system for operative surgery.
A versatile suction system utilizing a hand-held suction head with on-off control is described. Interchangeable nozzles and guards adapt the sucker to work appropriately in most operative situations.


Eating habits, beliefs, attitudes and knowledge among health professionals regarding the links between obesity, nutrition and health.
To document knowledge, attitudes, beliefs and eating habits of health professionals with respect to obesity, nutrition and weight management. A self-complete questionnaire postal survey. Primary care and dietetic practice in Scotland. A systematic stratified sample of 2290 subjects incorporated general practitioners (n=1400), practice nurses (n=613) and all practising dietitians (n=360) who were members of the British Dietetic Association. The overall response rate was 65%. All professionals showed a clear understanding of nutrition and health. Understanding of obesity as a disease and of the effectiveness of weight management using low-energy diets was limited. Below 10% had carried out audit to determine the incidence of obesity and overweight, and most were uncertain about their own effectiveness in delivering weight management advice. This study confirms that health professionals have some knowledge of nutrition and weight management but are unclear how to deliver effective weight management advice. Further training is justified to ensure the effective provision of nutritional advice to patients.


[Fast-tracking and regional anaesthesia: preliminary feasibility study].
The monitoring in the post-anaesthesia care unit (PACU) improves the safety, the comfort and the analgesia of patients. At present, studies suggest the possibility to bypass the PACU according to the principle of fast-tracking (FT). The aim of this study was to evaluate the feasibility and the safety of a simulated protocol of FT after a regional anaesthesia. Seven hundred patients were prospectively included in this study over a period of 6 months. The Withes' scoring system was used for determining when patients could be safely discharged from PACU. We added a variable concerning the monitoring of surgical site. A minimum score of 14 was required on arrival to the PACU to consider a FT. The success rate of blocks, the use of sedation or general anaesthesia were noted. Adverse events were recorded. The success rate of blocks was 93 %. The score was higher than 14 in 98 % of case on arrival to the PACU. Thirteen adverse events were reported before surgery and/or operating room. No adverse events were reported during the stay in the PACU. Regional anaesthesia seems to be an appropriate principle to fast-track the PACU. It could be a way to reduce health care costs, and can offer solution for the PACU congestion problem. In France, the fast-tracking is a marginal concept without any support regulatory. An evolution to such a practice could be considered.


Chemotaxis between Vibrio cholerae O1 and a blue-green alga, Anabaena sp.
The chemotactic response of Vibrio cholerae O1 towards the mucilaginous sheath of Anabaena sp. was investigated by capillary tube method using a virulent strain of V. cholerae O1, El Tor, Ogawa (3083-T) and its isogenic mutant (HAP-1-T) that lacks the hap gene, which codes for mucinase (HA/protease). Homogenates of Anabaena sp. and purified mucin were used in this study as chemoattractants. Results showed 5.7% bacterial accumulation of wild-type V. cholerae O1 towards 4% homogenates of Anabaena sp. whereas, its mutant (hap-) showed 2.9% accumulation after 90 min. The higher percentage of attraction of wild-type V. cholerae O1 than the mutant (hap-) towards mucin and the homogenates of Anabaena sp. might be due to the activity of mucinase. These results indicate the role of mucinase in the chemotactic motility of V. cholerae O1 towards Anabaena sp.


Plant-Derived Insecticides Under Meta-Analyses: Status, Biases, and Knowledge Gaps.
Plant-derived or botanical insecticides are biopesticides experiencing substantial ongoing increase in interest. The 74 years of our literature survey tracked over 2500 papers on botanical insecticides published between 1945 and 2019 (Web of Science database). Such a survey allowed meta-analyses to recognize current status and biases of the studies providing important insights into the research topic. They include the recognition of the exponential growth of such studies since the 1990s, the prevalent interest on the Meliaceae plant species and a dozen additional families, although some 190 families have been investigated. The arthropods targeted by such studies were pest species (ca. 95%) with rather little attention devoted to non-target species (p < 0.001). This bias is followed by another one-mortality assessments are prevalent among target and non-target arthropod species when contrasted with sublethal assessments (p < 0.01). These omissions are pivotal, as they fail to recognize that sublethal effects may be as important or even more important than mortality, and that initial insecticide deposits quickly degrade over time leading to prevailing sublethal exposure. Furthermore, although the target of control is limited to few species, non-target species will be exposed and as such need to be factored into consideration. Thus, these biases in studies of botanical insecticides incur in knowledge gaps with potential consequences for the practical use of these compounds as pest management tools.


Inhibition of sterol biosynthesis in Saccharomyces cerevisiae by N,N-diethylazasqualene and derivatives.
The ability of some azasqualene derivatives to inhibit yeast cell growth was compared with their inhibition activity on squalene-2,3-oxide cyclase (EC 188.8.131.52) both in living cells and in microsome preparations. Among the compounds tested, N,N-diethylazasqualene showed the best correlation between the activity on squalene-2,3-oxide cyclase and its inhibition of yeast growth. The N-oxide derivative, N,N-diethylazasqualene N-oxide, which was as active as the amine in microsomes, was much less active in living cells, probably because it could not easily penetrate the cell wall. Kinetic analysis of the inhibitory activity of compounds on squalene-2,3-oxide cyclase revealed a sharp difference between N,N-diethylazasqualene and its N-oxide; the former showed a non-competitive-type inhibition, whereas the latter behaved as a competitive inhibitor.


Comparison of conventional and macrophyte-based systems for the treatment of domestic wastewater.
Different wetland and stabilisation ponds, comprising of duckweed, reed and algal systems, were compared for the treatment of domestic sewage. Within the large performance variations observed within systems, the differences observed between systems can be considered to be insignificant.


Trpm2 Ablation Accelerates Protein Aggregation by Impaired ADPR and Autophagic Clearance in the Brain.
TRPM2 a cation channel is also known to work as an enzyme that hydrolyzes highly reactive, neurotoxic ADP-ribose (ADPR). Although ADPR is hydrolyzed by NUT9 pyrophosphatase in major organs, the enzyme is defective in the brain. The present study questions the role of TRPM2 in the catabolism of ADPR in the brain. Genetic ablation of Trpm2 results in the disruption of ADPR catabolism that leads to the accumulation of ADPR and reduction in AMP. Trpm2-/- mice elicit the reduction in autophagosome formation in the hippocampus. Trpm2-/- mice also show aggregations of proteins in the hippocampus, aberrant structural changes and neuronal connections in synapses, and neuronal degeneration. Trpm2-/- mice exhibit learning and memory impairment, enhanced neuronal intrinsic excitability, and imbalanced synaptic transmission. These results respond to long-unanswered questions regarding the potential role of the enzymatic function of TRPM2 in the brain, whose dysfunction evokes protein aggregation. In addition, the present finding answers to the conflicting reports such as neuroprotective or neurodegenerative phenotypes observed in Trpm2-/- mice.


Single-dose cefotetan versus multiple-dose cefoxitin as prophylaxis in colorectal surgery.
The safety and effectiveness of a single 2 g preoperative dose of cefotetan to reduce postoperative infectious complications after colorectal surgery was compared with multiple 2 g perioperative doses of cefoxitin in 289 patients enrolled in a multicenter trial; of the 239 evaluable patients, 164 received cefotetan and 75, cefoxitin. No statistically significant difference was detected in the successful clinical response rates for cefotetan and cefoxitin (88 percent and 92 percent, respectively). The difference in median increase in oral body temperature before and after the study (2.5 degrees F for cefotetan and 2 degrees F for cefoxitin) was statistically but not clinically significant (p = 0.03). Although nearly four times as many cefotetan patients as cefoxitin patients had surgery lasting 4 hours or more, the satisfactory bacteriologic response rates for cefotetan and cefoxitin were similar (88 percent and 93 percent, respectively). Nonobese patients and patients whose surgical procedures lasted less than 4 hours treated with either drug had significantly higher success rates (p less than 0.01). The incidence of major wound infection was approximately 8 percent for both treatment groups. Mean concentrations of cefotetan in plasma, specimens of colon, and subcutaneous fat were 128 +/- 61.8 micrograms/ml, 57.2 +/- 40.4 micrograms/g, and 26.8 +/- 19.4 micrograms/g, respectively. The incidence of adverse reactions was 12 percent for each group, and no reaction was considered treatment-related, including changes in results of clinical laboratory tests. A single 2 g preoperative dose of cefotetan was as safe and effective as multiple doses of cefoxitin in the reduction of postoperative wound infections after colorectal surgery.


New Challenge: Mitochondrial Epigenetics?
Epigenetics can be explored at different levels and can be divided into two major areas: epigenetics of nuclear-encoded DNA and epigenetics of mitochondrial-encoded DNA. In epigenetics of nuclear-encoded DNA, the main roles are played by DNA methylation, changes in histone structure and several types of non-coding RNAs. Mitochondrial epigenetics seems to be similar in the aspect of DNA methylation and to some extent in the role of non-coding RNAs but differs significantly in changes in components coiling DNA. Nuclear DNA is coiled around histones, but mitochondrial DNA, together with associated proteins, is located in mitochondrial pseudocompartments called nucleoids. It has been shown that mitochondrial epigenetic mechanisms influence cell fate, transcription regulation, cell division, cell cycle, physiological homeostasis, bioenergetics and even pathologies, but not all of these mechanisms have been explored in stem cells. The main issue is that most of these mechanisms have only recently been discovered in mitochondria, while improvements in methodology, especially next-generation sequencing, have enabled in-depth studies. Because studies exploring mitochondria from other aspects show that mitochondria are crucial for the normal behavior of stem cells, it is suggested that precise mitochondrial epigenetics in stem cells should be studied more intensively.


Quantitative phosphoproteomic analysis of mice with liver fibrosis by DIA mass spectrometry analysis with PRM verification.
Liver fibrosis (LF), commonly associated with chronic liver diseases, is a major public health problem worldwide. Protein phosphorylation is not only an important form of protein modification in organisms but also the most important mechanism to regulate and control the activity and function of proteins, affecting the occurrence and development of many diseases. However, comprehensive phosphoproteomic profiling in LF has not been fully elucidated. In this study, data-independent acquisition (DIA) was used to analyse the phosphoproteomics of mice with LF. A total of 553 phosphopeptides (representing 440 phosphoproteins) had significant phosphorylation levels. Among these phosphoproteins, 49 were upregulated and 401 were downregulated, and 5 phosphoserine (P-Ser) motifs and 2 phosphothreonine (P-Thr) motifs were conserved in LF. GO and KEGG pathway enrichment analyses identified 769 significant GO terms and 49 significant KEGG pathways. Four phosphorylated proteins were selected for parallel reaction monitoring (PRM) verification, and the results were consistent with DIA data. Together, there were significantly different phosphoproteomic profiles in LF, suggesting that protein phosphorylation was related to the occurrence and progression of LF, which could pave the way for further investigation into the related regulatory mechanisms. SIGNIFICANCE: LF is a necessary stage in the development of chronic liver disease to liver cirrhosis and has attracted wide attention. To the best of our knowledge, there are few reports on the phosphorylated proteomics of LF. In this study, DIA and PRM techniques were used to study the liver tissue of mice induced by CCl4. The results showed that phosphorylation had a significant effect on the activity and function of proteins, and the PRM results were consistent with the trend observed in DIA analysis. This study will help to better reveal the relationship of phosphorylated proteins in LF and lay a foundation for further study of related regulatory mechanisms.


Small Mammals: Common Surgical Procedures of Rodents, Ferrets, Hedgehogs, and Sugar Gliders.
Small mammal surgical procedures are a part of clinical veterinary practice and are performed with regularity. Anesthetic and analgesic techniques are important components of any successful small mammal surgical procedure. Many basic surgical principles used in dogs and cats can be directly applied to small mammals, but tissues tend to be smaller and thinner, and hemostasis is critical with small patients due to risk of death with minimal blood loss. Common surgical procedures in small mammals include integumentary mass and abscess excision, reproductive procedures, gastrointestinal foreign body removal, urolith removal, prolapsed tissues associated with the gastrointestinal tract, intra-abdominal mass excision, and hepatic surgery.


Predictors of binge eating in male and female youths in the United Arab Emirates.
Binge eating is a health-risk behavior associated with obesity, eating disorders and many other diseases. However, binge eating research remains narrow especially in Arab countries where obesity is a primary health concern but studies on psychological factors of compulsive overeating are rare. The present study addressed this gap by examining prevalence rates and key predictors of binge eating among youths in the United Arab Emirates (UAE). Binge eating was assessed together with stress levels, emotional eating, body-related shame and guilt, obsessive-compulsiveness and depression in 254 youths using standardized self-report measures. The study comprised three online-based assessments over a 3-month period. Moderate to severe binge eating was reported by one-third of participants. Emotional eating and body-related guilt were the most consistent and powerful positive binge eating predictors. While stress levels and body-related shame were statistically significant predictors at follow up, neither obsessive-compulsiveness nor depressive symptomatology predicted binge eating in this study. Findings highlight binge eating as a common concern among youths in the UAE with prevalence rates similar to Western samples. Furthermore, the data suggest that binge eating may operate as a maladaptive coping strategy by alleviating negative emotions including boredom and loneliness. The finding that body-related guilt predicted binge eating is important as until now inconsistencies persist as to the relationship between body-related guilt and eating pathology. The study points towards multifactorial risk and maintenance factors of binge eating and extends our understanding within a population where until now research is poor.


The effects of ultrasonication on the phytochemicals, antioxidant, and polyphenol oxidase and peroxidase activities in coffee leaves.
In the present study, we investigated the impacts of ultrasonic conditions on the phytochemical profiles, antioxidant activity, and polyphenol oxidase (PPO) and peroxidase (POD) activities in coffee leaves. Ultrasonic frequency, power, and time, pH, and incubation time affected PPO and POD differently, thus resulting in different ABTS scavenging capacity and phenolic content in coffee leaves. Triple-frequency (20/35/50 kHz) ultrasound significantly (P < 0.05) inhibited trigonelline, caffeine, mangiferin, rutin, chlorogenic acids, antioxidant activity, and PPO activity, while the single frequency of 35 kHz increased the phenolics compounds, which was associated with the lowest POD activity. Increasing the incubation time after ultrasonication gradually decreased phenolic compounds and antioxidant activities, however, POD activity followed a temporal pattern of first increase and then decrease. Our results showed that PPO and POD were temporally inactivated after ultrasonication, which leading to the continuous decrease of phenolics in coffee leaves.


Sense and antisense transcripts in the histone H1 (HIS-1) locus of Leishmania major.
Histone H1 in the parasitic protozoan Leishmania is a developmentally regulated protein encoded by two genes, HIS-1.1 and HIS-1.2. These genes are separated by approximately 20 kb of sequence and are located on the same DNA strand of chromosome 27. When Northern blots of parasite RNA were probed with HIS-1 strand-specific riboprobes, we detected sense and antisense transcripts that were polyadenylated and developmentally regulated. When the HIS-1.2 coding region was replaced with the coding region of the neomycin phosphotransferase gene, antisense transcription of this gene was unaffected, indicating that the regulatory elements controlling antisense transcription were located outside of the HIS-1.2 gene, and that transcription in Leishmania can occur from both DNA strands even in the presence of transcription of a selectable marker in the complementary strand. A search for other antisense transcripts within the HIS-1 locus identified an additional transcript (SC-1) within the intervening HIS-1 sequence, downstream of adenine and thymine-rich sequences. These results show that gene expression in Leishmania is not only regulated polycistronically from the sense strand of genomic DNA, but that the complementary strand of DNA also contains sequences that could drive expression of open reading frames from the antisense strand of DNA. These findings suggest that the parasite has evolved in such a way as to maximise the transcription of its genome, a mechanism that might be important for it to maintain virulence.


Formation of a new fibrous attachment to human dental roots. Effect of co-culturing periodontal ligament-derived and allogenic cortical bone-derived cells.
Human periodontal ligament cells have been shown to produce a new fibrous attachment at the surface of scaled dental root discs in vitro. The purpose of this investigation was to answer the question whether cells derived from human alveolar bone would enhance this attachment. Three partially erupted third molars were extracted and collected from one female patient and used for harvesting periodontal ligament cells as well as for cutting 0.3 mm dental root discs. Cells derived from alveolar bone were obtained by enzymatic digestion of bone chips harvested after extraction of wisdom teeth from three additional patients. Experimental cultures were prepared by seeding 1.0 x 10(6) suspensions of periodontal ligament cells onto five Puropor-200 filters. The following day, root disc pairs were placed on the cell layer, leaving a gap (interdental space) of 0.1-0.3 mm. Five days later, all cultures received equal aliquots of alveolar bone cells. The cultures were terminated and processed for microscopic and morphometric evaluation after 56, 112 and 124 days. All cultures demonstrated a dense fiber-fringe attachment along most of the cementum-lined surfaces of root discs. Adjacent to other root-disc surfaces, cells were surrounded by halos of their collagenous product. Mean diameters of collagen fibrils for the 56-, 112- and the two 124-day cultures were 64.6, 48.9 and 62.6 nm, respectively. Compared to results obtained in this system with periodontal ligament cells alone (Bernstein et al. 1988), the fiber fringe in this experiment was denser, composed of collagen fibrils with a larger diameter, and maintained for longer duration in culture.(ABSTRACT TRUNCATED AT 250 WORDS)


Conformational change following conversion of inactive rhinophrynin-33 to bioactive rhinophrynin-27 in the skin of the frog Rhinophrynus dorsalis.
Skin secretions of the Mexican burrowing toad Rhinophrynus dorsalis (Rhinophrynidae) contain the proline-arginine-rich peptide, rhinophrynin-27 (RP-27; ELRLPEIARPVPEVLPARLPLPALPRN) with insulinotropic and immunomodulatory properties, together with a higher concentration of the biologically inactive form, rhinophrynin-33 (RP-33) that constitutes RP-27 extended from its C-terminus by the hexapeptide KMAKNQ. Determination of the conformation of RP-33 by NMR demonstrates that in both water and in a solvent that promotes protein folding (50% trifluoroethanol-water), the majority of the proline residues are found in a polyproline type II helical region. The peptide adopts a horseshoe (U-shaped) conformation with pronounced bends in the molecule of around 100°-120° at Glu13 and Arg18. The hexapeptide extension adopts a α-helical conformation. When the hexapeptide is excised to generate RP-27, the molecule adopts an L-shaped conformation with a single bend at Glu13. A search of protein sequence databases indicated the P-X-P-XXX-P-XXX-P-X-P motif found in RP-27 and RP-33 occurs in a number of proteins although its functional implications are unclear. The data suggest that RP-33 represents a biosynthetic precursor of RP-27 that is activated by a protease cleaving at a single lysine residue of the type previously identified in Xenopus laevis skin secretions.


Fibrinogen Level and Bleeding Risk During Catheter-Directed Thrombolysis Using Tissue Plasminogen Activator.
The purpose of this study was to determine whether low fibrinogen levels (fibrinogen level <1.5 g/L) during catheter-directed thrombolysis are associated with an increased bleeding risk. A retrospective review was performed on patients undergoing extremity arterial or venous thrombolysis between 2005 and 2013. Patients in the low fibrinogen group were younger (P = .006) and had a higher number of venous occlusive events (P = .004). The low fibrinogen group received a larger dose of tissue plasminogen activator (tPA; P = .009) and had a longer duration of thrombolysis (P = .010). The rates of major bleeding were not significantly different (P = .139). Univariate analysis showed that larger total dose and longer duration of tPA infusion were associated with increased bleeding complications (P < .01 and P = .03). A fibrinogen level <1.5 g/L during thrombolysis was not associated with an increased bleeding risk. However, larger dose and longer duration of thrombolysis were associated with increased bleeding risk.


Coping self-efficacy mediates the effects of negative cognitions on posttraumatic distress.
Although cognitive distortions have predicted posttraumatic distress after various types of traumatic events, the mechanisms through which cognitive distortions influence posttraumatic distress remain unclear. We hypothesized that coping self-efficacy, the belief in one's own ability to manage posttraumatic recovery demands, would operate as a mediator between negative cognitions (about self, about the world, and self-blame beliefs) and posttraumatic distress. In the cross-sectional Study 1, data collected among 66 adult female victims of child sexual abuse indicated that coping self-efficacy mediated the effects of negative cognitions about self and about the world on posttraumatic distress. The same pattern of results was found in a longitudinal Study 2, conducted among 70 survivors of motor vehicle accidents. Coping self-efficacy measured at 1 month after the trauma mediated the effects of 7-day negative cognitions about self and about the world on 3-month posttraumatic distress. In both studies self-blame was not related to posttraumatic distress and the effect of self-blame on posttraumatic distress was not mediated by coping self-efficacy. The results provide insight into a mechanism through which negative cognitions may affect posttraumatic distress and highlight the potential importance of interventions aimed at enhancing coping self-efficacy beliefs.


Take-home message in times of crisis: Is it really better to treat with cisplatin & pemetrexed than cisplatin & gemcitabine in first line NSCLC? The power of statistical considerations.
During the last decade, the cost of healthcare in oncology is world widely increased both for new drugs and even for traditional chemotherapy when new criteria for selection of patients, for example histology, are applied. Physicians are one of the principal actors in the field, having the initial responsibility to understand and interpret the scientific results in order to reduce the pharmaco-economic impact. Platinum-based doublet chemotherapy is the standard of care in advanced unselected population of Non Small cell Lung cancer (NSCLC) patients. Since the data of pemetrexed in combination with cisplatin were published, several oncologists chose this schedule as first choice in non squamous NSCLC. Another scheme, gemcitabine plus cisplatin, was the comparator for the pivotal study of pemetrexed. In this editorial we critically analyze the real data of this noninferiority study and the importance of statistical knowledge by oncologists for correct interpretation of study results.


Molecular genetic diagnosis of sickle cell disease using dried blood specimens on blotters used for newborn screening.
The protein-based technologies used to screen newborns for sickle cell disease require confirmation with a liquid blood specimen. We have developed a strategy for rapid and specific genotypic diagnosis using DNA extracted from a dried blood spot on the filter paper blotter used to screen newborns. DNA could be microextracted from a specimen as small as a 1/8 inch diameter punched disc representing the dried equivalent of approximately 3 microliters of whole blood. We utilized the DNA from a 1/4 inch diameter specimen (12 microliters equivalent) for polymerase chain reaction amplification of the beta-globin region spanning the sickle cell mutation with detection by allele-specific oligonucleotide probes. Molecular confirmation of genotype from the original blotter would reduce the personnel costs associated with obtaining follow-up liquid blood specimens and would provide information to the family in a more timely and less equivocal manner.


Stability of the transverse carpal arch: an experimental study.
The mechanical characteristics of the transverse carpal arch were studied using fresh-frozen human cadaveric wrists. Tensile properties of the ligaments involved in this structure were also analyzed. The flexor retinaculum did not prove to be a major factor in the maintenance of the carpal arch since its division only reduced the global transverse carpal arch stiffness an average of 7.5%. On the contrary, the transverse intercarpal ligaments connecting the bones of the distal carpal row were shown to have an essential role in providing stability to the carpal tunnel.


Selection affecting enzyme polymorphisms in laboratory populations of Drosophila melanogaster.
Gene frequencies at nine polymorphic enzyme loci were followed in 22 cage populations of D. melanogaster all founded from the same stock but subsequently maintained in different environments. The three factors distinguishing the different environments were temperature and the alcohol and yeast in the medium and for each factor each population experienced either a constant or variable condition. The variable conditions were either coarse-grained (period between changes longer than the generation time) or fine-grained (the period less than the generation time).Six polymorphisms were found to be unaffected by any experimental condition. However, the various constant temperatures tested differed in their effects on Alcohol dehydrogenase (Adh), Amylase (Amy) and Isocitrate dehydrogenase (Idh-NADP) gene frequencies. Furthermore, coarse-grained variation between high and low temperatures increased Amy and Idh-NADP heterozygosity and decreased Amy heterozygosity while fine-grained variation between such temperatures promoted Amy heterozygosity. In addition, joint coarse-grained variation for the type of alcohol and yeast promoted Amy and Idh-NADP heterozygosity as well as heterozygosity averaged over all nine loci.In general, the results suggested two major modifications to the hypothesis of a positive relationship between environmental and genetic variability. First, they indicated that the relationship is not always positive. It varies both between loci and between environments. Second however, they indicated that the relationship is more likely to be positive when the environmental variability is coarse- rather than fine-grained.


Sorption-Desorption Behavior of Doxycycline in Soil-Manure Systems Amended with Mesquite Wood Waste Biochar.
Elevated levels of doxycycline (DC) have been detected in the environment due to its extensive utilization as a veterinary antibiotic. Sorption-desorption behavior of DC in soil affects its transport, transformation, and availability in the environment. Thus, sorption-desorption behavior of DC was explored in three soils (S1, S2, and S3) after manure application with and without mesquite wood-waste-derived biochar (BC) pyrolyzed at 600 °C. Sorption batch trials demonstrated the highest DC sorption in soil S1 as compared to S2 and S3, either alone or in combination with manure or manure + BC. Chemical sorption and pore diffusion were involved in DC sorption, as indicated by the kinetic models. Soil S1 with manure + BC exhibited the highest Langmuir model predicted sorption capacity (18.930 mg g-1) compared with the other two soils. DC sorption capacity of soils was increased by 5.0-6.5-fold with the addition of manure, and 10-13-fold with BC application in a soil-manure system. In desorption trials, manure application resulted in 67%, 40%, and 41% increment in DC desorption in soil S1, S2, and S3, respectively, compared to the respective soils without manure application. In contrast, BC application reduced DC desorption by 73%, 66%, and 65%, in S1, S2, and S3, respectively, compared to the soils without any amendment. The highest DC sorption after BC application could be due to H bonding, π-π EDA interactions, and diffusion into the pores of BC. Hence, mesquite wood-waste-derived BC can effectively be used to enhance DC retention in contaminated soil to ensure a sustainable ecosystem.


Large Pleural Effusion: A Pitfall in the Quantitation of 99m Tc-PYP Imaging for ATTR Cardiac Amyloidosis.
Transthyretin cardiac amyloidosis (ATTR and ATTRv) is an underrecognized cause of heart failure that results from myocardial deposition of misfolded protein (TTR or prealbumin). The diagnosis can be confirmed by uptake of 99m Tc-pyrophosphate ( 99m Tc-PYP) in the heart with serologic studies to rule out light chain disease. We present the case of a 70-year-old woman who underwent a 99m Tc-PYP scan. The patient had a large right-sided pleural effusion that lowered counts in the right chest on planar imaging, interfered with ratio-based grading of PYP uptake, and highlighted the importance of obtaining SPECT/CT for problem-solving in cases where uptake ratios may be spurious.


A novel PCR-based approach for the detection and classification of potential cellulolytic fungal strains isolated from museum items and surrounding indoor environment.
To develop a novel PCR-based method able to detect potential cellulolytic filamentous fungi and to classify them exploiting the amplification of the cellobiohydrolase gene (cbh-I) and its polymorphism. A mixed approach including the combination of (i) fungal cultivation and isolation, (ii) classification of fungal isolates through the amplification of the cbh gene using a fluorescently labelled primer (f-CBH-PCR) and (iii) final fungal identification based on amplification and sequencing of the ITS1-5.8S rDNA-ITS2 region of the selected fungal strains was developed. By this approach, it was possible to screen 77 fungal strains belonging to 14 genera and 26 species. The f-CBH-PCR permitted the discrimination of fungal species, producing typical f-CBH profiles. In this study, the cbh gene was used as a preliminary classification tool able to differentiate among themselves the fungal members isolated from indoor museum items and surrounding environment. Such mixed approach consented the fast identification of all isolated fungal strains. The f-CBH-PCR method demonstrated its discrimination power, and it can be considered as a new molecular system suitable for the classification of fungal strains isolated from different environments.


Tyrosyl-DNA Phosphodiesterase 1 Inhibitors: Usnic Acid Enamines Enhance the Cytotoxic Effect of Camptothecin.
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top1) cleavage complexes and other 3'-end DNA lesions. TDP1 is a perspective target for anticancer therapy based on Top1-poison-mediated DNA damage. Several novel usnic acid derivatives with an enamine moiety have been synthesized and tested as inhibitors of TDP1. The enamines of usnic acid showed IC50 values in the range of 0.16 to 2.0 μM. These compounds revealed moderate cytotoxicity against human tumor MCF-7 cells. These new compounds enhanced the cytotoxicity of the established Top1 poison camptothecin by an order of magnitude.


Sterically biased 3,3-sigmatropic rearrangement of azides: efficient preparation of nonracemic alpha-amino acids and heterocycles.
[reaction: see text] Homochiral alpha-amino acids, heterocycles, and carbocycles are efficiently constructed via a short sequence of reactions starting from the chiral auxiliary p-menthane-3-carboxaldehyde. The key feature of the sequence is a highly selective tandem Mitsunobu/3,3-sigmatropic rearrangement of hydrazoic acid that procures enantiomerically enriched allylic azides. The sequence is either terminated by oxidative cleavage to provide amino acids or by ring-closing metathesis to provide heterocycles or carbocycles bearing nitrogen.


Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood.
Little is known about the prevalence of atopic eczema outside Northern Europe. We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.


Ontogenetic changes in relative levels of cyclic AMP-dependent and cyclic GMP-dependent protein kinases in prostates, epididymides and testes from guinea-pigs.
Changes in relative levels of cyclic AMP-dependent protein kinase (A-PK) and cyclic GMP-dependent protein kinase (G-PK) in prostates, epidymides and testes from guinea-pigs were examined at 3 different ages. During postnatal development, a decrease in the ratio of the 2 classes of protein kinases was seen in prostates, whereas increases of the ratios of the enzymes were found in epididymides and testes.


Estrogenic effect of estradiol-sulfamate on the male rat anterior pituitary.
Estrogen sulfamates (ES) are used for a new treatment strategy to avoid liver-hormone and hormone-liver interactions. ES represent new synthetic steroids having an increased systemic and reduced hepatic estrogenicity when given orally [1,2]. In the present study effects of ES and estradiol-benzoate (EB) on adenohypophyseal (AP) and serum concentrations of prolactin (PRL), luteinizing hormone (LH), and pituitary contents of cAMP and cGMP in the male rat are demonstrated. The weight gain of experimental animals treated by ES, EB or both hormones simultaneously was significantly lower compared to controls. EB but not ES significantly increased the weight of the AP. The amounts of PRL in the AP and serum were significantly increased after EB administration. ES significantly increased only AP content of PRL. EB administered simultaneously with ES exhibited an additive effect on the AP plasma concentrations of PRL. The EB or ES significantly decreased AP and serum concentrations of LH. ES given simultaneously with EB further decreased AP and serum concentrations of LH. After administration of either ES or EB, AP contents of cAMP and cGMP were significantly increased. An additive effect of these estrogens on the cGMP content was found. ES given simultaneously with EB further increased cGMP content in the AP but partially inhibited the effect of EB on the AP cAMP content. The present results demonstrate that the effects of ES on the AP content of PRL, LH, cAMP, and cGMP differ from the effects of EB. Whether this is due to lower levels of estradiol after the administration of ES secondary to its different absorption when compared to EB is unknown. Thus, our data support the concept that the ES has a lesser estrogenic effect on the AP function.


Suppurative otitis media in the rabbit: prevalence, pathology, and microbiology.
The middle ears of 2001 young and 583 adult rabbits being slaughtered for human consumption were examined. Otitis media was found in 87 (4%) of the young rabbits, and in 188 (32%) of the adult rabbits. The condition was bilateral in 61% of the affected young rabbits and 70% of the affected adults. Pasteurella multocida was isolated from 60 (98%) of 61 affected young rabbits. The gross and microscopic lesions and secondary complications were similar to those described in children. Rupture of the tympanic membrane was observed in both affected young and affected adult rabbits.


Elucidation of the molecular mechanisms of two nanobodies that inhibit thrombin-activatable fibrinolysis inhibitor activation and activated thrombin-activatable fibrinolysis inhibitor activity.
Essentials Thrombin-activatable fibrinolysis inhibitor (TAFI) is a risk factor for cardiovascular disorders. TAFI inhibitory nanobodies represent a promising step in developing profibrinolytic therapeutics. We have solved three crystal structures of TAFI in complex with inhibitory nanobodies. Nanobodies inhibit TAFI through distinct mechanisms and represent novel profibrinolytic leads. Background Thrombin-activatable fibrinolysis inhibitor (TAFI) is converted to activated TAFI (TAFIa) by thrombin, plasmin, or the thrombin-thrombomodulin complex (T/TM). TAFIa is antifibrinolytic, and high levels of TAFIa are associated with an increased risk for cardiovascular disorders. TAFI-inhibitory nanobodies represent a promising approach for developing profibrinolytic therapeutics. Objective To elucidate the molecular mechanisms of inhibition of TAFI activation and TAFIa activity by nanobodies with the use of X-ray crystallography and biochemical characterization. Methods and results We selected two nanobodies for cocrystallization with TAFI. VHH-a204 interferes with all TAFI activation modes, whereas VHH-i83 interferes with T/TM-mediated activation and also inhibits TAFIa activity. The 3.05-Å-resolution crystal structure of TAFI-VHH-a204 reveals that the VHH-a204 epitope is localized to the catalytic moiety (CM) in close proximity to the TAFI activation site at Arg92, indicating that VHH-a204 inhibits TAFI activation by steric hindrance. The 2.85-Å-resolution crystal structure of TAFI-VHH-i83 reveals that the VHH-i83 epitope is located close to the presumptive thrombomodulin-binding site in the activation peptide (AP). The structure and supporting biochemical assays suggest that VHH-i83 inhibits TAFIa by bridging the AP to the CM following TAFI activation. In addition, the 3.00-Å-resolution crystal structure of the triple TAFI-VHH-a204-VHH-i83 complex demonstrates that the two nanobodies can simultaneously bind to TAFI. Conclusions This study provides detailed insights into the molecular mechanisms of TAFI inhibition, and reveals a novel mode of TAFIa inhibition. VHH-a204 and VHH-i83 merit further evaluation as potential profibrinolytic therapeutics.


The distribution of acetylcholine receptors in the normal and denervated neuromuscular junction of the frog.
A combined light and electron microscopic investigation was performed to study the distribution and fate of clusters of horseradish peroxidase (HRP)-labelled or rhodamine-labelled alpha-bungarotoxin binding sites in normal and denervated cutaneous pectoris muscles of the frog. After staining for axon and cholinesterase (ChE) it appears that, in normal muscles, binding sites for rhodamine alpha-bungarotoxin are strictly confined to those parts of the synaptic gutter occupied by the nerve terminal. Binding sites are missing in axon-abandoned gutters or gutters occupied only by the Schwann cell. Similarly, in partially occupied gutters, HRP-toxin binding sites are confined to the parts of the muscle fibre membrane apposed to the nerve; they are missing at axon-free lateral parts at which secondary clefts and ChE are present. These observations suggest that junctional acetylcholine (ACh) receptor clusters are strictly controlled by the nerve. Thirty-five days after denervation, receptor density was apparently reduced in some parts of the gutters while other parts of the same gutters showed high receptor density. In addition, the length of gutter totally devoid of receptor clusters increased from an average fraction of 9% in control muscles to 14% in denervated muscles. Loss of receptors occurred both at Schwann cell-free and at Schwann cell-occupied gutters. In muscles denervated for 500-750 days, no toxin binding sites could be detected in the junctional membrane, whereas ChE was still present. Schwann cells had apparently abandoned some gutters but were present at others. Upon arrival of spontaneously reinnervating axons, muscle fibres accumulate ACh receptor clusters at the junctional membrane. Patches intensely labelled with alpha-bungarotoxin and associated with ChE reaction product were found near former junctions in long-term denervated muscles. It is concluded that after long-term denervation the muscle fibre cannot maintain junctional ACh receptor clusters by itself. In normally innervated muscles, receptor clusters are actively maintained by nerve-borne factors near the transmitter release sites.


Modelling major depression epidemiology and assessing the impact of antidepressants on population health.
Randomized controlled trials indicate that antidepressant treatment increases the probability of remission in acute treatment of major depression, diminishes the frequency of relapse during continuation phase treatment and diminishes the risk of recurrence during maintenance treatment. As antidepressant coverage increases in the population, the benefits of antidepressant treatment should begin to translate into improved population health. However, adverse effects can also occur, as can unnecessary treatment. Monitoring the impact of antidepressant treatment on population health should be a priority for health surveillance. Quantitative description of the relationship between treatment provision and population health status will require the use of epidemiological models. A variety of such models have been reported in the literature. None of the existing models, however, are fully satisfactory.


Handwashing.
Essential facts Antimicrobial resistance develops when medicines are used inappropriately. Global estimates suggest that every year more than 700,000 people die from drug-resistant strains of common bacterial and viral infections, such as tuberculosis, malaria and HIV. If antimicrobial resistance continues to increase, this number could rise to 10 million a year by 2050.


Prognostic value of the radiomics-based model in progression-free survival of hypopharyngeal cancer treated with chemoradiation.
To develop a radiomics-based model to stratify the risk of early progression (local/regional recurrence or metastasis) among patients with hypopharyngeal cancer undergoing chemoradiotherapy and modify their pretreatment plans. We randomly assigned 113 patients into two cohorts: training (n = 80) and validation (n = 33). The radiomic significant features were selected in the training cohort using least absolute shrinkage and selection operator and Akaike information criterion methods, and they were used to build the radiomic model. The concordance index (C-index) was applied to evaluate the model's prognostic performance. A Kaplan-Meier analysis and the log-rank test were used to assess risk stratification ability of models in predicting progression. A nomogram was plotted to predict individual risk of progression. Composed of four significant features, the radiomic model showed good performance in stratifying patients into high- and low-risk groups of progression in both the training and validation cohorts (log-rank test, p = 0.00016, p = 0.0063, respectively). Peripheral invasion and metastasis were selected as significant clinical variables. The combined radiomic-clinical model showed good discriminative performance, with C-indices 0.804 (95% confidence interval (CI), 0.688-0.920) and 0.756 (95% CI, 0.605-0.907) in the training and validation cohorts, respectively. The median progression-free survival (PFS) in the high-risk group was significantly shorter than that in the low-risk group in the training (median PFS, 9.5 m and 19.0 m, respectively; p [log-rank] < 0.0001) and validation (median PFS, 11.3 m and 22.5 m, respectively; p [log-rank] = 0.0063) cohorts. A radiomics-based model was established to predict the risk of progression in hypopharyngeal cancer with chemoradiotherapy. • Clinical information showed limited performance in stratifying the risk of progression among patients with hypopharyngeal cancer. • Imaging features extracted from CECT and NCCT images were independent predictors of PFS. • We combined significant features and valuable clinical variables to establish a nomogram to predict individual risk of progression.


Japonins A-D, cyathane diterpenoids with neurite outgrowth-promoting activity isolated from Onychium japonicum using NMR and MS/MS-based molecular networking.
Guided by MS/MS-based molecular networking strategy, four new cyathane diterpenoids japonin A-D (1-4), together with the known analogues (5 and 6), have been isolated from aerial parts of Onychium japonicum. The structures of the new compounds were elucidated through a combination of NMR and MS experiments. Through single-crystal X-ray diffraction analysis, and comparison of experimental and calculated computational electronic circular dichroism (ECD) spectra, the absolute configurations of compounds 1-4 were determined. The new compound 1 showed promoting effects on the differentiation of PC12 at a concentration of 40 μM.


Evaluating alternate discrete outcome frameworks for modeling crash injury severity.
This paper focuses on the relevance of alternate discrete outcome frameworks for modeling driver injury severity. The study empirically compares the ordered response and unordered response models in the context of driver injury severity in traffic crashes. The alternative modeling approaches considered for the comparison exercise include: for the ordered response framework-ordered logit (OL), generalized ordered logit (GOL), mixed generalized ordered logit (MGOL) and for the unordered response framework-multinomial logit (MNL), nested logit (NL), ordered generalized extreme value logit (OGEV) and mixed multinomial logit (MMNL) model. A host of comparison metrics are computed to evaluate the performance of these alternative models. The study provides a comprehensive comparison exercise of the performance of ordered and unordered response models for examining the impact of exogenous factors on driver injury severity. The research also explores the effect of potential underreporting on alternative frameworks by artificially creating an underreported data sample from the driver injury severity sample. The empirical analysis is based on the 2010 General Estimates System (GES) data base-a nationally representative sample of road crashes collected and compiled from about 60 jurisdictions across the United States. The performance of the alternative frameworks are examined in the context of model estimation and validation (at the aggregate and disaggregate level). Further, the performance of the model frameworks in the presence of underreporting is explored, with and without corrections to the estimates. The results from these extensive analyses point toward the emergence of the GOL framework (MGOL) as a strong competitor to the MMNL model in modeling driver injury severity.


Musculoskeletal disorders among doctors and nursing officers : an occupational hazard of overstrained healthcare delivery system in western Rajasthan, India.
The present study was conducted to estimate the prevalence and distribution of MSDs in different anatomical regions among Doctors and NO and to determine their ergonomic risk factors and predictors. This cross-sectional study was conducted in an apex institution in Western India. The socio-demographic information, medical and occupational history, and other personal and work-related attributes were captured using a semi-structured questionnaire, which was developed and finalized by piloting on 32 participants (who were not part of the study). Nordic Musculoskeletal and International Physical Activity Questionnaires were used to assess MSDs and Physical activity. Data were analyzed using SPSS v.23. Prevalence of Musculoskeletal Symptoms (M.S.), Multisite Musculoskeletal Symptoms (MMS), and Widespread Musculoskeletal Symptoms (WMS) were calculated. A comparison was made to estimate the burden and distribution of MSD among Doctors and Nursing officers. Logistic regression was applied to identify the predictors of MSDs and pinpoint the risk factors associated with MSDs. A total of 310 participants, of which 38.7% were doctors, and 61.3% were Nursing Officers (NOs) were included in the study. The mean age of the respondents was 31.63 ± 4.9 years. Almost 73% (95%CI: 67.9-78.1) of participants had MSD in the last 12 months, with approximately 41.6% (95%CI: 36.1-47.3) suffering from MSDs in the previous seven days of the survey. The lower back (49.7%) and the neck (36.5%) were the most affected sites. Working in the same position for a long time (43.5%) and not taking adequate breaks (31.3%) were the highest self-reported risk factors. Females had significantly higher odds of having pain in the upper back [aOR:2.49(1.27-4.85)], neck [aOR:2.15(1.22-3.77)], shoulder [aOR:2.8 (1.54-5.11)], hips [aOR:9.46 (3.95-22.68)] and knee [aOR:3.8(1.99-7.26)]. Females, who are NOs, work for > 48 h per week, and fall in the obese category were significantly at more risk of developing MSDs. Working in an awkward position, treating an excessive number of patients in a day, working in the same position for a long period, performing repeated tasks, and not having enough rest breaks were significant risk factors for MSDs.


Cryoelectron microscopy of Na+,K+-ATPase in the two E2P states with and without cardiotonic steroids.
Cryoelectron microscopy (cryo-EM) was applied to Na+,K+-ATPase (NKA) to determine the structures of two E2P states, one (E2PATP) formed by ATP and Mg2+ in the forward reaction, and the other (E2PPi) formed by inorganic phosphate (Pi) and Mg2+ in the backward reaction, with and without ouabain or istaroxime, representatives of classical and new-generation cardiotonic steroids (CTSs). These two E2P states exhibit different biochemical properties. In particular, K+-sensitive acceleration of the dephosphorylation reaction is not observed with E2PPi, attributed to the presence of a Mg2+ ion in the transmembrane cation binding sites. The cryo-EM structures of NKA demonstrate that the two E2P structures are nearly identical but Mg2+ in the transmembrane binding cavity is identified only in E2PPi, corroborating the idea that it should be denoted as E2PPi·Mg2+. We can now explain why the absence of transmembrane Mg2+ in E2PATP confers the K+ sensitivity in dephosphorylation. In addition, we show that ATP bridges the actuator (A) and nucleotide binding (N) domains, stabilizing the E2PATP state; CTS binding causes hardly any changes in the structure of NKA, both in E2PATP and E2PPi·Mg2+, indicating that the binding mechanism is conformational selection; and istaroxime binds to NKA, extending its aminoalkyloxime group deep into the cation binding site. This orientation is upside down compared to that of classical CTSs with respect to the steroid ring. Notably, mobile parts of NKA are resolved substantially better in the electron microscopy (EM) maps than in previous X-ray structures, including sugars sticking out from the β-subunit and many phospholipid molecules.


Monokines and platelet-derived growth factor modulate prostanoid production in growth arrested, human mesangial cells.
Previous studies have demonstrated considerable prostanoid production by cultured proliferating rat mesangial cells (MC). In this study, human mesangial cells (HMC) were examined during serum-free culture in which the cells were reversibly growth arrested and did not suffer obvious irreversible functional changes. Non-stimulated cells released 2 to 10 pg/24 hr/micrograms cellular protein of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, while TXB2 was not detectable. Stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) induced up to 18-fold (IL-1 beta) or up to fourfold (TNF alpha) increases of prostanoid release. Combinations of the two monokines resulted in significant synergistic induction of PGE2 and 6-keto-PGF1 alpha up to 38 times that of control cells. Interleukin-6 (IL-6) and the HMC-mitogen, platelet-derived growth factor-BB (PDGF-BB) only induced marginal increases in HMC prostanoid generation. However, when PDGF-BB or -AB was combined with IL-1 beta or IL-6, prostanoid generation by HMC was synergistically increased up to 222-fold (IL-1 beta) or 12-fold (IL-6) above the control values, with the induction of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha much greater than TXB2. In the case of IL-1 beta + PDGF-BB the induction of PGE2 release was at least partly due to the synergistic induction of cyclooxygenase activity. These findings demonstrate that both proliferating and reversibly growth arrested HMCs release prostaglandins in response to various inflammatory stimulators and combinations thereof. The findings support the important role of HMC in the regulation of glomerular hemodynamics during inflammatory processes.


Transanal Total Mesorectal Excision for Rectal Cancer.
Transanal total mesorectal excision (taTME) is a technique where rectal dissection is begun transanally in a "bottom-up" fashion. This technique facilitates dissection of the most distal part of the rectum and allows the establishment of the distal margin for rectal cancer. TaTME has proven its utility in facilitating low rectal dissection with significantly lower conversion rates and acceptable perioperative, oncological, and functional outcomes. However, taTME remains a challenging technique to learn and adopt. This article describes the technique, indications, and outcomes of taTME in rectal cancer during the last decade.


Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail.
The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-gamma), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-gamma cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-gamma of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-gamma had not been investigated previously so we first demonstrated the activity of native IFN-gamma in assays of IFN-gamma-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-gamma could influence its biological activity. A truncated hamster IFN-gamma, in which the C-terminal 17 aa were removed by insertion of a stop codon at the position corresponding to the stop codon in the mouse sequence, had approximately 10-fold greater activity than the full length protein when measured in the two bioassays. Polyclonal and monoclonal anti-hamster IFN-gamma antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-gamma.


Gliomas of visual pathways and hypothalamus in children--a preliminary report.
26 children with gliomas of the visual pathway and hypothalamus were seen during 5 years. 4 of them had intraorbital tumors, in 22 children tumors were localized in the chiasmal/hypothalamic regions. In 25 patients the tumors were surgically explored. All 4 intraorbital gliomas were radically removed using a transcranial approach. Exploration without biopsy was performed 7 times, exploration plus limited biopsy in 3 cases. In the remaining 11 operated children partial or subtotal removal of the tumor was possible. One of the 18 histologically verified tumors was an anaplastic glioma, the others were typical pilocytic astrocytomas. 12 children had hydrocephalus. 7 patients died, 19 are still alive. The operative mortality was 4 out of our 25 operated cases (16%). All of these patients had large tumors with posterior spread into the hypothalamus. In future, surgery in these children should be confined to exploration and limited biopsy followed by radiotherapy. We advocate exploration and biopsy in all chiasma/hypothalamic tumors. The growth potential of these tumors is individually variable. We recommend to follow-up all patients at 3 months' intervals by means of visual evoked potentials, visual acuity, fundoscopy and visual field testing. CT scans and X-rays of the optic canals should be performed once a year. Surgery should only be considered if clinical and/or neuroradiological progression has been documented.


A comparison of the sensitivity of PET and NMR for in vivo quantitative metabolic imaging.
Using positron emission tomography (PET) in combination with compounds labelled with positron-emitting radionuclides like 11C, 13N and 15O, it is possible to study metabolism in vivo in a non-invasive way. Nuclear magnetic resonance (NMR) imaging takes advantage of the spin of protons in water molecules to measure both their number and relaxation times in vivo, but is, in principle, not limited to protons and can also be used for other nuclei with a non-zero spin, e.g. 13C and 31P. The use of 13C opens the possibility of studying the metabolism of a large number of compounds. In order to choose the appropriate methodology for metabolic imaging, i.e. PET or NMR, it is important to know the sensitivity of each modality. The present study outlines the sensitivity of both techniques.


Oxidative Stress and Bronchopulmonary Dysplasia: Evidences From Microbiomics, Metabolomics, and Proteomics.
Bronchopulmonary dysplasia is a major issue affecting morbidity and mortality of surviving premature babies. Preterm newborns are particularly susceptible to oxidative stress and infants with bronchopulmonary dysplasia have a typical oxidation pattern in the early stages of this disease, suggesting the important role of oxidative stress in its pathogenesis. Bronchopulmonary dysplasia is a complex disease where knowledge advances as new investigative tools become available. The explosion of the "omics" disciplines has recently affected BPD research. This review focuses on the new evidence coming from microbiomics, metabolomics and proteomics in relation to oxidative stress and pathogenesis of bronchopulmonary dysplasia. Since the pathogenesis is not yet completely understood, information gained in this regard would be important for planning an efficacious prevention and treatment strategy for the future.


RESPIRATION-RELATED VARIATIONS IN CENTRAL VENOUS PRESSURE AS PREDICTORS OF FLUID RESPONSIVENESS IN SPONTANEOUSLY BREATHING PATIENTS.
Objective : The hemodynamic parameters used to accurately predict fluid responsiveness (FR) in spontaneously breathing patients (SB) require specific material and expertise. Measurements of the central venous pressure (CVP) are relatively simple and, importantly, are feasible in many critically ill patients. We analyzed the accuracy of respiration-related variations in CVP (vCVP) to predict FR in SB patients and examined the optimization of its measurement using a standardized, deep inspiratory maneuver. Patients and Methods : We performed a monocentric, prospective, diagnostic evaluation. Spontaneously breathing patients in intensive care units with a central venous catheter were prospectively included. The vCVP was measured while the patient was spontaneously breathing, both with (vCVP-st) and without (vCVP-ns) a standardized inspiratory maneuver, and calculated as: Minimum inspiratory v-wave peak pressure - Maximum expiratory v-wave peak pressure. A passive leg raising-induced increase in the left ventricular outflow tract velocity-time integral ≥10% defined FR. Results : Among 63 patients, 38 (60.3%) presented FR. The vCVP-ns was not significantly different between responders and nonresponders (-4.9 mm Hg [-7.5 to -3.1] vs. -4.1 mm Hg [-5.4 to 2.8], respectively; P = 0.15). The vCVP-st was lower in responders than nonresponders (-9.7 mm Hg [-13.9 to -6.2] vs. -3.6 mm Hg [-10.6 to -1.6], respectively; P = 0.004). A vCVP-st < -4.7 mm Hg predicted FR with 89.5% sensitivity, a specificity of 56.0%, and an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.58 to 0.86) ( P = 0.004). Conclusion : When a central venous catheter is present, elevated values for vCVP-st may be useful to identify spontaneously breathing patients unresponsive to volume expansion. Nevertheless, the necessity of performing a standardized, deep-inspiration maneuver may limit its clinical application.


Women's rape fantasies: an empirical evaluation of the major explanations.
This study evaluated explanations of rape fantasy in a sample of female undergraduates (N = 355) using a sexual fantasy checklist which included eight types of rape fantasy, participants' detailed descriptions of a rape fantasy they have had, a rape fantasy scenario audio presentation, and measures of personality. Three explanations of rape fantasy were tested: openness to sexual experience, sexual desirability, and sexual blame avoidance. Women who were higher in erotophilia and self-esteem and who had more frequent consensual sexual fantasies and more frequent desirability fantasies, particularly of performing as a stripper, had more frequent rape fantasies. Women who were higher in erotophilia, openness to fantasy, desirability fantasies, and self-esteem reported greater sexual arousal to rape fantasies. Sexual blame avoidance theory was not supported; sexual desirability theory was moderately supported; openness to sexual experience theory received the strongest support.


COVID-CCD-Net: COVID-19 and colon cancer diagnosis system with optimized CNN hyperparameters using gradient-based optimizer.
Coronavirus disease-2019 (COVID-19) is a new types of coronavirus which have turned into a pandemic within a short time. Reverse transcription-polymerase chain reaction (RT-PCR) test is used for the diagnosis of COVID-19 in national healthcare centers. Because the number of PCR test kits is often limited, it is sometimes difficult to diagnose the disease at an early stage. However, X-ray technology is accessible nearly all over the world, and it succeeds in detecting symptoms of COVID-19 more successfully. Another disease which affects people's lives to a great extent is colorectal cancer. Tissue microarray (TMA) is a technological method which is widely used for its high performance in the analysis of colorectal cancer. Computer-assisted approaches which can classify colorectal cancer in TMA images are also needed. In this respect, the present study proposes a convolutional neural network (CNN) classification approach with optimized parameters using gradient-based optimizer (GBO) algorithm. Thanks to the proposed approach, COVID-19, normal, and viral pneumonia in various chest X-ray images can be classified accurately. Additionally, other types such as epithelial and stromal regions in epidermal growth factor receptor (EFGR) colon in TMAs can also be classified. The proposed approach was called COVID-CCD-Net. AlexNet, DarkNet-19, Inception-v3, MobileNet, ResNet-18, and ShuffleNet architectures were used in COVID-CCD-Net, and the hyperparameters of this architecture was optimized for the proposed approach. Two different medical image classification datasets, namely, COVID-19 and Epistroma, were used in the present study. The experimental findings demonstrated that proposed approach increased the classification performance of the non-optimized CNN architectures significantly and displayed a very high classification performance even in very low value of epoch.


Intermolecular contact-tuned magnetic nature in one-dimensional 3d-5d bimetallic systems: from a metamagnet to a single-chain magnet.
Assembling [W(CN) 6(bpy)] (-) and magnetic anisotropic Mn Schiff bases produced two Mn (III)(3d)-W (V)(5d) bimetallic chains. Modulation of the types and degrees of interchain pi-pi interactions in the one-dimensional coordination polymers leads to the variation of the magnetic behavior from a metamagnetic character to a single-chain magnet property.


Nucleoside transport in guinea pig myocytes. Comparison of the affinities and transport velocities for adenosine and 2-chloroadenosine.
The affinities of adenosine and 2-chloroadenosine for the nucleoside transport system of guinea pig myocytes were evaluated indirectly by studying the inhibition of the binding of [3H]nitrobenzylthioinosine and directly by measuring the influx of [3H]radiolabeled substrates. Maximal transport velocities of the two nucleosides were also obtained. [3H]Nitrobenzylthioinosine bound to a single class of high-affinity sites (KD of 0.8 nM) which possessed a maximal binding capacity (Bmax) of 870,000 sites/cell. Adenosine, 2-chloroadenosine or the nucleoside transport inhibitor, dipyridamole, competitively inhibited the site-specific binding of [3H]nitrobenzylthioinosine with Ki values of 318 microM, 22 microM and 75 nM respectively. Both [3H]adenosine and [3H]2-chloroadenosine entered myocytes in a saturable and inhibitible manner. Observed transport kinetic constants (Km and Vmax) were 146 microM and 24.2 pmoles/10(6) cells/sec, respectively, for adenosine and 36 microM and 11.7 pmoles/10(6) cells/sec, respectively for 2-chloroadenosine. Affinities of adenosine, 2-chloroadenosine, nitrobenzylthioinosine and dipyridamole for the nucleoside transport system derived from binding and influx methodologies were equivalent which confirms that [3H]nitrobenzylthioinosine binding sites are closely associated with the nucleoside transporter.


Outcomes of quantitative flow ratio-based functional incomplete revascularization after coronary artery bypass grafting surgery.
Quantitative flow ratio is a novel functional assessment tool of coronary diseases. Whether quantitative flow ratio could improve the outcomes of coronary artery bypass grafting is undetermined. This study aimed to investigate the association between the quantitative flow ratio based functional incomplete revascularization and the outcomes after coronary artery bypass grafting surgery. The quantitative flow ratio assessment was retrospectively performed in patients undergoing coronary artery bypass grafting surgery in the PATENCY trial. The anatomic complete revascularization denoted revascularizing each territory with stenosis greater than 50% evaluated by angiography. The functional complete revascularization was defined as grafting all vessels with a quantitative flow ratio 0.80 or less. The primary end point was the 12-month composite major adverse cardiac or cerebral vascular events. A total of 2024 patients with available quantitative flow ratio values were included. Functional complete revascularization was achieved in 1846 patients (91.2%), and 1600 received anatomic complete revascularization (79.1%). Both the functional incomplete revascularization and anatomic incomplete revascularization groups were associated with significantly increased risks of 12-month major adverse cardiac or cerebral vascular events (functional: hazard ratio, 2.91; 95% confidence interval, 1.56 to 5.43; P = .001; anatomic: hazard ratio, 2.82; 95% confidence interval, 1.54 to 5.16; P = .001). Additionally, for the subgroup of patients (n = 246) receiving anatomic incomplete revascularization but judged as functional complete revascularization by quantitative flow ratio, the risk of the 12-month major adverse cardiac or cerebral vascular events was not significantly increased (adjusted hazard ratio, 1.36; 95% confidence interval, 0.71-2.60; P = .35). Both the functional incomplete revascularization and anatomic incomplete revascularization were associated with increased risks of 12-month major adverse cardiac or cerebral vascular events after coronary artery bypass grafting surgery. The quantitative flow ratio can serve as a supplementary tool for the decision-making of surgical revascularization.


Congenital lobar emphysema.
Congenital lobar emphysema is an uncommon but potentially life-threatening cause of respiratory distress in the newborn. The clinical picture and radiologic findings are diagnostic. Lobectomy in the distressed neonate is curative. In infants with onset of symptoms between one and four months of age surgery may not be necessary. Etiology and pathology of congenital lobar emphysema are not clear at present and require further elucidation.


Correction: A 3-D NanoMagnetoElectrokinetic model for ultra-high precision assembly of ferromagnetic NWs using magnetic-field assisted dielectrophoresis.
[This corrects the article DOI: 10.1039/D0RA08381J.].


Capsaicin-evoked brain activation and central sensitization in anaesthetised rats: a functional magnetic resonance imaging study.
Functional magnetic resonance imaging (fMRI) of blood oxygen level dependent (BOLD) haemodynamic responses was used to study the effects of the noxious substance capsaicin on whole brain activation in isofluorane anaesthetised rats. Rats (n=8) received intradermal injection of capsaicin (30 microg/5 microl), or topical cream (0.1%) capsaicin and BOLD responses were acquired for up to 120 min. Effects of capsaicin versus placebo cream treatment on the BOLD response to a 15 g mechanical stimulus applied adjacent to the site of cream application were also studied. Both injection and cream application of capsaicin activated brain areas involved in pain processing, including the thalamus and periaqueductal grey (PAG) (p<0.05, corrected for multiple comparisons). Capsaicin also produced increases in BOLD signal intensity in other regions that contribute to pain processing, such as the parabrachial nucleus and superior colliculus. Mechanical stimulation in capsaicin-treated rats, but not placebo-treated rats, induced a significant decrease in BOLD signal intensity in the PAG (p<0.001). These data demonstrate that the noxious substance capsaicin produces brain activation in the midbrain regions and reveals the importance of the PAG in central sensitization.


Percutaneous treatment of facial venous malformations: a matched comparison of alcohol and bleomycin sclerotherapy.
Venous malformations (VMs) are common vascular anomalies; 40% are found in the head and neck. Percutaneous sclerotherapy is 1 treatment of choice. In all, 17 patients with facial VMs were treated by percutaneous sclerotherapy using alcohol and individually matched to lesions treated with bleomycin. Treatment details and outcomes were compared. The average numbers of sessions were 1.7 for alcohol and 3.4 for bleomycin. Average dose administered was 8.1 cm³ alcohol and 9.1 units bleomycin. Of those treated with alcohol, 2 developed adverse effects and 7 developed complications. None treated with bleomycin developed adverse effects or complications. All patients treated with alcohol improved clinically. In all, 15 patients treated with bleomycin improved after treatment and 2 were unchanged. Alcohol has a slightly higher success rate and requires fewer treatment sessions. Bleomycin has a lower complication rate and less postprocedural swelling. Bleomycin treatment may be better tolerated and is thus preferred over alcohol sclerotherapy.


Development of cupping and pallor in posterior ischemic optic neuropathy.
A case of arteriosclerotic posterior ischemic optic neuropathy without optic disc edema is described and documented photographically. The development of optic disc cupping and pallor with ischemia in this patient supports the vascular basis for development of similar cupping and pallor in open angle glaucoma and low tension glaucoma.


Burden, risk factors, and infectious complications of cellulitis and erysipelas in US adults and children in the emergency department setting.
Little is known about the use and burden of emergency department (ED) visits for cellulitis/erysipelas in the United States. To determine the prevalence, risk factors, complications, and cost of emergency care for cellulitis/erysipelas in the United States. Cross-sectional study of the 2006 to 2016 National Emergency Department Sample, including a 20% sample of US ED visits (N = 320,080,467). The mean annual incidence of ED visits with a primary diagnosis of cellulitis/erysipelas was 2.42 to 3.55 per million adult and 1.14 to 2.09 per million pediatric ED visits. ED visits for cellulitis/erysipelas decreased significantly from 2006 to 2015 (Rao-Scott chi-square, P < .0001). ED visits with versus without a primary diagnosis of cellulitis/erysipelas were associated with public or no insurance and lower household income quartiles, and were more likely to occur during weekends and summer months. The mean cost of ED visits for cellulitis/erysipelas more than doubled in adults (from $720 to $1680) and tripled in children (from $939 to $2,823) from 2006 to 2016. ED visits for cellulitis/erysipelas were associated with multiple risk factors and increased infectious complications. No data on cellulitis and erysipelas treatment or recurrence. There is a substantial and increasing burden of ED visits for cellulitis/erysipelas in the United States. Many ED visits occurred for uncomplicated cellulitis/erysipelas, in part because of health care disparities.


Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons.
Fractionation of octyl glucoside-solubilized proteins from young rat brain was monitored using rat brain neurons, which were cultured in microwells coated with various protein fractions to be studied. An adhesive protein that promotes neurite outgrowth in rat brain neurons was isolated by chromatography on heparin-Sepharose followed by Affi-Gel blue. The apparent molecular mass of the protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions was about 30 kilodaltons (p30). Under nonreducing conditions a closely spaced doublet band was observed corresponding to 27-28-kilodalton size. Gel filtration in the presence of 4 M urea indicated the molecular size of 58 kilodaltons suggesting a dimeric structure. Western blotting experiments using affinity-purified rabbit antibodies detected p30 as an immunochemically distinct protein in brain and in N18 neuroblastoma cells. The p30 protein was also detected in the N18 cells by lactoperoxidase-catalyzed cell surface iodination. Western blotting of heparin-binding proteins solubilized from brains of rats of various age groups indicated that p30 is clearly more abundant in perinatal brain as compared to adult tissue. The neuron-binding and neurite outgrowth-promoting properties of p30 as well as the developmental regulation of its content in brain tissue suggest a role in neuronal growth.


Changes in left ventricular contractility with the phase of respiration.
The end-systolic wall stress (sigma(es))-velocity of circumferential fiber shortening (V(cfsc)) relation was defined during the respiratory cycle, in order to obtain a totally noninvasive measure of left ventricular contractility. Eight young, healthy subjects were studied with echocardiography and calibrated carotid pulse tracings, while performing slow paced breathing. Left ventricular sigma(es) vs. V(efsc) relation was determined by fitting linear regression line to data points obtained at different times during the respiratory cycle. Data are given as mean+/-1SD. Left ventricular sigma(es) and V(efsc) exhibited small but significant changes during the respiratory cycle: sigma(es) was highest in late inspiration (56.9+/-4.8 g/cm2) and lowest in late expiration (49.2+/-3.7 g/cm2); inversely, V(cfsc) was lowest during late inspiration (1.18+/-0.17 circ/s) and highest during late expiration (1.34+/-0.20 circ/s). The relation was significant in each subject (r = -0.64+/-0.13) and remained inverse and significant, when it was determined separately for inspiration and expiration (r = -0.61+/-0.17 and -0.68+/-0.12, respectively). At identical end-systolic wall stress, the velocity of shortening was greater during inspiration then expiration, suggesting that contractility was reduced during the expiratory phase. The reduced expiratory contractility might reflect increased vagal influence on the ventricular myocardium.


Mechanism of reductive protein unfolding.
The reductive unfolding of ribonuclease A with dithiothreitol proceeds through parallel pathways with the formation of two well-populated partially-unfolded three-disulphide intermediates. Two distinct local unfolding events rather than a global one are involved in the rate-limiting steps. These results are contrary to the current view that protein unfolding generally follows an all-or-none mechanism, and that the rate-limiting step is controlled by an extensive rearrangement of the native structure. Sequential breakage of disulphide bonds through local unfolding events is energetically more favourable than disruption of the native structure through global unfolding. The results also indicate that the oxidative refolding of ribonuclease A from the fully-reduced form proceeds through parallel conformationally-distinct transition states.


Casein kinase II accumulation in the nucleolus and its role in nucleolar phosphorylation.
A rabbit antiserum against highly purified casein kinase II from mouse tumor cells was used for immunolocalization of the enzyme in fixed, permeabilized mouse cells. Casein kinase II was highly accumulated in nucleoli compared to the extra-nucleolar space of the nucleus or to the cytoplasma. Casein kinase II samples highly purified from the cytoplasma, from the extra-nucleolar fraction of the nucleus or from nucleoli exhibited no differences with respect to structure and function. All samples originally had an alpha 2 beta 2 structure (alpha, 42 kDa; beta, 24 kDa) showing formation of the alpha'-chain (36 kDa) only in the late steps of purification. The isoelectric point of the alpha-chain of all three samples was pH 7.7 and that of the beta-chain was pH 6.4-6.6. Using ATP or GTP, all three casein kinase II samples gave the same results of maximum phosphorylation of purified nucleolar marker phosphoproteins pp105/C23, pp135 and B23, yielding pp135 as one of the most highly phosphorylated proteins with an incorporation of about 75 phosphate groups per molecule pp135. Studies on optimum conditions of phosphorylation of nucleolar phosphoproteins by casein kinase II revealed that each of the protein substrates individually responded to alterations of assay parameters such as pH, magnesium ion and sodium chloride concentrations indicating that predominantly individual structural criteria were responsible for optimum phosphorylation. The determination of the apparent Km of casein kinase II for purified nucleolar phosphoproteins yielded values of 0.15 microM (pp105/C23), 0.1 microM (pp135) and 1.0 microM (B23) identifying them as high-affinity substrates of casein kinase II.


Cobblestone-area forming cells derived from patients with mantle cell lymphoma are enriched for CD133+ tumor-initiating cells.
Mantle cell lymphoma (MCL) is associated with a significant risk of therapeutic failure and disease relapse, but the biological origin of relapse is poorly understood. Here, we prospectively identify subpopulations of primary MCL cells with different biologic and immunophenotypic features. Using a simple culture system, we demonstrate that a subset of primary MCL cells co-cultured with either primary human mesenchymal stromal cells (hMSC) or murine MS-5 cells form in cobblestone-areas consisting of cells with a primitive immunophenotype (CD19-CD133+) containing the chromosomal translocation t (11;14)(q13;q32) characteristic of MCL. Limiting dilution serial transplantation experiments utilizing immunodeficient mice revealed that primary MCL engraftment was only observed when either unsorted or CD19-CD133+ cells were utilized. No engraftment was seen using the CD19+CD133- subpopulation. Our results establish that primary CD19-CD133+ MCL cells are a functionally distinct subpopulation of primary MCL cells enriched for MCL-initiating activity in immunodeficient mice. This rare subpopulation of MCL-initiating cells may play an important role in the pathogenesis of MCL.


Gas chromatographic studies of vinyl chloride in air by catalytic hydrogenation to ethyl chloride.
In order to investigate the amount of vinyl chloride in air, the hydrogenation of vinyl chloride to ethyl chloride is used. This method of determination is preferable to the other methods described in the literature because: (a) it proves that only vinyl chloride goes through hydrogenation by its displacement to the ethyl chloride peak in the chromatogram; (b) the actual amount of vinyl chloride can be obtained in the case of superimposed or interfering peaks (e.g., various gases contained in air samples), either by calculating the ethyl chloride peak area or by the reduction of the peak area in the region of the same retention time as the vinyl chloride peak in the related chromatogram. In this study various kinds of catalysts for hydrogenation purposes at temperatures ranging from -20 to 250 degrees have been used. Among the catalysts used palladium gives the best results at low temperature.